IAP Textbook of Pediatrics (2 Volumes), 4th Edition PDF

IAP
Textbook
of Pediatrics
4th Edition
IAP
Textbook
of Pediatrics
4th Edition
Editor-in-Chief
A Parthasarathy
Professor of Pediatrics, Madras Medical College, and

Deputy Superintendent, Institute of Child Health and Hospital for Children, Chennai (Retired)
National President, IAP 1997, Regional Advisor, APPA, 199799
Founding Editor-in-Chief, Indian Journal of Practical Pediatrics
Contributory Editor, ColorAtlas of Tropical Pediatrics, American Academy of Pediatrics 2009
Executive Academic Editor

PSN Menon
Sub-Dean, Professor of Pediatrics, Division of Pediatric Endocrinology and

Officer in-Charge Genetic Unit, All India Institute of Medical Sciences, New Delhi (Retired)
Consultant and Head, Department of Pediatrics
Jaber Al-Ahmed Armed Forces Hospital, Kuwait
Senior Editors
RK Agarwal
Naveen C Thacker
Deepak Ugra
President, IAP 2006

Senior Consultant Pediatrician and Director
Deep Children Hospital and Research Centre
Gandhidham (Kutch), Gujarat, India
Piyush Gupta
Panna Choudhury
President, IAP 2009

Editor-in-Chief, Indian Pediatrics 2005-7
Consultant Pediatrician
Lok Nayak Hospital, New Delhi, India
President, IAP 2008

Senior Consultant Pediatrician and Director
RK Hospital
Udaipur, Rajasthan, India
President Elect, IAP 2010

Lilawati Hospital and Research Centre, Mumbai
Guru Nanak Hospital and Research Centre, Mumbai
Senior Academic Editors
Professor of Pediatrics
University College of Medical Sciences
New Delhi, India
Editor-in-Chief, Indian Pediatrics 2008-10
MKC Nair
Professor of Pediatrics and Clinical Epidemiology

Director, Child Development Centre
Medical College, Thiruvananthapuram, Kerala, India
President IAP 2004, President INDIACLEN 2005-7
Executive Editors
Rohit C Agrawal
Tanmay Amladi
Honorary Secretary General, IAP 2007-08

Director, Chandra-Jyoti Children Hospital
Mumbai, Maharashtra, India
Treasurer, IAP 2007-8, Honorary Neonatologist

Nowrosjee Wadia Maternity Hospital and NICU
Parel, Mumbai, Maharashtra, India
Academic Editor
K Nedunchelian
Editor-in-Chief, Indian Journal of Practical Pediatrics

Assistant Professor of Pediatrics, Madras Medical College
Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, India
JAYPEE
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IAP Textbook of Pediatrics , 4th edition
2009, Indian Academy of Pediatrics, Kailas Darshan, 1st Floor, Kennedy Bridge, Nana Chowk, Mumbai 400 007, India
Tel: (022) 23887906/23887922/23889565 Fax: (022) 23851713
E-mail: iapcoff@bom5.vsnl.net.in; centraloffice@iapindia.org
Websites: www.iapindia.org/www.ijpp.org/www.indianpediatrics.net/www.iapdrugformulary.com
All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or by any means:
electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the Indian Academy of Pediatrics and
the publisher.
This book has been published in good faith that the material provided by editors is original. Every effort is made to ensure accuracy of
material, but the publisher, printer and Indian Academy of Pediatrics will not be held responsible for any inadvertent error(s). In case of
any dispute, all legal matters are to be settled under Delhi jurisdiction only.
First Edition: 1999, 2000
Second Edition: 2002, 2003
Third Edition: 2006
Revised Reprint 2007
Fourth Edition: 2009
ISBN 978-81-8448-580-6
Typeset at JPBMP typesetting unit
Printed at Ajanta
To
The Children of India
Whose Care, Survival and
Development are Our Concern
IAP Textbook of Pediatrics

This textbook has covered all aspects of child health contributed by reputed authors, in addition to
National Health Programs. Thus, it has fulfilled all the criteria of a reader friendly treatise
Dr Uday Bodhankar
President, IAP 1995
President, ISTP 1999-2001
Nagpur
Several luminaries who are past and present teachers have contributed their might which has made the
present textbook a novel production in many aspects
Prof YC Mathur
President, IAP 2001
Hyderabad
Indeed it is a millennium gift to students and practitioners in a well written and well presented
comprehensive format covering A to Z in Pediatric care
Dr Swati Y Bhave
President, IAP 2000
New Delhi
Teachers of Pediatrics will find in this book guidelines for the course contents in undergraduate and
postgraduate medical education. Medical students will find readable and reasonably detailed, yet concise
information in this book, not only to complete the course and pass the final examination, but also to guide
them during their clinical career as intern, house surgeon and medical practitioner
Prof T Jacob John
President, IAP 1999
Vellore
I hope this textbook finds an appropriate place in the students' and practitioners' bookshelf. I sincerely
wish that this book is also suitable for undergraduates and postgraduates
Prof MR Lokeshwar
President, IAP 1998
Mumbai
Contributors
Aditi Sinha
Senior Research Associate
Department of Pediatrics
All India Institute of Medical
Sciences, New Delhi 110 029
Residence
5B Srijan Apartments
B 9/8 Sector 62
Noida
Uttar Pradesh
Email: aditisinha4@rediffmail.com
Advani SH
Director
Department of Medical Oncology
Jaslok Hospital, Peddar Road
Mumbai
Maharashtra
Residence
201 Satyam Shivam Sunderam
Ghatkopar
Mumbai 400 077
Maharashtra
Email: shadvani2000@rediffmail.com
Agarwal DK
D-115 Sector 36, Noida
Gautam Budh Nagar 201 301
Uttar Pradesh
Agarwal KN
D-115 Sector 36, Noida
Uttar Pradesh
Email: kna_noida@hotmail.com;
adolcare@hotmail.com
Agarwal R
BJ Wadia Hospital for Children and
Institute of Child Health
Parel, Mumbai 400 012
Maharashtra
Agarwal RK
Consultant Child Specialist
RK Hospital
5A Madhuban
Opposite RSEB Window
Udaipur 313 001, Rajasthan
Email: rk_hospital@hotmail.com;
presidentiap2008@gmail.com
Ajit Kumar
3/6/69/B/20/4/A
Avanti Colony
Near Skyline Theatre
KB Lal Road, Bashirbag
Hyderabad 500 029
Andhra Pradesh
Amdekar YK
151 Tushar 1st Floor
14th Road Chembur
Mumbai 400 071, Maharashtra
Email: ykasya@gmail.com
Amit Upadhyaya
Consultant Hematologist
Sunflag-Pahuja Center for
Blood Disorders
Sunflag Hospital, Faridabad
Haryana
Email: dramit.upadhyay@yahoo.co.in
Amrish Vaidya
Consultant Pediatric Surgeon
Kokilaben Dhirubhai Ambani
Hospital, Andheri West
Mumbai 400 053
Maharashtra
Residence
5E Sundatta Apartments
10A Mount Pleasant Road
Mumbai 400 006
Maharashtra
Email: amrishvaidya@yahoo.com
Anand N Pandit
British Council Building
917/1 Fergusson College Road
Pune 411 004, Maharashtra
Email: kemhrc@vsnl.com
Anand RK
55 Kavi Apartments, Worli
Email: ishanand@rediffmail.com
Anandam R
Professor of Pediatric Neurology (Retd)
Consultant Neurologist
PRS Hospital, Killippalam
Thiruvananthapuram, Kerala
Residence
RAJCOT
Thycaud
Thiruvananthapuram 695 014
Kerala
Email: anandam45@yahoo.com
Anil Mokashi
Ramabai Maternity General
and Childrens Hospital
Baramati, Pune 413 102
Maharashtra
Anil Sachdev
63/12
Old Rajinder Nagar
New Delhi 110 060, Delhi
Email: anilcriticare@hotmail.com
Anita Khalil
The Heart Centre
2 Ring Road
Lajpat Nagar IV
Email: anitakhalil@yahoo.com
Anju Aggarwal
Reader in Pediatrics
University College of Medical
Sciences and Guru Tegh Bahadur
Hospital
Delhi
Residence
Flat # 3C Block C2B, Janakpuri
Email: aggar_anju@yahoo.com;
aanju67@gmail.com
Anju Virmani
C 6/6477
Vasant Kanj
New Delhi 110 070
Email: virmani.anju@gmail.com
Anupam Sachdeva
C-107 Neelambar Apartment
Near Sainik Vihar
Shakurbasti
New Delhi 110 034
Email: anupamace@yahoo.co.in
Anupama Borker
Consultant Pediatric
Hemato-Oncologist
SL Raheja Hospital
Mahim, Mumbai
Maharashtra
Residence
22 Kaustubh Plot # 8
Bandra Reclamation
Bandra (West)
Mumbai 400 050
Maharashtra
Email: anupamasb@hotmail.com
Archana Sathe
Om Padmalaya
1123/A Shukrawar Peth
Opposite Hirabag
Pune 411 002
Maharashtra
Ashish R Bavdekar
11 Yeshwant Nagar
Ganeshkhind Road
Pune 411 007
Maharashtra
Email: bavdekar@vsnl.com
Armida Fernandez
53 Sea Springs
BJ Road, Band Stand
Bandra (West)
Mumbai 400 050
Maharashtra
Email: drfernandez@snehamumbai.org
Ashok Gupta
25 Chetak Marg
Near JK LON Hospital
Jaipur 302 004, Rajasthan
Email: dr_ashok_05@hotmail.com
Arun Gupta
BP 33, Pitampura
Email: ritarun@vsnl.com
Arun Kumar Gupta
Professor and Head
Department of Radiodiagnosis
All India Institute of
Medical Sciences, New Delhi 110 029
Email: arun676@hotmail.com;
arunk676@yahoo.com
Arun Phatak
102 Ambica Apartments
Shanker Tekri
Dandia Bazaar
Vadodara 390 001
Gujarat
Email: atphatak@satyam.net.in
Anurag Tomar
4 Govind Marg
Jaipur 302 004
Rajasthan
Email: anurag@nimsr.com
Arunmozhi T
Assistant Professor of
Community Medicine
Madras Medical College
Residence
8I Block, 2nd Main Road
Chennai 600 102
Tamil Nadu
Archana S Kher
6/A Anand Bhavan
36th Road, TPS III
Bandra (West)
Mumbai 400 050
Maharashtra
Email: kheras@bom8.vsnl.net
Arvind Bagga
Division of Nephrology
Sciences, Ansari Nagar
New Delhi 110 029
Email: arvindbagga@hotmail.com
Ashok K Deorari
Division of Neonatology
Medical Sciences
New Delhi 110 029
Residence
D-II/22, Ansari Nagar
Email: sdeorari@yahoo.com;
ashokdeorari_56@hotmail.com
Ashok K Gupta
50 B/D, Gandhinagar
Jammu 180 004
Jammu and Kashmir
Email: doc_ashokg@yahoo.com
Ashok K Patwari
Readers Flat # 4
LHMC Campus
Bangla Sahib Road
New Delhi 110 001
Email: akpatwari@hotmail.com;
akpatwari@gmail.com
Ashok S Kapse
Kapse Children Hospital
1st Floor, Akshar Complex
B/H Rang Upvan, Makkaipool
Surat 395 001, Gujarat
Email: ashokkapse@hotmail.com
Babu George
Medical Superintendent
Child Development Centre
Medical College Campus
Thiruvananthapuram,
Kerala
Contributors XI
Balachandran A
F/177 Plot # 235
Anna Nagar, Chennai 600 102
Tamil Nadu
Email:dr_abalachandran@hotmail.com;
drabalachandran@yahoo.com
Baldev S Prajapati
Aakanksha Children Hospital
Opposite Tulsishyam Flats
Nava Vadaj Road
Ahmedabad 380 013
Gujarat
Email: drbprajapati@yahoo.co.in
Balvir S Tomar
4 Govind Marg
Jaipur 302 004
Rajasthan
Banapurmath CR
DOOR # 176 3rd Main Road
PJ Extension
Devangere 577 002, Karnataka
Email: crbanapurmath@hotmail. com
Banerjee SR
8 Jessore Road, Dum Dum
Kolkata 700 028, West Bengal
Email: purnima@cal.bsnl.net.in;
srbanerjee@vsnl.net
Baskar PK
Director
Sri Viveka Institute of Dental
Sciences
54, GN Chetty Road, T Nagar
Chennai 600 017, Tamil Nadu
Bhandari B
90/L Road, Bhupalpura
Udaipur 313 001, Rajasthan
Bhandari NR
C-32 Koh-e-Fiza
BDA Colony
Bhopal 462 001
Madhya Pradesh
Email: bhandari33@rediffmail.com;
nr_bhandari@yahoo.com
Bharat Agarwal
A1101 Jagat Vidya CHS
Behind Guru Nanak Hospital
Bandra-Kurla Complex
Bandra (East)
Mumbai 400 051
Maharashtra
Email: parul@bom5.vsnl.net.in
Bharat Dalvi
Division of Pediatric Cardiology
Department of Cardiology
King Edward VII Memorial Hospital
Mumbai, Maharashtra
Bhaskar Raju B
# 11 Sringeri Mutt Road
Ramkrishna Nagar
Chennai 600 028
Tamil Nadu
Email: drbhaskarraju@yahoo.com
Bhavuk Garg
Department of Orthopedics
Medical Sciences
New Delhi 110 029
Residence
525 Masjid Moth Doctors Hostel
Masjid Moth
New Delhi 110 049
Email: drbhavukgarg@gmail.com
Bina Ahuja
Clinical Specialist
National Polio Surveillance Project
India-WHO
RK Khanna Tennis Stadium
Africa Avenue
New Delhi 110 029
Residence
E 285 Narain Vihar
New Delhi 110 028,
Email: ahujabina@rediffmail.com;
ahujabi@npsuindia.org
Brijesh Arora
Associate Professor
Pediatric Oncology
Tata Memorial Hospital
Ernest Borges Marg
Maharashtra
Residence
House No 7 Anand Bhavan
Bhula Bhai Desai Road
Near Breech Candy Hospital
Mumbai 400 026
Email: brijesharora@rediffmail.com
Chandan J Das
Department of Radiodiagnosis
Sciences
New Delhi 110 029
Email: chandanjd@yahoo.com
Choudhry VP
A-26 Shivalik
Malviya Nagar
Email: vedpchoudhry@yahoo.co.in
Dadhich JP
23 Canara Apartments
Sector 13, Rohini
Email: jpdadhich@gmail.com
Dagar KS
Consultant
Department of Pediatrics and
Congenital Heart Surgery
Escorts Heart Institute and
Research Centre, Okhla Road
New Delhi
Dani VS
Gandhi Sagar (East)
Mahal
Nagpur 440 002
Maharashtra
Email: visadani@nagpur.dot.net.in
XII
Deepak Bansal
House # 1334, Sector 19
Faridabad, Haryana
Email: deepakkritu@yahoo.com
Deepak Seth
Himalayan Institute of
Medical Sciences
Post Doiwala, Dehradun 248 140
Uttarakhand
Email: drdeepakseth@rediffmail.com
Deepak Ugra
A-402/403 Sausalito
Kia Park Prathamesh Complex
Veera Desai Road, Andheri (West)
Mumbai 400 053
Email: deepakugra@hotmail.com
Desai AB
1004 Panchtirth
Jodhpur Char Rasta, Satellite
Ahmedabad 380 015, Gujarat
Email: drabdesai@hotmail.com
Digant D Shastri
Killol Children Hospital
303-304 Takshashila Apartments
Majuragate, Surat 395 002
Gujarat
Email: drdigant@hotmail.com
Dilip Mukherjee
9/1 Ramnath Pal Road
Kolkata 700 023
West Bengal
Email: dilipmukherjee@rediffmail.com
Divya Prabhat
Ear Nose Throat Specialist and
Head and Neck Surgeon
Jeevak Hospital
Opposite Asiad Bus Stand
Dadar (East) Mumbai (East)
Dubey AP
6E MS Flats
Mint Road Complex
New Delhi 110 002
Email: apdubey52@rediffmail.com;
anand_dubey52@hotmail.com
Dutta AK
Flat # 8
Lady Hardinge Medical College
Campus, New Delhi 110 001, Delhi
Email: drdutta@gmail.com
Gadadhar Sarangi
Professor
Hitech Medical College, Pandara,
Bhubaneswar, Orissa
Residence
C/o Dr Laxmi Kanta Mohapatro
At Telisahi (Parijat Lane)
Ranihat, Cuttack 753 001, Orissa
Email: gdsarangi@sify.com;
gdsarangi@hotmail.com
Ganessan KM
13 Chinna Mudali Street
Gudiyattam
Gudiyattam 632 602, Tamil Nadu
Email: dr_kmganessan@ rediffmail. com
George Moses L
Prof of Microbiology (Retd)
Director
Kilpauk Laboratory Services
27(12) Vasy Street
Near Ega Theatre
Kilpauk, Chennai - 600 010
Gowrishankar NC
Assistant Professor
Department of Pulmonology
Institute of Child Health and
Hospital for Children
Chennai 600 008
Residence
12/A Balasubramaniam Street
Mylapore
Chennai 600 004
Tamilnadu
Gupta BD
Vrandwan 120
Bhagat Ki Kothi Extension
Near Asha Hospital
Opposite New Campus
Pali Road, Jodhpur 342 001
Rajasthan
Email: Brahmadgupta@Hotmail.com
Guruprasad G
2164 Veda IV Main X Cross
MCC A Block
Devangere 577 004
Karnataka
Email: gurug61@hot.com;
dr_g_gp@yahoo.com
Harish Kumar
12/406 Sunder Vihar
New Delhi 110 041
Email: harishalwadhi@hotmail.com;
hkumar@unicef.org
Indra Shekhar Rao M
Former Medical Superintendent
Niloufer Hospital, Hyderabad
Andhra Pradesh
Residence
Indra Prastha
Plot # 106
Abhinav Nagar
Secunderabad 500 025
Andhra Pradesh
Email: indramummulla@yahoo.co.in
Iyer KS
Senior Consultant and Head
Department of Pediatrics and
Congenital Heart Surgery
Escorts Heart Institute and
Research Centre, Okhla Road
New Delhi
Jacob John T
Thekkekara 439 Civil Supplies
Godown Lane
Kamalakshipuram, Vellore
North Arcot 632 002
Tamil Nadu
Email: vlr_tjjohn@sancharnet.in
Jain MK
Quarters # 2
Opposite District Hospital
Vidisha, Madhya Pradesh
Jayakar Thomas
Senior Consultant Dermatologist
Kanchi Kamakoti Childs TRUST
Hospital and Mehtas Hospital
Chennai, Tamil Nadu
Residence
2 West Mada Church Road
Royapuram
Email: jayakarthomas@gmail.com
Contributors XIII
Jayashree A Mondkar
22/24 Vaibhav Apartments
SK Bole Road, Dadar
Mumbai 400 028
Maharashtra
Email: jamond@vsnl.com;
jayashreemondkar@hotmail.com
Jayashree Muralidharan
127 Type V PGI Flats
Sector 24-A
Chandigarh 160 023
Email: mjshree@hotmail.com
Jaydeep Choudhury
Assistant Professor
Kolkata, West Bengal
Residence
95/2 Ballygunge Place
Kolkata 700 019
West Bengal
Email: drjaydeep_choudhury@
yahoo.co.in
Jnanindra Nath Behera
Associate Professor of Pediatrics
SCB Medical College
Cuttack 753 007, Orissa
Email:jnanindranathb@gmail.com
Joshi NC
19-B Kumkum Apartments
SV Road, Vile Parle (West)
Jugesh Chhatwal
CMC Hospital
Ludhiana 141 008, Punjab
Email:pediatricscmcl@rediffmail.com
Kabra SK
Additional Professor
Sciences
New Delhi 110 029
Email: skkabra@rediffmail.com
Kalpana D
Assistant Professor
Department of Pediatric Neurology
SAT Hospital
Medical College
Thiruvananthapuram 695 004,
Kerala
Residence
KALPANA
NSP Nagar
Kesavadasapuram
Kerala
Email: vijaykal@hotmail.com
Kamath SS
XL/5152 TD Road (North End)
Kochi, Ernakulam 682 035
Kerala
Email: sskamath@vsnl.net
Karmarkar DP
1165 Harbhat Road
Karmarkar Wada
Sangli 416 416, Maharashtra
Ketan Praveen Parikh
Consultant Pediatric Surgeon and
Pediatric Laparoscopist
Hospital, Andheri West
Mumbai 400 053
Maharashtra
Residence
B-404 Kukreja Palace
Vallabhbaug Lane Extension
Ghatkopar (East)
Mumbai 400 075
Maharashtra
Email: ketan40@hotmail.com
Keya R Lahiri
Professor and Head
Seth GS Medical College and
KEM Hospital
Residence
Vijay Kunj B/10
JN Road, Santacruz (East)
Mumbai 400 055
Maharashtra
Email: infopediatrics@gsmc.edu
Kochupillai N
Director, Medical Research
MS Ramaiah Medical College and
Hospitals, MSR Nagar, MSRIT PO
Bengaluru 110 029, Karnataka
Email: kochupillai@gmail.com
Kotwal PP
Professor and Head
Medical Sciences
New Delhi 110 029
Residence
C 1/19 Ansari Nagar
New Delhi 110 029
Email: prakash_kotwal@hotmail.com
Krishan Chugh
J-5/169
Rajouri Garden
New Delhi 110 027
Email: chughk2000@yahoo.co.in
Kulkarni ML
2373 MCC A Block
Devangere 577 004
Karnataka
Email: rajappanpillai@hotmail.com
Kumud P Mehta
Mother and Child Hospital
Gita 2nd Floor
P Ramabai Road
Gamdevi
Mumbai 400 007
Maharashtra
Email: mehtakumud@hotmail.com
Kundan Kumar Mittal
227-B Medical More
Model Town
Rohtak 124 001, Haryana
Email: kundanmittal@yahoo.co.in
Lokeshwar MR
19/54 Welfare Mansion
Sion, Mumbai 400 022
Maharashtra
Email: mrl123@roltanet.com;
mrlokeshwar@gmail.com
XIV
Madhulika Kabra
Genetic Unit
All India Institute of Medical Sciences
Email: mkabra_aims@yahoo.co.in;
madhulikakabra@hotmail.com
Madhusudhana SN
Department of Virology
National Institute of Mental Health
and Neurological Sciences
Bengaluru, Karnataka
Mahadeviah M
518 Rajmahal Vilas Extension
Sadashiv Nagar
Bengaluru 560 080
Karnataka
Email: rmv518@yahoo.com
Maiya PP
343 25th Cross
9th Main Road
Banashankari II Stage
Email: p_maiya@hotmail.com
Major K Nagaraju
Senior Consultant in
Pediatric Allergy
Hospital
12 A Nageswara Road
Nungambakkam
Chennai 600 034
Email: majorknr@yahoo.co.in
Malathi Sathiyasekaran
# 16th Cross Street
Indira Nagar
Chennai 600 020
Tamil Nadu
Email: mal.bwcs@gmail.com
Mamta V Manglani
A-202 Casuarina, Evershine Greens
New Link Road, Andheri (West)
Email: mmanglani@hotmail.com
Manju Mehta
Professor of Clinical Psychology
Department of Psychiatry
New Delhi 110 029
Email: drmanju.mehta@gmail.com
Manorama Verma
8 SF HIG Flats
Bhai Randhir Singh (BRS) Nagar
Ferozepur Road
Ludhiana, Punjab
Marwaha RK
Incharge, Division of Pediatric
Hematology-Oncology
Advanced Pediatric Centre
Postgraduate Institute of Medical
Education and Research
Chandigarh 160 012
Email: rammarwaha1@rediffmail.com
Mathur RC
4-1-1233/5
Subhodaya Apartments
Bogulkunta, ABIDS
Hyderabad 500 001
Andhra Pradesh
Email: rcmathur@hotmail.com
Mayilvahanan Natarajan
Professor and Head
Department of Orthopedic Surgery
Madras Medical College and
Government General Hospital
Chennai 600 003
Tamil Nadu
Residence
4 Lakshmi Street
Kilpauk
Chennai 600 010
Tamil Nadu
Meena P Desai
307 Samudra Mahal
Dr AB Road, Worli
Mumbai 400 018
Maharashtra
Email: drmeenadesai@gmail.com
Meena R Malkani
F-6 Model House
158 Sion (East)
Email: mmalkani@hotmail.com
Meenakshi N Mehta
Shaivali C/3 9, BMC Colony
Kag Khan Road, Worli
Meharban Singh
A-47 Sector 31, Noida
Uttar Pradesh
Email: meharbans_singh@gsk.com
Menon PSN
Consultant and Head
Jaber Al-Ahmed Armed Forces
Hospital, Kuwait
Residence
W1C 055 Wellington Estate
DLF City Phase V
Gurgaon 122 002, Haryana
Email: psnmenon@hotmail.com
Milind S Tullu
Associate Professor
Seth GS Medical College
KEM Hospital
Residence
1 Sankalp Siddhi
Service Road, Kher Nagar
Bandra East
Mumbai 400 051
Nagabhushana S
Visiting Consultant
Columbia Asia Hospital
Hebbal, Bengaluru
Residence
Aditya # 37/22/1
2nd Cross 1st Main
Sundarnagar
Post Gokula
Email: nagabhushana_s@rediffmail.com;
respicon2005@yahoo.co.in
Contributors XV
Nair MKC
TC 24/2049
Near Rose House
Womens College Junction
Thycand
Kerala
Email: nairmkc@rediffmail.com;
nairkc@rediffmail.com
Nammalwar BR
2 Main Road, Seetha Nagar
Nungambakkam
Chennai 600 034
Tamil Nadu
Email: brn@biosys.net
Nandini Mundkur
Bangalore Children Hospital
City Centre # 6 Chitrapur
Bhavan 8th Main 15th Cross
Malleswaram
Bengaluru 560 055
Karnataka
Email: bchrc@vsnl.com
Naveen Thacker
Past President, IAP
Deep Children Hospital
Plot 208, Sector 1-A
Opposite Hero Honda Showroom
Gandhidham, Kutch 372 201
Residence
D-70 Shaktinagar
Gandhidham
Kutch 370 201, Gujarat
Email: drnaveenthacker@gmail.com
Neeraj Jain
Associate Professor
Himalayan Institute of Medical
Sciences
Jolly Grant, Dehradun 248 140
Uttarakhand
Residence
A1/2 Maa Ganga Vaatika
Rishikesh, Uttarakhand
Email: neerajjain@vsnl.net
Niranjan Shendurnikar
C/21 Nandigram # 2
Sindhwai Maata Road
Vadodara 390 004, Gujarat
Email: drnsps@gmail.com
Nitin Chandra Mathur
4-1-1233/5 Subhodaya
ABIDS
Hyderabad 500 001
Andhra Pradesh
Email: nitincmathur@gmail.com
Nitin Shah
186-A Vaswani Villa
1st Floor Block # 3
Jain Society, Near Jain Temple
Sion (West), Mumbai 400 022
Maharashtra
Email: drnitinshah@hotmail.com
Noel Narayanan S
TC 1/1991 9(1)
Keezhchira, Doctors Lane
Kumarapuram
Kerala
Nupur Ganguly
Assistant Professor of Pediatrics
Institute of Child Health, Kolkata
107 Garfa Pratapgarh
Kolkata 700 075
Email: nupur_diya@yahoo.com
Pankaj Hari
Sciences, New Delhi 110 029
Email: pankajhari@hotmail.com
Panna Choudhury
Maulana Azad Medical College
and Lok Nayak Hospital
Email: pannachoudhury@gmail.com;
drpchoudhury@gmail.com
Paramesh H
Medical and Managing Director
Lakeside Medical Center and
Hospital
33/4 Meanee Avenue Road
Near Ulsoor Lake
Email: dr_paramesh1@yahoo.com
Parang N Mehta
2/C Anjani Towers
Parle Point
Athwa Lines
Surat 395 007
Gujarat
Email: parang@rediffmail.com
Omprakash S Shukla
33-B Shilalekh Bunglows
Opposite Nandanvan Society
Behind Railway Station, Alkapuri
Vadodara 390 007, Gujarat
Email: opshukla2004@yahoo.co.in
Parthasarathy A
Brindavan
166 Park Road
Western Extension
Anna Nagar
Chennai 600 101
Email: apartha2000@yahoo.com
Pandian K
9B Medawakkam Road
Adambakkam
Email: pandianking@yahoo.com
Phadke KD
707 14th Cross
JP Nagar II Phase
Bengaluru 560 078
Karnataka
XVI
Piyush Gupta
University College of Medical Sciences
New Delhi
Editor-in-Chief, Indian Pediatrics
Residence
Block # R-6-A
Dilshad Garden
Near Telephone Exchange
Delhi 110 095
Email: prof.piyush.gupta@gmail.com
Potdar RD
Laxmi Gruha
69 DV Pradhan Road
Dadar (East)
Mumbai 400 014
Email: rdpotdar@snehamrc.com
Prahlad N
22/1 Poes Road, II Street
Teynampet
Chennai 600 018
Tamil Nadu
Email: drprahlad@yahoo.com
Pratibha D Singhi
Chief Pediatric Neurology and
Neurodevelopment
Postgraduate Institute of
Medical Education and Research
Chandigarh 160 012
Email: pratibhasinghi@yahoo.com
Prisca Colaco
D-107 Gasper Enclave
St Johns Road, Bandra
Mumbai 400 050
Maharashtra
Purna A Kurkure
Professor-in-Charge
Pediatric Endocrinology Division
HOD, Departemnt of
Medical Oncology
Dr Ernest Borges Marg
Maharashtra
Residence
B 301 Greenfields
Lokhandwala Complex
Andheri West
Mumbai 400 053
Email: purna.kurkure@gmail.com
Purvish M Parikh
9 Neeta Building
Above Computer Point
Opposite Poddar Hospital
227 Annie Besant Road
Worli, Mumbai 400 025
Maharashtra
Raghupathy P
# 39 6th Cross 35th Main
KAS Officers Colony
BTM Layout IInd Stage
Bengaluru 560 068
Karnataka
Email: p.raghupathy@gmail.com
Rajeshwar Dayal
Opposite Kidwai Park
Rajamandi
Agra 282 002, Uttar Pradesh
Email: r_dayal123@rediffmail.com
Rajniti Prasad
Senior Lecturer
Institute of Medical Sciences
Banaras Hindu University
Varanasi 221 005
Residence
7 FF Kabir Colony
Banaras Hindu University
Varanasi 221 005
Email: rajaniti_prasad@hotmail.com
Rajput CS
C/o Dr Mrs MC Rajpur
Department of OBGYN
Wanless Hospital
Miraj 416 410, Maharashtra
Raju C Shah
Ankur Children Hospital
Behind City Gold Cinema
Ashram Road Navarangpura
Email: rajucshah@rediffmail.com;
rajucshah@lycos.com
Rakesh Lodha
Assistant Professor of Pediatrics
Medical Sciences
New Delhi 110 029
Residence
A-5 Type # 5
IARI, Pusa, New Delhi 110 012,
Email: rakesh_lodha@hotmail.com,
rlodha1661@gmail.com
Ramachandran P
Egmore, Chennai
Tamil Nadu
Ramakrishnan S
Shreyas
15/7 Vidya Marg
Old Fatehpura
Udaipur 313 004
Rajasthan
Ramaswamy Ganesh
Registrar in Pediatrics
Hospital
12-A Nageswara Road
Nungambakkam
Chennai 600 033
Tamil Nadu
Residence
3-A Raju Street
West Mambalam
Chennai 600 033
Ramesh S
BRS Hospital
28, Cathedral Garden Road
Chennai 600 034
Residence
New No 28 Old No 37
Madava Road
Mahalingapuram
Email: rameshsanthanakrishnan
@gmail.com
Contributors XVII
Rana KS
Senior Advisor Pediatrics and
Pediatric Neurology
Army Hospital R & R, Delhi Cantt
New Delhi 110 010
Email: kamersinghrana@yahoo.com.in
Rao KS
Ragasudha
13/242 Matwada
Warangal 506 002
Andhra Pradesh
Rashmi Dalvi
C/o Dr BV Dalvi
A-10 Mutual CHS
Mogul Lane, Mahim
Rashmi Kumar
HIG 111 Sector E
Aliganj, Lucknow 226 020
Uttar Pradesh
Email: rashmik2005@gmail.com;
rashmik06@yahoo.co.in
Ravichander B
Senior Pediatric Consultant
Military Hospital
Ravikumar T
New # 31 Old # 14
Jaganathapuram
3rd Street Chetpet
Chennai 600 031
Tamil Nadu
Email: trkoomar@hotmail.com
Ravikumar VR
66 Cooperative Colony
KK Pudur
Coimbatore 641 038
Tamil Nadu
Email: masr.mar@usa.net
Renu Sexena
Professor and Head
Department of Hematology
Medical Sciences
New Delhi 110 029
Ritabrata Kundu
Kolkata, West Bengal
Residence
26A Sarat Chatterjee Road
Lake Town
Kolkata 700 089
Email: rkundu22@gmail.com
Riyaz A
Arakkal
Chalappuram
Kozhikode 673 002
Kerala
Email: saif_gem@hotmail.com
Rohit C Agrawal
Director
Chandra-Jyoti Children Hospital
Mumbai, Maharashtra
Residence
603/4 Vindyachal
Neelkanth Valley
7th Road Raja Wadi
Ghatkopar (East)
Mumbai 400 077
Maharashtra
Email: drrohitag@hotmail.com
Roshani N Taori
Research Officer
Seth GS Medical College
KEM Hospital, Parel
Email: roshanitaori@hotmail.com
Roshni Bhagwat
Consultant Pediatric Oncologist
Mahakoshal Hospital
Jabalpur, Madhya Pradesh
Residence
Vatika Duplex
65 Napier Town
Jabalpur 482 001
Madhya Pradesh
Email: roshni26@yahoo.com
Sachdev HPS
E 6/12, Vasant Vihar
New Delhi 110 057
Email: hpssachdev@hotmail.com
Sajid Qureshi
Assistant Professor
Pediatric Surgical Oncology
Maharashtra
Residence
1/26 Merchant Building
3rd Sankli Street
Byculla, Mumbai 400 008
Maharashtra
Email: sajidshafique@rediffmail.com
Sandeep B Bavdekar
A-2/9 Worli Seaside CHS
Kag Khan Road, Worli
Mumbai 400 018
Maharashtra
Email: drsbavdekar@vsnl.com
Sankaranarayanan VS
16 Balaji Avenue
T Nagar, 1st Street
Email: drvssankaranarayanan@gmail.com
Santosh K Bhargava
D 7 Gulmohar Park
New Delhi 110 049
Email: santoshb@ndf.vsnl.net.in
Saradha Suresh
Director and Superintendent
Egmore, Chennai 600 008
Tamil Nadu
Saroj Mehta
1159/15C, Chandigarh 160 015
Chandigarh
Email: ssmehta100@yahoo.com
XVIII
Shah MD
51 2nd Floor Jashoda Niwas
Nehru Road
Vile Parle (East)
Mumbai 400 057
Maharashtra
Email: shahmdip@vsnl.net
Shailesh Kanvinde
Consultant Pediatric Hematologist
and Oncologist
Deenanath Mangeshkar Hospital
Pune, Maharashtra
Residence
Prerana Society
Opposite New Abhinav Vidyalaya
37/2 Erandavane
Pune 411 038
Maharashtra
Email: skanvin@vsnl.net;
skanvinde@123inida.com
Shanti Ghosh
5 Sri Aurobindo Marg
Email: sghosh@del13.vsnl.net.in
Shashi N Vani
10 Shamiana
61 Brahmin Mitra Mandal Society
Sheila Bhave
9 Solapur Road
Pune 411 001
Maharashtra
Email: sheilabhave@vsnl.net
Shivananda
Siddhi 608 3rd Stage
3rd Block, 7th Main
Basaveshwaranagar
Bengaluru 560 079
Karnataka
Email: sssidhi@rediffmail.com
Shivbalan SO
Consultant Pediatrician and
Pulmonologist
Sundaram Medical Foundation
Chennai, Tamil Nadu
Email: sivabalan.somu@gmail.com
Shobha Banapurmath
390 8th Main
PJ Extension
Devangere 577 002
Karnataka
Email: sbanapurmath@hotmail.com
Shreekant W Chorghade
Rajeev
Dharampeth
Nagpur 440 010, Maharashtra
Email: chorghade1@hotmail.com
Shripad Banavali
Professor of Pediatric Oncology
Department of Medical Oncology
Maharashtra
Residence
# 11-A Jyoti Sadan,
Sheetla Devi Temple Road, Mahim
Mumbai 400 016
Email: banavali_2000@yahoo.com
Soumya Swaminathan
B-8 Sagarika
15-III Seaward Road
Valmiki Nagar
Chennai 600 041
Tamil Nadu
Email: doctorsoumya@yahoo.com
Srikanta Basu
# 318 Aashirwad Enclave
104 IP Extension
Patparganj
New Delhi 110 092
Email: srikantabasu@hotmail.com;
srikantab@yahoo.com
Srinivas S
Department of Gastroenterology
Royal Children's Hospital
Melbourne
Australia
Residence
14 Balaji Avenue
1st Street
Thiagarajanagar
Chennai 600 017

Tamil Nadu
Email: dr.srinivas@gmail.com
Srinivasan S
C II/4 Dhanvanthari Nagar
JIPMER, Puducherry 605 006
Puducherry
Email: srinivasan_jip@yahoo.co.uk
Srivastava RN
487 Mandakini Enclave
Alaknanda
New Delhi 110 019
Email: rnsri@vsnl.net
Srivastava SP
S-104 Udai Giri Bhavan
Budh Marg Road, Patna 800 001
Bihar
Email: spsrivastava13@yahoo.com
Subhash J Dalal
Consultant Pediatric Surgeon
Former Dean, Wadia Childrens
Hospital
Residence
3 Maheshwar Niketan
Peddar Road, Mumbai 400 026
Maharashtra
Subramanyam L
9-A Karneeswarar Koil Street
Santhome, Chennai 600 004
Tamil Nadu
Email: shivbalam1@rediffmail.com
Suchitra Ranjit
G/A Ranga Nivas
40 Barnaby Road, Kilpauk
Email: chitrasona@rediffmail.com
Sudeshna Mitra
Postgraduate Institute of Medical
Education and Research
Chandigarh 160 012
Email: mitrasudeshna@hotmail.com
Contributors XIX
Sumathi B
Assistant Professor
Department of Pediatric
Gastroenterology
Egmore, Chennai 600 008
Residence
New No 6 (Old 24)
Kutchery Lane
Mylapore
Chennai 600 004
Tamil Nadu
Email: drbsumathi@rediffmail.com
Sunanda K Reddy
Consultant Neurodevelopmental
Pediatrician
K-118 Ground Floor
Hauz Khas Enclave
New Delhi 110 016
Email: write2sunanda@gmail.com;
carenidhi@gmail.com
Sunil Karande
Flat # 24 Joothica, 5th Floor
22A Naushir Bharucha Road
Mumbai 400 007
Maharashtra
Email: karandesunil@yahoo.com
Sunit C Singhi
Professor and Head
Advanced Pediatric Centre
PGIMER, Chandigarh 160 012
Email: sunit.singhi@gmail.com;
dr_singhi@yahoo.com
Supriyo Ghose
Chief, Professor and Head of
Department of Ophthalmology
Rajendra Prasad Centre for
Ophthalmic Sciences
New Delhi 110 029
Surjit Singh
PGIMER, Chandigarh 160 012
Chandigarh
Email: surjitsinghpgi@hotmail.com;
surjitsingh@sify.com
Sushil Madan
804-2A Brindaban Apartments
Poonam Nagar, Andheri (East)
Swati Kanakia
2/10 Shreeji Sadan
Vrindavan Society
Vrindavan Chowk
Sion, Chunabhatti
Mumbai 400 022
Maharashtra
Email: drkanakia@vsnl.com
Swati Y Bhave
C II/47 Shahjahan Road
Opposite UPSC Office
Email: sybhave@yahoo.com;
sybhave@gmail.com
Tanmay Amladi
Honorary Neonatologist
Nowrosjee Wadia Maternity
Hospital and NICU Parel, Mumbai
Residence
A/50/1368 MIG
Adarsh Nagar CHS Ltd
Prabhadevi
Mumbai 400 025
Maharashtra
Email: tanmayamladi@gmail.com
Tanu Singhal
Hospital and Medical Research Institute
Four Bungalows, Andheri West
Email: tanusinghal@yahoo.com
Tapan Kumar Ghosh

Scientific Coordinator
Kolkata
Residence
13 Neogi Pukur Bye Lane
Kolkata 700 014
West Bengal
Email: dr_tkghosh@rediffmail.com,
dr.tkghosh@yahoo.in
Tewari AD
1459 Sector 3, Rohtak 124 001
Haryana
Email: ad_tewari@hotmail.com
Thangadorai C
18 Taylors Road, Kilpauk
Chennai 600 010
Tamil Nadu
Email: thangadorai@yahoo.com
Thangavelu S
H-15, G-2 Sea Breeze Apartments
Thiruvalluvar Nagar
Thiruvanmiyur
Email: thangavelu_s@yahoo.com
Thapa BR
Division of Pediatric
Gastroenterology
PGIMER
Chandigarh 160 012
Chandigarh
Email: brthapa1@yahoo.co.in;
pgimer@chd.nic.in
Thirugnanasambandham C
8 I Block
2nd Main Road
Chennai 600 102
Tamil Nadu
XX
Uday B Nadkarni
2 Vaibhav, Plot # 12-13
Linking Road Extension
Santacruz (West)
Mumbai 400 054
Maharashtra
Vasanthi T
Old # 4/123 New # 4/693
7th Main Road, Swaminatha Nagar
Kottivakkam
Chennai 600 041
Tamil Nadu
Email: drvasanthi@hotmail.com
Vijay Agarwal
Cottage # 15
Oberai Apartments
2 Sham Nath Marg
Delhi 110 054
Email: vijay@webcottage.com
Upadhyay SK
402 Bhimarathi Building
Road # 3 Daulal Nagar
Borivali (East)
Mumbai 400 066
Maharashtra
Veena Kalra
Senior Consultant Pediatrics
(Pediatric Neurology)
Indraprastha Apollo Hospitals
Sarita Vihar, Delhi Mathura Road
New Delhi 110 076
Residence
101 Jorbagh
Email: kalra.veena@gmail.com
Vijay N Yewle
Yewale Hospital
Plot 6B Sector 9
Vashi 400 703
Navi Mumbai
Maharashtra
Email: vnyewale@vsnl.com;
vntewale@gmail.com
Utpal Kant Singh

Professor and Head
Nalanda Medical College
Patna, Bihar
Residence
8 Rajendra Nagar
Patna 800 016, Bihar
Email: utpalkant.singh@yahoo.co.in
Vaman V Khadilkar
B-3 Shashi Kiran Apartment
Ashok Path
Off Law College Road
Erandwane
Pune 411 004, Maharashtra
Email: vkhadilk@vsnl.com;
akhadilkar@vsnl.net
Varshney MK
New Delhi 110 029
Residence
521 Masjid Moth Doctors Hostel
Masjid Moth
New Delhi 110 049
Email: drmkvarshney@gmail.com
Vibha Jain
Consultant
Medical Sciences
Jolly Grant, Dehradun 248 140
Uttarakhand
Residence
77 SBM Complex
Haridwar Road
Rishikesh
Vibha Mangal
Consultant
Medical Sciences
Swami Rama Nagar
Dehradun 248 140
Uttarakhand
Vibhu Kwatra
Vibhu Nursing Home
11/137 Malviya Nagar
New Delhi
Vijayakumar M
Flat # 4 Muktha Vandan
Old # 4 New # 7
Ramanathan Street
Kilpauk
Chennai 600 010
Email: drmvk@vsnl.net
Vijayalakshmi Bhatia
Professor
Department of Endocrinology
Sanjay Gandhi Postgraduate
Institute of Medical Sciences
Post Box # 375
Lucknow 226 001
Uttar Pradesh
Email: vbhatia@sushrut.s.gpgi.ac.in
Vijayasekaran D
# 43rd Cross Street
Dr Subbaraya Nagar
Kodambakkam
Chennai 600 024
Tamil Nadu
Email: vijsekar@hotmail.com
Contributors XXI
Vimlesh Seth
N-14/D DDA Flats (SFS)
Mandir Marg, Saket
Email: drsdseth@yahoo.com
Vinod K Paul
Professor and Head
Ansari Nagar
Email: vkpaul@medinst.ernet.in;
vinodkpaul@hotmail.com
Vipin M Vashishtha
Consultant Pediatrician and
Neonatologist, Mangla Hospital
Shakti Chowk, Station Road
Bijnor 246 701, Uttar Pradesh
Email: vipin@iappec.com,
vipinipsita@gmail.com
Vrajesh P Udani
69 Al Jebreya Court
Marine Drive, Mumbai 400 020
Maharashtra
Email: vrajesh@vsnl.com;
vrajeshudani@yahoo.co.in
Walia BNS
1004 Sector 11-C
Chandigarh 160 011
Email: bnswalia@hotmail.com
Wilson CG
House # 117 Sector A
A WHO Colony
Gautam Enclave
Secunderabad 500 009
Andhra Pradesh
Email: info@kimsmedicalcollege.org
Yogesh C Govil
4006/1/2, A-2 Balda Colony
New Hyderabad
Lucknow 226 007
Uttar Pradesh
Email: yogeshgovil@usa.net
Yogesh Jain
Jan Swasthya Sahyog
I-4 Parijat Colony
Nehru Nagar
Bilaspur 495 001
Chhattisgarh
Email: janswasthya@gmail.com
Yuvaraj Chandra Mathur

4-1-1233 Boggul Kunta
Subodaya
Hyderabad 500 001
Andhra Pradesh
Email: ycmathur@hotmail.com
Zeenat Currimbhoy
Division of Pediatric
Hemato-Oncology
LTMG Hospital and
LTM Medical College
Sion, Mumbai 400 022
Maharashtra
Email: currimbhoyzinet@gmail.com
Zulfikar Ahamed M
SAJAN, TC 1072/4
Pazhaya Road MCPO
Kerala
Email::mzulfikarahamed@rediffmail.com;
zulfikarahamedm@sancharnet
Foreword
Child health needs of developing countries are altogether different. Indian Academy of Pediatrics is dedicated for
total child welfare from zero to eighteen years of age. With this aim, the first edition was published in 1999 and in
ten years it has been so popular, not only in India but in SAARC and many developing countries. It speaks of its
receptivity, utility, affectivity and relevance. And now with much enthusiasm and pleasure, the fourth edition is in
your hands.
I sincerely appreciate Dr A Parthasarathys dedication and commitment to the children and in the professional
front in our country. His untiring efforts will serve as an inspiration for young pediatricians to emulate and encourage
them to contribute to ailing society along their professional path with sincere services.
It is certainly a matter of pride to note that many senior pediatricians have been taking time off their innumerable
social commitments to pool valuable knowledge in the form of this book. I admire all the editors and contributors
for this rich compilation.
The contents of the book have been chosen very carefully for developing as well as developed countries and
have broadly covered the relevant and vital issues of Comprehensive Child Health Care. Considering the caliber
and expertise of contributors and authors, I am convinced that the book will be a treasure of knowledge to be
cherished by the pediatricians across the world.
RK Agarwal
National President, 2008
Indian Academy of Pediatrics
Foreword
Specialty of Pediatrics covers more than 50 percent of the population. Infant and childhood morbidity continue to be
very high and adolescent health problems are still not adequately addressed by medical profession. Thus, it is
imperative that budding doctors need to have sound training to look after the children from birth to 18 years.
Pediatrics is a part of undergraduate curriculum and there is tremendous demand for a textbook on pediatrics. For
credibility it is also necessary that the book is evidence based. IAP Textbook of Pediatrics fulfills an important void
in this direction and has become immensely popular with all its editions. The book has been well received in many
developing countries having similar health scenario.
Contributors of this book are renowned experts in their respective fields. An invariable problem with multiauthored texts is the diversity of presentations adopted by a multitude of contributors. Dr A Parthasarathy, Editorin-Chief of the book since inception and an accomplished academician with tremendous zeal, managed this issue by
carefully crafting a common editorial style. In this venture he has been aptly assisted by Dr PSN Menon and
Dr Piyush Gupta, along with many highly reputed chapter editors. Keeping with time, the text of the book has been
aptly modified and all the chapters have been thoroughly revised.
The book is designed to be relevant to the need of the developing countries. Emphasis has been on common
prevalent conditions though allied subjects seen in children have also received due attention. Section on Community
Pediatrics deserves special mention as most textbooks with western approach hardly provide any information in
this respect. The book is voluminous which is inherent in a textbook trying to cover all aspects related to pediatric
care.
Apart from fulfilling the main function of an excellent undergraduate textbook, this edition would be invaluable
for residents and medical practitioners interested to know in detail various childhood conditions. Even postgraduate
students will find much useful information. The book certainly will continue to remain as a very prestigious
publication of Indian Academy of Pediatrics and serve the nation by helping doctors engaged in the care of children
needing latest updates.
Panna Choudhury
Lok Nayak Hospital
New Delhi 110 002 and
National President
Indian Academy of Pediatrics 2009
Preface to the Fourth Edition

The last few years have witnessed a rapid progress in medicine and technological advances in biological sciences.
The specialty of Pediatrics has perceived further advances in preventive and therapeutic care. These have provided
impetus to revise knowledge, harvest new information and thus continue the process of learning. There was a felt
need for publication of an updated fourth edition of this book after a gap of three years. This was also prompted by
the enthusiastic response to the previous editions from practicing pediatricians, postgraduates, undergraduates as
well as faculty of Departments of Pediatrics throughout the country.
It has been our endeavor to present this subject in a simplified, practical manner to provide adequate clinical
guidance to pediatricians so that children derive the benefits of early diagnosis and optimal treatment. The basic
outline of the book is retained. We have tried our best to oversee that the art and science of clinical pediatrics
maintains its central position without being overshadowed by newer technical advances.
This fourth edition of the IAP Textbook represents a substantial revision and reorganization of the text based on
a complete review of the field of Pediatrics. It has 36 chapters and is being published in two volumes for the first
time. The first volume consists of 16 chapters with 195 subchapters contributed by 171 authors and the second
volume contains 20 chapters with 95 subchapters by 89 authors. The first volume features 28 new authors while the
second volume has 14 new authors representing the continuum of the best available talent, both experienced and
young with vast experience and expertise. Almost all the chapters have been thoroughly revised and updated in a
lucid and readable style.
Several new chapters have been added keeping in mind the changing concepts of pediatric care in the global
scenario. Some of these include child and adolescent school health education, vaccine storage and handling adverse
effects following immunization, parent counseling, practical approach to fever in children, pneumococcal infection
and its prevention, chikungunya fever, hemoptysis, gastroesophageal reflux, allergen-specific immunotherapy,
antiphospholipid syndrome, vasculitis, intravenous immunoglobulin, polycystic ovarian syndrome, etc. The chapters
on research methodology and computers serve a long felt need.
In addition, the IAP Infectious Diseases Chapter Protocols on selected infectious diseases viz. malaria, enteric
fever, pyogenic meningitis and rabies have been incorporated in the Miscellaneous Topics. This edition also provides
the most recent IAP recommendations on immunization of children and adolescents. The current IAP and WHO
growth charts have been appended with details on the techniques of measurement and interpretation. Unfortunately
many children, especially from the rural and remote areas have not yet benefited from the significant advances in
the prevention and care of many health problems. In this context the two chapters viz. National Rural Health Mission
and Pediatric Priorities in the 21st Century are rewritten. The chapter on Common Procedures has been updated.
The Academy would like to place on record its appreciation to all the authors for their contributions to the fourth
edition. It also gratefully acknowledges the efforts and time spent by Senior Editors and Chapter Editors who have
devoted great deal of their time reviewing and editing the manuscripts. The support from the office-bearers and
staff of the IAP Central Office Secretariat at all stages is appreciatively accredited. The book would not have seen the
light of the day but for the support and excellent cooperation of M/s Jaypee Brothers Medical Publishers (P) Ltd,
New Delhi.
It is our earnest hope that this new edition of the IAP Textbook will help in early diagnosis and efficient
management leading to optimal outcome and improving the quality of patient care.
A Parthasarathy
PSN Menon
Piyush Gupta
MKC Nair
Preface to the First Edition

Pediatrics has grown and developed with significant milestones in preventive and therapeutic care over the past
few decades. The WHO and UNICEF in their Primary Health Care (PHC) approach, have given due importance for
effective child survival programs. So much so the medical students need to be well oriented towards these approaches
in Pediatrics as the future middle level managers in Primary Health Care.
Several luminaries in the Indian pediatric scenario, have contributed their might in bringing out books for the
undergraduate medical students. However, the rapid advances made in the various pediatric subspecialties have
necessitated the updating of these books from time to time. Nevertheless, the need for a full fledged textbook was
felt for long. The Indian Academy of Pediatrics thought it fit, to shoulder the responsibility of bringing out such a
need based Textbook in Pediatrics for medical students. Our erudite and enthusiastic editors and contributors
made it possible at a record time. The Academy owes its gratitude to all these experts for their worthy contribution.
The book has been divided into several sections. A few chapters included in this book are entirely newer concepts
which are not usually found in the conventional pediatric textbooks. It has also worthy annexures to the main
contents. However, editing the text to suit the needs of medical students was a Himalayan task. The idea is to equip
the medical students with adequate knowledge in Pediatrics in order to make them confident to shoulder the
responsibilities concerned with preventive and curative Pediatrics. Thus, it is hoped that the practitioners of Pediatric
Medicine will benefit from this book.
We are confident that this book will serve the needs of medical students especially at a time when the Medical
Council of India has made Pediatrics as a major examination subject. Thus, the publication of the book is not only
timely but also out of necessity.
The Academy would like to place on record its appreciation to the senior editors, chapter editors, contributors,
and staff members of IAP Central Secretariat for help rendered in the creation of this book and M/s Jaypee Brothers
Medical Publishers (P) Ltd., New Delhi, for their excellent cooperation in bringing out the First Edition at record
time.
A Parthasarathy
PSN Menon
MKC Nair
Acknowledgements
We are indebted to the President and members of the Executive Board 1997 of the Indian Academy of Pediatrics
(IAP) for the initiation and completion of the project of bringing out the first ever Academys textbook for medical
students and practitioners. We are also thankful to the successive Presidents and members of the Executive Boards
1998-2008 for their encouragement in sustaining the project towards the publication of the Fourth Edition.
Our grateful thanks go to the various contributors and senior editors, past and present teachers of Pediatrics who
have made this Himalayan task a reality by their precise and updated text. We are indebted to the faculty and
residents of the All India Institute of Medical Sciences, New Delhi for shaping the contents of the First Edition which
has made the production of the subsequent editions an easy task and to Ms Manju, Ms Chitra and Ms Suman for
their assistance in typing and drafting the text of the book for the first edition.
The secretarial and organizational skills of Mr Joseph A Gonzalves and his supportive staff of IAP Central Office,
Mumbai, so ably and meticulously guided by Dr Rohit Agrawal, Secretary General and Dr Tanmay Amladi, Treasurer
are also gratefully acknowledged. The coordination efforts of Mrs Lokanayaki Ethirajan, Mrs Nirmala Parthasarathy,
Dr (Mrs) Pratibha Janardhanan, Mrs Kavitha Balaji, Mr A Sriramulu and Mr Louis Francis are acknowledged with
thanks.
Mr R Janardhanan, Mr P Balaji, Ms Shruthi Pavana, Ms Swathi Pavana, Ms Kavya Balaji and Ms Mahia Balaji at
Chennai need special mention for their untiring assistance in correspondence and formatting of the book with
updated contents.
Our grateful thanks are due to Mr Shaji Jacob Ninan and Dr Nazeer Ahamed at Kuwait for the assistance rendered
to the senior editor in editing, scrutinizing and proofreading of the individual chapter files.
Our sincere and grateful thanks go to the family of Jaypee Brothers Medical Publishers (P) Ltd, New Delhi,
especially Shri Jitendar P Vij (Chairman and Managing Director), Mr Tarun Vij (Director-Pharma), Mr Tarun Duneja
(Director-Publishing), Mr KK Raman (Production Manager), Ms Samina Khan (PA to the Director-Publishing),
Mr Ashutosh Srivastava (Assistant Editor), Ms Yashu Kapoor and Ms Kamlesh Bisht (DTP Operators) and
Ms Sonia Mehta (Graphic Designer) for their untiring coordination efforts in the production of the Fourth Edition.
We also place on record our sincere appreciation of the help rendered by the local branch managers of the Jaypee
Brothers Mr Mukherjee, (Chennai), Mr Uday Honnemadi (Mumbai), Mr Jayanandan (Author Co-ordinator,
Chennai), Mr Damodharan (Field Executive, Chennai) and the headquarters staff at New Delhi for the help
rendered to the Editor-in-Chief and Academic/Senior Editors.
All attempts have been made to acknowledge the sources of information and illustrations. Inadvertent omission,
if any, is regretted.
A Parthasarathy
PSN Menon
Piyush Gupta
MKC Nair
Contents
Volume 1
1. PEDIATRIC CARE IN DEVELOPING COUNTRIES
Chapter Editor: Piyush Gupta
1.1 Importance of Pediatrics ............................................................................................................................ 2
RD Potdar
1.2 Attaining Proficiency in Pediatrics .......................................................................................................... 3
BNS Walia
1.3 Pediatric Care in Developing Countries ................................................................................................. 5
BNS Walia
1.4 Primary Health Care ................................................................................................................................... 7
Yuvraj Chandra Mathur, Nitin Chandra Mathur
1.5 Primary Neonatal Care .............................................................................................................................. 9
Santosh K Bhargava
1.6 Management of Primary Health Center ............................................................................................... 12
Piyush Gupta
1.7 Training of Medical Graduate as Middle Level Manager ................................................................ 16
C Thirugnanasambandham, T Arunmozhi
2. HISTORY ELICITATION AND PHYSICAL EXAMINATION

Chapter Editors: PSN Menon, Piyush Gupta
2.1 History Elicitation ..................................................................................................................................... 24
T Ravikumar, C Thangadorai
2.2 Physical Examination and Clinical Skill Development .................................................................... 30
C Thangadorai, T Ravikumar
2.3 Parent Counseling .................................................................................................................................... 40
Parang N Mehta
3. NEWBORN CARE
Chapter Editor: Ashok K Deorari
3.1 Neonatal Nomenclature and Definitions ............................................................................................. 46
Meharban Singh, Vinod K Paul
3.2 Resuscitation of an Asphyxiated Newborn Baby ............................................................................... 50
Meharban Singh, Ashok K Deorari
3.3 Care of a Normal Newborn Baby .......................................................................................................... 56
XXXIV
3.4 Common Developmental and Physiological Problems in Newborn Babies ................................. 61

3.5 Management of Low Birth Weight Babies ........................................................................................... 65
Vinod K Paul, Ashok K Deorari, Meharban Singh
3.6 Common Diseases of Newborn Babies ................................................................................................ 71
Meharban Singh, Vinod K Paul, Ashok K Deorari
4. GROWTH AND DEVELOPMENT

Chapter Editor: KN Agarwal
4.1 Growth and Development: Basic Concepts ......................................................................................... 80
AB Desai, Dilip Mukherjee
4.2 GrowthBirth to Puberty ....................................................................................................................... 83
KN Agarwal, DK Agarwal, SK Upadhyay
4.3 Physical Growth and Sexual Development in Adolescence ............................................................. 96
4.4 Development ........................................................................................................................................... 105
4.5 Failure to Thrive ...................................................................................................................................... 111
Madhulika Kabra, PSN Menon
5. INFANT FEEDING
Chapter Editor: RK Anand
5.1 Infant and Young Child Feeding ......................................................................................................... 116
RK Anand, SP Srivastava
5.2 Breastfeeding and Weaning .................................................................................................................. 122
RK Anand, SP Srivastava, Arun Gupta, JP Dadhich
6. NUTRITION
Chapter Editor: Meenakshi N Mehta
6.1 Protein Energy Malnutrition ............................................................................................................... 136
Meenakshi N Mehta
6.2 Water Soluble Vitamins: B Complex Vitamins ................................................................................ 163
Shashi N Vani
6.3 Fat Soluble Vitamins ............................................................................................................................. 166
Panna Choudhury
6.4 Trace Elements ....................................................................................................................................... 171
B Bhandari
6.5 Child and Adolescent School Health Education .............................................................................. 176
Sushil Madan
Contents XXXV
7. COMMUNITY PEDIATRICS
7.1 Community Pediatrics .......................................................................................................................... 188
Shashi N Vani
7.2 National Health Programs .................................................................................................................... 190
Shashi N Vani, Piyush Gupta
7.2.1 National Rural Health Mission (NRHM) 2005-2012 ........................................................... 191
Piyush Gupta
7.2.2 Maternal and Child Health (MCH) Programs ...................................................................... 193
Shashi N Vani
7.2.3 Integrated Child Development Services (ICDS) Program ................................................. 194
BNS Walia
7.2.4 Child Survival and Safe Motherhood (CSSM) Program .................................................... 196
BNS Walia
7.2.5 Reproductive and Child Health (RCH) Program ................................................................. 197
BNS Walia, Shashi N Vani
7.2.6 Integrated Management of Neonatal and Childhood Illness (IMNCI) Strategy .......... 200
BNS Walia
7.2.7 National Programs on Immunization .................................................................................... 200
A Parthasarathy, Shashi N Vani, BNS Walia
7.2.7.1 Universal Immunization Program (UIP) .................................................................. 200
KM Ganessan
7.2.8 Acute Respiratory Infections (ARI) Control Program ........................................................ 202
Keya R Lahiri, BNS Walia, Shashi N Vani
7.2.9 Control of Diarrheal Disease (CDD) Program ..................................................................... 203
7.2.10 National Leprosy Eradication Program ................................................................................. 204
BNS Walia
7.2.11 National Vector Borne Disease Control Program (NVBDCP) .......................................... 206
Piyush Gupta
7.2.11.1 National Malaria Control Program ................................................................... 206
BNS Walia
7.2.11.2 National Filaria Control Program ...................................................................... 207
BNS Walia
7.2.12 National AIDS and STD Control Program ........................................................................... 207
BNS Walia
7.2.13 Nutrition Programs ................................................................................................................... 208
Shashi N Vani
7.2.14 Mid-day Meal Program ............................................................................................................ 209
HPS Sachdev
7.2.15 Anemia Control Program ......................................................................................................... 209
Shashi N Vani
7.2.16 Control of Vitamin A Deficiency ........................................................................................... 210
BNS Walia
7.2.17 National Iodine Deficiency Disorders Control Program ................................................... 210
N Kochupillai
XXXVI
7.3
7.4
7.5
7.6
7.7
7.8

7.2.18 National School Health Program .......................................................................................... 211
BNS Walia
7.2.19 National Cancer Control Program ......................................................................................... 211
BNS Walia
7.2.20 National Mental Health Program (NMHP) ......................................................................... 211
BNS Walia
7.2.21 National Program for Control of Blindness ........................................................................ 211
BNS Walia
Community Newborn Care .................................................................................................................. 212
Shashi N Vani
Under Five Clinics ................................................................................................................................. 215
Ajit Kumar
The Girl Child ........................................................................................................................................ 218
Shanti Ghosh
Customs and Beliefs in Child Rearing .............................................................................................. 220
Anil Mokashi
International Agencies and Child Health ......................................................................................... 225
Shashi N Vani
Adoption and Care of Orphans ........................................................................................................... 226
RD Potdar
8. CHILD ABUSE, NEGLECT AND CHILD LABOR

Chapter Editors: Meenakshi N Mehta, SR Banerjee
8.1 Child Abuse and Neglect ...................................................................................................................... 230
Meenakshi N Mehta
8.2 Child Labor .............................................................................................................................................. 244
Meenakshi N Mehta, SR Banerjee
9. IMMUNIZATION AND INFECTIOUS DISEASES

Chapter Editors: A Parthasarathy, Tapan Kumar Ghosh
9.1 The Principles and Practice of Immunization ................................................................................... 258
T Jacob John
9.2 Vaccines and Vaccine Preventable Diseases: Today and Tomorrow ............................................ 262
AB Desai
9.3 Newer Vaccines ....................................................................................................................................... 265
AK Dutta, Anju Aggarwal
9.4 Vaccine Storage and Handling ............................................................................................................. 271
RK Agarwal, Digant D Shastri
9.5 Management of Adverse Effects Following Immunization (AEFI) ............................................... 277
M Indra Shekhar Rao, Tanmay Amladi
9.6 Approach to Management of Fever in Newborns, Children and Adolescents
in Office Practice ..................................................................................................................................... 285
Digant D Shastri
Contents XXXVII
9.7 Fever and Fever of Unknown Origin .................................................................................................. 295
PP Maiya
9.8 An Approach to a Child with Fever and Skin Rash ......................................................................... 302
Jayakar Thomas
9.9 Tuberculosis in Children....................................................................................................................... 315
Vimlesh Seth
9.10 Abdominal Tuberculosis ....................................................................................................................... 332
Saroj Mehta, Vimlesh Seth
9.11 Neurotuberculosis .................................................................................................................................. 336
Vimlesh Seth
9.11.1 Revised National Tuberculosis Control Program (RNTCP) including
Directly Observed Treatment .................................................................................................. 342
Vimlesh Seth
9.12 Poliomyelitis ............................................................................................................................................ 350
Ashok K Gupta
9.12.1 Differential Diagnosis of Acute Flaccid Paralysis ............................................................... 354
AD Tewari
9.12.2 National Immunization Days (NIDs) as a Vital Component of Polio Eradication
Strategy ......................................................................................................................................... 359
Vipin M Vashishtha, Naveen Thacker
9.13 Diphtheria ................................................................................................................................................ 362
AP Dubey, Jaydeep Choudhury
9.14 Pertussis (Whooping Cough) ................................................................................................................ 364
YK Amdekar
9.15 Tetanus ..................................................................................................................................................... 366
9.16 Measles ..................................................................................................................................................... 368
9.17 Mumps: Epidemic Parotitis ................................................................................................................... 370
Ashok Gupta
9.18 Rubella ...................................................................................................................................................... 372
9.19 Staphylococcal Infections ...................................................................................................................... 374
9.20 Pneumococcal Disease and its Prevention ......................................................................................... 376
Rohit C Agrawal
9.21 Hemophilus Influenzae b Disease ...................................................................................................... 383
RK Agarwal, Anju Aggarwal
9.22 Typhoid Fever ......................................................................................................................................... 383
YK Amdekar
9.23 Leprosy ..................................................................................................................................................... 387
Rajeshwar Dayal
9.24 Leptospirosis in Children ...................................................................................................................... 392
S Ramesh
9.25 Chickenpox (Varicella) .......................................................................................................................... 394
XXXVIII
9.26 Dengue Illnesses ..................................................................................................................................... 396

Ashok S Kapse
9.27 Infectious Mononucleosis ..................................................................................................................... 404
S Ramesh
9.28 Respiratory Syncytial Virus Infection ................................................................................................ 405
A Balachandran, SO Shivbalan
9.29 Rotavirus Disease ................................................................................................................................... 408
Raju C Shah
9.30 Rabies ........................................................................................................................................................ 409
Tapan Kumar Ghosh, A Parthasarathy
9.31 Pediatric HIV Disease ............................................................................................................................ 414
Meena Malkani
9.32 Chikungunya Fever ................................................................................................................................ 419
Utpal Kant Singh, Rajniti Prasad
9.33 Malaria in Children ................................................................................................................................ 423
Ashok S Kapse
9.34 Kala-azar (Visceral Leishmaniasis) ..................................................................................................... 440
Yogesh Jain, Rakesh Lodha
10. DISEASES OF CENTRAL NERVOUS SYSTEM

Chapter Editors: Veena Kalra, PSN Menon
10.1 Anatomical Localization of Neurological Problems ....................................................................... 444
CS Rajput, DP Karmarker
10.2 Normal Development and Malformations of Central Nervous System ..................................... 448
Veena Kalra, Rashmi Kumar
10.3 Degenerative Disorders of the Central Nervous System ............................................................... 453
Veena Kalra
10.4 Seizure Disorders in Children ............................................................................................................ 455
Veena Kalra
10.5 Infections of the Central Nervous System ........................................................................................ 462
Veena Kalra
10.6 Coma in Children .................................................................................................................................. 470
CR Banapurmath, Shobha Banapurmath, G Guruprasad
10.7 Brain Tumors in Children .................................................................................................................... 477
KS Rana
10.8 Raised Intracranial Pressure ................................................................................................................ 486
AD Tewari, Kundan Kumar Mittal
10.9 Benign Intracranial Hypertension ...................................................................................................... 489
10.10 Motor Weakness in Infancy and ChildhoodClinical Approach ............................................... 491
Vrajesh Udani
10.11 Floppy Infant Syndrome ...................................................................................................................... 495
R Anandam, D Kalpana
10.12 Muscular Disorders in Children ......................................................................................................... 499
K Pandian
Contents XXXIX
11. DISEASES OF CARDIOVASCULAR SYSTEM

Chapter Editors: Anita Khalil, Srikanta Basu
11.1 Congenital Heart Disease: General Aspects ..................................................................................... 504
NC Joshi
11.2 Common Congenital Heart Diseases in Children ........................................................................... 509
Anita Khalil, M Zulfikar Ahamed
11.3 Medical Management of Congenital Heart Diseases ..................................................................... 518
Anita Khalil, Bharat Dalvi
11.4 Surgery for Congenital Heart Diseases ............................................................................................. 521
KS Dagar, KS Iyer, Srikanta Basu
11.5 Rheumatic Fever and Rheumatic Heart Disease .............................................................................. 526
Anita Khalil
11.6 Congestive Heart Failure in Children ................................................................................................ 534
Anita Khalil
11.7 Systemic Arterial Hypertension in Children .................................................................................... 538
Srikanta Basu, S Srinivasan
11.8 Pericardial Diseases and Disorders .................................................................................................... 548
S Srinivasan, Srikanta Basu
11.9 Cardiac Arrhythmias in Children ....................................................................................................... 551
12. DISEASES OF RESPIRATORY SYSTEM

Chapter Editor: A Balachandran
12.1 Examination of the Respiratory System ............................................................................................ 558
YK Amdekar
12.2 Diagnostic Procedures and Investigations in Respiratory Diseases ............................................ 560
Archana S Kher, Soumya Swaminathan, Milind S Tullu
12.3 Flexible Fiberoptic Bronchoscopy (FFBS) ......................................................................................... 564
D Vijayasekaran
12.4 Respiratory Distress .............................................................................................................................. 567
MD Shah
12.5 Upper Respiratory Tract Infection ..................................................................................................... 573
SK Kabra
12.6 Infections of Larynx, Trachea and Bronchi ....................................................................................... 576
Keya R Lahiri, Roshani N Taori
12.7 Pneumonia in Children ........................................................................................................................ 578
12.8 Acute Bronchiolitis ................................................................................................................................ 583
Uday B Nadkarni
12.9 Empyema ................................................................................................................................................. 586
A Balachandran, Swati Y Bhave, S Thangavelu
12.10 Bronchiectasis ......................................................................................................................................... 588
A Balachandran, Swati Y Bhave, NC Gowrishankar
XL

12.11 Lung Abscess .......................................................................................................................................... 589
12.12 Hemoptysis ............................................................................................................................................. 591
Vibha Mangal, Neeraj Jain, Vibhu Kwatra
12.13 Bronchial Asthma .................................................................................................................................. 593
H Paramesh, L Subramanyam, SO Shivbalan
13. DISEASES OF GASTROINTESTINAL SYSTEM AND LIVER

Chapter Editor: VS Sankaranarayanan
13.1 Diarrheal Diseases ................................................................................................................................ 602
Ashok K Patwari
13.2 Persistent and Chronic Diarrhea in Children ................................................................................... 609
Gadadhar Sarangi, Jnanindra Nath Behera
13.3 Parenteral Nutrition in Children ........................................................................................................ 613
Anand N Pandit, Ashish R Bavdekar
13.4 Parasitic Bowel Diseases ...................................................................................................................... 616
BD Gupta
13.5 Vomiting in Infants and Children ...................................................................................................... 620
S Nagabhushana
13.6 Gastroesophageal Reflux in Infants and Children .......................................................................... 622
Neeraj Jain, Vibha Jain, Deepak Seth
13.7 Gastrointestinal Bleeding in Infants and Children ......................................................................... 624
Saroj Mehta, RC Mathur
13.8 Constipation ........................................................................................................................................... 627
VR Ravikumar
13.9 Abdominal Pain ..................................................................................................................................... 629
S Srinivas
13.9.1 Acute Abdominal Pain in Children ...................................................................................... 629
13.9.2 Chronic Abdominal Pain in Children .................................................................................. 632
13.10 Helicobacter Pylori Infection in Children ........................................................................................ 637
Neeraj K Jain, Vibha Mangal
13.11 Cystic Fibrosis ........................................................................................................................................ 639
Sushil K Kabra, Madhulika Kabra
13.12 Juvenile Tropical Pancreatitis ............................................................................................................. 644
A Riyaz
13.13 Liver and Biliary System ...................................................................................................................... 646
B Bhaskar Raju, B Sumathi
13.14 Hepatosplenomegaly: A Practical Diagnostic Approach ............................................................... 650
Sheila Bhave, Ashish Bavdekar
13.15 Differential Diagnosis of Jaundice in Infancy ................................................................................. 653
MK Jain, Sunil Karande
13.16 Viral Hepatitis ........................................................................................................................................ 655
Malathi Sathiyasekaran, Ramaswamy Ganesh
Contents XLI
13.17 Chronic Hepatitis in Children ............................................................................................................. 667
BR Thapa
13.18 Chronic Liver Disorders in Children ................................................................................................. 672
VS Sankaranarayanan, S Srinivas
13.19 Cirrhosis of Liver ................................................................................................................................... 675
13.20 Neonatal Cholestasis Syndrome ......................................................................................................... 682
BR Thapa
13.21 Fulminant Hepatic Failure ................................................................................................................... 692
Rajiv Chandra Mathur
13.22 Ascites ...................................................................................................................................................... 695
Balvir S Tomar, Anurag Tomar
14. DISEASES OF KIDNEY AND URINARY TRACT

Chapter Editors: Arvind Bagga, RN Srivastava
14.1 Renal Anatomy and Physiology ......................................................................................................... 714
Arvind Bagga
14.2 Diagnostic Evaluation ........................................................................................................................... 715
RN Srivastava, Aditi Sinha
14.3 Imaging of the Urinary Tract ............................................................................................................... 719
Arvind Bagga, Aditi Sinha
14.4 Developmental Anomalies .................................................................................................................. 722
M Vijayakumar
14.5 Acute Proliferative Glomerulonephritis ........................................................................................... 724
BR Nammalwar, T Vasanthi, M Vijayakumar
14.6 Renal Vasculitis ..................................................................................................................................... 729
BR Nammalwar, N Prahlad
14.7 Acute Renal Failure ............................................................................................................................... 737
14.8 Nephrotic Syndrome ............................................................................................................................. 743
RN Srivastava, Arvind Bagga
14.9 Urinary Tract Infection, Vesicoureteric Reflux and Reflux Nephropathy .................................. 750
M Vijayakumar, RN Srivastava
14.10 Obstructive Uropathy ........................................................................................................................... 754
Kumud P Mehta
14.11 Disorders of Micturition ...................................................................................................................... 755
Kumud P Mehta
14.12 Chronic Kidney Disease ....................................................................................................................... 757
KD Phadke, Pankaj Hari
14.13 Hypertension .......................................................................................................................................... 761
Kumud P Mehta
14.14 Renal Tubular Disorders ...................................................................................................................... 763
Aditi Sinha, Arvind Bagga
XLII
15. PEDIATRIC HEMATOLOGY

Chapter Editor: MR Lokeshwar
15.1 Anemia in Children ............................................................................................................................... 768
MR Lokeshwar, VP Choudhry
15.2 The Value of a Complete Blood Count in Children ........................................................................ 771
Zeenat Currimbhoy
15.3 Anemia in the Newborn ....................................................................................................................... 775
Jayashree A Mondkar, Mamta Manglani, Armida Fernandez
15.4 Nutritional Anemias in Infancy and Childhood ............................................................................. 780
Niranjan Shendurnikar, Omprakash Shukla, Sushil Madan
15.5 Nutritional Anemias in Adolescence ................................................................................................. 785
Sushil Madan
15.6 Thalassemia ............................................................................................................................................ 794
MR Lokeshwar, Nitin Shah, Swati Kanakia, Mamta Manglani
15.7 Sickle Cell Disease ................................................................................................................................ 816
VS Dani
15.8 Red Cell Membrane Disorders ........................................................................................................... 820
Rashmi Dalvi, Bharat Agarwal, R Agarwal
15.9 Autoimmune Hemolytic Anemia ....................................................................................................... 822
Bharat Agarwal, Rashmi Dalvi
15.10 Bone Marrow Failure Syndrome ........................................................................................................ 824
Nitin Shah, MR Lokeshwar
15.11 Physiology of Hemostasis: Approach to a Bleeding Disorder ...................................................... 828
Renu Saxena
15.12 Platelet and Bleeding Disorders ......................................................................................................... 831
VP Choudhry, Amit Upadhyay
15.13 Disseminated Intravascular Coagulation (DIC) .............................................................................. 843
Anupam Sachdeva, VP Choudhry
15.14 Bleeding Disorders in the Newborn .................................................................................................. 854
15.15 Hematopoietic Growth Factors ........................................................................................................... 858
Purvish M Parikh, MR Lokeshwar
15.16 Transfusion Medicine and Component Therapy in Pediatrics ..................................................... 861
RK Marwaha, Sudeshna Mitra, Deepak Bansal
16. PEDIATRIC ONCOLOGY

Chapter Editor: Purna A Kurkure
16.1 Malignancies in Children .................................................................................................................... 874
Purna A Kurkure
16.2 Acute Leukemia ..................................................................................................................................... 874
Anupama Borker, SH Advani
16.3 Hodgkins Disease ................................................................................................................................. 880
Purna A Kurkure, Brijesh Arora, Roshni Bhagwat
Contents XLIII
16.4 Non-Hodgkins Lymphoma .................................................................................................................
16.5 Wilms Tumor .........................................................................................................................................
Purna A Kurkure, Brijesh Arora, Shailesh Kanvinde
16.6 Neuroblastoma .......................................................................................................................................
16.7 Soft Tissue Sarcoma ..............................................................................................................................
Sajid Qureshi, Purna A Kurkure
16.8 Retinoblastoma ......................................................................................................................................
Sripad Banavali
16.9 Bone Marrow Transplantation ............................................................................................................
Brijesh Arora, Purvish M Parikh, MR Lokeshwar
883
887
890
895
901
903
Volume 2
17. ENDOCRINOLOGY
Chapter Editor: PSN Menon
17.1 Disorders of Growth ............................................................................................................................. 912
PSN Menon
17.2 Disorders of Pituitary ........................................................................................................................... 919
PSN Menon
17.3 Obesity ..................................................................................................................................................... 925
Anju Virmani
17.4 Disorders of the Thyroid Gland ......................................................................................................... 931
Meena P Desai
17.5 Disorders of Bone and Mineral Homeostasis .................................................................................. 935
17.6 Disorders of Puberty ............................................................................................................................. 941
Prisca Colaco
17.7 Disorders of Sexual Differentiation .................................................................................................. 947
P Raghupathi
17.8 Disorders of Adrenocortical Biosynthesis ........................................................................................ 951
P Raghupathy
17.9 Disorders of Adrenal Glands .............................................................................................................. 955
PSN Menon
17.10 Diabetes Mellitus .................................................................................................................................. 962
18. GENETICS
Chapter Editor: ML Kulkarni
18.1 Basic Genetics for Genetic Counseling ............................................................................................. 972
ML Kulkarni
XLIV
18.2 Common Genetic Disorders ................................................................................................................ 989

ML Kulkarni
18.3 New Genetics and Advances in Genetics ....................................................................................... 1013
ML Kulkarni
18.4 Inborn Errors of Metabolism ............................................................................................................. 1029
ML Kulkarni
19. CHILDHOOD DISABILITIES

Chapter Editor: MS Mahadeviah
19.1 Developmental Disabilities in Children ......................................................................................... 1044
MS Mahadeviah
19.2 Cerebral Palsy ...................................................................................................................................... 1045
Pratibha D Singhi
19.3 Attention Deficit Hyperactivity Disorders ..................................................................................... 1049
Nandini Mundkur
19.4 Learning Disability ............................................................................................................................. 1051
MS Mahadeviah
19.5 Childhood Autism ............................................................................................................................... 1053
MS Mahadeviah
19.6 Early Detection and Early Intervention Therapy for Developmental Delay ........................... 1055
MKC Nair, Babu George
19.7 Mental Retardation ............................................................................................................................. 1072
Sunanda K Reddy
20. PEDIATRIC IMMUNOLOGY, ALLERGY AND RHEUMATOLOGY

Chapter Editor: Surjit Singh
20.1 Basics of Immune System in Children ............................................................................................ 1080
20.2 Immunodeficiency Disorders ............................................................................................................ 1085
Surjit Singh, H Paramesh
20.3 Allergic Rhinitis ................................................................................................................................... 1087
H Paramesh
20.4 Food Allergy and Related Gastrointestinal Tract Diseases ......................................................... 1091
VS Sankaranarayanan
20.5 Value of Allergy Tests in Pediatrics ................................................................................................. 1095
L George Moses, A Parthasarathy
20.6 Allergen Specific Immunotherapy ................................................................................................... 1099
K Nagaraju
20.7 Rheumatological Disorders in Children ......................................................................................... 1101
S Ramakrishnan, A Parthasarathy
20.8 Antiphospholipid Syndrome ............................................................................................................ 1112
Surjit Singh
20.9 Approach to Vasculitis in Children ................................................................................................. 1113
Surjit Singh
Contents XLV
20.10 Kawasaki Disease ................................................................................................................................ 1115
Noel Narayanan
20.11 Intravenous Immunoglobulin ........................................................................................................... 1118
Surjit Singh
21. THERAPEUTICS
Chapter Editor: Sandeep B Bavdekar
21.1 Basics of Pediatric Therapeutics ....................................................................................................... 1122
Sandeep B Bavdekar, S Ramesh
21.2 Adverse Drug Reactions, Drug Interactions and Therapeutic Drug Monitoring .................... 1126
Archana Kher, Milind S Tullu
21.3 Rational Drug Therapy in Children ................................................................................................. 1130
Arun Phatak
22. PEDIATRIC INTENSIVE CARE

Chapter Editor: Sunit C Singhi
22.1 The Need and Scope of Intensive Care in Pediatrics .................................................................... 1136
Krishan Chugh
22.2 Organization of a Pediatric Intensive Care Unit ........................................................................... 1138
Sunit C Singhi
22.3 Cardiopulmonary Resuscitation ....................................................................................................... 1141
Yogesh C Govil
22.4 Shock ...................................................................................................................................................... 1148
22.5 Acute Respiratory Failure .................................................................................................................. 1153
Uday B Nadkarni
22.6 Assisted Ventilation in Children ...................................................................................................... 1156
Suchitra Ranjit
22.7 Monitoring a Child on Intensive Care ............................................................................................. 1160
Archana Sathe
22.8 Interpretation of Laboratory Findings in a PICU .......................................................................... 1168
Anil Sachdev
23. ADOLESCENT CARE

Chapter Editor: MKC Nair
23.1 Introduction: Why Adolescent Care? ............................................................................................... 1176
MKC Nair, SS Kamath
23.2 Adolescent Care and Family Life Education .................................................................................. 1178
Manorama Verma
23.3 Adolescent Nutrition .......................................................................................................................... 1180
Jugesh Chhatwal
23.4 Adolescent Psychology ....................................................................................................................... 1183
Jugesh Chhatwal
XLVI
23.5 Identity Crisis and Adolescents ........................................................................................................ 1186

Shrikant W Chorghade
23.6 Adolescent Sexuality ........................................................................................................................... 1189
Jugesh Chhatwal
23.7 Common Health Problems in Adolescents ..................................................................................... 1192
Manorama Verma, Jugesh Chhatwal
23.8 Polycystic Ovarian Syndrome ........................................................................................................... 1200
MKC Nair
24. ACCIDENTS AND POISONINGS

Chapter Editor: CG Wilson
24.1 Injuries in Children and Injury Control ......................................................................................... 1204
CG Wilson
24.2 Poisoning in Children ......................................................................................................................... 1207
KS Rao, B Ravichander
25. CHILD PSYCHIATRY

Chapter Editor: Manju Mehta
25.1 Child Psychiatry ................................................................................................................................... 1216
Manju Mehta
25.2 Child Guidance Clinic (CGC) ........................................................................................................... 1229
T Ravikumar
26. PEDIATRIC SURGERY

Chapter Editor: Ketan Praveen Parikh
26.1 Common Pediatric Surgical Problems ............................................................................................. 1232
Subhash J Dalal, Ketan Praveen Parikh, Amrish Vaidya
27. PEDIATRIC ORTHOPEDICS

Chapter Editor: Mayilvahanan Natarajan
27.1 Congenital Anomalies ........................................................................................................................ 1264
PP Kotwal, Bhavuk Garg
27.2 Infections of Bones and Joints .......................................................................................................... 1268
27.3 Neuromuscular Disorders .................................................................................................................. 1278
27.4 Osteochondritis .................................................................................................................................... 1282
27.5 Inequality of Limb Length ................................................................................................................. 1285
Mayilvahanan Natarajan, PP Kotwal, MK Varshney
27.6 Pediatric Bone Tumors ....................................................................................................................... 1288
27.7 Miscellaneous Orthopedic Conditions ............................................................................................ 1296
PP Kotwal, MK Varshney
Contents XLVII
28. PEDIATRIC RADIOLOGY

Chapter Editor: Arun Kumar Gupta
28.1 Pediatric Radiology ............................................................................................................................. 1300
Arun Kumar Gupta, Chandan B Das
29. PEDIATRIC OPHTHALMOLOGY

Chapter Editor: Supriyo Ghose
29.1 Common Eye Problems in Children ................................................................................................ 1316
Supriyo Ghose
30. PEDIATRIC OTORHINOLARYNGOLOGY

Chapter Editor: Divya Prabhat
30.1 Common Problems of Ear, Nose and Throat in Children ............................................................ 1334
Divya Prabhat
31. PEDIATRIC DERMATOLOGY

Chapter Editor: Jayakar Thomas
31.1 Skin Diseases in Children ................................................................................................................. 1336
Jayakar Thomas
32. PEDIATRIC DENTISTRY

Chapter Editor: PK Baskar
32.1 Common Dental Problems ................................................................................................................. 1372
PK Baskar
33. PEDIATRIC PRIORITIES IN THE 21ST CENTURY

33.1 Pediatric Priorities in the 21st Century ............................................................................................ 1384
RK Agarwal, Piyush Gupta
33.2 Pollution and Child Health in the 21st Century ............................................................................ 1389
NR Bhandari
33.3 Pediatric Environment Health-Hazards .......................................................................................... 1392
Anupam Sachdeva, MKC Nair, Swati Y Bhave
33.4 Research Methodology in Pediatric Practice .................................................................................. 1410
Saradha Suresh, P Ramachandran
33.5 Computers in Pediatric Medicine ..................................................................................................... 1414
Neeraj Jain, Vibha Jain
XLVIII
34. PEDIATRIC PROCEDURES

Chapter Editors: Piyush Gupta, PSN Menon
34.1 Common Procedures in Pediatric Practice ...................................................................................... 1420
Baldev S Prajapati, A Parthasarathy
35. PHYSICAL MEDICINE AND REHABILITATION

Chapter Editors: A K Dutta, Piyush Gupta
35.1 Physical Medicine and Rehabilitation in Pediatric Practice ........................................................ 1446
Bina Ahuja, AK Dutta
35.2 Chest Physiotherapy in Children ..................................................................................................... 1452
D Vijayasekaran
36. Miscellaneous Topics

Chapter Editors: Piyush Gupta, PSN Menon
36.1 Vital Statistics in India ....................................................................................................................... 1458
Piyush Gupta, HPS Sachdev
36.2 The Infant Milk Substitutes, Feeding Bottles and Infant Foods (Regulation of
Production, Supply and Distribution) Act, 1992 ............................................................................ 1459
SP Srivastava
36.3 Normal Laboratory Values ................................................................................................................ 1465
36.4 Principles of Fluids and Electrolytes in Diarrheal Dehydration ................................................ 1474
S Ramesh
36.5 Drugs and Drug Dosage ..................................................................................................................... 1480
S Ramesh
36.6 Essential Drugs in Pediatrics ............................................................................................................. 1488
Arun P Phatak
36.7 Growth Charts: ..................................................................................................................................... 1490
Vaman V Khadilkar, Dilip Mukherjee, MKC Nair
36.7.1 IAP Growth Charts ................................................................................................................... 1490
Vaman V Khadilkar
36.7.2 Appendix .................................................................................................................................... 1498
Vaman V Khadilkar
36.7.3 WHO Growth Charts ............................................................................................................... 1502
Dilip Mukherjee, MKC Nair
36.8 Safe Injection Practices ....................................................................................................................... 1507
Baldev S Prajapati, Swati Y Bhave, SS Kamath
36.9 Searching and Researching Online .................................................................................................. 1516
Vijay Agarwal
36.10 The IMNCI Case Management Process ........................................................................................... 1522
Harish Kumar, Raju C Shah, Naveen Thacker, Deepak Ugra
Contents XLIX
36.11 IAP Infectious Diseases Chapter Protocols: ................................................................................... 1525
Ritabrata Kundu, Nupur Ganguly, Tapan Kumar Ghosh
36.11.1 Malaria .................................................................................................................................... 1525
Raju C Shah, Tapan Kumar Ghosh, Ritabrata Kundu, Nupur Ganguly
36.11.2 Enteric Fever .......................................................................................................................... 1528
Nitin K Shah, Raju C Shah, Tapan Kumar Ghosh, Ritabrata Kundu, Nupur Ganguly
36.11.3 Pyogenic Meningitis ............................................................................................................. 1531
Veena Kalra, Tapan Kumar Ghosh, Ritabrata Kundu, Nupur Ganguly, Vijay N Yewle
36.11.4 Rabies ...................................................................................................................................... 1534
Tapan Kumar Ghosh, SN Madhusudhana, Shivananda
36.12 IAP Consensus Recommendations on Immunization, 2008 ........................................................ 1538
Tanu Singhal, YK Amdekar, Piyush Gupta
Index ...................................................................................................................................................... 1545
1.1 Importance of Pediatrics: RD Potdar ....................................................................................................................................................... 2

1.2 Attaining Proficiency in Pediatrics: BNS Walia ...................................................................................................................................... 3
1.3 Pediatric Care in Developing Countries: BNS Walia .............................................................................................................................. 5
1.4 Primary Health Care: Yuvaraj Chandra Mathur, Nitin Chandra Mathur .................................................................................................... 7
1.5 Primary Neonatal Care: Santosh K Bhargava .......................................................................................................................................... 9
1.6 Management of Primary Health Centers: Piyush Gupta ....................................................................................................................... 12
1.7 Training of Medical Graduate as Middle Level Manager: C Thirugnanasambandham, T Arunmozhi ............................................... 16
1.1 Importance of Pediatrics

RD Potdar
Till nearly 50 years back, Pediatrics used to be considered
as subsidiary of internal medicine in India and other
developing countries. It was but natural that many
internists while treating children as small adults, realised
that children form a unique, definitive and a fairly large
segment of human population. Some of them started
studying the health and diseases of children exclusively
and in depth and established that Pediatrics was a science
and a subject by itself.
Undergraduate students of Medicine must clearly
understand the attributes, significance, importance and
the necessity of the subject of Pediatrics before they
embark on Pediatrics itself, merely as an examination
subject. Whether they aspire to become specialists in
Pediatrics or its subspecialities or otherwise, knowledge
of Pediatrics is essential for every medical student because
nearly 42 percent of our population is below 18 years and
every physician is bound to face children in his/her
medical career as frequently, if not more often than adults.
It is necessary to know the special situation of
Pediatrics as a subject because of the following reasons:
second hand coming from the caregiver more often than

the child itself.
Many symptoms get converted into presenting features which are a series of common symptoms representing different organ affections or problems as under:
Crying: It is the most common presenting feature of many
conditions such as pain, hunger, thirst, wetting, fear,
anxiety, local hurt, etc.
Vomiting: It may be a presenting feature of any system
malfunction apart from or in addition to gastrointestinal
disease.
Paucity of Signs
One may not be able to elicit all classical signs that can
be elicited in adults. In Pediatrics, clinicians have to use
comprehensive findings of history, examination,
investigations and natural history and course of the
disease to arrive at a specific diagnosis.
Growth and Development
Age Group
Pediatrics, unlike the other subjects includes a wide spectrum of age groups. Each of these age groups have their
own physiological, pharmacological, pathological and
therapeutic characteristics which need to be remembered
while handling respective age groups in clinical
situations. The age groups are: (1) fetal period including
embryogenesis, (2) perinatal period, (3) prematurity,
(4) natal period, (5) neonatal period, (6) infancy, (7) toddler
group, (8) preschool, (9) schoolprimary, middle and
high, and (10) adolescence.
The pattern of health norms, presentation of diseases,
common causes of diseases as well as dosage and tolerance of drugs differ at these ages. Hence, age becomes a
very important consideration in treating a child.
A child is a constantly growing and developing organism making it highly susceptible and vulnerable to
various invasive, diagnostic and therapeutic actions. This
makes the responsibility of the clinician towards the child
far greater than that for the adult. Child is always the
passive recipient of treatment and hardly has any choice
taking any decision concerning itself.
Early Diagnosis and Early Intervention
These have tremendous rewards and importance in
children as compared to an adult, e.g. TB meningitis
suspected and diagnosed at an early stage can prevent
many a tragic sequelae as compared to an adult where
early intervention may not be that cost-effective.
Presenting Features
Drug Tolerance, Interaction and Toxicity
In most pediatric patients, symptoms are not directly

brought out like those in the adults. History is always
It is different for different drugs at different ages of a

child. Since the dosage is related to the body surface or
Pediatric Care in Developing Countries 3

the weight, it is essential that a drug dosage guide
should always be referred to by the treating doctor. The
drug dosage in adults, is generally, in fixed formulation
since there is no extreme variation in all ages of
adulthood unlike the pediatric age group.
Intergenerational Impact
Studies all over the world are proving that impact of
previous generations can manifest in the present generation both as far as genetic and environmental factors
are concerned. New vistas have opened in causation,
prenatal diagnosis as well as therapy in terms of genetic
engineering and gene therapy.
Pediatric Specialties
Even as the science of Pediatrics has come to stay on its
own, further subspecialties are continuously being
developed. Neonatology and Pediatric Hemato-Oncology
as pediatric superspecialties have already been accepted
for DM degree which is a postgraduate qualification.
Other specialties are also increasingly developing.
It may be, therefore, said that Pediatrics, the science
related to children has come of age in 2009 with adolescents forming integral part of Pediatrics, and its importance in India where most young population of coming
century in world will form the major segment.
Pediatrics thus needs a constant attention from all
medical aspirant students.
1.2 Attaining Proficiency in Pediatrics

BNS Walia
The time required for mastery of the art of treatment of
sick children is not proportional to the size of the child vs
the adult human. In fact, it is longer and more arduous.
Physical, physiologic and metabolic growth which is
taking place from birth to maturity as an adult makes the
task as difficult as learning to shoot at a moving target,
which is more difficult than shooting at a sitting duck!
Learning the fundamentals of growth are therefore a
prerequisite key to understanding several aspects of
pediatrics.
Diseases occur in humans and humans are already
nine months old on the day of birth! Therefore knowledge
of embryology and prenatal development not only helps
to understand the genesis of congenital malformations,
but also guides regarding vulnerable periods in the
evolution of a fetus, which may affect its entire life span.
Osler had said that a physician is as good as his
pathology. Knowledge of underlying pathology is
important to understand the symptoms observed in a
disease process and help to understand its evolution.
A sound knowledge of pharmacology helps one to
choose the right drug in the right dose. Medicines are
the main armamentarium of a physician. He must be
aware of what is available, but he must also find out more
about their indications, contraindications, side effects,
interactions and dosages before he uses any. This applies

especially to uncommonly used drug.
Amongst the common drugs, about which a doctor
is expected to be well informed, suffice it to say that you
need not burden yourself with the names and details of
all the brands of a molecule available in the market. Select
some reliable brands and stick to them. It has been well
said that drugs are like friends, which must be chosen
wisely and once trusted, kept close to ones bosom.
The basic sciences enable you to understand the why
and how of clinical phenomena and therefore must form
the core foundations for your clinical progress. The
foundation must be deeper, the higher the structure you
wish to construct upon it.
The clinical years are the most interesting period of
medical studies. Learn first of all how to take a good
clinical history. A well recorded history should not only
provide clues to diagnosis and differential diagnosis but
also how the patient has responded to the treatments
offered so far as well as how advanced the condition is
and what the prognosis might be. This must be followed
by a complete and thorough examination of the patient
howsoever minor the complaint that brings him to you.
Many a time you may be able to detect a corroborative
sign or another disease, which is unrelated with the
presenting symptoms.
Though the method of systemic examination of a child

is in no way different from that of an adult, the order of
examination should begin from least discomforting
aspects. Also several differences exist in the interpretation
of physical signs when seen in a child as compared to an
adult e.g. tremors in a newborn, brisk tendon reflexes in
a child, extensor plantar response, presence of bronchial
breathing in interscapular region or even presence of
palpable liver in childhood! You must be aware of these
differences and every book on physical examination of
the child emphasizes these.
A special effort must be made to learnsome special
aspects of physical examination in pediatrics. These
include examination of newborn, assessment of
gestational age of a neonate and toddler, neurological
examination of a neonate, developmental assessment,
assessment of growth and sexual development. Identification of signs of nutritional deficiency and ability to
conduct neurological examination of a preschool child
also require special attention.
Whereas theoretical knowledge is best obtained as
described above, clinical skills are acquired by seeing
someone perform the clinical examination. Excellent
audio and video recordings are now available to practice
clinical skills, after seeing these videos. It is important
that some one should watch you while you are performing the developmental examination of a child or
maturity rating of a newborn infant. Both of you should
point out any faults of the partner and if necessary settle
your doubt by asking the advice of a person senior to
you. Later on practice case presentations to each other
and correct each other on history taking, clinical skills.
Make a provisional diagnosis and be able to justify it on
the basis of history and clinical sign. It is essential to write
down a provisional diagnosis or the next best possibility,
so that if you are proved wrong, you can go back to the
case and reexamine it to see what you had missed to do,
which resulted in a diagnostic error. Do not be depressed
if you are proved wrong. Only the persons, who do not
commit to a diagnosis, never make a mistake. Clinical
pediatrics is not like mathematics. There is a lot of
intelligent guess work involved depending upon family,
occupational history, epidemiologic conditions and
prevalence rates of different diseases in a country. But at
all times remember that an uncommon manifestation of
a common disease is more likely to be the cause of a
difficult diagnostic riddle than a rare disease. When faced
with a difficult diagnosis sit down with a list of
possibilities which can be considered in the differential
diagnosis. Score out those that have features that do not

fit and start investigating for those conditions, for which
the clinical possibility exists. Arriving at a diagnosis
should not be like searching for a needle in a haystack
but on the other hand, it can be compared to a concerted
pursuit of a crime investigator who is gathering evidence
against suspects, to whom the needle of suspicion points.
Inspite of learning all that is said above; your training
will be still far from complete. The ability to interpret
findings on otoscopy and fundoscopy may have to be
learnt by visits to the special clinics of department of ENT
and Ophthalmology. A week spent in the department of
dermatology will familiarize you with the common
dermatological problems seen in pediatrics. Similarly,
one requires interactions with a child psychiatrist to
understand identification and management of behavior
disorders which may masquerade with somatic symptoms.
Cardiopulmonary resuscitation should be learnt on
a mannequin before you enter a clinical ward. Who
knows you may be required to resuscitate a baby on your
first night duty, because none else is available!
Competence and confidence in performing procedures is acquired only by doing the procedures. The more
you do, the more proficient you become. There is no place
for complacency in dealing with sick children. If you do
not know how to do a procedure competently, refer the
patient to someone who can. If you mess up the life or
limb of a child, remember, there is COPRA waiting to
sting you!
Basic science related to the disease conditions you are
being taught in clinical pediatrics must be revised at the
same time. For instance study of diseases of thyroid
should start with embryology and anatomy of thyroid
gland, the biochemistry related to synthesis of thyroxin
and proceed with clinical manifestations of thyroid deficit
or excess. This will enable you to understand why and
how certain clinical features of the disease manifest.
Information on developmental testing will enable you
to pick up children who are slow in their development.
Read about the growth parameters at the relevant age
and about procedures of bone and sexual maturity rating.
Next assess your patient. Make a diagnosis and write
down the suspected cause for the abnormality. Read
about what tests are best for establishing the diagnosis
and for repeated evaluation. Now look at treatment
options. Talk to parents of the child on how to use the
medicines and what response to expect. Explain why
medicines must be continued for life time in a dose that

may vary depending upon patients response. Inform
parents when to suspect side effects of drugs and when
to come for follow up to evaluate that the medicines
prescribed are acting and there are no adverse side
effects. This is just an example of how medicine should
be studied and practiced to obtain a clear idea of what
needs to be done and its scientific basis. Studied in this
way a proper understanding of medicine is obtained and
once understood, it is retained for a long time. The above
described method may appear to be too time consuming,
but infact, each aspect reinforces the other and the whole
exercise becomes enjoyable when you understand its
why and how.
When bored or tired pick up any of the numerous
atlases available on different subjects or Caffees book
on Pediatric Radiology. Several websites also have
excellent picture collections. Look at the pictures and try
to store these images in your memory bank. You will be
surprised at your own memory which will download a
picture several years later and provide you a diagnosis.
Even a life time is not enough to attain mastery over
entire field of pediatrics but if you can master the
diagnosis and treatment of about 50 clinical conditions,
you will be known and respected amongst your
colleagues as a competent pediatrician. Surely that is not
asking for too much. Each one of you has the potential to
achieve that status, provided you focus, continue efforts
to improve your skills and have the humility to learn
from anyone who knows more than you.
Watch the bedside manners of your seniors who are
popular with patients. Note how they approach the
patient and the way they interact with parents. When
social competence combines with clinical competence,
nothing can come between you and success. A friendly
helpful and sympathetic attitude is essential at all times
for building good relationships that last. Never exploit
the misery of a patient who is already in distress.
Remember always that a patients best interest must be
first and foremost in your mind.
What you learn at the medical school is a minuscule
of the vast ocean of knowledge. You mainly learn to
acquire knowledge and some practical skills, which will
form the foundation of your future career. What you
build on it depends on the inputs of hard work,
methodically carried out over span of a life time. A life
time is too a short period to master even one specialty or
sometimes even one medical disease, but if the quest is
continuous, you will enjoy the journey, whatever be the
distance you cover.
1.3 Pediatric Care in Developing Countries

BNS Walia
Most of the developing countries suffer from the twin
scourges of large populations, with vast numbers living
in dire poverty and subhuman living conditions. More
than half of the population lives below the breadline,
which leads to nutritional deficits. Frequent episodes of
infectious diseases further sap away the already poor
nutritional status.
Adding to these widely prevalent disadvantages are
the complexities of living in deep interiors of countryside,
where means of transport are either scarce or nonexistent,
health centers are miles away and health service
providers are either unskilled or not available at all. These
people live on the edge, where ruthless nature and state
of neglect takes a heavy toll on the weak and the
vulnerable, i.e. women and children. Modern medical
care is a distant dream and mere survival is a boon from

the Gods.
How and why the situation has been allowed to
deteriorate to this extent, is an uncomfortable question.
The answer lies in the wrong policies pursued by the
government of most of the developing countries, with
few exceptions. Over the last few decades, these policies
have led to a grave imbalance in the allocation of funds
for health projects, so that urban health has been given
precedence over health of rural populations which
constitute 7580 percent of toal population of a country.
Hospitals have been preferred to dispensaries and
maternal and child health (MCH) centers; superspecialty
hospitals devoted to cardiology and neurology have been
given priority over general hospitals, production of
doctors have been given precedence over availability of

paramedics. This imbalance in the disbursement of scant
resources has resulted in a situation, where the interests
of many have been sacrificed for the sake of the few. Thus,
a vast number of people get no medical care. Hospitals,
and dispensaries have been starved of supplies. Doctors
and their overproduction have culminated in a situation
where doctors have to join the queue of educated unemployed, whereas the country is facing grave shortage of
nurses, physiotherapists, speech therapists, audiologists,
radiographers and laboratory technicians.
A young doctor who begins a career in medicine has
to be aware of these shortcomings in the system into
which he has stepped, so as to be able to chart his way to
be able to accomplish his lifes mission in a meaningful
way. The first few years of his professional life are to be
spent in a rural dispensary or a health center, where
leading a health team is going to be his most important
task. It is quite likely, that he will discover that his 5 years
at the medical college did not prepare him to effectively
cope with his responsibilities. The first lesson that he
learns is that he has to learn a lot and that this learning
shall continue throughout life. He also feels, that his teammates also, either do not know how to do what is
expected of them or are not motivated to do it. Setting
standards, and training each member of the team to fulfill
his role, meeting the standards expected, is his next
important task. Knowing the epidemiologic profile of the
geographic area where he is located, helps him to set his
priorities correctly and equip himself with medicines and
supplies for geographic pathology pertaining to that area.
Having ensured himself of a constant supply line of
medicines and other articles needed, he has the
wherewithal to get started. However, his success is
determined by the response that he gets from the
populace and its local leaders.
Illiterate, ignorant of the miracles which modern
medicine can perform, suspicious of new experiments
to be conducted by strangers and misguided by the
indigenous quacks whose vested interests, threatened by
the availability of effective medical care to population
where the quacks hold a monopoly, the villager is often
confused as to where to seek medical relief, even if he is
convinced of its greater effectiveness. There are several
hurdles to cross before he can reach a primary health
center. These include: inability of women folk to travel
alone; (none to care for children and animal stock left
behind while the family is away), loss of a days earnings;
lack of means of transport; and finally the cursory and

callous behavior of health workers, who are generally
overworked and steeped in their own professional and
domestic worries connected with rural living.
The prescriptions obtained after much effort are often
not purchased because the poor patient cannot afford
them or they are not locally available. Compliance with
a full course of treatment is often neglected because
instructions are not clearly given or understood and relief
of presenting symptoms is mistaken as cure. This often
leads to disastrous results in diseases like pulmonary
tuberculosis, where bacteria are liable of becoming
resistant to commonly used drugs. Supervision of
therapy by domicilliary visits of health staff, is often
lacking as numerous vertical programs functioning in
the health services encourage an attitude amongst
workers of doing their bit for their own program and
ignoring the other multiple problems being faced by the
patient. Thus, a leprosy worker will not take a malaria
slide or look at a conjunctivitis eye, because his target is
leprosy eradication. The same is true for workers engaged
in blindness control, reproductive health or malaria
eradication. Whereas most of the world is depending on
the single window approach for numerous public
services, we are going on opening new windows,
serviced by one disease specialists who fail to relate
with their clients, and thus fail to win their confidence.
It is often forgotten that advice on promotive health care
programs, e.g. family welfare which forms a predominant part of primary health care, can only be accepted
by a woman from a health worker who has helped her
to recover from her last episode of dysentery or assisted
her last delivery, and not from a stranger, who is chasing
her for his personal targets. The recent change in the
objectives of the family welfare program to reproductive
health program, is indeed a welcome step and is expected
to divert the attention of workers from achievements of
targets to quality services, to be provided to their clients.
Imparting health education should be an important
task of every health worker. He must try to impart some
messages related to the problems the patients are facing,
at every encounter. This is the only way to counter the
scepticism rooted in age-old beliefs in witchcraft and
supernatural powers. All traditional beliefs may not be
harmful and some indeed may be beneficial to the
patient. Unnecessary confrontation of views should be
avoided.

Patients are often brought late to the hospital, and in
a critical condition. Their patience as well as their financial resources get exhausted. Promptness in attending to
the patient, politeness in dealings, and an attitude of
concern and care by the staff is essential. Our patients
believe us to be Gods, and not mere Docs as

compared to our co-professionals in developed countries.
We must try to live up to the expectations of the people,
by showing compassion, and concern, in our dealings
and competence in our jobs, to deserve that appellation.
1.4 Primary Health Care

Yuvaraj Chandra Mathur, Nitin Chandra Mathur
All countries of the world are concerned about the
problem of primary health care (PHC) for their people.
This concern includes such aspects as how to provide it,
how to achieve coverage for all of the people, how to
provide primary health care of some quality, how to
make the maximum use of the countrys and communitys existing resources, both personnel, equipment, and
supplies, and how to link up primary health care at the
local community level with secondary and tertiary health
resources.
It is for these reasons that the international conference
on primary health care was held by the World Health
Organization at Alma-Ata in 1978.
Definition
Primary health care is essential health care made universally accessible to individuals and families in the
community by means acceptable to them, through their
full participation and at a cost that the community and
country can afford. It forms an integral part both of the
countrys health system of which it is the nucleus.
Content
Primary health care addresses the main health problem
in the community, providing promotive, preventive
curative and rehabilitative services accordingly. Since
these services reflect and evolve from the economic
conditions and social values of the country and its communities, they will vary by country and community, but
will include at least: promotion of proper nutrition and
an adequate supply of safe water, basic sanitation,
maternal and child care, including family planning,
immunization against the major infectious diseases, prevention and control of locally endemic diseases,
education concerning prevailing health problems and the
methods of preventing and controlling them, and

appropriate treatment for common diseases and
injuries.
General Principles
1. PHC should be shaped around the lifestyles of the
people to be served.
2. PHC should be an integral part of the National Health
Care System and other services, in particular supplies,
supervision, referral and technical, and it should be
designed to support the needs at the peripheral level.
3. PHC activities should be fully integrated with the
activities of the other sectors involved in community
development (agriculture, education, public works,
housing, communications).
4. The local population should be actively involved in
planning health care, so that it suits their needs and
priorities. Decisions on what are the community
needs requiring solution should be based upon a
continuing dialogue between the people and the
services.
5. The health care offered should make use of the available community resources, especially those which
have hitherto remained untapped, and should remain
within the limits of the funds available.
6. PHC should use an integrated approach of preventive, promotive, curative, and rehabilitative services
for individual, family, and community. The balance
among these services should vary according to community needs and may well change over time.
7. The majority of health interventions should take place
in or as near as possible to the patients home and be
carried out by the worker most simply (but
adequately) trained to give the treatment in question.
Primary health care is usually delivered by community

health workers. These are public health workers, usually
from the local villages which they serve. They may be
full time or part time, they are usually paid. The PHC
worker needs to understand and be knowledgeable about
the major health problems and needs in his or her
community. For primary health care of women, infants,
and children, the traditional birth attendant (TBA) has
been the person providing primary health care in the
villages.
mother who raises and cares for the children, as well as

other family members. It is the mother who usually cooks
the food and feeds the family. It is she who observes the
condition of children, and who notices and attempts to
treat illness in the children. This means that women of
the family need to have a good working knowledge of
health care, including hygiene, feeding, family planning,
and how to follow the childs development and recognize
the signs of early illness. Health education as well as
general education of women is essential. Womens
organizations can play an important role in this matter.
Training of Primary Health Care Workers
The Risk Approach
In order to provide safe basic PHC, one of the early steps

required is to define the roles, duties, and functions, the
PHC worker is expected to carryout this job description
for the community health worker then needs to form the
basis, for the content of the training program for the PHC
worker. This also means that the workers/trainers of the
PHC need to be prepared in the appropriate content
expected of the PHC staff.
Not only appropriate teaching/training of the PHC
staff is essential, careful supervision of the PHC staff is
also essential on the job. Responsibility for their supervision needs to be clearly delineated. The supervisors
need to be familiar with the job description of the PHC
staff, and with the content necessary to supervise them,
as well as methods of supervision.
In a similar fashion, there needs to be a job description of traditional birth attendants (TBAs). Courses for
TBAs need to contain content to enable them to provide
good safe basic prenatal, labor and delivery, and
postpartum care for the mother. They need to be able to
teach and carry out principles of safe hygiene, and health
education for mother and baby. They need to be taught
the principles and content of safe care of the newborn,
of observation of the infant, and of breastfeeding, and
carefully timed supplementary food and weaning. They
need to be trained in family planning education, and in
well child supervision of the infants and children.
Besides, all PHC staff need to be well-trained in the
content of prenatal, intrapartum, postpartum, family
planning, and child health care.
PHC workers need to be taught and be able to utilize the

risk approach. This consists of the ability to follow
carefully and observe pregnant women, infants, and
children, for symptoms/signs/risk factors which might
lead to suspect the presence of a potential health problem
requiring special care and referral. The concept of highrisk at a simple basic level needs to be taught to PHC
workers. Risk factors recognizable by the PHC worker
need to be included in the training of PHC staff. Patients
suspected of being potentially at high-risk need to be
observed and followed more carefully. Arrangements for
quick referral of high-risk patients are essential.
Who Provides Primary Health Care?
Role of Family Members, Especially the Mother

Family members, especially the mother, are often the
main providers of health care for the family. It is the
Linkages to Secondary and Tertiary Care,

Referral System, and Transport
Patients suspected of high-risk need to be referred to a
resource available to the community, able to provide
special diagnostic treatment, and management service
and care, especially a health center or local/district
hospital. A referral system needs to be established so that
easy, smooth, quick and efficient referrals may be made
through a prearranged system. Quick safe transport is
an important aspect of such a referral system.
Indicators of Care and Outcome
As with any activity in public health practice, evaluation
of results is essential for primary health care. Record
keeping is essential. The use of home-based mother
health records is being tested. The development of a
system and of indicators is an important aspect. Basic
indicators such as accessibility to health care, births
attended by a trained attendant, access to safe drinking
water, level of immunization, contraceptive prevalence
are frequently utilized to evaluate outcome of PHC.
1.5 Primary Neonatal Care

Santosh K Bhargava
Primary Neonatal Care
The sustained decline in infant mortality rate, caused
largely by a decrease in post-neonatal period mortality
has focussed attention to neonatal mortality and newborn care. If the national goals in child health care are to
be achieved then it is essential to improve neonatal care
at all the three levels namely primary, secondary and
tertiary level. The primary neonatal care deserves highest
priority as even today more than 75 percent of births occur
at home in both urban and rural community and are
attended by trained or untrained birth attendants.
Primary care is intended for all parturient mothers and
their offsprings irrespective of rural or urban community,
institutional, hospital or home delivery for successful
outcome of pregnancies. To achieve this and the birth of
a healthy newborn it is necessary to care and improve
essential prenatal, intranatal, and postnatal care to an
expectant mother and neonatal care at birth subsequently.
Antenatal Care
The most crucial period for a parturient mother and her
fetus is the antenatal period because it is during this time
inappropriate or inadequate care may result in problems

to both. All pregnant women should have access to
antenatal care by trained health professionals. It should
include assessment of maternal health, including weight,
height, midarm circumference, nutritional assessment,
obstetric history and obstetric examination for intranatal
risk, follow-up for pregnancy complications such as
anemia, hypertension, urinary infection, etc. and
assessment for fetal growth. Figure 1.5.1 provides a plan
for antenatal care. In our limited resources it is essential
to categorize a pregnancy at low or high-risk because a
timely referral of a high-risk pregnancy for appropriate
care will prevent adverse outcome. Simple information
such as bad obstetric history, maternal weight less than
45 kg, height less than 140 cm, birth interval of less than
2 years between two successive pregnancies, pregnancy
complications, etc. are indicators of high-risk mothers.
Intranatal Care
Safe and clean delivery remains the main objective of
good intranatal care. The community must be made
aware and encouraged to use safe delivery kit
Figure 1.5.1: Delivery of perinatal care at primary level
10 IAP Textbook of Pediatrics

TABLE 1.5.1: Birth attendants kit of safe
delivery and newborn care
TABLE 1.5.2: Some harmful traditional

practices of newborn care
Soap
Harmful Practices
Plastic sheet
Cotton and gauze pads
Umbilical cord
Cord cutting
Thread or ligature
Razor blade
Mucus suction trap (may be disposable)
Spring balance (reusable)
Measuring tape (reusable, fiber glass)
(Table 1.5.1) and delivery by trained birth attendant.

Hand washing with soap, use of sterile thread and blade,
facilities for oropharyngeal suction and warmth at birth
are key components of ensuring safe birth.
Postnatal Care
A postnatal mother needs to be looked after not only for
postdelivery complications such as bleeding and
infections but also for initiating and maintaining successful breastfeeding. She must be informed about harmful
traditional practices for maternal and newborn care and
advised on routine newborn care.
Cord tying
Cord application
Sickle- or knife-shaped instruments,

bamboo spike
Thread, cloth, bamboo shred
Ghee, turmeric, cow dung, ash
Resuscitation
Slapping, ringing bell, blowing air

across mouth, roasting placenta, etc.
Cleaning oropharynx
Bath
Finger, cloth
Immediately or within few hours of
birth
Prelacteal feeds
Honey, jaggery, glucose, janam ghutti
Time to first feed
Delayed from 6-48 hours or more
Breast milk
Discarding colostrum
Eyes, ear, nose
Kajal and oil application
All newborns irrespective of place of birth, person conducting the birth, whether preterm, term or post-term,
normal or low birth weight, apparently well or sick need
care for their survival and well-being. This care is a
newborns primary need as prior to birth it is wellprotected in safe, sterile and suitably warm in utero
environment. The primary care is thus intended to
support it to establish successfully its respiration, temperature, nutrition and provide safe environment. In our
country almost two-thirds of births occur at home and
the remaining at hospital or health care facility. Thus, a
newborn is to be cared at home by traditional birth
attendants or family and at varying levels of health care
by medical professionals who themselves may or may
not have been suitably trained.
necessary to be aware of these practices, their sensitivity

to the family to provide appropriate beneficial advice
and warning against harmful practices (Table 1.5.2). The
advice for home care should be simple and acceptable to
family. This should include provision of clean birthing
place, delivery by trained birth attendant, use of safe
delivery methods and the mother and the newborn to
be nursed in warm, clean, well-lighted rooms.
The basic features and components of primary
newborn care have been well-defined and accepted for
delivery of newborn care at primary level as a package
comprising of care at birth, in the immediate neonatal
period and subsequently. This package is known and
described as essential newborn care (Table 1.5.3). It aims
to assist the newborn in establishment of cardiorespiratory effort, prevention of hypothermia and maintenance of body temperature, a physical clinical
examination for identification of at risk infant, congenital
malformation; early initiation and maintenance of
successful breastfeeding and referral of a high-risk or sick
newborns for appropriate care to higher level of care.
Domiciliary Care
Care at Birth
The domiciliary care of a newborn is usually determined

by the family tradition, grandmother or any elderly lady
in the house. The family practices are usually steeped in
tradition, cultural and religious practices. It is therefore
The birth of a newborn should always occur in a clean

environment. The room temperature should be suitably
warm. The newborn should be received in a prewarm
clean cloth and dried immediately preferably under a
Neonatal Care
Pediatric Care in Developing Countries

TABLE 1.5.3: Essential newborn care
Care at Birth
Warmth
Initiation and Maintenance of adequate respiratory
effort
Prevention of Infection
Referral for appropriate care
Care During Immediate and Early Neonatal Period

Warmth
Early Breastfeeding
Early diagnosis, appropriate care and referral of a sick
newborn
Care in Late Neonatal Period and Beyond

Follow-up
Intervention
radiant heat source and kept warm. The time to first cry
and breath should be recorded. Most of the newborn cry
immediately at birth. Those who fail to cry may need
resuscitation.
There are several methods to assess the cardiorespiratory effort of the newborn but the most commonly
used method is the Apgar score. The Apgar score consists
of giving a score of 0, 1 and 2 to color, heart rate, reflex
irritability, muscle tone, respirations at 1, 5 and 10
minutes of birth. A score of 7 or more is considered
normal and lower score indicates the need to resuscitate
the infant as described elsewhere. However, at peripheral
level and for primary care health professional such as
traditional birth attendant the time to first cry and
whether it is lusty, feeble or poorly sustained and the
color are reasonably good indicators to reflect newborns
condition at birth.
A clinical examination at the earliest opportunity after
birth is mandatory for all newborns. This is aimed to
identify an infant whether he/she is normal or at risk
and for determining appropriate level of neonatal care.
It is ideal to measure an infant by recording birth weight
or by surrogate to birth weight such as midarm circumference by using measuring tape or bangle. A newborn
is at a very high-risk of acquiring infection and susceptible to adverse effects of cold or hot environment
resulting in hypothermia or fever. It is therefore critical
to ensure asepsis and suitable environmental temperature of 26-28oC for protection of the newborn.
11
Care in Immediate Neonatal Period

Warmth
A newborn continues to remain susceptible to hypothermia and hence it is necessary to provide warmth to
him by radiant heat source such as infant warmers,
lighted bulb or other suitable means such as nursing of
the mother and the infant in same bed. A heat source
should never come in direct contact with the infant or
very close to him as this may cause burn or hyperthermia.
The child should be appropriately clothed.
Early and Sustained Breast Milk Feeding
All newborns should be put to mothers breast as soon
as possible after the birth. Early and sustained breast milk
feeding is vital for a newborns survival not only in the
immediate neonatal period but also in later months. It is
constant suckling of the breast by the infant which results
in successful breastfeeding. In case it is not possible for
an infant to directly breastfeed, the breast milk should
be expressed and the infant fed the same by cup and
spoon. Feeding of a newborn with artificial milk feeds
endangers it to preventable morbidity and mortality.
A newborn is at a very high-risk of acquiring infections
from surroundings and/or by people visiting or handling
him. It is therefore necessary to wash hands with soap
and water before handling the newborn, avoid unnecessary handling by person other than mother or visiting of
the newborn by relatives and friends. All newborn must
be exclusively breastfed and water, prelacteal feeds such
as honey, ghutis, gripe water or unnecessary medication
by mouth must be prohibited. The dangers of such
practices must be explained to family and mother.
Early Diagnosis, Appropriate Care for a High-risk or
Sick Newborn
A good history and clinical examination will help in
identifying almost all at risk and sick newborns. Birth
weight, gestational age, cry at birth, color, movement,
activity, body temperature, abdominal distention,
tachypnea, refusal or decrease in feeds are dependable
signs or symptoms for an early diagnosis. Infants with
birth weight less than 2 kg, preterm irrespective of birth

weight, feeble, ill-sustained or excessive crying, poor
color and decreased activity warrant careful observation
and need for appropriate or higher level of supervised
medical care preferably in a health care facility.
nutritional advice, growth assessment, immunization

and for an early diagnosis of developmental delay or
disability for appropriate optimal care.
BIBLIOGRAPHY
Immunization
1.
It is preferrable to immunize the newborn at birth or

within two weeks with oral polio and BCG vaccination.
Hepatitis B vaccine may be administered in high-risk
infants or where the family is able to afford it.
2.
3.
Care in Late Neonatal Period and Beyond

The care of the newborn does not end with the discharge
from the health care facility or postnatal follow-up of
the mother. All infants should be advised adequately on
need to follow-up in well baby/immunization clinics for
4.
5.
Bhargava SK. Recent Trends in Neonatal Health and Care

in India-International WorkshopImproving Health of
the Newborn Infant in Developing countries.
Kathmandu-Nepal, 1997;7-10.
Health Information of India 1994.
National child survival and safe motherhood program,
integrated clinical skills course for physicians, MCH
division, Ministry of Health and Family Welfare, 1993.
National Health Policy, Govt. of India, Ministry of Health
and Family Welfare, 1985.
National Neonatology Forum, Proceedings of National
Workshop on traditional practices of neonatal care in
India, 1991.
1.6 Management of Primary Health Centers

Piyush Gupta
The basic aim of the Primary Health Center is to provide
primary health care to the people it serves.
WHAT IS PRIMARY HEALTH CARE?
Primary health care is essential health care based on
practical, scientifically sound and socially acceptable
methods and technology made universally accessible to
individuals and families in the community through their
full participation and at a cost that the community and
country can afford to maintain at every stage of their
development in the spirit of self-reliance and selfdetermination.
Thus the doctor at a Primary Health Center (PHC)
has a different role to play. He/she not only delivers the
health care but manages the center in totality, trains and
leads the team, involves with the community, gets to
know the local people, geography and epidemiology of
diseases, devises strategy, and coordinates with other
managers and stakeholders (both in public and private
domains) under the jurisdiction of the PHC.
Steps in the Management of Primary Health Care
1. Assessment of the situation
2. Selection of priorities
3. Defining objectives and deciding possible strategies

to accomplish them
4. Involving community
5. Mobilization of resources
6. Selection and training of personnel
7. Identification and supply of essential drugs and
equipment
8. Patient management
9. Monitoring and supervision of the progress of work
10. Team management
Assessment of the Situation
Health situation in the PHC area should be reviewed with
reference to health profile of the people. Availability of
local resources should be estimated. Details of other
demographic and cultural characteristics of the population in the catchments of the PHC should be obtained.
Before hand knowledge of the following factors is
generally valuable in planning out of health facility:
demography (age and sex distribution, spread of
education, average income and economic stratification,
religion and caste groups, cultural beliefs and taboos,
attitudes towards health, expectations from the proposed
health facility and identification of influential as well as
13
functional community leaders), health profile

(prevailing disease pattern, number of people with
disability or handicap, proportion of expectant mothers,
infants and young children; age-related death rates, food
habits, other health practices, the level of sanitation and
hygiene in the community), available resources (the state
of agricultural development and irrigation facilities in
the area, income stratification, availability of food and
sources of potable water, existing health facilities in the
area and their utilization, presence and number of
available traditional faith healers, traditional birth
attendants, practitioners of indigenous systems of
medicine, and information regarding organized
voluntary agencies or establishments such as village
panchayat, health clubs, youth or womens clubs and
other voluntary non governmental bodies), and the
catchment area (geographic terrain, climate, roads and
other means of communication).
needs. It should be possible to quantify the results of

health interventions so that their cost-benefit or costeffectiveness can be evaluated.
An objective may be achieved by several possible
alternate strategies. As a general principle, relatively
inexpensive and flexible strategies should be adopted for
the management of prevalent common health problems.
After carefully reviewing various alternate strategies,
their advantages, disadvantages, cost-effectiveness,
scientific soundness and cultural acceptability, decision
should be made about the activities that should actually
be undertaken in accordance with the declared national
health policy. The decisions should be technically sound
and correct. Possible constraints and obstacles in
implementing these activities should be carefully looked
into. Adequate prior planning should be done by interaction between the community, members of the health team
and the administrative officers.
Selection of Priorities
Community Involvement in Primary Health Care
There may be several compelling health problems

necessitating attention in the territory. With the meager
health resources generally made available through
government agencies for primary health care, every
health need of the community cannot be satisfied. It is
necessary to be selective. The health issues and the target
group of people who merit preferential attention should
be recognized and looked after first. Most people seek
prompt relief from pain and affliction. Provision should
be made for emergency treatment of life threatening
conditions. It is more realistic and expedient to try to
prevent large number of deaths due to vaccine preventable diseases by immunization than using enormous
money to extend the life of a few terminally-sick cancer
patients. Cost effective health interventions should
receive precedence in planning in relation to those
illnesses which though common are hard to prevent or
manage.
Active participation of community in health care is vital

to make health services readily accessible to the people
and for better utilization of the PHC. This approach relies
on creating increasing awareness among local people
about health and health related activities, so that they
can commit themselves and have stakes in the success of
health activities. People should be actively mobilized to
take more interest in development of health services in
their area by explaining the purpose of health activity
and describing an action plan. Individuals who can
assume leadership role are identified. A health committee
should be formed from among these influential
community leaders to analyze health needs of people and
to plan and execute health projects. The committee
should interact with health professionals to find locally
feasible solutions to the identified problems. The
Committee should assess and mobilize resources and
assign responsibility for achieving objectives.
Defining Objectives and Deciding Strategies
Mobilization of Resources
The next step is to identify the objectives proposed to be

achieved through the health care activities. It is not
always necessary to formulate idealistic health objectives.
It is more important to be rational and set objectives,
which are feasible and attainable within a reasonable
time, with the given resources. The objectives should also
be pertinent to the countrys national health policy and
Money, personnel and time are the three most important

resources that need proper mobilization at a PHC. There
should be adequate working space at the health post for
members of the health team to operate from a base.
Means of communication with the referral centers should
also be easily available. A critical minimum amount of
resources is needed to maintain the quality of health

services at an effective level. The resources can be
mobilized, either from the government, community, nongovernment-voluntary agencies or recognized international agencies. It is advisable to rely only on those
funding agencies, who assure help on a longterm basis
and who create a permanent infrastructure, so that the
projects aided by them can become self reliant in the long
run.
Selecting and Training Personnel
It is almost impossible for a developing country to
employ fully trained graduate physicians for all aspects
of primary health care. At a PHC, you will need to
delegate some of the simpler health tasks to the
paramedical workers. Increasing dependence on other
categories of personnel with limited on the job training
in specific areas of work becomes necessary. Preferably,
they should be drawn from as well as chosen by the
community they are expected to serve. It does not matter
even if they have a lower academic background. These
paramedical workers will have to be increasingly
employed for assisting the busy and overworked
physician for routine and simpler health related tasks.
The latter will, then be able to devote more of his time
for complex health chores, administration and planning.
It is necessary to supervise the work of these specially
trained health workers and retrain them periodically for
the expected job requirements. Physician should provide
technical guidance and support to these workers. The
training can be extended to the practitioners of
indigenous or traditional systems of medicine, traditional
birth attendants, local priest, faith healer or exorcist in
the village who performs witchcraft, branding or other
rituals; and even the quacks.
Identification and Supply of
Essential Drugs and Equipment
Essential medicines (those that satisfy the priority health
care needs of the population) should be made available
at the PHC. Selection of these drugs also depends on local
health needs and health services. Ensure adequate and
timely supplies of drugs, and immunizing agents. You
should be aware of the sources of supply of drugs and
procedure for ordering these. The requirements of drugs
should be estimated for at least a quarter of the year.
The drugs are best stored in a cool-dry place away from
direct sunlight. Vaccines should be stored in refrigerator
and electricity supply should be ensured. Drugs should

be arranged by their generic names in shelves in
alphabetical order or according to the therapeutic class
(their usage or indications) but not according to the
manufacturer or suppliers. Drugs with a recent date of
expiry should be used early. Record of all drugs should
be kept in a stock book. Drugs should be issued by the
storekeeper to the dispenser against issue vouchers and
an entry should always be made in the stock book and
stock card. Only the minimum essential quantity of drugs
required for use on that day or week should be issued at
a time, to prevent excessive wasteful use and to minimize
the possibility of pilferage.
Medical, surgical equipment, furniture, stationery
and other consumable and nonconsumable stores are also
essential resources for primary health care posts. Nonexpendable stores such as furniture, weighing scales,
bedpans, screens, surgical equipment, microscopes and
motor vehicles if properly handled, are not easily
damaged and can be kept in use for several years. These
should be maintained in working order by regular and
timely repairs. Drugs, food, paper, syringes, laboratory
reagents, kerosene, petroleum, candles, match boxes,
torch cells, cotton wool and surgical dressings etc. are
actually expended and are called expendable stores.
Architecturally, the space within the building should be
so arranged, that it facilitates smooth and orderly work,
and does not cause inconvenience or obstruct the
movement of staff or the patients. A to and fro flow of
patients or a common entrance and exit are not conducive
to good working arrangement. Records and paper work
are essential and unavoidable in a primary health care
setting. Stock books and ledgers have to be maintained
and general correspondence attended. Periodic report of
work is to be submitted to the higher authorities. Poorly
maintained and disorganized records books indicate
poor management, inefficient patient care, inadequate
supervision, mishandling and wasteful use of resources.
Stationery and printed forms should be available for
outpatient registration, treatment, referral laboratory and
X-ray requisition, growth monitoring, immunization and
follow up of special diseases such as tuberculosis and
leprosy. If the primary health care post has some
maternity or general beds, inpatient admission forms,
record forms and discharge summary will also be
needed.
Health care forms should be designed for easy and
effective use. Paper should be used economically, but

there should be enough space for writing the data. A
badly printed form may be used badly, making if difficult
to retrieve useful information.
Patient Management
Disease management is a priority as it relieves distress
of the patient and develops confidence. A delay in
initiation of medical care raises the tensions and temper.
First Aid should be provided promptly. If a patient
requires referral, arrangement for a transfer should be
made, transport arranged and a summary of treatment
received by the patient should be provided. Emergencies
should be given priority. Outpatients should be seen
during a fixed time. Other services, which are not run
on daily basis, should be clearly advertised. A paramedical worker or a physician should be the first person
of contact at the primary health center.
Monitoring the Progress of Work
The leader of the health team is expected to set targets
for different members of the health team. He should
define the tasks to be accomplished within an agreed
schedule of time.
The efficiency of different workers may vary and
certain essential inputs for optimal functioning may not
be available at the appropriate time. To achieve the best
results, you should periodically review the progress of
all work at specified intervals. You should judge the pace
of the work by relating it to the earlier agreed job
schedules, reports of their achievements and site visits
for personal observations and discussion with the staff.
Periodic monitoring helps in recognizing obstacles or
unforeseen difficulties in accomplishing the desired
objectives. Monitoring is useful in good management but
it should be minimal, flexible and timely.
Leading the Health Team
Because of the nature of his training, education and
status, the primary health center doctor has to assume
the role of a natural leader of the PHC team. All personnel
working in the PHC constitutes the health team. As a
team leader, you should be able to induce colleagues and
teammates to work to the best of their capacity, and
motivate them. The team leader should be able to achieve
perfect coordination and cooperation with all members
15
of the team, so that the efficiency and output of the health

team are high and the work is interesting, satisfying and
rewarding.
The leader of the health team should realize that the
health team consists of individuals, who have feelings,
personal interest, anxieties, stresses, conflicts, likes and
dislikes, just as other people. People like to be useful and
important. Their emotional needs are better satisfied, if
they are given the responsibility and authority to carry
out the jobs assigned to them. Their efficiency and work
output improves, if their working conditions are
congenial, peaceful and relaxed with the least tensions
and conflicts. The efficiency of a worker declines if he or
she remains preoccupied with personal needs, such as
lack of adequate lodging close to the place of work, long
hours of work, want of personal security, financial
worries, inadequate facility for childrens education, poor
health or perfunctory personal medical care. It is
distressing to them if their salaries are not paid in time.
Monetary incentive by itself is not adequate for
motivating a health worker to do his work more
conscientiously. Monetary reward should be judiciously
combined with recognition and approbation for his good
work .
The leader should be competent in his own technical
work, so that his team mates respect him for his
knowledge and skills. He should zealously guard his own
credibility for fairness, impartiality, honesty and
integrity. The leader should be easily approachable, so
that the team members can reach him and seek his help
and guidance for solution of their personal, technical and
official administrative problem. The leader should
always appear to be disciplined and well organized in
his thought and work. Delegation of responsibility and
authority to the health team is equally important in the
PHC.
Health team is like a chain: One weak link in the chain
breaks the entire chain. A good leader identifies the weak
links by constant supervision at regular intervals. He then
reinforces them by appropriate measures such as
technical guidance, administrative support and corrective retraining. Regular supervisory control helps the
leader to discover other constraints such as nonavailability or delay in supplies of such needed items.
1.7 Training of Medical Graduate as

Middle Level Manager
C Thirugnanasambandham, T Arunmozhi
The World Health Organization, at Alma-Ata conference
on 12th September, 1978, declared that Health, a state
of complete physical, mental and social well-being and
not merely the absence of disease or infirmity, is a
fundamental human right. There is also an increased
realization, backed by scientific evidence, that neither
the individual nor the nation can achieve optimal health
until we tackle what are commonly known determinants
of health-broadly associated with and arising out of
physical, social, economic, cultural and political
environment. The national and state governments are
committed to the achievement of Health for All, as early
as possible through the primary health care approach.
That these efforts have had substantial success can be
seen from some of the indices like reduction in crude
birth rate (CBR) from 40.8 (1951) to 25.8 (2002); halving
the infant mortality rate from 146 per thousand live births
(1951) to 60 (2001); reduction in crude death rate from 25
(1951) to 8.5 (2002); addition of 31 years to life expectancy
from 32 to 64 (2000); and reduction in total fertility rate
from 6.0 (1951) to 3.0 (2000). In spite of these successes,
the unfinished task for achievement is still high as can
be seen from the sociodemographic goals set for the 11th
Five Year Plan. Currently India is committed to become
a developed nation by the year 2020, which calls for very
substantial improvement in health, education, economic
development and other areas. A revised strategy for the
achievement of these goals have also been formulated
and consists of provision of integrated service delivery
for reproductive and child health care; decentralized
planning and program implementation; convergence of
service delivery at village level and empowering women
to function as change agents in addition to being
consumers of health care services; removal of gender
inequalities, and special attention to removing inequity
in health care by focusing services to underserved areas
like urban slums and hilly and tribal areas and
disadvantaged groups like women, female children and
adolescents; diverse health care providers; collaboration
with Non- Governmental Organizations (NGOs);
intensified information, education and communication
activities; intersectoral coordination and providing for

older population. In addition, the strategy provides for
social inputs like increasing literacy and raising age of
marriage. In general, the program will continue to be
community and maternal and child health (MCH) based.
Primary Health Care
The health infrastructure for the delivery of services in
health and family welfare consists of the primary health
care system. Presently, one primary health centre (PHC)
caters to about 30,000 population (20,000 in hilly and
tribal areas), one subcentre to about 5000 population
(3000 in hilly and tribal areas). In addition, there is one
community health centre (CHC) with 30 beds for every
3 PHCs. Both the Taluk and District headquarters
hospitals are being equipped and staffed to provide for
referral services.
Epidemiological Transition
Technological advances in medical and allied sciences
have brought down the mortality rate to the targeted
level, but the morbidity burden on the society continues
to remain high. Both communicable and non communicable diseases rank almost equally in contributing to the
high level of morbidity. An additional challenge is the
wide disparity in health status between states, within
the state and between social groups.
While the disease burden remains unchanged, the
pattern has been changing. It is now certain that the
health challenges for the next few decades will consist
of communicable diseases like HIV/AIDS, drug resistant
malaria, tuberculosis, diarrhea and acute respiratory
infection among children. The second challenge concerns
non communicable diseases like the upsurge of cancer
and cardiovascular diseases and other life-style related
diseases such as diabetes, high blood pressure, mental
depression and suicide and accidents. Increase in tobacco
consumption is a cause for added concern. The spread
of HIV/AIDS has the potential to offset the hard gains
achieved in child survival and life-expectancy.
Widespread malnutrition, poverty and illiteracy, as well

as the generally low status of women impede equitable
health development in the country.
Significant changes have taken place in the health
scenario in the country since independence.
1. The predominantly clinical approach in solving
health problems has given rise to a mix of curative,
preventive, promotive and rehabilitative approach.
2. A huge infrastructure has been created in the rural
areas for delivery of health care and family welfare
services. The workload of the medical officers,
custodian of health in their areas, has very much
increased and consists of integrated curative,
preventive and promotive service delivery. Over and
above, are the essential management functions in
terms of planning, coordination, supervision, training
and others.
3. Renewed emphasis on community involvement,
through the recently introduced Panchayati Raj
system, in planning and implementing various
programs resulting in a need to readjust responsibility
and authority and changes in the working of the
bureaucracy.
4. Integration of a number of vertical programs into the
rural health services.
5. The realization that national/state governments
working through health sector, by themselves can
never achieve the health and demographic goals set.
The private sector, NGOs and sectors other than
health, like education, industry, social welfare, rural
development and civic society can and should play a
critical role in health development. Partnerships with
all sectors of society and at all levels are imperative if
we are to bridge the equity gap in health.
6. Major shift from the clinic-catered approach to one
of a suitable mix of clinic and outreach services.
7. The total expenditure on the health system has been
increasing every year, but has remained static at about
0.9% of the Gross National Product (GNP) over the
past two decades. The current level of expenditure is
inadequate to bring about reduction in infant
mortality rates envisaged under the eleventh plan and
reach the millennium development goals. The
government has planned to increase the expenditure
to 2-3% of GDP by the year 2010 and it is hoped it
will materialize.
The above shifts have resulted in major changes in
the roles and functions of the middle level managers of
health delivery system, particularly of medical officers
17
from that of a pure clinician to include public health

practice, communication and health management.
Health Services Management
A neglected area so far is that of health services
management. The effectiveness and efficiency of the
health care delivery system cannot improve significantly,
unless sound administration or management practices
are adopted to improve the system. It has been the
assumption till recently that persons trained in medicine
or public health automatically qualify to become
managers. Only in the last few years, it has been
recognized that this assumption needs change and good
managers need sound training in principles and practice
of health management or administration.
Administration or management could be defined as
a process by which, the potentials of men, money and
materials are synthesized and synchronized for the
achievement of well-defined goals. It is a way to structure
and direct human groups function cooperatively to
achieve predetermined goals. Generally, administrative
process involves: (i) technical functions, (ii) political
functions, and (iii) conflict resolution functions.
Technical functions are best indicated by the wellknown seven letters namely POSDCoRB: P for planning,
O for organizing, S for staffing, D for directing, Co for
coordinating, R for reporting and B for budgeting.
Political function is not to be conceived as partisan
function of politics, it is concerned with making of
policies and structuring of power relationship in an
organization. Conflict resolution process aims at resolving
conflicts amongst individuals, organizations and
between individual and organization goals.
The middle level functionaries in health system
should possess sound knowledge and skills in the process
of planning, coordination, supervision, training,
monitoring and evaluation, communication, community
participation and management of subsystems like office
management, logistics, budgeting, vehicle management,
etc.
Planning
A plan is predetermined course of action, it involves the
intelligent use of resources and working out the broad
outline of things that need to be done and the methods
for doing them. The middle level managers are concerned
with operational level planning. They are concerned with
area planning, area being determined by geographic

jurisdiction of workers and also governed by those of
panchayats and panchayat unions.
The essential steps of planning include collecting
baseline information, setting objectives, deciding on
courses of actions and programming. Monitoring and
evaluation is an integral part of planning. The planning
cycle consisting of: planning, implementation, monitoring, replanning with repeat, contributing to a greater
progress. However, it will also call for increased
managerial skills on the part of medical officers.
Collection of baseline data is a prelude to community
diagnosis which helps to define community health
problems, their severity, place of occurrence, etc. The
process involves decision on information to be gathered,
framing and administration of questionnaire, data
analysis and report writing. Maximum use has to be
made of existing sources of information, restricting
household/community surveys to a bare minimum.
Once the problems are identified, various options to solve
these have to be considered and the ones that are
technically feasible, cost-effective, administratively
feasible and politically acceptable are chosen.
A problem usually encountered at this level is the
need to strike a balance between what community
perceives as their felt needs, epidemiologically determined needs of the area and nationally determined
priority needs. The medical officer will have to feed all
necessary information at this stage to the community and
of which they are not aware of. It has been the experience
that the community will be able to make sound decisions
irrespective of illiteracy, when once they have the
information to base the decisions upon. This way, an
agreed level of needs with priorities could be reached.
Planning process should also ensure that consumer
representatives are involved in the planning process at
every stage. Involvement of community through leaders,
teachers, students and others in the information
gathering process is highly rewarding as it helps to
conserve time and energy and arouses the perceptual
curiosity of the people and successful implementation
of programs decided upon.
Detailed programming for each activity is also part
of planning. Programming calls for decision of the
agencies involved, manpower, roles of agencies and
workers, training, coordination, supervision, logistics,
budget, etc. Finally, program developed for separate
activities are synthesized into a complete plan.
The middle level manager should possess not only

knowledge about planning, but also skills in the planning
process.
Coordination
Health delivery system consists of a number of workers
belonging to different disciplines. Usually, even for
achievement of a single goal, work is divided among
people, resulting in need to secure coordination or
teamwork. Health administration at all levels are faced
with bringing about two types of coordinationintradepartmental and interdepartmental.
Within the present setup, even intradepartmental
coordination is not an easy task to achieve. Integration
of a number of vertical programs into the PHC system
resulting in pooling of workers belonging to various
agencies and changes in their job descriptions and
patterns of work make coordination difficult. A number
of factors like status, beliefs, leadership, clarity of
functions act as major blocks to coordination. The
manager should know various coordinating measures
and which combination to use under particular
circumstances. The measures available to him include
hierarchial control, organizational charts, manuals,
reports, staff conferences, supervision, training,
consultation, etc.
There will be major factors that inhibit interdepartmental cooperation. These should be identified
and solved. Naming a nodal agency for coordination,
nodal officers at various levels, clear definition of roles
of agencies, training, coordinating mechanisms are
important measures to bring about coordination.
Coordination should be in all phases of planning,
implementation and evaluation.
Good coordination also involves getting the right
things done, in the right place, at the right time, in the
right way and by the right people.
Supervision
A major function of medical officers, at intermediate
levels is supervision. It is an educational process in which
the supervisor takes responsibility for helping the
supervisee develop himself and become more competent
in discharging his duties. Supervision aims at goal
achievement, work facilitation and building human
relations. Staff usually look to the manager for a standard
of leadership. Thus, the way in which the managers

conduct themselves, manage a program and its people
will affect how the staff work. It will also influence the
thinking and behavior of future managers. One has to
lead by example for success.
There are a number of supervisory methods, about
which supervisor should be familiar with. These include
individual conferences, staff meetings, in work situations,
evaluations, etc.
Authority and leadership are concepts which
influence supervisory style, i.e. the way a manager
behaves when trying to influence the behavior of
someone else. Authority is the right to command and is
vested in the supervisor by the organization. Leadership
is a process of influence. Supervisory style will fall at
some point in a continuum between authority and
leadership. The mix to be adopted will depend upon the
forces in the supervision and situation.
Appraisal of supervisions should form a basis for
supervision. Apart from ascertaining the quantitative
achievement of those supervised, the supervisor should
know what traits he is looking for in the supervision,
viz., knowledge, quality of performance, ability to learn,
initiative, cooperative attitude, commonsense, etc.
Feedback to staff on their performance is rarely
carried out despite its importance. Clear and direct
feedback induces certainty, solves problems, builds trust,
strengthens relationships and improves work.
Communication
Medical officers, to be effective, must be able communicators. The communication skills has to extend to various
levels. At the first level, being manager, he/she should
be skilled in various methods of official communication.
He/she should encourage vertical communications, both
from top to bottom and from bottom to top and also
horizontal communication between workers at various
levels. Two-way communication should be encouraged
as a rule, since this leads to better understanding and
reduces gaps in communication. As a supervisor, he/
she has to be a good listener. Instructions issued orally
or in writing should be clear and unambiguous.
In dealing with communication with community the
emphasis should be on empowerment of people. People
do take responsibility for their own health, their familys
health and the communitys health, provided they are
given adequate information and technical support.
The communication strategy should be to use a
combined approach of mass media, group and individual
19
approach. Audiovisual aids can help communication

provided they are relevant and used effectively. Villagebased communication should make use of established
channels of communication in the village and of indigenous media. Training of village leaders, individual and
group meetings should be strengthened. Efforts should
be made to utilize workers of health-related developmental agencies having contact at the grass root level.
Training in communication methods and media and
evaluation of their effectiveness should be an integral
part of training.
Teamwork
One of the managerial functions of medical officers is to
promote teamwork. By sharing skills and knowledge as
a team, people can work more effectively than an individual. Teams can work better when members feel accepted
and trust one another, goals are set and tasks defined,
roles are clarified, members listen, communicate and
participate, conflicts are resolved equitably, leadership is
shared and members are mutually supportive. Incentives
for team commitment go beyond salaries. People are also
driven by their pride in producing excellence.
Training
The goal of training is to provide staff with knowledge
and skills they do not have and as such an assessment of
training needs will be the first and useful step, and
managers, employees and clients should be involved. The
training curriculum will depend on the assessment. The
next step is to identify good trainers from within and
outside since a training program is only as-good as the
trainer. Other inputs that need attention are development
of lesson plans, procurement of training materials, place
of training, proper mix of theory and practice, training
evaluation and feedback.
Looking holistically, the medical officers are
concerned with human resources development, for which
training is a tool. Apart from the staff of the health sector,
training has to be imparted to community representatives,
elected representatives of the civic society and others.
Under these circumstances, focus should be on team
training which will contribute to teamwork.
Building Partnership
It is now widely recognized that we must face new
challenges in health that arise out of lack of attention to

factors influencing health like poverty, illiteracy,
nutrition, population, globalization, gender inequalities,
pollution and many others. This calls for new forms of
action and the challenge is to unlock the potential for
health promotion inherent in many health related sectors,
societies, local communities, local bodies and families.
Health should be the responsibility of all. The primary
health care system should therefore focus on building
partnerships with all sectors at that level and involve
them in health planning and implementation.
Community Involvement
Involvement of the community both as individuals and
collectively, in the process of decision- making for health
and health development is the essence of community
involvement. They should be responsible for health needs
identification, prioritization of identified needs,
preparation of action plans, monitoring and evaluation.
Community involvement helps in improving coverage,
reduction in inequity and promotion of self-reliance.
Management of community involvement in health
requires both knowledge and skills on the part of medical
officer. The medical officer should be prepared to work
with the people rather than for the people. Success of
community involvement, depends upon a number of
factors. First is political commitment to transfer
responsibility to people. Second is a high degree of
bureaucratic commitment to translate the policies into
action. Thirdly, the role of the agencies shift to one of
directing, supporting and facilitating the process of
community involvement in health. Fourthly, the district
health organization needs to be reoriented to provide the
necessary support. Finally, action is required to
decentralize authority and responsibility to the lower
levels of PHCs and community.
Involvement of women in health care delivery is
crucial as they are the key to primary health care and
general welfare of the communities in all developing
countries and hence community involvement should pay
special attention to participation by women.
Monitoring and Evaluation
Monitoring and evaluation is an important management
activity. It is an integral part of the program plan and
must be built into it. It is an effective tool for testing
program promises, planning and improving the program
performance.
Monitoring generally refers to the .process of checking

the status of the program by comparing the actual
implementation of the activities against work plan,
including the time frame.
On the other hand, evaluation is directed at
measuring progress towards the achievement of
objectives and the impact of the program. Evaluation is
linked to program planning and implementation cycle
and assists the program management in making
midcourse corrections in the program.
The monitoring system should be designed to provide
disaggregated data to reflect the health condition of the
disadvantaged groups, so as to enable to mount more
focused responses to them. This will contribute to
promote equity in health.
To sum up, effective discharge of managerial
functions are critical to the success of all our health and
family welfare programs. Managers have to see that both
the organization and program goals are achieved. No
organization can function without competent managers
and, indeed, in their absence organizations are often
paralyzed or chaotic.
Building up competencies of the medical officers in
the planning process, program implementation,
supportive supervision, training of health care providers,
building partnerships, provision of leadership to health
team, promote social action for health, making the system
responsive to the health care needs of the population,
monitoring and evaluation and many others is therefore
vital. Those competencies are in addition to those related
to making them effective clinicians and public health
program implements.
XI FIVE YEAR PLAN
Monitorial Socioeconomic Targets
Income and Poverty
Accelerate growth rate of GDP from 8 to 10% and
then maintain at 10% in the 12th Plan in order to
double per capita income by 2016-17.
Increase agricultural GDP growth rate to 4% per year
to ensure a broader spread of benefits .
Create 70 million new work opportunities.
Reduce educated unemployment to below 5%.
Raise real wage rate of unskilled workers by 20
percent.
Reduce the head count ratio of consumption poverty
by 10 percentage points.
21
Education
Environment
Reduce dropout rates of children from elementary

school from 52.2% in 2003-04 to 20% by 2011-12.
Develop minimum standards of educational attainment in elementary school, and by regular testing
monitor effectiveness of education to ensure quality.
Increase literacy rate for persons of age 7 years or
more to 85%.
Lower gender gap in literacy to 10 percentage points.
Increase the percentage of each cohort going to higher
education from the present 10 to 15% by the end of
the 11th Plan.
Increase forest and tree cover by 5 percentage points.

Attain WHO standards of air quality in all major cities
by 2011-12.
Treat all urban waste water by 2011-12 to clean river
waters.
Increase energy efficiency by 20 percentage points by
2016-17.
Health
Reduce infant mortality rate (IMR) to 28 and maternal
mortality ratio (MMR) to 1 per 1000 live births.
Reduce Total Fertility Rate to 2.1.
Provide clean drinking water for all by 2009 and
ensure that there are no slip-backs by the end of the
11th Plan.
Reduce malnutrition among children of age group
0-3 to half its present level.
Reduce anemia among women and girls by 50% by
the end of the 11th Plan.
Women and Children
Raise the sex ratio for age group 0-6 to 935 by 2011-12
and to 950 by 2016-17.
Ensure that at least 33 percent of the direct and
indirect beneficiaries of all government schemes are
women and girl children.
Ensure that all children enjoy a safe childhood,
without any compulsion to work.
MDG-THEN AND NOW

Indias MDG 2005 Report Released
On February 13, 2006, the Union Ministry of Statistics
and Program Implementation released Indias first
Millennium Development Goals country report for the
year 2005.
The Millennium Declaration adopted by the General
Assembly of the United Nations in September 2000
committed member countries to achieving eight Millennium Development Goals (MDGs) within a specified
timeframe. The 2005 report on the MDGs gives an
indication of the current status of progress achieved in
the country.
MDG 1: Eradicate Extreme Poverty and Hunger
Indias target: Reduce the proportion of people below the
poverty line to 18.75% by 2015.
Status: As on 1999-2000, the poverty headcount ratio
stood at 26.1%. The share of the poorest quintile in
national consumption is 10.1% for the rural sector and
7.9% for the urban sector. Prevalence of underweight
children is in the order of 47%.
Infrastructure
MDG 2: Achieve Universal Primary Education
Ensure electricity connection to all villages and BPL

households by 2009 and round-the-clock -power by
the end of the Plan.
Ensure all-weather road connection to all habitation
with population 1000 and above (500 in hilly and
tribal areas) by 2009, and ensure coverage of all
significant habitation by 2015.
Connect every village by telephone by November
2007 and provide broadband connectivity to all
villages by 2012.
Provide homestead sites to all by 2012 and step up
the pace of house construction for rural poor to cover
all the poor by 2016-17.
Indias target: Increase the primary school enrolment rate

to 100%, with no dropouts, by 2015.
Status: Dropout rate for primary education during 200203 was 34.89%. The gross enrolment ratio at primary
schools was near 100% for boys and 93% for girls. The
literacy rate (seven years and above) in 2000-01 was
65.4%.
MDG 3: Promote Gender
Equality and Empower Women
Indias target: There should be gender parity in the
number of boys and girls enrolled in schools by 2015.

Status: Female-male proportion in primary education is
78:100, and 63:100 in secondary education (2000-01).
MDG 4: Reduce Child Mortality
Indias target: Under-five mortality rate (U5MR) must be
reduced to 42 for 1,000 live births by 2015.
Status: U5MR was 98 per 1,000 live births in 1998-2002.
Infant mortality rate was 60 per 1,000 live births (2003).
Proportion of one-year-old children immunized against
measles was 58.5% (2002-03).
MDG 5: Improve Maternal health
Indias target: Reduce the Maternal Mortality Rate (MMR)
to 109 per 100,000 live births by 2015.
Status: MMR for 1998 was 407. The proportion of births
attended by skilled health personnel was 39.8% in 200203.
MDG 6: Combat HIV/AIDS, Malaria and
other Diseases
Status: The prevalence rate for HIV/AIDS increased from
0.74 per 1,000 pregnant women in 2002 to 0.86 in 2003.
This trend needs to be reversed in order to achieve MDG
6. The prevalence and death rate associated with malaria
is consistently dropping. The death rate associated with
tuberculosis came down from 67 deaths per 100,000
population in 1990 to 33 per 100,000 population in 2003.
The proportion of TB patients successfully treated rose
from 81% in 1996 to 86% in 2003.
MDG 7: Ensure Environmental Sustainability

Status: In 2003, the total land area covered by forests was
20.64%. Reserved and protected forests together
accounted for 19% of total land area. Energy use declined
from around 36 kilogram oil equivalent in 1991-92 to
about 32 kilogram oil equivalent in 2003-04.
The proportion of people without sustainable access
to safe drinking water and sanitation is to be halved by
2015. India is on track to achieving this target, says the
report.
Goal 8: Develop a Global Partnership for
Development
According to the report, developed countries must
provide development assistance to developing countries.
The report says the financial support needed to achieve
targets under this goal for less developed countries and
smaller countries falls short of what developed countries
pledged. It notes, however, that actual disbursements of
overseas development assistance in recent years have
shown a reversal of the declining trend that lasted for
almost a decade since the early 1990s.
In one of the targets under this goalto make
available the benefits of new technologies in cooperation
with the private sectorIndia has made considerable
progress:
Overall tele-density increased from 0.67% in 1991 to
9.4% in June 2005.
Use of personal computers increased from 5.4 million
PCs in 2001 to 14.5 million in 2005.
There are 5.3 million Internet subscribers, as on March
2005 (2.3 Internet users per 100 population).
2.1 History Elicitation: T Ravikumar, C Thangadorai ................................................................................................................................. 24

2.2 Physical Examination and Clinical Skill Development: C Thangadorai, T Ravikumar ................................................................... 30
2.3 Parent Counseling: Parang N Mehta .................................................................................................................................................... 40
2.1 History Elicitation

T Ravikumar, C Thangadorai
Treatment begins the moment the family walks in the door.
Richard B Goldbloom
The interview and history elicitation are very important
tools in the field of Pediatric Medicine. Though it is of
much diagnostic value, the very process of interaction
with the parents and the child during history taking also
has therapeutic value. A pleasant and patient interaction
is what any parent desires. There should be fewer distractions during the interview. It is good to use lay terms
when talking to the parents and avoiding medical jargon.
In pediatrics the most important and distinct aspect
is the fact that the person giving the history is usually
not the patient (unless the child is about 4 or 5 years old).
The parents are the usual source of information and in
certain cases when caretakers (other than the parents)
are bringing up the children then they will be the source
of information.
Demography
Make a note of the name of the child, his/her age in years
(with months and days), parents names, address, date
and time of interview, informations name and
relationship to child and their reliability (with regard to
the consistency of the information they provide).
Presenting Complaints
The main problem or complaints for which the child has
been brought for medical attention should be recorded
in the informations own terms and should be recorded
in chronological order with the duration of each
complaint.
Examples:
Fever5 days
Vomiting4 days
Loose motions4 days
Decreased urine output2 days
Lethargy1 day
Fast breathing1 day
History of Present Illness

It is important to gather more information on the specific
complaints mentioned above. Find out the onset of the
complaints (the time up to which the child was apparently

well). The evolution of the problems should then flow in a
clear, concise, temporal sequence, leading up to the present
moment. They should be evaluated in order of occurrence
and an account of any repeated episodes of symptoms
(like seizures or respiratory infections) should be given.
Complications expected for the primary complaint and
other symptoms that will help in detecting associated
conditions and in differential diagnosis should be
enquired. The details of treatment given so far and the
response should also be noted.
Past History
Ask for details of relevant past illness, whose knowledge
will help you in diagnosis or management. History of
occurrence of similar complaints in the past should be
noted. In child with chronic suppurative lung disease or
malnutrition a history of previous exanthematous illness
or whooping cough will help, in failure to thrive a history
of recurrent diarrhea and in a child with fever and fits a
history of febrile fits will be supportive. Past medication
history will also be helpful, for example past history of
antiepileptic drugs or antituberculous drugs [history of
red urine (rifampicin) while on treatment with anti-TB
drugs]. Information on previous significant hospitalizations, accidents or surgeries may also be helpful.
Contact History
History of contact with communicable illnesses (like TB,
chickenpox) must be elicited with tact and patience. It is
often denied and repeated probing with leading
questions may be necessary.
Antenatal History
As many illnesses in children have their origin in the
womb it is important to get a good history about the
period of pregnancy of the index child. Note the three
Is for the mother during pregnancyillness, irradiation and injections (i.e., drugs). Maternal illnesses like
syphilis, toxoplasmosis, AIDS, rubella, cytomegalovirus
and herpes virus infections (STARCH) are associated with
specific syndromes in the child. Folic acid supplementation during early pregnancy (the first trimester) prevents
neural tube defects like meningomyelocele, etc.
History Elicitation and Physical Examination

Birth History
The actual events occurring during delivery must be
enquired. The period of gestation, duration of labor, nature
of delivery, drugs administered during labor and any
complications during delivery (like cord around neck, low
Apgar score) should be noted. The normal first stage of
labor, from the onset of labor pains to the rupture of
membranes, is about 12 to 24 hours and 6 to 12 hours in a
primi and multigravida respectively. The second stage of
labor, from the rupture of membranes to the delivery of the
child, is about 1 to 2 hours in a primi and 1/2 to 1 hour in
a multigravida. The third stage, which is the delivery of
the placenta, lasts about 15 minutes. The duration of every
stage of labor (especially the second stage) is important as
prolonged labor may result in fetal hypoxia.
Postnatal History
The neonate and its state afterbirth should be enquired.
The term of the child, birth weight, cry, activity and color
immediately after birth should be noted. Presence of
jaundice or cyanosis, resuscitation steps used (if any) and
whether hospitalized afterbirth must be detailed. Poor cry
and lethargy suggest perinatal depression. Paucity of
movements of one side or a particular limb may suggest
stroke or birth injury. The sucking effort of a child usually
gives a clue to the neurological status of the child. All
infants pass meconium within the first 24 hours, any delay
would suggest cystic fibrosis while absence of passage
would indicate intestinal obstruction or anal atresia. Most
infants void urine on the first day while all will void within
48 hours, any delay would point towards an obstruction
or agenesis of the renal system.
Developmental History
Development is one aspect of pediatrics that makes it
unique as compared to adult medicine. The developmental
milestones that a child attains are a good reflection of its
physical and neurological maturity. They may be divided
into gross motor (head control, rolling over, crawling,
sitting, standing, walking, etc.), fine motor or adaptive
(grasping reaching tranferring objects, scribbling, etc.),
social (smile, recognition, response to calls, etc.) and
language (cooing, babbling, saying syllables, vocabulary,
etc.). Tailor the development history to the childs age. In
case of more than one child in the family and if the other
siblings are normal, the parents may be asked if the index
child developed similar to the other siblings. The pace of
development differs from child to child. As the child grows
25
older the age range of attainment of specific developmental

milestones usually widens. For example, a normal child
may begin to sit without support between 5 to 8 months as
compared a young infant developing social smile between
6 to 8 weeks. Notice the range of normality becoming more
in the older child. Always tabulate the attained milestones
against the normal age for attainment of that particular
milestone (Table 2.1.1).
Dietetic History
This history is highly problem oriented and age dependent.
Details of the food and dietary patterns help in diagnosing
protein energy malnutrition and failure to thrive. In
addition it helps us to formulate a diet plan for nutritional
rehabilitation of the child for specific diseases. The
calculation of the dietary values of the food consumed
should provide the actual value of proteins, calories and
fats and must mention whether it is sufficient in vitamins,
minerals and other micronutrients. Always state the
amount of calories and proteins the child is getting for
that age as compared to what is expected which will help
us to calculate the calorie and protein gap. Any problem
like feeding difficulty, regurgitation or vomiting should
be noted. Any possible natural toxins in the food consumed
(fungal aflatoxins, copper, etc.) and feeding patterns
during times of illnesses should also be mentioned. In
young children the complete breast-feeding history
including whether colostrum was given, duration of
exclusive breastfeeding, weaning pattern, etc. must be
elucidated. In children given other milk substitutes detail
the type of formula or cows milk, its dilution, bottle or
cup and spoon-feed, frequency and the amount taken
during each feeding (Table 2.1.2).
Family History
The health details of all the family members must be
obtained. This includes their age, sex, present and past
health status, treatment taken and their proximity to the
child. History of similar illness in the family must be looked
for. History of stillbirths or abortions in the family should
be noted (habitual abortions occur in maternal syphilis).
The birth of abnormal or children with illness in the family
and the reasons for death of children or adults at a young
age should be specifically enquired into. The consanguinity pattern with the degree of relationship may be helpful
for genetic disorders. The pedigree chart will help record

TABLE 2.1.1: Developmental milestones
Milestones
Gross motor
Fine motor
Personal social
Language
1 month
Grasp reflex
Starts to smile
2 months
Hands closed
Social smile
Cooing
3 months
Head mostly held up but

still bobs forwards
Hand open most often
Sustained social smile
Says aah
4 months
Head held steady
Reaches for objects, grasps

objects and brings to mouth,
hands in midline
Excited at site of food
Laughs out aloud
7 months
Rolls over, creepingcrawling, sits with hands

leaning forwards
Reaches out and grasps larger

objects, palmar grasp, transfers
objects from hand-hand
Smiles at mirror
Babbling
10 months
Sits without support,

cruises
Pincer grasp
Waves bye-bye
Baba, mama
1 year
Walks with one hand held
Releases object to other

person on request/gesture
Plays simple ball game
2-3 words with

meaning
15 months
Walks alone, crawls

upstairs
Tower of 3 cubes
Asks for objects by

pointing
Follows simple
commands
18 months
Runs stiffly, goes upstairs

by holding the rails
Tower of 4 cubes, initiates

vertical stroke scribbles
Feeds self. Dry by day
Speaks 10 words,
Identifies parts of the
body
2 years
Runs well, walks upstair

and downstair one foot
at a time, jumps
Makes tower of 7 cubes,

initiates horizontal stroke
Handles spoon well and

helps to undress
Puts sentence of 3
words
2 years
Goes upstairs with

alternating feet
Makes tower of 9 cubes
Helps put things away
Knows full name
3 years
Rides tricycle, stands

momentarily on one foot
Draws circle, makes tower of

10 cubes, constructs bridge of
3 cubes
Dresses and undresses

fully when helped with
buttons, joins in play
Knows age and sex
4 years
Hops on one foot, throws

ball overhead, climbs well
Draws cross and square, copies

a bridge, constructs a gate of
5 cubes
Plays with several children

with beginning of social
interaction, goes to toilet
alone
Tells story
5 years
Skips
Draws triangle
Dresses and undresses

self, Asks question about
meaning of words
Names 4 colors,
Repeats sentence of
10 syllables
the family history in a pictorial manner helping us to

derive the inheritance pattern of a particular illness.
Usually three full generations are recorded. Individuals
of the same generation should be recorded in the same
horizontal line and numbered from left to right using
arabic numerals. Males are usually placed on the left
side of the pedigree and sib-ship listed in both orders.
The maternal age at the time of child delivery is also
important. Young mothers (less than 18 years) have more
chance of preterm, IUGR babies while older mothers
(more than 32 years) have more chance of having
children with Down syndrome and Klinefelter

syndrome. In children with diseases showing
hereditary traits, an enquiry of a much wider circle of
relatives must be made.
Sociocultural and Economic History
This has a bearing on the type of disease the child might
be suffering from and it also helps in planning
rehabilitation and treatment options in addition to helping
in giving preventive advice.

TABLE 2.1.2: The recommended caloric
and protein requirements
Ages
Calories required/day
Protein/day
1 month-1 year
100-110 kcal/kg/day
2 g/kg
1 year
1000 kcal/day
20 g/day
2 year
1100 kcal/day
20 g/day
3 year
1200 kcal/day
20 g/day
4 year
1300 kcal/day
30 g/day
5 year
1400 kcal/day
30 g/day
6 year
1500 kcal/day
30 g/day
7 year
1600 kcal/day
40 g/day
8 year
1700 kcal/day
40 g/day
9 year
1800 kcal/day
40 g/day
10 year
1900 kcal/day
50 g/day
11 year
2000 kcal/day
50 g/day
12 year
2100 kcal/day
50 g/day
Adolescent boy
2400 kcal/day
70 g/day
Adolescent girl
2100 kcal/day
65 g/day
The following points are worthwhile noting:

Type of family: joint or nuclear
Occupation and employment history
Per-capita income (total income divided by the number

of dependent family members)
Type of housing, ventilation, toilet and potable water
facilities
Psychiatric illness and substance abuse (alcoholism,
drugs)
Marital stability
Traditional beliefs and child rearing practices
Immunization History
It is important to record the details of vaccines given to the
child in chronological order. The vaccination schedule of
the Indian Academy of Pediatrics or at least the Universal
Immunization Program should have been followed.
Special vaccines (like pulse polio vaccine) must also be
enquired. Look for BCG scar at the outer aspect of the left
arm at the insertion of the deltoid. If any vaccine has not
been given, note the reason for not doing so.
History of Allergies
It is important to note down any known specific allergies
in the child, either for drugs or food.
2.1.1 MODEL PEDIATRIC CASE RECORD

DEMOGRAPHY
Name: ............................... Date of birth: ...................... Age: ...................... Sex: ...........................
Address: ..........................................................................................................
Informant: ......................... Relationship: ..................... Reliability: ...........
Date and time of examination: .......................................
HISTORY TAKING
Presenting complaints: ...
............................................ History of present illness: ......................................................
Past history: ..................... ............................................

(including treatment history)
Contact history. ...............
27
............................................ Antenatal history:
Birth history: .................... ............................................ Postnatal history:

Developmental history: .. ............................................ Dietetic history: ..
........................................... ............................................ (including nutrition chart)
Family history: .................
............................................ Sociocultural history: .............................................................
Immunization history: ....
............................................ History of allergies: .................................................................

PHYSICAL EXAMINATION
General examination:............................................ .............. Vital signs: ...............................................................................
(including ENT, skin, eye, spine and cranium) .................. SMR: .........................................................................................
Anthropometry: ...............
............................................ Developmental assessment: ..................................................
SYSTEMIC EXAMINATION
Cardiovascular system ...
............................................ Respiratory system .................................................................
Abdomen .......................... ............................................ Nervous system ..

PROVISIONAL DIAGNOSIS
Differential diagnosis ....................................................................................
Investigations .................................................................................................
Final Diagnosis ...............................................................................................
2.1.2 MODEL NEONATAL CASE RECORD
DEMOGRAPHY
Name: .............................. Sex: .............................................. Identity number: ............................................
Age (in hours/days/months): .............................................. Date and time of birth: ..................................
Date and time of examination: ... .................... ........................
Name of mother: ................... Name of father: ....................
Address: ................................. Informant: ............................ Relationship: .................................................
Reliability:
CLINICAL HISTORY OF CHILD
Maturity: ................................
Anthropometry: .................... Birth weight: ........................ Length: ............................................................
Head circumference: ............. Chest circumference:.......... .
Presenting complaints: ..........................................................
History of present illness: ......................... Previous illness: .........................................................................
Feeding history: ............................................ Family history: .........................................................................
..................................................................... (including previous congenital anomalies/neonatal problems in siblings)
MATERNAL HISTORY
Age of mother: .......................................... Date of last childbirth: .................................. Blood group: ............................
Para: .......................................................... Gravida: .............. ....................................... Abortions: ................................
Weight of mother: .................................... Nutritional status: ............ Consanguinity:
Last menstrual period: ............................ Expected date of delivery: ............................ Paternal age: ............................
Maternal transfusion: ..........................
29
Antenatal period(illnesses/drugs/radiation, etc): ....................

Antenatal ultrasound: ............................. 1st Trimester ........ 2nd Trimester ................ 3rd Trimester .............................
Labor (spontaneous/induced/not known):
Duration of labor: .................................... 1st Stage ............... 2nd Stage ......................
Drugs used during labor (analgesic/anesthetic/others/not known): ..................................
Mode of delivery: ....................................................................
(Spontaneous/manipulated/breech/forceps/vacuum/cesarean/others)
Indication for assistance (if any): ..........................................
Complications during delivery (if any): ...............................
Place of delivery: ......................................
(Hospital/health post/primary health center/private nursing home/others)
Single/twin/others: ..................................... Birth order (if applicable): ...............................
Fetal distress: .........................................
Evidence of fetal distress: ....................
Apgar score: .............................. 1 minute ................................ 5 minutes
Resuscitation: ........................................
(The actual procedures done, in detail)
EXAMINATION OF THE BABY
Neurological sign
Scoring for assessment (shown below):
Posture
External sign
Edema
Skin texture
Skin color
Skin opacity
Lanugo
Plantar creases
Nipple formation
Breast size
Ear form
Ear firmness
Male genitalia
Female genitalia
TOTAL SCORE
Score
Score
Square window
Ankle dorsiflexion
Arm recoil
Leg recoil
Popliteal angle
Heel to ear
Scarf sign
Head lag
Ventral suspension
TOTAL SCORE
Gestational age
(in weeks):
By history:
Impression:
Term/Pre-term/Post-term
AGA/SGA/LGA
By assessment:

Nervous system:
GENERAL APPEARANCE
Cry:
Activity/Movement:
Skin:
Head:
Mouth:
Ears:
Color:
Muscle:
Posture:
PROVISIONAL DIAGNOSIS
Face
Palate:
Nose:
Eyes:
Throat:
Neck:
INVESTIGATIONS
FINAL DIAGNOSIS
Cardiovascular system:
(including heart rate, femoral pulse)
BIBLIOGRAPHY
1.
Respiratory system:
(including respiratory rate and pattern)
Abdomen:
Kidney:
Spleen:
Genitalia:
Liver:
Anus:
2.
Limbs and bones:

Feet:
Arms:
Legs:
Hands:
Toes:
3.
4.
Spine and back:
Barness LA. In pediatric history and physical examination.

In McMillan JA, DeAngelis CD, Feigin RD, Warshaw JB
(Eds): Oskis PediatricsPrinciples and Practice, 3rd edn.
Philadelphia, JB Lippincott Williams and Wilkins, 1999;3952.
Harris R. The examination of children. In Swash M (Ed):
Hutchisons Clinical Methods, 20th edn. London, ELBSWB Saunders Co, 1995;365-86.
Rees PE. Evaluating the newborn infant: Diagnostic
approach. In: Pediatric Clinical Skills, 2nd edn.
Philadelphia, Churchill Livingstone, 1997;47-76.
Singh M. Pediatrics clinical methods, 1st edn. New Delhi:
Sagar Publication, 1992;1-94,174-211.
2.2 Physical Examination and

Clinical Skill Development
C Thangadorai, T Ravikumar
The physical examination in a child is distinct in certain
areas from that of the adult. In this discussion, only the
facts that differ from that of an adult examination have
been mentioned. As far as possible, no child should cry
or get irritated while you are examining. If a child cries
when you examine it, then its probably your fault. This
statement by John Apley sums up the care one should
take, while handling the child. There is no definite order
to be followed while examining a child. Individualize
the examination for every child. Do the invasive and
potentially discomforting examinations at the end. Allow
the child to be in its most comfortable position, and place
it in the mothers lap. Both the child and the mother,
must feel secure and confident about the examining

doctor.
GENERAL EXAMINATION
Before starting general examination; analyse the history
and based on that, look for the specific features that you
think to be relevant to the history which will help you to
give a perfect diagnosis. Examining aimlessly is unhelpful,
time consuming and irritating to the child and parents.
General examination must be thorough from head to foot.
Always examine the childs throat irrespective of the
complaint. The golden rule is Head to foot and back, but

forget not the ear, throat and urine. The sensorium (e.g.,
stuporous or unconscious in intracranial pathology),
posture and attitude (e.g., frog like and limp in floppy infant),
activity (e.g., apathetic in kwashiorkor), looks (acutely or
chronically ill looking), nutrition (i.e., marasmic,
undernourished or moderately nourished) need special
mention.
Note the shape of the head (Fig. 2.2.1) whether microcephaly, macrocephaly (Table 2.2.1), plagiocephaly
(asymmetrical due to lying of the normal infants with their
heads persistently on one side), scaphocephaly (boat
shaped with increased AP diameter due to premature
Figure 2.2.1: Different shapes of the cranium in a child
31
TABLE 2.2.1: Few of the features to be looked for in the

head and the associated conditions
Features
Few associated conditions
Microcephaly
Familial, craniostenosis, intrauterine

infections,
Trisomy 13 and 21 (Down syndrome)
Macrocephaly
Hydrocephalus, hydranencephaly,
porencephaly, some neurodegenerative
disorders like metachromatic
leukodystrophy, Alexander and Canavan
disease, certain intrauterine infections
Frontal bossing
Rickets, congenital syphilis, mucopolysaccharidoses
Cranio-tabes
(ping-pong skull)
Increased interpupillary distance
(hypertelorism)
Physiological (in preterm), rickets,

Congenital syphilis
Genetic (racial), mongolism
(Down syndrome),
Cri-du-chat syndrome, hypothyroidism
Proptosis
(Sclera is visible
above and below
the cornea)
Thyrotoxicosis, orbital leukemic

deposits, orbital cellulitis,
Arteriovenous aneurysm (pulsatile),
Cavernous sinus thrombosis,
Neurofibromatosis, Crouzons disease
Cataract
Idiopathic, traumatic, intrauterine

infections, galactosemia, diabetes
mellitus, Down syndrome
Mongoloid eyes
(upward slant)
Down syndrome, racial, Prader-Willi

syndrome
Antimongoloid
slant (downward
slant)
Turner syndrome, cri-du-chat

syndrome, Treacher-Collins
syndrome
Depressed
nasal bridge
Low set ears
Down syndrome, mucopolysaccharidoses, hypothyroidism, familial

Down syndrome, mucopolysaccharidoses, Turner syndrome, Potter facies
(renal agenesis)
Facial puffiness
Renal disorder, kwashiorkor, congestive

cardiac failures, angioneurotic edema,
cavernous sinus thrombosis
Large tongue
Hypothyroidism, mucopolysaccharidoses, glycogen storage disorders,

Down syndrome (relative)
Small mandible
Pierre Robin syndrome
Short neck
Turners syndrome, Down syndrome,

mucopolysaccharidoses, hypothyroidism
closing of sagittal suture), brachycephaly (decreased AP

diameter) and oxycephaly (tower-shaped skull).
Figure 2.2.2: Method of measuring the size

of the anterior fontanelle
The size of the anterior fontanelle (AF) (about 2.5 cm

2.5 cm) must be measured across the borders as shown in
Figure 2.2.2. It normally closes by 9 to 18 months. Delayed
closure is seen in rickets, hypothyroidism, hydrocephalus,
Down syndrome, achondroplasia and mucopolysaccharidoses. The AF in a quiet child usually shows a very slight
depression from the surface and may pulsate. It is bulging
when the child cries and in hydrocephalus, intracranial
hypertension and pseudotumor cerebri, i.e. after drugs
like nalidixic acid, tetracyclines, steroids and hypervitaminosis A. A sunken fontanelle is a sign of dehydration.
The posterior fontanelle can be felt by running the finger
along the sagittal suture to its junction with the lambdoid
sutures. It normally closes by 2 to 4 months of age. Ridging
and overriding of sutures may normally be seen in the first
few hours afterbirth, due to moulding of the skull during
delivery. It may also be seen in craniostenosis due to
premature fusion of the sutures. Sutures normally get
ossified by 6 months of age (Fig. 2.2.3).
The Macewens sign is useful in clinically detecting
raised intracranial tension after the sutures have closed.
It is the crack pot sound elicited by percussing the skull.
Transillumination of the skull in a dark-room, is useful
in children below one year, to detect subdural effusion or
hematoma, if transluceny extends beyond 2 cm in the
frontal and 1 cm in the occipital region.
The face must be observed for any dysmorphic
features that may suggest chromosomal or developmental
anomalies. Table 2.2.1 shows some common abnormal
features and a few conditions where they are seen. The
inter-palpebral line of the eyes when continued
horizontally backwards, normally divides the ears into
the upper one-third and lower two-thirds. If the line
passes above the ears, it is suggestive of low set ears. The
Figure 2.2.3: The sutures and fontanelles in an infant
neck should be examined for lymph node enlargement,

short neck (normal neck length : height ratio is 1:13) and
low hair line (below C5). The examination should also
include the hair (e.g. pale hair with flag sign in
kwashiorkor), eyes (signs of vitamin A deficiency, icterus,
pallor, etc.) ears (examine tympanic membrane and for
chronic suppurative otitis mediaCSOM), oral cavity
(with special reference to the dentition), extremities (limb
deformities in skeletal dysplasias, widened wrists in
rickets), nails (koilonychia in anemia) and skin for pallor,
icterus, scabetic lesions, impetigo, etc. Fundus examination
is important to make out papilledema, optic atrophy or
retinitis pigmentosa. The mouth is examined for the state
of the gums, dental caries and dentition. Delayed dentition may be familial or due to rickets or osteogenesis
imperfecta.
The correct position for doing the ear, nose and throat
examination is shown in Figure 2.2.4 but this should be
done preferably at the last. While examining lymph nodes,
note the site, size, consistency, tenderness, warmth,
matting and scarring. Always remember to examine the
drainage areas, for focus of sepsis, if there is significant
lymph node enlargement. In older children, discrete and
non-tender lymph node enlargement up to 1.5 cm in the
cervical and inguinal region is not significant.
The skin is examined (Fig. 2.2.5) by rolling a fold of
loosely adherent skin on the abdominal wall between
the thumb and forefinger to determine its consistency,
the amount of subcutaneous tissue present and the
degree of hydration. Examination of the hips must always
be carried out in younger children and infants, to look for
33
Temperature above 41C is hyperpyrexia. In conditions

like PEM, where hypothermia is a problem, special low
reading thermometers (30-40C) must be used.
Respiratory Rate
Figure 2.2.4: The correct position of the child for

ENT examination
The rate of respiration in children is important for diagnosing respiratory disease and certain other non-respiratory conditions like acidosis and congestive cardiac
failure. The rate varies in different age groups (Table 2.2.2).
But for practical purposes, the guidelines offered in the
child survival and safe motherhood (CSSM) Program,
serve as a good guide to clinically suspect respiratory
disease (Table 2.2.3).The pattern of respiration must also
be noted whether regular, irregular, Cheyne-Stokes type,
acidotic, etc. In children the respiration is predominantly
abdominothoracic.
Pulse Rate
The pulse is felt mainly over the radial artery at the wrist.
The character, regularity and volume must be observed.
All the peripheral palpable vessels must be examined.
The superficial temporal, carotid, brachial, radial, femoral,
popliteal, posterior tibial and dorsalis pedis arteries are
usually accessible. In infants and very young children, it
may not be possible to palpate the peripheral vessels and
in such situations, the heart rate must be measured using
auscultation. The normal heart/pulse rates in the different
age groups in children are given in Table 2.2.4. For
Figure 2.2.5: The method of examining the skin in a child

with dehydration
dislocation. The Ortolani or Barlow procedure is done

and the typical clunk of the hip moving in and out of its
socket is looked for. Infants and young children do not
exhibit classical pedal edema, but because of this, they are
confined to the bed, sacral edema should be looked for.
TABLE 2.2.2: Normal respiratory rate in

children of different age groups
Age groups
Normal respiratory
rate (Per minute)
Newborn
40
1 year
30
5 years
20
10 years
18
VITAL SIGNS
Temperature
Oral temperature should be taken in children older than 5
years while in infants and younger children the
thermometer may be placed in the axilla, i.e. the groin also
can be used or the rectum. The temperature in the axilla or
the groin is about 0.5C lower and the rectal temperature
about 0.5C higher than the oral temperature. The normal
temperature in children is between 36.5 and 37.5C.
TABLE 2.2.3: Tachypnea indicating significant

respiratory disease (from CSSM program)
Age groups
Respiratory rate
(per minute)
Below 2 months
60 or more
2 to 12 months
50 or more
12 months to 5 years
40 or more

TABLE 2.2.4: The normal heart rates in children of
different age groups
Age groups
Normal heart rate

(per minute)
TABLE 2.2.5: Normal blood pressure values in children

Age groups
Blood pressure
(systolic/diastolic)
Newborn
65/45 mm Hg
1 year
75/50 mm Hg
3 years
90/60 mm Hg
Newborn
140
1 year
110
3 years
100
8 years
90
8 years
95/65 mm Hg
10 years
80
10 years
100/70 mm Hg
practical purposes, heart rate of more than 200/minute in

newborns, more than 150/minute in infants and more
than 120/minute in older children can be taken as
significant tachycardia. The radial and femoral pulse must
be palpated simultaneously to look for any radiofemoral
delay. Remember, the heart rate in a struggling or crying
child will be more.
Blood Pressure
Recording of the blood pressure is one of the most
important aspects in a pediatric examination. Yet it is
surprising, how often it is neglected. The correct size of
the cuff must be used, i.e. the cuff should be two-thirds
size of the arm. A large cuff will give an erroneously low
reading while a small cuff will give a high reading. In
infants, the flush method may be used to check the
pressure. Here the childs arm is raised and a tight bandage
is applied up to the level of the cuff so as empty the blood
from the upper limb. Now, the cuff is inflated and the
bandage is removed so that the limb will be pale and
bloodless. Deflate the cuff slowly and note the reading at
which the skin flushes and the limb becomes red again.
This corresponds, approximately to the systolic pressure.
In younger children where auscultation at the cubital fossa
is difficult, the systolic reading obtained by palpation may
suffice. The Doppler technique of measuring blood
pressure is more accurate and can be used in children, if
available. For every pediatric examination, both the upper
limb and lower limb pressures must be recorded to detect
coarctation of aorta while in any child with a suspected
cardiac illness, the pressure must be recorded in all four
limbs. Normally, the pressure recorded in the lower limbs
is about 10 mm Hg higher than the upper limbs. Reserve
recording the pressure to the last in order not to irritate or
scare the child. Normal blood pressure readings in
children in the different age groups is given in (Table 2.2.5).
Normal blood pressure is defined as systolic and diastolic
pressure, less than 90th percentile for that age and sex.
Hypertension is defined as average systolic and/or
diastolic blood pressure equal to or greater than the 95th
percentile for that age and sex, on at least three occasions.
As per the American Heart Associations (Pediatric
Advanced Life Support Course) recommendations, a
formula has been deviced to approximate the 50th
percentile of systolic pressure in children over the age of 2
years [90 + (2 age in years)]. The lower limit of the systolic
blood pressure has been approximated by the formula 70
+ (2 age in years). An observed fall of 10 mm Hg in
systolic pressure suggests a shock.
ANTHROPOMETRY
The measuring of the various anthropometric data is
essential for assessing the growth of the child and its
nutritional status. It is also important for planning the
diet and following up the child especially while recuperating from an illness or during nutritional rehabilitation.
Weight
The child must be weighed during every examination.
The weight of the child is also useful for calculating the
right dosage of the drugs to be given. The newborn loses
up to 10 percent of its weight during the first week, but
regains it in the next few days. The child doubles its birth
weight by 4 months, triples it by 1 year and increases it
4 times by 2 years. For calculating expected normal
weight, the formula shown in Table 2.2.8 may be used.
While interpreting the weight of the child, the present
weight must be compared to the expected weight for age
and the percentage must be calculated in order to find
out which grade of nutrition the child falls under (as per
Tables 2.2.6 and 2.2.7). Weight is recorded on a weigh
scale which should be frequently checked with standard
weights and zero error must be adjusted before weighing.
35
TABLE 2.2.6: The Wellcome classification of

nutritional status
Nutritional
status
Expected
weight for age
Presence of
edema
Normal
more than 80%
no
Undernutrition
60 to 80%
no
Kwashiorkor
60 to 80%
yes
Marasmus
less than 60%
no
Marasmic kwashiorkor
less than 60%
yes
TABLE 2.2.7: Indian Academy of Pediatricsclassification of

nutritional status (the prefix 'K' is added to indicate presence of edema)
Level of undernutrition
Expected weight for age
I degree
70 to 79%
II degree
60 to 69%
III degree
50 to 59%
IV degree
less than 49%
TABLE 2.2.8: Weechs formulae for estimating weight and

height for age of normal children
Weights
Kilograms
Pounds
At birth
3.25
age in months + 9
age in months +11
1 to 6 years
2
(age in years 2) + 8
7 to 12 years
(age in years 7) 5
3 to 12 months
2
Heights
At birth
At 1 year
2 to 12 years
Centimeters
Inches
50
75
20
30
Height
The height of the child is a good indicator of the chronicity
of any debilitating illness. Height is normally measured
using Herpendens stadiometer. The child should stand
against a wall with his bare feet touching each other, the
heel, calf, buttock, upper back and occiput touching the
wall and the child looking straight ahead. A firm scale is
pressed to the head to mark the point indicating height.
The standing height can be measured for children more
than 2 years old, while for younger children, the recumbent
length should be measured using the infantometer (Fig.
Figure 2.2.6: The infantometer method of measuring

length of child
2.2.6). In exceptions like a child with quadriplegic cerebral

palsy, where the height/length could not be measured,
the length of various segments of the body are measured
separately and added together to get the length. The
formula shown in Table 2.2.8 may be used for calculating
the height for the age or alternatively the increase in height
is as shown in Table 2.2.9 may be used for calculating the
expected height. To make out short stature or dwarfism,
the McLarens classification (Table 2.2.12) may be used.
While measuring the height, it is also important to
measure the upper segment (from the vertex to the pubic
symphysis) and the lower segment (from the pubic
symphysis to the sole of the foot). The rate of growth of
the upper and lower segments varies with age as shown
in Table 2.2.10. Hence, any difference in the proportion
expected for that age may suggest the presence of specific
TABLE 2.2.9: Rate of increase in height in children
Ages
Height
At birth
50 cm
6 months
+ 12 cm (62 cm)
1 year
75 cm
2 years
85 cm (86 to 87 cm)
2 to 5 years
6 to 8 cm/year
5 years and above
5 cm/year
TABLE 2.2.10: Normal upper segment: lower segment ratio

in children
Ages
At birth
3 to 4 years
9 years
18 years
Upper segment
Lower segment
1.8
1
1.3
1
1
1
0.9
1

TABLE 2.2.11: Conditions with altered upper segment:
lower segment ratio
Upper segment:
Lower segment ratio
Probable disorder
Proportionate
(normal ratio for age)
Delayed adolescence, hypopituitarism, constitutional

dwarfism, nutritional dwarf
Hypothyroidism, chondrodystrophy, achondroplasia,
Ellis-van Creveld syndrome,
Turners syndrome
Hurlers syndrome, Morquios
syndrome, hypogonadism
High ratio
(upper segment > lower
segment)
Low ratio
(upper segment < lower
segment)
Figure 2.2.7: Method of measuring head circumference
TABLE 2.2.12: McLarens classification for interpreting

height for corresponding age
Height for age
Interpretation
>105%
93 to 105%
80 to 93%
<80%
Giant
Normal
Short
Dwarf
growth disorders (Table 2.2.11). Stature should also be

defined with parents height being taken into account,
referred to as the mid-parental height.
For girls: Approximate projected adult height (in cm)
=
[Mothers height + (Fathers height 13)]
_________________________________________________
For boys: Approximate projected adults height (in cm)

=
[(Mothers height + 13) + Fathers height]
_________________________________________________
be calculated from Tables 2.2.13 and 2.2.14. The adult head

size is reached between 5 to 6 years. Microcephaly is
defined as head circumference, more than 3 standard
deviations below the mean or less than the 5th percentile
for the age and sex. Head size more than the 95th percentile
for age suggests macrocephaly.
Chest Circumference
This is measured at the level of the nipples (Fig. 2.2.8). In
the infant, the chest circumference is lesser than the head
cicumference by about 2.5 cm, and the two become equal
by one year after which the chest circumference exceeds
the head circumference. In undernutrition, the chest
circumference remains lower than the head circumference
TABLE 2.2.13: Head circumference growth velocity
Ages
Head circumference
growth velocity
Till 3 months
2 cm/month
3 months to 1 year
2 cm/3 months
(1/3rd of initial velocity)
1 to 3 years
1 cm/6 months
(1/12th of initial velocity)
3 to 5 years
1 cm/year
(1/24th of initial velocity)
Head Circumference
The size of the head is a good indicator of the size of its
contents, i.e. viz., the brain and the ventricles. Any
abnormality in the head circumference should alert the
doctor towards any problem with the brain or its related
structures. Head circumference is measured with a nonstretchable tape passing through the maximum point of
the external occipital protuberance posteriorly and a point
just above the glabella anteriorly as shown in Figure 2.2.7.
The head circumference at birth varies from 32 to 35 cm at
one year, from 43 to 46 cm and from 48 to 51 cm at five
years. The expected head circumference for the age may
TABLE 2.2.14: Formula for estimating head

circumference in the first year (after Dine et al)
Normal range of head circumference in cm (5th to 95th percentile)
(length in cm + 9.5) + 2.5
__________________________________
37
measuring midarm circumference (MAC) in the

community and has color bands. Green color indicates
MAC is > 13.5 cm, yellow color a MAC between 13.5-12.5
cm and red colour a MAC < 12.5 cm.
Arm Span
Figure 2.2.8: Method of measuring the chest circumference
It is the distance between the tips of the middle fingers

with both arms held wide open, i.e. spread apart. Normally, in young children it is 1 to 2 cm less than the length/
height. It equals the height at 10 years, and after 10 years
it is 1 to 2 cm more than the height. Increased arm span is
seen in Marfans syndrome and homocystinuria.
even beyond one and half years whereas in well-nourished

children, the chest circumference may exceed the head
circumference even before one year.
Weight for Height (WFH)
Midarm Circumference
Values above 90 percent are normal, while values below

90 percent indicate malnutrition and values above 120
percent indicate overweight.
The midarm circumference is taken as the name suggests,

at the midpoint of between the acromion and the olecranon
with the arm hanging by the side of the body (Fig. 2.2.9). It
is useful to detect malnutrition in young children (1-4
years). Values more than 13.5 cm may be considered
normal, while values less than 12.5 cm indicate significant
wasting and undernutrition. Shakirs tape is used for
This is calculated as shown below (WFH):

WFH = (weight of child weight corresponding
to height of child) 100
Body Mass Index (BMI)

It is calculated as:
Body mass index (BMI) =
weight in kg
________________________
(height in meter)2
BMI of 15-25 is considered normal, 25-30 is grade I

obesity, 30-40 is grade II and above 40 is grade III.
BMI = [weight height2] 100
Value less than 0.15 indicates malnutrition. This remains
constant up to 5 years of age.
Kanawati Index (KI)
This is useful in detecting protein energy malnutrition in
children between 4 months and 4 years. It is calculated as
follows:
KI = Midarm cicumference Head circumference
Interpretationnormal > 0.32, mild undernutrition 0.28
to 0.32, moderate undernutrition 0.25 to 0.28, severe
undernutrition < 0.25.
Growth Patterns
Figure 2.2.9: Method of measuring midarm circumference
See Table 2.2.15.

TABLE 2.2.16: Primitive reflexes to be examined during
developmental assessment
TABLE 2.2.15: Growth patterns

Ages
Approximate
daily weight
gain (gm)
Growth in
Growth in head
length
circumference
(cm/month) (cm/month)
0-3 month
30
3.5
3-6 months
20
6-9 months
15
1.5
0.5
9-12 months
12
1.5
0.5
Reflexes
Age of appearance
Stepping
1-3 years
0.25
4-6 years
3 cm/year
1 cm/year
DEVELOPMENTAL EXAMINATION
Here, the developmental history obtained must be
confirmed by examining the child for the milestones
attained or lost. A large number of accepted methods are
available for assessing development. Of this, the Gessell
developmental scale and the Bayley developmental scale
are commonly used. The Baroda Developmental Screening
Tests and the Trivandrum Developmental Screening Chart
are useful for field assessment of chidrens development.
The development quotient (DQ) must be calculated
separately for motor and mental development.
Developmental age
DQ =
Chronological age
100
Developmental evaluation is of special value in

children with neurological diseases like neurodegenerative disorder and chromosomal anomalies like Downs
syndrome. It is also useful for following up children with
birth asphyxia or established cerebral palsy and mental
retardation. The common developmental/primitive
reflexes to be examined are shown in Table 2.2.16. The
absence of appearance of the primitive reflexes at the
expected time or their persistence beyond the time that
they should normally disappear should lead to a suspicion
of significant brain damage.
Birth
Age of disappearance
6 weeks
Placing
Birth
6 weeks
Moro
Birth
3 months
Sucking and
Birth
4 months while awake
Rooting
7 months while asleep
Palmar grasp
Birth
6 months
Plantar grasp
Birth
10 months
Tonic neck
2 months
4 to 6 months
Landau
3 months
24 months
Neck righting
4 months
24 months
Parachute
9 months
Persists
Sexual Maturity Rating

Sexual maturity rating in boys/girls is shown in
Table 2.2.17.
SYSTEMIC EXAMINATION
It is beyond the scope of this chapter to cover the
examination of every system in detail. Nevertheless it can
be obtained from a standard textbook of clinical
examination. Here we have attempted to give salient points
in clinical examination that are different in children as
compared to adults.
Respiratory System
Inspect the chest wall for any deformities. Costochondral
beading is seen in rickets (broad and dome-shaped), in
scurvy (sharp due to posterior subluxation of the sternum)
and in chondrodystrophy. Look for working of the
accessory muscles of respiration, i.e. flaring of alae nasi,
sternomastoid contraction, suprasternal, subcostal and
intercostal recession which indicate dyspnea. Observe for
TABLE 2.2.17: Sexual maturity rating in boys/girls

SMR stage
Pubic hair (boys/girls)
Breasts
Penises
Testes
Preadolescent
Preadolescent
Preadolescent
Preadolescent
Sparse, slightly pigmented
Breast and papilla elevated,

areolar diameter increased
Slight enlargement
Enlarged scrotum, pink
Darker, beginning to curl
Breast and areola enlarged,

no contour separation
Longer
Larger
Coarse, curly, abundant but

less than adult
Areola and papilla form

secondary mound
Larger
Larger, scrotum dark
Adult distribution, spreads to

medial surface of thighs
Mature, nipple projects
Adult size
Adult size

indrawing of the lower ribs (Harrisons sulcus) which
indicates chronic obstructive airway disease like bronchial
asthma. Vocal fremitus is rarely of value in young children.
Grunting respiration in a child indicates severe respiratory
disease. Percuss lightly in infants and small children, tap
the chest wall directly rather than using another
pleximeter finger. Due to the thin chest wall, the chest is
more resonant than adults. Before starting to auscultate,
allow the child to play with your stethoscope, to allay its
fears. Often it is less threatening to examine the back of the
chest first. Due to the thin chest wall, breath sounds are
louder in children than in adults and their character is
more like the bronchial breathing of adults. This is called
puerile breathing. Do not be disheartened with a crying
child, as breath sounds can be auscultated better in them.
Be careful to distinguish the conducted sounds from the
upper respiratory tract as in laryngomalacia, upper respiratory tract infection, etc.
Cardiovascular System
In a neonate the apical impulse is located slightly outside
the midclavicular line in the 4th intercostal space. By 2
years, it comes to the midclavicular line in the 4th
intercostal space and comes to the adult position, i.e. 5th
intercostal space 1 cm medial to the midclavicular line
between 4 to 7 years. In infants the right ventricles are
dominant as compared to adults (where left ventricle is
dominant). Due to the short neck of infants and young
children, it is difficult to see the jugular venous pulse and
pressure. Use a pediatric stethoscope with a small
diaphragm to auscultate, as the intercostal spaces are
narrow. It is preferable to auscultate the heart while the
infant is comfortably sleeping or feeding from the mother.
It is easier to hear the normal splitting of the heart sounds
and P2 is louder in young children, i.e. < 5 years.
Functional systolic flow murmurs and venous hum are
often heard in normal children.
Abdomen
The best place to examine the childs abdomen is the
mothers lap, preferably while the child is feeding. Even if
the child is struggling, it may be put on the mothers
shoulder and the abdomen is palpated from behind by
ballottment, i.e. palpation just when the child breathes
and the abdomen relaxes. Unlike in adults, it is not
necessary to fold the legs of the child while palpating the
abdomen. Young children normally have a protuberant
abdomen. Look for umbilical (which may be normally seen
in infants) and inguinal hernia. The liver is normally
39
palpable in children till the age of 4 years, i.e. up to 2 cm

below the costal margin. In view of this it is necessary to
measure the span of the liver in order to make out actual
enlargement. It is carried out by percussing the upper
margin of dullness and by palpating the lower edge of the
liver in the mid-clavicular line. The liver span ranges from
about 4.5 to 5 cm at 1 week of age to approximately 7 to 8
cm in males and 6 to 6.5 cm in females by 12 years of age.
The spleen may be normally palpable in infants up to 2 to
3 months. Examine the genitalia for intersex, phimosis,
undescended testis, hypospadiasis or epispadiasis. The
anus is examined for anal excoriation and pinworms.
Nervous System
Neurological examination of the young child is quite
difficult, especially sensory examination and requires
ingenuity on the part of the doctor to get the childs
cooperation. Developmental screening and assessing of
the primitive reflexes should be carried out as already
mentioned. Much information regarding the neurological
status of the child can be learnt by just observing the child,
as the history is being elicited. Coordination is best tested
by watching the child, play. Orientation is best tested only
in children above 4 to 5 years. Handedness becomes
apparent at about 3 years of age. Signs of meningeal
irritation, i.e. neck stiffness, Kernigs sign, Brudzinskis
sign must be looked for. They may not be present in infants
and in the presence of severe undernutrition or overwhelming sepsis. Fundus may be normally pale in infants.
Lifting the child gives a good idea about the muscle tone.
If it is hypotonic the child will slip through the hands.
The plantar reflex may be extensor up to 1 year of age. But
persistence of extensor plantar beyond 2 years, is definitely
pathological. Tendon reflexes in young infants tend to be
brisk. The deep tendon reflexes may be diagrammatically
represented as shown in Figure 2.2.10, using the notations
shown below.
0
+
++
+++
++++
= absent
= sluggish
= normal
= brisk
= exaggerated
History taking and clinical skill development in pediatrics are therefore to be learnt by repeated exposure to case
interviews and hands on training, in examination. The
more a student gets this type of exposure, the more he can
engage himself in self-analysis, which will help him to
carryout the clinical examination thoroughly.

THE PRACTICE OF DIFFERENTIAL DIAGNOSIS
Figure 2.2.10: Diagrammatic recording of

deep tendon jerks
During situations when the diagnosis of the child is not

very clear (which may be the case quite often), it becomes
necessary to make a set of most probable diagnoses. This
is called differential diagnosis. This should be based on
the history, clinical symptoms and clinical signs that have
been elicited. The differential diagnoses thus made will
help us to plan out investigations towards proving or
disproving each probable cause. Hence, to be of practical
value the list should be as short as possible and should
only include conditions that could reasonably explain
most of the child's history, symptoms and signs. The list
should be given in descending order of probability of the
various likely diagnoses, based on the positive and
negative points towards each.
2.3 Parent Counseling

Parang N Mehta
Once upon a time, parents would bring their sick child to

a doctor, and be happy to leave with a prescription.
Explanations, empathy, and politeness were never
expected of doctors.
Times have changed, however, and so have our patients
and their parents. In todays scenario, patients are health
care consumers, we are providers, and the traditional
doctor-patient relationship has changed. Patients and
parents today demand information, courtesy and time.
Arrogance, taciturnity, and a generalised lack of
communication skills are no longer acceptable to health
care consumers.
Apart from the demands of patients, good communication is good medicine. It enhances patients understanding and adherence to therapy, and has a therapeutic
effect. If the parents do not understand the disease and
treatment issues well, they may not adhere to therapy,
resulting in poor outcome. It is important for doctors to be
good communicators, and most medical colleges in USA
now teach and assess communication skills. In our
country, however, this essential component of a doctors

skill set is largely neglected.
COMMUNICATION SKILLS
These are, quite simply, the skills that allow human beings
to communicate with each other in an effective way. For
pediatricians, communication skills consist of:
i. The ability to talk with parents. Not to parents, not at
parents, but with them. Listening is an essential part;
communication must be a two-way process.
ii. The ability to communicate sufficiently well with patients
and parents so as to understand their concerns,
problems, and beliefs, and to elicit relevant
information.
iii. The ability to explain the childs illness and its treatment.
The explanation should be clear, complete, and in a
language that the parents can easily understand. The
treatment options should be explained clearly and
completely, so that they can make informed
decisions about treatment.

iv. The ability to convince parents to follow a treatment
plan. This is especially important when embarking
on prolonged, expensive, difficult, or culturally
unacceptable treatment for a child.
v. The ability to establish a relationship with the parents
and child, based on mutual respect and trust.
vi. Soft skills like being able to put all classes of parents
at their ease, being able to generate confidence, and
being comfortable holding conversations on nonmedical subjects with parents and patients. In days
of old, these were the components of a good
bedside manner, which was considered an
important attribute of a successful practitioner.
THE IMPORTANCE OF COMMUNICATION SKILLS
There are several advantages to possessing good
communication skills (Table 2.3.1). In general, a doctor
with these skills is more likely to have happy, satisfied
patients, than an equally technically competent doctor
who does not bother about communication. Even if a
pediatricians diagnosis and treatment are accurate,
thoroughly rational and successful, poor communication
leaves parents unhappy and resentful. On the other hand,
answering all questions without hesitation enhances
patients and parents belief in a doctors expertise. This
is especially so with chronic or incurable diseases, which
are associated with anxiety, stress, and uncertainty for
the whole family.A doctor who offers support, empathy,
and clear and complete explanations at every step can
help alleviate these to a significant extent. Good
communication also enhances adherence to long-term
therapy. On the other hand, lack of communication can
lead to treatment discontinuation and therapeutic failure.
This can extend to depression and despair, or to anger
and complaints.
Most complaints in health care systems, both public
and private, arise from poor communication. Very few
people can judge the quality of a doctors examination,
diagnosis, or prescription. Obviously, relatively few
complaints originate in poor performance in these areas.
TABLE 2.3.1: Advantages of good communications
Patient satisfaction, leading to regular visits and referrals.

Feeling of empowerment and control.
Adherence to treatment plans.
Loyalty even if treatment is not immediately effective.
Less chances of complaints and legal action in the event of
a mistake.
41
TABLE 2.3.2: What patients want
Clarity and directness.

Listening.
Honesty.
More and better information about their illness, treatment
plan, and expected outcome.
More openness about the hazards and side-effects of
treatment.
More information about the relief of symptoms and other
concerns.
Advice on what they can do to help themselves.
Information on other treatments available.
A supportive, non-judgmental, empathetic doctor.
Parents are angered by the doctors refusal to spend time

with them, refusal to give complete and clear explanations, a casual or callous approach to the childs problems,
and a lack of courtesy and care. When all these are followed
by a poor treatment outcome, complaints, quarrels, and
legal action are likely. On the other hand, good
communication can play a significant part in avoiding
complaints and malpractice claims.
BARRIERS TO GOOD COMMUNICATION
Traditionally, we have not paid much attention to
communicating well. Even today, few of us appreciate the
importance of communication skills, and hardly any make
a concerted effort to learn and apply such skills. This is
perhaps the single biggest barrier to good communication.
Unless we accept the contribution of good communication
to patient outcomes and parent satisfaction, poor communication is likely to remain the norm in the medical field.
Even doctors who realise the importance of good
communication are not always successful at implementing it. Many of us do not realise what patients want from
us (Table 2.3.2). Some other barriers to good communication are:
Lack of time: Most pediatricians see a large number of
patients every working day. This is true of both
government and private hospitals. History taking,
physical examination, and prescription writing are of
course, essential parts of a clinical encounter. When time
is short, it is the communication with parents that is
sacrificed. We can overcome this, partially, by deputing
some explanations to paramedical staff.
Arrogance: Arrogance is deeply ingrained into doctors. We
expect our patients and their parents to follow our
commands unquestioningly. We do not understand the
need for explanations, and often give none.

Shyness: The parents may be very shy and not ask the
questions they have in their minds. On the other hand, the
doctor may be shy, and either ignore questions, or give
minimal and incomplete answers. Shyness on either side
stands in the way of adequate information being imparted.
ii. Expected progress of the child during treatment.

iii. What to expect by way of improvement, side effects,
fresh problems, etc.
iv. Chances of complete cure.
v. Treatment options.
Language and jargon: In any major city of India, there is

likely to be a large population of people from other states
and linguistic groups. Communication with them can be
a problem, and needs a special effort.
Most such people will bring an interpreter with them
when coming to us. However, we must use such a person
well. It is necessary to give the interpreter the information
in small chunk, and have him translate it for the parents
as you go along. This is especially important with the
prescriptionexplain one drug at a time and have him
translate.
A major problem occurs when the parents speak
English. As soon as we meet an English speaking parent,
we start speaking in technical/medical language. This
leaves the parents confused and uninformed. When
talking in English, it is essential to make an effort to talk in
language that a non-medical person can understand.
The last point is especially important. Complementary and alternative medicine is a growing business, and
their remedies are often advertised and promoted
aggressively. Dismissing them off hand does not convince
parents. It is necessary to explain treatment goals, explain
how our treatment works, and convey to them the
unscientific basis and unreliability of advertised magic
remedies.
Deafness: Deafness is a major cause of poor communication,

and is a special concern when our patients are accompanied by their grandparents. When we suspect a hearing
impairment, we must speak loudly, slowly and distinctly.
Other useful measures are: voice amplification, if a devide
is available; a quiet room, to improve signal to voice ratio;
use of written communication; and asking the family, at
the end of the consultation, if they have understood
everything, and if they have any questions.
An important measure is to have the relatives repeat
the prescription instructions, to ascertain they have been
understood. This ensured that the child will receive the
medication as it has been prescribed.
Phones: Earliers, a telephone would buzz discreetly on
a receptionists desk, and a consultation would not be
interrupted. Today, theres a phone in everyones pocket
or hand, and calls can interrupt and hinder communication terribly.
INFORMATION NEEDS
When faced with a chronic/permanent condition, most
parents want to know:
i. What treatment can achieve for their childrelief of
symptoms, prolongation of life, shortening of the
course of the disease, etc.
STRATEGIES FOR IMPROVING COMMUNICATION

Check what the parents know: With intelligent and
knowledgeable parents, the discussion can begin at a
higher level. However, assessing the parents knowledge
is important, because some of their knowledge or
understanding may be faulty. Many parents get their
knowledge from magazines, lay books, and websites. Most
of these sources have no system of review or control of the
information published.
Assess what the parents want to know: Some parents want to
know every little fact and detail about their childs
condition. Others simply want a prescription and an
assurance that all will be well. It is important to assess the
parents desires, and communicate accordingly.
Assess understanding: The parents may not fully understand
what is being told to them. They are upset about the child
being sick, they have poor comprehensive skills, they have
language problemsthere could be many reasons. If the
parents indicate that they are not fully understanding
what is being told to them, stopping the explanations for
that session might be appropriate and take it up next time.
Understanding can be improved by giving time to absorb,
and by repetition. At the end of the consultation, the
parents can be asked to repeat some information, to ensure
it has been understood.
Listening skills: Most of us hardly allow the parents to speak.
As soon as they start their description of the childs
problem, we start asking questions, and attempt to keep
the consultation focussed. However, this often leads to an
incomplete description of the childs problems.
Listening well is an essential part of communication.
This requires the provision of adequate time and patience,
and the willingness to listen to parents concern. A quiet
43
TABLE 2.3.3: Dos and Donts of communication
Do
Dont
Greet the child and parent by name.

Smile.
Sit down when talking.
Try to talk in the patients language.
Direct the conversation to relevant directions.
At the end of the consultation, ask if the parents have
any questions.
Engage the parents in a dialogue.
Give time for the parents to absorb and understand the
content of your explanations, then to ask questions.
room, lack of interruptions, provision of chairs for the

parents, sitting at an appropriate distance, good eye
contact, etc. are helpful to enhance listening and learning
from the parents.
Build confidence: The parents confidence must be bolstered.
We need to accept what the parents say, without judging
it. A little specific praise for the parents efforts so far helps
significantly in building confidence and helping parents
to cope. Some suggestions for future care improve their
confidence that they will be able to manage the situation.
Giving false hope is wrong, but we can give information
in a positive manner.
Truth: Parents like to know the truth, but the bald truth
can be harsh and shocking. Parents deserve to know the
truth, but its delivery should be tempered with commonsense and empathy. If the facts are particularly unpleasant,
they can be delivered in small parts spread out over two
or more visits. However, if parents express a desire to know
everything, it must be told to them. Withholding
information leads to distrust.
Simplicity and clarity: Not all parents have a good
educational and intelligence level. Explaining things in
simple, clear, and direct language is very important. Clarity
and directness are particularly important with parents of
low comprehension abilities. Many people do not
comprehend words like growth and tumor, for
example. Cancer sounds shocking, but may be
necessary to drive home the problem to parents.
Be tolerant: Parents react in various ways, and we should
be prepared. Blame, anger, a sudden outpouring of grief
all these are common reactions. We should be ready to
deal with these emotions with understanding and
support.
Look at your watch frequently.

Appear to be in a hurry.
Use too many medical terms.
Talk with your hand on the door handle, or foot outside
the door.
Interrupt all the time.
Start examination and then write out a prescription
before the main problem has been identified.
Give long lectures as explanation.
Ignore concerns mentioned by parents.
Empathy: Parents of sick children are going through a

difficult experience. They appreciate the fact that their
doctor understands their situation and their difficulties.
While sympathy has overtones of pity and is likely to be
resented, empathy is simply an understanding of the
parents plight.
Apart from these broad principles, many small
factors affect communication positively or negatively
(Table 2.3.3).
KEY POINTS
Communication skills contribute to good medical care and

patient satisfaction.
Communication skills contribute to a doctors respect, a
patients faith, and adherence to treatment.
Doctors with good communication skills have better clinical
and commercial success, less stress, and more job
satisfaction.
CONCLUSION
Good communication is an art that is so far acquired,
developed and improved by experience. However, it can
also be taught, and assessed, by means of structured
programs. Medical students will gradually have
increasing levels of training in this essential aspect of
medicine. Though formal training is not easily available
to doctors in jobs or practice, we can improve our
communication skills with some personal efforts. This will
lead to better patient/ parent satisfaction and perhaps
better clinical outcomes. Compassion, explanation, and
reassur-ance are valued by our patients and their families
as much as a diagnosis, treatment, and cure.
ACKNOWLEDGEMENT
The article has been reporduced from Indian Pediatrics with
permission from the Editor-in-Chief.

BIBLIOGRAPHY
Bartel DA, Engler AJ, Natale JE, Misra V, Lewin AB, Joseph
JG. Working with families of suddenly and critically ill
children. Arch Ped Adolesc Med 2000;154: 1127-33.
2. Bull SA, Hu XH, Hunkeler EM, Lee JY, Ming EE, Markson
LE, et al. Discontinuation of use and switching of
antidepressants: Influence of patient physician
communication. JAMA 2002;288:1403-9.
3. Fook L, Morgan R, Sharma P, Adekoke A, Turnbull CJ.
The impact of hearing on communication. Postgrad Med
J 2000;76:92-5.
4. Langewitz WA, Eich P, Kiss A, Wossmer B. Improving
communication skills: a randomized controlled
behaviorally oriented intervention study for residents in
internal medicine. Psychosom Med 1998;60:268-76.
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Levinson W, Roter DL, Mullooly JP, Dull VT, Frankel

RM. Physician patient communication. The relationship
with malpractice claims among primary care physicians
and surgeons. JAMA 1997;277:553-9.
Meryn S. Improving doctor patient communication. Br
Med J 1998;316:1922-30.
Moore PJ, Adler NE, Robertson PA. Medical malpractice:
the effect of doctor patient relations on medical patient
perceptions and malpractice intentions. West J Med 2000;
173:244-50.
Partridge MR, Hill SR. Enhancing care for people with
asthma: the role of communication, education, training
and self management. Eur Resp J 2000;16:333-48.
Yedidia MJ, Gillespie CC, Kachur E, Schwartz MD, Ockene
J, Chepaitis AE, et al. Effect of communication training
on medical student performance. JAMA 2003; 290:115765.
3.1 Neonatal Nomenclature and Definitions: Meharban Singh, Vinod K Paul ........................................................................................... 46
3.2 Resuscitation of an Asphyxiated Newborn Baby: Meharban Singh, Ashok K Deorari ....................................................................... 50
3.3 Care of a Normal Newborn Baby: Meharban Singh, Ashok K Deorari .................................................................................................. 56
3.4 Common Developmental and Physiological Problems in Newborn Babies: Meharban Singh, Vinod K Paul ................................. 61
3.5 Management of Low Birth Weight Babies: Vinod K Paul, Ashok K Deorari, Meharban Singh ............................................................ 65
3.6 Common Diseases of Newborn Babies: Meharban Singh, Vinod K Paul, Ashok K Deorari ................................................................ 71
3.1 Neonatal Nomenclature and Definitions

It is essential to have uniformly accepted definitions to
express perinatal-neonatal morbidity and mortality for
ease of comparison with other national and international
studies. The adoption of standard nomenclature is
essential for generating meaningful data and for surveillance of impact of interventional strategies. The majority
of definitions and terminologies described below are
based on the standard sources such as tenth revision of
International classification of diseases (ICD) by WHO and
are duly approved and adapted by the Task Force of
National Neonatology Forum of India.
Fetus
Fetus is a product of conception, irrespective of the
duration of pregnancy, which is not completely expelled or extracted from its mother. Up to 9 weeks of
gestation, it is designated as embryo.
Live Birth
Live birth is defined as complete expulsion or extraction
from the mother of a product of conception (irrespective
of the duration of pregnancy) and which after such
separation, breathes or shows any other evidence of life
such as beating of the heart, pulsation of umbilical cord
or definite movements of the voluntary muscles
irrespective of the attachment of placenta and/or cord.
In 1970, WHO recommended that babies weighing
less than 500 g at birth should show signs of life for at
least one hour before they are designated as live born.
Fetal Death
Death prior to the complete expulsion or extraction from
its mother of a product of conception irrespective of the
duration of pregnancy, the death is indicated by absence
of any signs of life.
Early fetal death Death at a gestational age of less than
22 weeks or of a fetus weighing less than 500 g or crownheel length (CHL) of less than 25 cm.
Intermediate fetal death Death at a gestational age of 22
to 27 weeks or of a fetus weighing 500 to 999 g or CHL
between 25 cm to less than 35 cm.
Late fetal death Death at a gestational age of 28 weeks or

more of a fetus weighing 1000 g or more or CHL of at
least 35 cm. The body may be fresh or macerated.
Early fetal deaths are called abortions, while intermediate and late fetal deaths are designated as stillbirths.
Birth Weight
Birth weight is the first weight of a live or stillborn baby
which should preferably be taken within the first hour
of life and certainly during the first day of life before any
significant postnatal weight loss has occurred. If weight
is recorded after 24 hours, the age at which weight is
taken should be specified.
Birth Weight Groups
Low birth weight (LBW) babies Babies with a birth weight
of less than 2500 g (up to and including 2499 g)
irrespective of the period of gestation. These include
preterm (one-third) and small-for-dates term (two-thirds)
babies. In India, for purposes of according specialized
care, babies with a birth weight of less than 2000 g are
considered as high-risk and are admitted to the special
care neonatal unit (SCNU).
Very low birth weight (VLBW) babies Babies with a birth
weight of less than 1500 g (up to and including 1499 g).
Extremely low birth weight (ELBW) babies Babies with a
birth weight of less than 1000 g (up to and including
999 g).
Gestational Age
Gestational age is calculated from the first day of the last
normal menstrual period till the date of birth and is
expressed in completed weeks, e.g. 34 weeks + 6 days
are considered 34 weeks only.
Gestational Age Groups
Preterm (Immature, born early, "premature") Preterm is
defined as a baby with a gestation of less than 37 completed weeks, (up to 36 weeks or less than 259 days).
Term Babies with a gestational age between 37 to 41
weeks are called as term babies (259-293 days).
Newborn Care
Post-term (postmature) Babies with a gestational age of
42 weeks or more are classified as post-term babies (294
days or more).
Classification by Birth Weight and
Gestational Age Groups
Small-for-dates (SFD) babies (Small-for-gestational age, lightfor-dates, intrauterine growth retardation) Babies with a birth
weight of less than tenth percentile for their gestational
age are designated as SFD babies (Fig. 3.1.1). For purposes
of specialized care and monitoring of blood glucose
levels, babies with a birth weight of less than third
percentile for the period of their gestation are admitted
in the special care nursery unit (SCNU). Dysmaturity
refers to the characteristic marasmic appearance of a baby
reflecting placental dysfunction. This term should
preferably be avoided.
Ideally, regional intrauterine growth charts should
be constructed from a population of high socioeconomic
level with optimal maternal nutrition, and after
excluding known maternal and fetal conditions, which
cause intrauterine growth retardation (IUGR). It also
appears justified to employ one universally accepted
international reference standard for purposes of
comparison of the data.
47
Appropriate-for-dates (AFD) babies (Appropriate-forgestational age) Babies with a birth weight between 10th
to 90th percentile for the period of their gestation.
Large-for-dates (LFD) babies (Large-for-gestational age, heavyfor-dates) Babies with a birth weight of more than
ninetieth percentile for the period of their gestational age.
The babies with a birth weight of more than 97 percentile
for their gestation are considered high-risk and
monitoring for hypoglycemia.
By combining classification of the babies on the basis
of gestational age alone and gestational age with birth
weight, the newborn population can be divided into the
following 9 subgroups.
1. Preterm
I. SFD
II. AFD
III. LFD
2. Term
I. SFD
II. AFD
III. LFD
3. Post-term
I. SFD
II. AFD
III. LFD
The neonatal mortality is high among preterm babies
due to anatomical and functional immaturity of various
body organs. The least neonatal mortality is seen in term
appropriate-for-dates babies. In each gestational group
(whether preterm, term or post-term) mortality is higher
among LFD and SFD babies as compared to AFD babies.
Perinatal Period
Perinatal period extends from the twenty-eighth week
of gestation (or more than 1000 g) to the seventh day of
life (early neonatal).
PMR =
Total perinatal deaths
__________________________________
Total number of births
Extended PMR =
Intermediate Late
1000
Early
stillbirths + stillbirths + neonatal deaths 1000
_____________________________________________________________
Total number of births

Figure 3.1.1: Intrauterine growth curve. This helps in classifying neonates into three categories, viz. small-for-dates (SFD),
appropriate-for-dates (AFD) and large-for-dates (LFD)
In view of the increasing survival of the babies

weighing less than 1000 g as a result of improvements in
the perinatal care, the concept of extended perinatal

period has been introduced. This period extends from
twenty-second week of gestation (or more than 500 g) to
7th day of life.
Perinatal Mortality Rate (PMR)
Perinatal mortality rate (PMR) is defined as late fetal plus
early neonatal (first week) deaths of babies weighing
more than 1000 g (or 28th week of gestation or more) at
birth per 1000 total births weighing over 1000 g. It is
suggested that for international comparisons, the
numerator as well as the denominator in perinatalneonatal statistics should be restricted to fetuses and
infants weighing 1000 g or more.
Neonatal Period
Neonatal period extends up to 28 days of life. Infant up
to 28 days of life is called a newborn baby or neonate.
Early neonatal period refers to first 7 days or 168 hours
of life, while late neonatal period signifies period from
7 days to under 28 completed days of life.
Neonatal Deaths
First day death is defined as deaths occurring within 24
hours of age (exclude if baby had completed 24 hours of
age).
Early neonatal deaths include deaths within 168 hours
of age (exclude if baby had completed 168 hours of age).
Neonatal deaths include all deaths within 28 days of
age.
Neonatal Mortality Rate (NMR)
Early NMR Neonatal deaths of babies weighing over
1000 g during first 7 days per 1000 live births.
Late NMR or unspecified NMR Neonatal deaths of babies
weighing over 1000 g during 28 days of life per 1000 live
births.
The extended neonatal mortality rate can be calculated by including babies weighing up to 500 g. It is
suggested that the hospital-based neonatal-perinatal
statistics may be presented separately for booked and
unbooked cases.
Birth Weight Classification for
Perinatal-neonatal Data
The morbidity and mortality can be expressed by weight
intervals of 500 g, i.e. 1000 to 1499 g, 1500 to 1999 g, 2000
to 2499 g and so on.
Gestational Age Classification for

Perinatal-neonatal Data
Less than 28 weeks (less than 196 days)

2831 weeks (196223 days)
3236 weeks (224258 days)
3741 weeks (259293 days)
42 weeks and more (294 days and more)
Calculation of Incidence
The incidence of neonatal conditions (e.g. LBW babies,
preterm and birth asphyxia, etc.) should be calculated
per 100 live births, while that of pregnancy and labor
related conditions (e.g. toxemia, maternal anemia,
cesarean deliveries, etc.) should be calculated per 100
total births.
Maternal Mortality
The maternal death is defined as a death of a woman
known to be pregnant within 42 days of termination of
pregnancy, irrespective of the duration or site of the
pregnancy. The death may be due to any cause related
to or aggravated by the pregnancy or its management
but not from accidental or incidental causes. The maternal
mortality rate is expressed as maternal deaths per 1000
live births.
Direct obstetric death Death resulting from complications
of pregnancy, childbirth or puerperium including
interventions, omissions, incorrect treatment or from a
chain of events resulting from any of the above causes.
Indirect obstetric death Death resulting from previous
existing disease or a disease that developed during pregnancy, childbirth or the puerperium which was not due
to direct obstetric causes, but which was aggravated by
physiologic effects of pregnancy.
Clinicopathological Classification of
Perinatal Deaths
There is a lack of unanimity and considerable confusion
exists regarding the most acceptable method for classification of deaths during perinatal period. It is essential
that all perinatal centers should adopt an identical or
uniform protocol for clinicopathological classification of
perinatal deaths so that mortality data is comparable in
order to identify any regional differences. During
perinatal period, many deaths cannot be classified merely
on the basis of clinical findings unless it is complemented
Newborn Care
by autopsy data. Efforts should always be made to obtain
an autopsy in each and every case of perinatal death. It
is generally easier to obtain permission for autopsy in a
case of perinatal death due to relatively less emotional
bondage of parents and their concern for having a normal
healthy baby during next pregnancy. A routine autopsy
performed by an adult-oriented pathologist may not be
informative and may be unable to identify the cause of
death.
Neonatal and Perinatal Mortality
When NMR was 70 per 1000 live births (Fig. 3.1.2), it
contributed to 63 percent of infant mortality rate (IMR
of 110 per 1000 live births). The current NMR is 39 per
1000 live births and the current IMR is 57 per 1000 live
births at the national level (Table 3.1.1). The most
important causes of NMR are bacterial infections (sepsis,
pneumonia), LBW and birth asphyxia. Congenital
malformations also contribute to neonatal deaths to a
small extent. Tetanus neonatorum which was the single
most important cause of neonatal deaths until a few years
ago has now been virtually eradicated. This is responsible
for the decline of neonatal mortality from 70 per 1000
live births in 1981 to the current level.
Neonatal Mortality in Different States
India is an immense country with a wide range of
neonatal mortality rates in different states, from as low
as 1.3 per 1,000 live births in Kerala to around 51 in
Chattisgarh and 48.6 in Jharkhand (Table 3.1.1). ENMR
and late neonatal mortality rates (LNMR) together make
up the NMR.
49
TABLE 3.1.1: Neonatal and infant mortality rates by state

State
Neonatal
mortality
Postneonatal Infant
mortality
mortality
(PNM)
(IMR)
India
39.0
18.0
57.0
North
Delhi
Haryana
Himachal Pradesh
Jammu & Kashmir
Punjab
Rajasthan
Uttaranchal
29.3
23.6
27.3
29.8
28.0
43.9
27.6
10.5
18.1
8.9
14.9
13.7
21.4
14.3
39.8
41.7
36.1
44.7
41.7
65.3
41.9
Central
Chhattisgarh
Madhya Pradesh
Uttar Pradesh
51.1
44.9
47.6
19.7
24.7
25.0
70.8
69.5
72.7
East
Bihar
Jharkhand
Orissa
West Bengal
39.8
48.6
45.4
37.6
21.9
20.2
19.3
10.4
61.7
68.7
64.7
48.0
Northeast
Arunachal Pradesh
Assam
Manipur
Meghalaya
Mizoram
Nagaland
Sikkim
Tripura
34.0
45.5
18.7
23.6
16.3
19.8
19.4
33.1
26.7
20.6
11.1
21.0
17.7
18.5
14.3
18.3
60.7
66.1
29.7
44.6
34.1
38.3
33.7
51.5
West
Goa
Gujarat
Maharashtra
8.8
33.5
31.8
6.5
16.2
5.7
15.3
49.7
37.5
South
Andhra Pradesh
Karnataka
Kerala
Tamil Nadu
40.3
28.9
11.5
19.1
13.2
14.3
3.8
11.2
53.5
43.2
15.3
30.4
Common Causes of Perinatal Deaths
Figure 3.1.2: Infant mortality in India, with changes in neonatal

(black bar) and postneonatal (white bar) mortality rates per
1000 live births
Perinatal deaths include late fetal and early neonatal (first

week) deaths. Perinatal mortality rate in India is around
8.5 per 1000 live births. There is almost equal contribution
by stillbirths and early neonatal deaths. A large majority
of stillbirths are attributable to placental insufficiency due
to pregnancy-induced hypertension (PIH) and maternal
malnutrition, fetal and intranatal hypoxia, antepartum
hemorrhage and congenital malformations.

Nearly one-half of early neonatal deaths occur
during first 24 hours of life. Neonatal mortality is
directly related to birth weight and gestational maturity
of the infant. In India it varies between 0.5 percent
among healthy term infants to about 30 percent in
preterm or infants with a birth weight of less than 2000
g. It is estimated that about 30 to 40 percent infants born
in India are LBW (<2500 g at birth), and about 85 percent
of all neonatal deaths occur among them. The neonatal
mortality of LBW babies is about 20 times of mortality
among term-AGA infants. Generally, several factors
operate in most perinatal deaths. Placental insufficiency,
premature separation of placenta and obstetrical
difficulties are important predisposing factors. Bacterial
infections and septicemia account for one-fifth of all
neonatal deaths.
REFERENCE
1.
National Family Health Survey (NFHS-3), 2005-06.

Ministry of Health and Family Welfare www.nfhsindia.
org accessed on 14th June, 2008.
BIBLIOGRAPHY
1. Singh M, Deorari AK, Khajuria RC, et al. A four-year
study on neonatal morbidity in a New Delhi hospital.
Indian J Med Res 1991;94:186-92.
2. Singh M, Deorari AK, Khajuria RC, et al. Perinatal and
neonatal mortality in a hospital. Indian J Med Res
1991;94:1-5.
3. Singh M, Deorari AK, Paul VK, et al. Primary causes of
neonatal deaths in a tertiary care hospital in Delhian
autopsy study of 331 cases. Ann Trop Pediatr
1990;10:151-57.
4. Singh M, Paul VK. Standard nomenclature and definitions for expressing neonatal morbidity: A plea for
uniformity. Indian Pediatr 1989;26:1089-95.
3.2 Resuscitation of an Asphyxiated

Newborn Baby
Establishment of spontaneous breathing afterbirth is
most crucial for the survival of a newborn baby. Most
babies have a smooth transition from fetal to neonatal
life, and they are able to establish spontaneous breathing without any active assistance. Nevertheless, 4 to 6
percent of the neonates are likely to face difficulties in
initiating spontaneous breathing at birth and they require
active resuscitation. Perinatal hypoxia and birth asphyxia
are the leading cause of perinatal mortality in our
country. Apart from high perinatal mortality, birth
asphyxia is an important cause of neuromotor disability.
In order to improve survival of newborn babies due to
perinatal hypoxia and improve the quality of life, it is
essential that every birth is considered as a medical
emergency, and labor room area is adequately provided
with infrastructure and facilities for resuscitation of
newborn babies. Effective resuscitation demands availability of at least two persons, one who is actively resuscitating and the other who is monitoring the condition of
the baby and assisting the resuscitator for administration
of drugs and external cardiac massage when required.
Fetal Hypoxia
The existence of certain high-risk factors during pregnancy and labor may forewarn and alert the labor room
staff that they should be fully prepared to meet the
challenge of an asphyxiated baby (Table 3.2.1). All highrisk pregnancies should be monitored for fetal growth,
TABLE 3.2.1: Conditions demanding resuscitation alert
1. Fetal distress
2. Meconium-stained liquor
3. Placental insufficiency (PIH, hypertension, postmaturity)
4. Premature onset of labor
5. Antepartum hemorrhage
6. Malpresentation, difficult and abnormal or operative
delivery
7. Cord prolapse
8. Rhesus isoimmunization
9. Multiple gestation
10. Bad obstetric history
Newborn Care
presence of congenital malformations, adequacy of
placental function and evidences of fetal hypoxia.
Nonstress test, oxytocin challenge test and biophysical
profile score on ultrasound examination are useful to
identify early evidences of fetal hypoxia. The time
honored clinical parameters of fetal distress offer useful
guidelines to an experienced obstetrician. The asphyxiated fetus initially behaves like a strangulated individual
and makes violent efforts leading to exaggerated fetal
movements which is followed by reduced or absent fetal
movements. Due to the release of catecholamines,
initially there is tachycardia followed by bradycardia and
slow, irregular heart beats. The presence of meconium
due to visceral over activity in a baby presenting as vertex
is an important and ominous sign of fetal hypoxia
specially when associated with an abnormal fetal heart
pattern.
Pathophysiology of Asphyxia
Birth asphyxia is associated with reduction in arterial
oxygen tension, accumulation of carbon dioxide and fall
in blood pH. These biochemical changes lead to rightto-left shunt with the perpetuation of birth asphyxia.
During the early phase of birth asphyxia, the blood
glucose level is significantly elevated due to the
breakdown of glycogen to glucose, while severe and
prolonged hypoxia in preterm and growth retarded
babies is associated with hypoglycemia. Hypothermia
and hypoglycemia lead to accumulation of non-esterified
free fatty acid and glycerol. Anoxic damage to cells leads
to failure of energy-dependent sodium pump mechanism
with release of potassium and phosphates into the
extracellular fluid.
Assessment of the Infant at Birth
Despite its limitations, Apgar scoring system is conventionally used for assessing the condition of a newborn
baby at one minute afterbirth (Table 3.2.2). The
respiratory effort and heart beats are the most critical
components of Apgar scoring system because muscle
tone, response to reflex stimulus and color are dependent
upon the gestational maturity and cardiorespiratory
status of the baby.
Resuscitation Kit
The resuscitation table or trolley must be available in the
same room where the mother is being delivered. Each
51
TABLE 3.2.2: Apgar scoring system

Score/item
2
Crying
1. Breathing
Nil
Slow
2. Heart rate
Nil
Up to 100
> 100
3. Tone
Flaccid
In-between
Flexed
4. Reflex response
Nil
Grimace
Cry
Blue or pale
Peripheral
cyanosis
Pink
to catheter
5. Color
delivery room must have a well-lighted and warm

microenvironment to receive the newborn baby. The
resuscitation tray must contain a pencil handle laryngoscope with infant (0 and 1) blade, resuscitation bag and
mask, De Lee suction trap, gamma-irradiated disposable
endotracheal tubes with internal diameters of 2.5, 3.0,
3.5, 4.0 mm mounted with adaptors, suction catheters,
syringes and needles, 7.5 percent sodium bicarbonate
solution, epinephrine 1 in 10,000 solution, naloxone,
physiological saline and 5 percent dextrose. Electrical
points and the suction machine should be in working
order. The oxygen cylinder should be checked for its
contents. Sterile neonatal packs containing a bowl,
scissors, cotton swabs and umbilical ties should be
available for each delivery. The bassinet on which the
baby is received should be kept warm and provided with
an overhead radiant heat source and a stop clock to
accurately time the sequence of events afterbirth. It is
mandatory that the resuscitation kit must be checked by
the staff nurse of every duty shift and rechecked by the
physician before each delivery. It is desirable that the
equipment for resuscitation is maintained in a sterile
condition. Above all, the health professional attending
the delivery must be skilled and experienced in the art
of cardiopulmonary resuscitation. The art of endotracheal
intubation should be learnt by continuous practice on
stillborn and dead neonates.
Basic Care of the Baby at Birth
The umbilical cord should be clamped as soon as the
infant is completely delivered. There should be no undue
delay or unnecessary anxiety or hurry to clamp the cord.
Early and immediate clamping of the cord is indicated
in babies with severe birth asphyxia, cord around the
neck and rhesus isoimmunization.

Routine Care
Nearly 90 percent of newborns are vigorous term babies
with no risk factors and clear amniotic fluid. These babies
do not need to be separated from their mothers to receive
initial steps. Temperature can be maintained by putting
the baby directly on the mothers chest, drying and
covering with dry linen. Warmth is maintained by direct
skin to skin contact. Clearing of the airway can be done
by wiping the babies nose and mouth.
Assess for the Four Questions (Refer to Algorithm)
If answer is `No to any of these questions, begin initial
steps of resuscitation. Provide initial care (refer to
alogrithm). Provide warmth, position, clear airway (as
necessary), dry, stimulate, reposition and give O2 (as
necessary).
If answer to any of four is `No baby needs initial
steps. In this efforts are directed to prevent hypothermia
and attention is focussed on the airways so that they are
cleared off any secretions and kept patent. The overhead
radiant warmer of the resuscitation trolley or table should
be put on 15 minutes before the birth of the baby. The
baby should be received in a prewarmed linen and dried
from top to bottom immediately afterbirth. The wet linen
should be removed and baby should be covered
effectively with a dry and warm towel. The practice of
bathing the babies soon afterbirth is dangerous and must
be abandoned.
The baby should be placed either in a head low
position to ensure drainage of oropharyngeal secretions
or kept flat with 1/2 inch to 3/4 of an inch towel roll
under the shoulders to maintain slight extension of the
neck for ensuring patency and adequacy of airways. The
mouth should be suctioned first followed up suctioning
of the nose using 10 Fr catheter. The suction force should
be gentle and intermittent using a maximum suction
pressure of 100 mm Hg (136 cm of water). Suctioning
should not be done for more than 5 seconds at a time,
Figure 3.2.1
Figure 3.2.2
Figures 3.2.1 and 3.2.2: Two methods of
tactile stimulation over the soles
and the heart rate should be monitored for possible

bradycardia. These steps usually take around 30 to 45
seconds and by this time most babies are vigorously
crying, actively moving and pink. Centrally cyanosed
baby requires free flow of oxygen with the help of tube
or mask. If the baby is not crying by this time and he or
she is gasping or having no breathing efforts give one or
two flicks or slaps over the soles to stimulate breathing
(Figs 3.2.1 and 3.2.2). Prolonged stimulation or use of
violent maneuvers like pouring cold water on the baby's
face and slapping the back are not only dangerous but
useless resulting in delay in the resuscitation of the baby.
Approach to a Meconium Stained Baby
The amniotic fluid is meconium stained in 10 to 15
percent of deliveries. When baby passes meconium in
utero, there is a chance that the meconium will be
aspirated into infants mouth and potentially into the
Newborn Care
trachea and lungs. Appropriate steps must be taken
immediately after delivery to reduce the risk of serious
consequences resulting from aspiration of the meconium
(Note: Intrapartum suctioning of the mouth and nose after
delivery of the head and before delivering the shoulders is no
longer recommended). Direct endotracheal suctioning,
using the endotracheal tube as a suction catheter, should
be performed in cases of non-vigorous baby born with
meconium stained liquor. Vigorous baby (as defined by
strong respiratory effort, good muscle tone and a HR
>100/mt) do not require endotracheal suction.
Endotracheal suctioning may not be necessary the
newborn is vigorous. The infant may have to be intubated
two to three times till all traces of meconium has been
sucked out and baby has not developed bradycardia. The
meconium-stained baby should never be ventilated till
the air passages have been effectively cleared of all
possible meconium.
Bag and Mask Ventilation
If despite stimulation, the baby is still apneic or having
ineffective ventilation as evidenced by heart rate of less
than 100 per minute, he or she should be given bag and
mask ventilation. The mask should tightly fit on the face
enclosing nose and mouth of the baby. The oxygen
reservoir should be attached to the bag to increase the
concentration of oxygen delivered to the baby (Fig. 3.2.3).
The infant should be ventilated at a rate of 40 to 60 per
minute. There should be a noticeable rise and fall of the
chest during each ventilation (Fig. 3.2.4). Naloxone 0.1
ml/kg should be administered intravenously through
umbilical vein if mother had received pethidine or
morphine within 4 hours before delivery after initiating
baby and mask ventilation. During bag and mask
53
Figure 3.2.4: The procedure of bag and mask ventilation. Mask

should enclose both nose and mouth resting snugly over the
chin and just below the eyes. There should be gentle but visible
rise and fall of chest with each inflation
ventilation, heart rate should be closely monitored after

every 20 to 30 seconds. To save time, heart rate is counted
for 6 seconds and multiplied by 10 to get the heart rate
per minute. If despite effective bag and mask ventilation,
heart rate is not coming up or it further slows down and
drops below 100 per minute, the infant should be
intubated. A large majority of asphyxiated babies can be
effectively revived and resuscitated by using bag and
mask ventilation alone and intubation is usually not
required. There is no role of dexamethasone, atropine,
calcium and respiratory stimulants like nikethamide,
lobeline, etc. in resuscitation. The Apgar scoring system
is not taken into consideration while taking management
decisions during resuscitation of a newborn baby. The
management is guided by the status of breathing, heart
rate and color of the baby. Apgar score may be recorded
at 1 minute, 5 minutes and subsequently (till it is more
than 7) to serve as a prognostic indicator of the outcome
of an asphyxiated baby.
Endotracheal Intubation
Figure 3.2.3: Self-inflatable resuscitation bag and mask. A

reservoir (corrugated tube or a bladder) should be attached at
the air inlet to increase the oxygen concentration delivered to
the baby
Endotracheal intubation is indicated if bag and mask

ventilation fails to maintain adequate ventilation as
evidenced by persistent bradycardia (heart rate below
100 per minute). Infants with diaphragmatic hernia and
thickly meconium stained babies are electively intubated because bag and mask ventilation is contraindicated
in these situations. The art of intubation cannot be taught
and must be learnt by practicing on stillborn babies and
neonates dying in the nursery. The appropriate sized

Flow chart 3.2.1: Neonatal resuscitation
(4.0 mm in a term baby and 2.5 mm in a tiny baby)

endotracheal tube should be prepared by shortening it
to 13 cm and attaching a connector. It is easy to intubate
an asphyxiated baby with some practice because of lack
of resistance and hypotonia. The endotracheal tube
should be suctioned before starting positive pressure
ventilation with a bag or machine. The ventilation can
be stopped as soon as the baby establishes spontaneous
breathing and heart rate is maintained above 100 per
minute (See Flow Chart 3.2.1).
External Cardiac Massage and Medications
External cardiac massage is indicated in babies in whom
heart rate drops below 60 per minute despite effective
ventilation. The ventilation should be continued and
simultaneously heart should be massaged either by using
two fingers of one hand or encircling the chest of the

baby with both the hands and applying sternal
compressions with two thumbs (Fig. 3.2.5). Press the
lower part of the sternum to a depth of 1 to 2 cm at a rate
of 90 compressions and 30 ventilations in 1 minute (3:1
ratio) per minute. The thumbs and tips of fingers
(depending upon the method used) should remain in
contact with the sternum all the time, and they should
not be lifted off after each compression. Check the heart
rate after every 20 to 30 seconds, and chest compressions
may be stopped when heart rate goes above 60 per
minute.
If heart rate is not picking up despite effective ventilation and external cardiac massage, administer 0.5 to
1.0 ml of 1.10,000 solution of epinephrine through the
umbilical vein or endotracheal tube. Intracardiac route
Newborn Care
55
administration of 10 ml/kg of fresh blood, fresh frozen

plasma or physiological saline. A skiagram of chest
should be taken to exclude pneumothorax and congenital
malformations of the respiratory system. The infant
should be closely monitored and observed to detect any
manifestations of hypoxic damage to various organs.
Seizures should be promptly managed by correction of
any metabolic disturbances and by administration of
phenobarbitone 20 mg/kg intravenously slowly over 20
minutes. The neurological behavior of the infant should
be closely watched till he or she is able to establish selffeeding.
Figure 3.2.5: Chest compressions with two-finger technique.
Bag and mask ventilation must be continued while providing
chest compressions
is dangerous and should be avoided. The dose of epinephrine may be repeated after 10 minutes. If a baby is
in shock, consider the use of plasma expander (blood,
plasma, saline) in a dose of 10 ml per kg intravenously.
Sodium bicarbonate 1 to 2 ml/kg of 7.5 percent solution
(adequately diluted with equal volume of distilled water
or double volume of 5% dextrose) should be administered intravenously slowly at a rate of 1.0 ml/minute if
effective ventilation is not established even by 10 minutes
or later (Apgar score of less than 7 at 10 minutes).
Early Care of an Asphyxiated Baby
Infants with birth asphyxia should be admitted to the
SCNU for observation and management. A stomach
wash should be done with normal saline and vitamin K
0.5 to 1.0 mg should be given intramuscularly. The infant
should be nursed in a thermoneutral environment.
Intravenous infusion with 10 percent dextrose (without
sodium and potassium) should be started immediately
to prevent any hypoglycemia. Fluid volume should be
restricted to two-thirds because of syndrome of inappropriate antidiuretic hormone (ADH) secretion. Infants
with prolonged birth asphyxia (infants needing bag and
mask ventilation even at 5 minutes) should be given
7.5 percent sodium bicarbonate 1 to 2 ml/kg diluted with
equal volume of distilled water or double volume of
5 percent dextrose slowly to correct any acidosis. Sodium
bicarbonate should be administered only when effective
respirations have been established, otherwise, it will lead
to further accumulation of carbon dioxide in the blood.
Hypovolemic shock should be corrected by the
Prognosis
Early neonatal mortality due to birth asphyxia is higher
in preterm babies, but later neuromotor outcome is often
better in preterm babies as compared to term babies. It is
difficult to prognosticate the future neuromotor outcome
in an individual baby. Most infants with an Apgar score
of 3 or less at 5 minutes do fairly well on follow-up. Term
infants with Apgar of 0 to 3 at 10, 15 and 20 minutes
have mortality rates of 18, 48 and 59 percent respectively;
in survivors the risk of developing cerebral palsy are 5, 9
and 57 percent respectively. Therefore, as a general rule,
a guarded rather than hopeless prognosis should be
communicated to the parents to prevent anxiety.
Relatively adverse outcome is anticipated if 15 minutes
Apgar score is less than 3, cord blood pH of less than 7.0,
hypoglycemia, occurrence of neonatal seizures or
abnormal neurological behavior for more than 7 days
and in infants with acute renal failure. Preterm infants
with evidences of intraventricular or parenchymal
hemorrhage on ultrasound examination of the brain are
likely to manifest neurological handicaps in later life.
BIBLIOGRAPHY
1. Behrman RE, James LS, Klaus M, et al. Treatment of an
asphyxiated newborncurrent opinions and practices
expressed by a panel. J Pediatr 1969;79:981.
2. Cross KW. Resuscitation of asphyxiated infant. Br Med
Bull 1966;22:73.
3. Kattwinkel J. Textbook of Neonatal Resuscitation, 5th ed,
Dallas, American Heart Association, and Elk Grove
Village, Ill, American Academy of Pediatrics 2005.
4. Paul VK, Shankar V, Deorari AK, et al. Tracheal suction
in meconium stained neonates. J Pediatr 1989;144:508.
5. Singh M. Recommendations for creation of a modest level
II neonatal care facilities in India. Indian Pediatr
1992;29:891-94.

6.
Singh M. Care of normal newborn babies: Some practical

points. IAP J Pract Pediatr 1993;1:6-13.
7. Singh M. Monitoring of perinatal asphyxia in the
hospital. Indian J Pediatr 1991;58:51.
8. Svenningsen NW, Blennoh G, Lindroth M, et al. Brain

oriented intensive care treatment in severe neonatal
asphyxia. Arch Dis Child 1982;57:176.
9. Sykes GS, Johnson P, Ashworth F, et al. Do Apgar scores
indicate asphyxia? Lancet 1982;27:494.
3.3 Care of a Normal Newborn Baby

Grades of Neonatal Care
Neonatal morbidity and mortality is directly related
to the birth weight and gestational maturity of the
newborn. High-risk pregnancies (which are associated
with the birth of high-risk infants) must be identified
during antenatal period and referred to an appropriate
center for skilled management. Based upon birth weight
and gestational age, a three tier system of neonatal care
is proposed for the developing countries.
Level I Care
Over 80 percent of newborn babies require minimal care
which can be provided by their mothers under the
supervision of basic health professionals. Neonates
weighing above 2000 g or having a gestational maturity
of 37 weeks or more belong to this category. The care
can be provided at home, primary health center level.
Basic care at birth, provision of warmth, maintenance of
asepsis and promotion of breastfeeding form the
mainstay of level I care.
Level II Care
Infants weighing between 1500 and 2000 g or having a
gestational maturity of 32 to 36 weeks need specialized
neonatal care supervised by trained nurses and
pediatricians. First referral units, district hospitals,
teaching institutions and nursing homes should be
equipped to provide intermediate neonatal care.
Equipment for resuscitation, maintenance of thermoneutral environment, intravenous infusion and gavage
feeding, phototherapy and exchange blood transfusion
should be provided. There should be no compromise on
the basic needs of adequate space, nursing staff and
maintenance of asepsis including provision for dispo-
sable gamma-irradiated suction catheters, feeding tubes,

endotracheal tubes, small-vein infusion sets, etc.
Intermediate neonatal care is needed for about 10 to 15
percent of the newborn population and should be
available at all hospitals catering to 1000 to 1500 deliveries
per year.
Level III Care
Intensive neonatal care is required for babies weighing
less than 1500 g or those born before 32 weeks of
gestation. Apex institutions or regional perinatal centers
equipped with centralized oxygen and suction facilities,
servocontrolled incubators, vital sign and transcutaneous
monitors, ventilators and infusion pumps, etc. are best
suited to provide intensive neonatal care. Skilled nurses
and neonatologists especially trained in the art of
neonatal intensive care are required to organize this
service. About 3 to 5 percent of the newborn population
qualify for intensive care. Establishment of intensive care
neonatal center demands a sound infrastructure and
should be envisaged only when optimal intermediate
neonatal care facilities have already been in existence for
some time. The capital and recurring expenditure for
level III care is exhorbitant, and it is not cost-effective
unless the service is regionalized.
Care at Birth
After having ensured that the baby has established
effective breathing, it is essential that all efforts are made
to prevent the occurrence of hypothermia. The baby
should be promptly dried and effectively covered with
prewarmed clothes. The baby should be placed under a
radiant warmer or any heat source during the procedure
of resuscitation. A sterile disposable delivery kit should
be used for each baby to prevent cross-infection. The eyes
Newborn Care
should be cleaned with sterile normal saline using one
swab for each eye. When prophylaxis against gonococcal
ophthalmia is required, it can be ensured either by
instillation of 1.0 percent silver nitrate drops or 0.5
percent tetracycline or erythromycin ophthalmic
ointment. The umbilical cord should be tied using two
ligatures or rubber band or a disposable clamp. The
clamp or ligature should be applied at least 2 to 3 cm
beyond the base of the cord to avoid inadvertent incision
of gut contained in minor exomphalos. The base and tip
of the umbilical stump should be painted with triple dye
or absolute alcohol. Vitamin K 0.5 to 1.0 mg is administered intramuscularly to all babies weighing less than
2000 g, traumatic deliveries following difficult forceps
or vacuum extraction, preoperatively and to babies
whose mothers had received dicoumarol derivatives,
salicylates, anticonvulsants (phenytoin, phenobarbitone)
and antituberculous agents like isoniazid or isonicotinic
hydrazide (INH) and rifampicin. The baby must have
an identification tag before being transferred out of the
labor room.
Quick but thorough clinical screening is essential to
identify any life-threatening congenital anomalies and
birth injuries. The cut end of the umbilical cord should
be inspected for the number of vessels. Normally, there
are two umbilical arteries and one umbilical vein. The
presence of a single umbilical artery is associated with
internal congenital malformations in 15 to 20 percent of
the cases. The commonly associated malformations
include esophageal atresia, imperforate anus and
genitourinary anomalies. Single palmar crease (simian
crease) has increased association with additional
anomalies including Down syndrome. The face and head
should be closely observed for any asymmetry and
dysmorphic features. If while crying the angle of the
mouth and the mandible are pulled down and infant has
asymmetric crying, it is indicative of hypoplasia of the
depressor anguli oris muscle. This is a useful marker of
associated cardiovascular anomalies and congenital
dislocation of hips. The infant should be examined for
location and patency of all the orifices, because anomalies
are frequently encountered around the orifices. The oral
cavity must be examined to exclude the cleft palate. The
patency of the esophagus should be checked by passing
a stiff rubber catheter into the stomach in the following
situations:
i. Small-for-dates baby
ii. Single umbilical artery
57
iii. Polyhydramnios, and

iv. Excessive drooling of saliva.
If there is no esophageal atresia and the catheter has
reached the stomach, gastric contents should be
aspirated. If gastric aspirate exceeds 20 ml in volume, it
is strongly suggestive of high intestinal obstruction due
to pyloric or duodenal atresia. The anomalies are also
concentrated over the midline areas in the front and back,
e.g. spina bifida, meningomyelocele, pilonidal sinus,
ambiguous genitalia, hypospadias, exomphalos, cleft lip,
cleft palate, etc. The abdomen should be palpated for any
masses and heart examined for its position and any
murmurs. Displacement of the heart towards the right
side in association with respiratory difficulty and
resuscitation problems, is suggestive of either diaphragmatic hernia or pneumothorax on the left side.
Breastfeeding
The milk of different mammals is species-specific and
human milk is most suitable to serve the physiological,
biochemical, immunological and emotional needs of the
baby. The low protein content of human milk is in
accordance with the slow rate of growth of the human
infant. The relatively high concentration of lactose and
galactolipids in breast milk is most suited to enhance the
maturation and myelination of the brain which is highly
evolved in human beings.
The preparation and motivation for breastfeeding
should begin during the antenatal period. Inverted and
cracked nipples must be managed during pregnancy so
that the baby is not faced with any mechanical difficulties
during breastfeeding. The mother is advised to put the
baby to the breast as soon as she has recovered from the
exhaustion of labor. According to baby friendly hospital
initiative guidelines breastfeeding should be started
within half an hour of normal delivery and within four
hours of cesarian section. Most babies can be put to the
breast within (half to) one hour of birth. There is no need
for any prelacteal feeds. During the first two to three days,
relatively small quantity of highly concentrated milk
known as colostrum is produced which is extremely rich
in secretory IgA and proteins. It is most suited to serve
the immediate biological needs of the baby. It is essential
that the baby receives the colostrum, and the prevalent
practice of discarding the colostrum must be condemned.
The mother should be advised to feed the baby every
two to three hours on a demand schedule. During each
Figure 3.3.1: Burping after a feed helps to eructate swallowed air and reduces the risk of regurgitation after feeds
feed, one breast should be completely emptied before

the baby is put to the other breast. The mother should sit
up comfortably and keep the baby's head slightly raised
and supported on her elbow, and she should offer
alternate breasts at each feed. The baby should not be
allowed to merely suck on the nipple, but he or she must
grasp the areola and part of the breast tissue into his or
her mouth.
After each feed the baby should be burped by holding
him/her upright against the shoulder to prevent
regurgitation of the feeds (Fig. 3.3.1). It is preferable to
put the baby in a prone position or right lateral position
with head end slightly raised to prevent regurgitation
due to gastroesophageal reflux. During the first few days,
many babies fall asleep after taking a few sucks of milk.
It is important that the mother actively interacts with
the baby during breastfeeding. Breastfeeding is not a
passive ritual, and the mother must intently look towards
the baby and gently cuddle and fiddle with the baby by
stroking and tickling behind his or her ears or on the
soles so that he or she does not lapse into sleep without
taking adequate feeds. When the mother perceives that
the baby is becoming slow in his or her sucking efforts,
she should try to gently pull her nipple out when baby
will come out of slumber and restart sucking with
renewed vigor. During the first two to three days, when
lactation is not fully established, the mother is often
anxious that her baby is not getting adequate milk. It
must be explained to her that the act of sucking enhances
lactation and whatever little colostrum the baby receives
during the first few days of life is enough to meet the

nutritional needs of a normal baby. It is absolutely
essential that bottle feeding is not instituted at this stage
with the mistaken belief that lactation is inadequate.
Sucking is the best stimulation both for the enhancement
of milk production and for the ejection of milk. The
mother should be relaxed, free from any anxiety and pain
and reassured that her baby is getting enough nutrition.
Within two to three days, this problem is resolved if
proper support and guidance is given to the mother.
During the first four to six weeks, most babies need to be
fed round-the-clock. Subsequently, one late night feed
and another in the early hours of the morning are enough
to satisfy most babies. During the first four months, the
baby should be exclusively breastfed, and there is no need
to give him or her additional water even during summer
months. This policy is the best safeguard against the
occurrence of infective diarrhea in developing countries.
Ten Steps to Successful Breastfeeding
Every facility providing maternity services and care for
newborn infants should:
1. Have a written breastfeeding policy that is routinely
communicated to all health care staff
2. Train all health care staff in skills necessary to
implement this policy
3. Inform all pregnant women about the benefits and
management of breastfeeding
4. Help mothers initiate breastfeeding within half-hour
of birth
5. Show mothers how to breastfeed, and how to
maintain lactation even if they should be separated
from their infants
6. Give newborn infants no food or drink other than
breast milk, unless medically indicated
7. Practise rooming-in to allow mothers and infants
to remain together throughout 24 hours a day
8. Encourage breastfeeding on demand
9. Give no artificial teats or pacifiers (also called
dummies or soothers) to breastfeeding infants
10. Foster the establishment of breastfeeding support
groups and refer mothers to them on discharge from
the hospital or clinic.
Maintenance of Body Temperature
Newborn babies are homeothermic but their thermoregulatory mechanisms are physiologically unsatisfactory.
Newborn Care
They are very prone to develop hypothermia unless
adequate precautions are taken to protect them. The
environmental temperature that may feel relatively
uncomfortable to an adult may impose serious thermal
stress to a newborn baby. The baby must be kept dried
and effectively clothed using a cap and socks. The ritual
of bathing babies at birth must be condemned. The baby
bath should be delayed till the next day when his or her
temperature has stabilized. During winter, the linen and
clothes of the baby should be prewarmed before dressing.
The room should be kept warm in winter with the help
of a heater. The baby should be nursed in close proximity
to the mother so that the baby is kept warm by maternal
warmth. The oil massage is both culturally and
scientifically acceptable as it provides insulation against
heat loss and reduces insensible water loss. The cultural
practice of keeping the mother-baby dyed isolated for
40 days is useful and needs to be promoted. It prevents
exposure of the baby to cold and safeguards against the
occurrence of infections. In summer months, depending
upon the environmental temperature, the baby should
be dressed in loose cotton clothes and kept indoors as
far as possible. Exposure of the baby to direct sunlight
during the hot summer months can lead to serious
hyperthermia.
Skin Care
The baby should be bathed or sponged on the next day
afterbirth using unmedicated soap and lukewarm water.
Special precautions must be taken during bath to prevent
draught and chilling. It is preferable to perform the ritual
of bathing and nursing toilet of each baby by the cotside. This would provide the unique opportunity and
advantage for imparting health education and active
participation of the mother. The routine use of hexachlorophene for skin prophylaxis is not recommended
because of its risk of toxicity to newborn babies. During
an epidemic of staphylococcal infection, hexachlorophene lotion or medicated soap can be used taking care
that the skin is thoroughly rinsed with water after its
application. Dip baths should be avoided till the cord
has fallen. Special attention should be paid to clean the
scalp, skin creases (neck, axillae, groins) and the diaper
area. Vigorous attempts should not be made to scrub off
the vernix caseosa which provides a protective covering
to the delicate skin of the baby. During the winter months,
59
instead of bathing, the baby can be sponged daily to avoid

unnecessary exposure and risk of hypothermia. During
the procedure of bathing or sponging, the nurse should
specifically look for any superficial infections like
pyoderma, umbilical sepsis, conjunctivitis, oral thrush,
etc. and bring them to the notice of the physician.
Handwashing, barrier nursing and storing separate
articles for personal use of each baby in their individual
lockers is desirable to prevent nosocomial infections.
Care of the Umbilical Stump
The umbilical cord is an important portal of entry for
Clostridium tetani in domiciliary midwifery. Health
personnel must be told the importance of using a sterile
disposable dai-kit to prevent the occurrence of tetanus
neonatorum. The cord should be cut with a sterilized
blade. The umbilical stump must be inspected after 2 to
4 hours of clamping. Bleeding may occur at this time due
to shrinkage of cord and loosening of the ligature. The
use of a rubber band or a disposal clamp safeguards
against the hazard. Triple dye or ethyl alcohol should be
applied at the tip and around the base of the umbilical
stump every day to prevent colonization. The cord must
be left open without any dressing. The cord usually falls
after 5 to 10 days, but may take longer if it has been kept
moistened, when it is infected and in immunocompromised babies. The stump should be inspected for any
discharge or infection and kept clean and dry till
complete healing takes place.
Care of the Eyes
The eyes should be cleaned at birth and once every day
using sterile cotton swabs soaked in sterile water or
normal saline. Each eye should be cleaned using a
separate swab by modified crede method (cleaning from
media) to lateral canthus by swab) saline soaked. The
cultural practice of instillation of human colostrum in
the eyes has been found to be useful in reducing the
incidence of sticky eyes. The practice of applying kajal
in the eyes is not recommended because it may transmit
infections like trachoma or may even cause lead
poisoning. If the eyes are sticky, they can either be
managed by frequent cleaning using sterile cotton swabs
soaked in normal saline or by instillation of 10 percent
sulfacetamide eyedrops every two to four hours. Some

neonates may develop persistent epiphora due to
blockage of nasolacrimal duct by epithelial debris. The
mother should be advised to massage the nasolacrimal
duct area (by massaging the outer side of the nose
adjacent to the medial canthus) 5 to 8 times, each time
before she feeds the baby.
Weight Record
Most healthy term babies lose weight during the first 2
to 3 days of life. The weight loss is usually up to 5 to 7
percent of birth weight. The weight remains stationary
during the next one to two days and birth weight is
regained by the end of first week. The factors contributing
to physiological weight loss include removal of vernix
caseosa, mucus and blood from skin, passage of
meconium and reduction of extracellular blood volume.
Delayed feeding and unsatisfactory feeding schedule is
associated with excessive weight loss. There is no need
to monitor early weight changes in a healthy newborn
baby, because it can cause unnecessary anxiety to the
mother and may lead to lactation failure. Babies who are
adequately fed are contented, playful, have good sleep
and are satisfied for at least two to three hours after a
feed. The adequately fed baby passes urine at least 5 to 6
times in a day, while many babies may pass urine (even
stools) after each feed during the first 3 months of life.
The average daily weight gain in term babies is around
30 g, 20 g and 10 g during the first, second, third, fourthmonth periods respectively. Most infants double their
birth weight by 4 to 5 months of age, and triple it by
their first birthday.
Immunization
It is recommended to give the Bacille Calmette-Gurin
(BCG) and a first dose of oral polio vaccine (OPV) as
early as possible preferably within the first week of
life. It should be explained to the mother that the child
must receive all the vaccinations at the proper time
as recommended in the National Immunization
Schedule (Chapter 9, Table 9.1.1). Hepatitis B vaccine
can be administered in 3 doses at birth, 6 weeks and
14 weeks.
Early Identification of Disease

Most mothers do observe their babies carefully and are
often worried by minor physical peculiarities and
problems which are of no serious consequence. She must
be adequately informed and appropriately advised
regarding minor problems to prevent undue anxiety,
concern and worry. The baby-mother dyed should be
approached twice a day to enquire about any feeding
problems, vomiting, bowel disorders and to identify any
problems and relieve the anxiety of the mother regarding
various developmental peculiarities and minor physical
problems which may be bothering her. The onset and
intensity of jaundice should be watched in good natural
daylight. The infant should be closely watched for
following danger signs which should be brought to the
attention of the physician for prompt management:
bleeding from any site, appearance of jaundice within
24 hours of age or yellow staining of palms or soles,
failure to pass meconium within 24 hours or urine within
48 hours, persistent vomiting or diarrhea, poor feeding,
undue lethargy or excessive crying, drooling of saliva or
choking during feeding, respiratory difficulty, apneic
attacks or cyanosis, sudden rise or fall in body temperature, seizures and evidences of superficial infections such
as conjunctivitis, pustules, umbilical sepsis, oral thrush,
etc.
Follow-up
Each baby should be followed up in the well baby clinic
for assessment of growth and development, early diagnosis and management of illnesses and health education
of parents. It is preferable that every baby is seen and
assessed by a health worker at least once every month
for 3 months and subsequently 3 monthly till 1 year of
age.
BIBLIOGRAPHY
1. Davies PA, Robinson RJ, Scopes JW et al: Routine care of
the normal term baby. Medical Care of Newborn Babies
1972;44/45:73.
2. Singh M. Care of the normal baby, Care of the Newborn
(4th edn) Sagar Publications, New Delhi; 1991.
3. Singh M. Care of normal newborn babiessome practical
points. IAP J Pract Pediatr 1993;1:6-13.
Newborn Care
61
3.4 Common Developmental and Physiological

Problems in Newborn Babies
Most mothers observe their babies carefully and are often
worried by minor physical or physiological peculiarities
which are of no consequence. It is important that her
complaints are listened to carefully, and they are not
ignored lightly without doing proper evaluation of the
baby. She must be given reassurance and advice
regarding the minor problems and difficulties that may
be bothering her. Adequate explanation and reassurance
is necessary to allay her anxiety which may lead to lactation failure.
Regurgitation of Feeds and Vomiting
Most normal newborn infants regurgitate some amount
of milk soon after feeds. Babies swallow air (aerophagy)
while sucking and as the air is expelled, part of the feed,
looking like curd, also comes out. Unlike vomiting, the
expulsion of stomach contents is without force and
nonprojectile. All mothers must be given proper advice
regarding the technique of feeding and burping after each
feed. The baby must be held upright against the shoulder
or made to sit up in the lap for at least 5 to 10 minutes to
eructate the air swallowed during the feeding before he
or she is put back to the cot. Most babies enjoy being
placed in the prone position which is associated with
less risk of regurgitation, and it relieves abdominal
distention and colic. When vomiting is persistent,
projectile or bile-stained and associated with failure to
pass meconium during the first 24 hours and/or abdominal distention, the baby should be investigated for
intestinal obstruction.
Bowel Disorders
The baby may pass meconium in utero or soon afterbirth,
but all healthy newborn babies must evacuate within 24
hours of birth. During the first two to three days, the
baby passes black, tarry meconium stools which is
followed by greenish (transitional) stools for the next one
or two days. The breastfed baby usually passes 4 to 8
semisolid sticky golden-yellow stools everyday. Some
babies may pass stools after each feed due to the

exaggerated gastrocolic reflex. The stools are often very
small (at times like droppings of the birds) with normal
consistency. The babies continue to gain weight. The
family should be reassured and advised against any
medication as this physiological problem will settle in
due course of time. The breastfed babies may develop
increased frequency of stools if the mother is taking
ampicillin, cephalexin and certain laxatives. Milk of
magnesia, bulk laxatives and a glycerine suppository are
safe for a nursing mother. The administration of glucose
water or honey to the baby may cause osmotic diarrhea
and can lead to infective gastroenteritis due to contamination. When the baby is exclusively breastfed, he or she
is unlikely to develop infective diarrhea. A sudden
change in the baby's established bowel pattern leading
to greater frequency and change in the character of stools
should be taken seriously. Infective diarrhea occurs in
top-fed babies. The stools are often watery with mucus
and plenty of pus cells. Neonatal diarrhea may also occur
in association with septicemia, necrotizing enterocolitis
(NEC), Hirschsprung's disease and phototherapy.
Maternal drug addiction, congenital thyrotoxicosis and
metabolic disorders, such as the salt-losing variety of
congenital adrenal hyperplasia and disaccharidase and
enterokinase deficiency are rare causes of diarrhea in
neonates.
Babies fed on cow's milk are often constipated due to
hard casein curds. Constipation may also occur due to
inadequate feeding or gastrointestinal obstruction.
Infants with congenital hypothyroidism, Hirschsprung's
disease and anal stenosis are often constipated. Mild
constipation in the absence of any underlying disease
process often needs no treatment. Insertion of a glycerine
suppository is often followed by a motion if constipation
is significant. At times offering sugar water, honey or
orange juice for a day or so may be advised. For infants
who are on top-milk, addition of sugar to the feed will
often take care of the problem. The use of laxatives should
be avoided in newborn babies.

Delayed Passage of Urine
Most newborn babies pass urine during the first day of
life, but all must void within first 48 hours of birth. If a
baby has not passed urine by 48 hours, he or she should
be examined to rule out renal agenesis and obstructive
uropathy. However, the most common cause of the
alleged nonpassage of the urine is that the baby has
actually passed urine but it has been overlooked by the
mother. The normal frequency of micturition in a
newborn baby varies between (5-10 times per day). Some
babies may cry before passing urine due to discomfort
of a full bladder, they become quiet and dazed while
passing urine and start crying again after having passed
urine due to wet napkins. This should not be considered
as an evidence of urinary tract infection or obstructive
uropathy. The narrow stream of urine, straining and
crying during the act of micturition, dribbling in the end
and presence of palpable urinary bladder or enlarged
kidneys are suggestive of obstructive uropathy.
Physiological Jaundice
About 60 to 70 percent of newborn babies develop
jaundice on the second or third day of life. The icterus is
detectable on the face and the trunk, sparing the palms
and the soles. The serum bilirubin level does not cross
15 mg/dl. Jaundice disappears within 7 to 10 days.
Physiological jaundice does not need any treatment, and
the mother should be reassured that it will disappear
spontaneously. It is not indicative of any infection and
does not require administration of extra water. The
occurrence of jaundice within the first 24 hours of life or
when it is deep and intensely staining the trunk, causing
yellow discoloration of the palms and the soles or if it
persists beyond 2 weeks need investigations and
management.
Jitteriness
Many normal babies are jittery or tremulous on touch
and handling. They are easily startled by loud noise or
rough handling. When jitteriness is excessive and persists
even during feeding, it is important to exclude hypoglycemia and hypocalcemia.
Superficial Infections
Sticky red eyes or purulent conjunctivitis are common
during the newborn period. Gonococcal ophthalmia
should be suspected if there is history of gonorrhea in

the mother or conjunctivitis characterized by abundant
purulent discharge and chemosis of eyelids. It should be
confirmed by microscopic examination of a Gram stained
preparation of purulent discharge. It is best treated by
parenteral and topical administration of crystalline
penicillin and frequent cleaning of eyes. Nongonococcal
purulent conjunctivitis is usually caused by staphylococci, but other pathogens may be responsible
depending upon the microbial ecology of the environment. It is best treated with local instillation of
chloramphenicol or gentamicin eyedrops hourly. After
24 hours intervals between local medications can be
gradually increased. The chlamydial conjunctivitis
characteristically manifests as purulent blenorrhea, often
unilateral, during the second week of life. It is managed
by oral erythromycin therapy (40 mg per kg per day, in
four divided doses) for 2 weeks. In addition, topical
instillation of 10 percent sulfacetamide eyedrops or 0.5
percent erythromycin ophthalmic ointment should be
advised. The eyes should be cleansed with sterile wet
cotton swabs prior to the instillation of eyedrops by using
one swab for each eye.
Pyoderma
Pyoderma manifests as multiple pustules especially over
the scalp, neck, axillae and groins. The infection is usually
transmitted by the hands of personnel and is caused by
staphylococci. The large pustules can be punctured with
a sterile needle to drain the pus. The skin should be
washed with soap and water. The skin lesions should be
painted with triple dye or an antibiotic cream two to three
times a day. When despite this therapy the skin lesions
are increasing in size or number, oral administration of
erythromycin or cloxacillin is recommended. Close
observation for signs of septicemia should be maintained.
Umbilical Sepsis
Umbilical sepsis manifests as redness and edema at the
base of the cord and a foul smelling purulent discharge.
The presence of mucoid discharge on the stump and even
isolation of bacteria are not indicative of umbilical sepsis
unless there are clinical evidences of periumbilical
inflammation or there are pus cells in the exudate. The
umbilical stump should be cleaned with spirit and treated
with local application of triple dye or antibiotic lotion. If
periumbilical inflammation is spreading or the infant is
Newborn Care
showing evidences of systemic spread of infection as
evidenced by fever, lethargy, poor feedings, etc. he or
she should be managed with parenteral antibiotics as in
a case of neonatal septicemia.
Oral Thrush
Oral thrush manifests as white patches with erythematous margins distributed over the tongue and buccal
mucosa. Unlike milk curds, the patches of thrush are
adherent and they often bleed when attempts are made
to remove them. Local application of 0.5 percent aqueous
solution of gentian violent or nystatin or ketoconazole
after each feed is followed by prompt recovery. The
mother should be examined for vaginal and mammary
candidiasis and given appropriate treatment.
Dehydration Fever
During the summer months, when the environmental
temperature approaches 40oC, some healthy newborn
babies may develop transitory fever during the second
or third day of life. The fever is usually moderate in
intensity (up to 38.5oC) and the child is active and keen
to feed. The condition is transient and is best managed
by lowering the environmental temperature. Once the
lactation is established and adequate feeding is ensured,
the infant becomes afebrile.
Excessive Crying
During the first few weeks most newborn babies sleep
during the day and they are awake, playful and
troublesome during the night. This behavior is probably
due to continuation of their in utero pattern of activity.
During pregnancy when the mother is up and about
during daytime, the baby is rocked in the pool of amniotic
fluid and sleeps. During the night when mother is resting,
the fetus is active and playful. Moreover, during the
solitude of night even the normal cry of a baby sounds
too loud and disturbing, both to the mother and the
neighbors. This pattern of activity or behavior spontaneously disappears after 4 to 6 weeks of age. Most babies
usually cry when they are either hungry or are having
discomfort. The cry may be a signal of unpleasant
sensation of a full bladder before passing urine, painful
evacuation of hard stools or discomfort of wet napkins.
At times insect bites, nose block and inapparent trauma
are the reasons for cry. The experienced mother and
physician are able to differentiate between the cry used
as a signal for feed and the cry of discomfort. An infant
63
with abdominal colic would have audible gurgling

sounds in the abdomen and usually feels comfortable
when placed in a prone position which facilitates the
expulsion of gas. The presence of excessive inconsolable
crying or a high-pitched cry is always indicative of
serious disorder like meningitis or a painful inflammatory condition.
Excessive Sleepiness
During the first few days of life, many infants keep their
eyes closed most of the time, and they readily go to sleep
after taking only a few sucks at the breast. This excessive
sleepiness may be aggravated by heavy maternal
sedation during labor. Barbiturates and opium derivatives when taken by the nursing mother may cause
sleepiness in her suckling infant. Infants with Down
syndrome and hypothyroidism are often lazy and lack
activity due to generalized hypotonia. The sudden
appearance of lethargy or lack of interest in feeding, in a
baby who had been feeding adequately in the past, is
often ominous and may be the only manifestation of a
serious illness like septicemia or a metabolic disorder.
Cephalhematoma
It is a subperiosteal collection of blood secondary to injury
during vaginal delivery. It may occur both following an
obstructed or a precipitate delivery. The swelling is not
present at birth and it manifests after a couple of hours
when sufficient amount of blood has extravasated. It is
characterized by a fluctuant swelling which is limited
by suture lines. It gradually resolves over a period of
several days or weeks depending upon the size of the
swelling. Incision or aspiration is contraindicated unless
it gets infected or is associated with critical hyperbilirubinemia.
Cephalhematoma should be differentiated from
caput succedaneum which manifests as a boggy, pitting
edema of the scalp on the presenting part. It is a nonfluctuant swelling and is not limited by the suture lines.
The caput succedaneum is present right at birth and
rapidly disappears during the next 24 to 48 hours.
Umbilical Granuloma
It manifests as a slightly red flesh-like nodule at the base
of the umbilical cord with persistent nonpurulent
discharge after the cord has fallen. This can be managed
by cautery with silver nitrate or application of common
salt for 2 to 3 days.

Napkin Rash
Vaginal Bleeding
The perineal skin may become red, indurated and excoriated due to ammoniacal dermatitis if the infant is not
promptly cleaned and dried after the passage of urine or
stools. Occurrence of diarrhea and the use of nylon or
watertight plastic napkins aggravate the condition. The
bottom should be kept dried and exposed to air or
sunlight. Application of coconut oil or a bland ointment
is promptly followed by recovery. The causative factors
should be identified and eliminated. In resistant cases,
infection of the skin by Candida albicans should be ruled
out and appropriately managed with a topical lotion.
About 20 to 25 percent female babies may develop

menstruation like withdrawal vaginal bleeding after 4
to 5 days of birth. The bleeding is usually mild and lasts
for 2 to 4 days. It does not need any specific therapy apart
from local aseptic cleaning of genitals.
Sneezing and Nose Block

Sneezing is common in healthy newborn babies due to
irritation of the nose by amniotic fluid, meconium, blood,
or debris, etc. It should not be considered as a sign of a
common cold. The nostrils should be cleaned with sterile
cotton buds if sneezing is excessive.
Nose block is another common problem. Often there
is no obvious nasal discharge. The infant may be in
discomfort because he or she is an obligatory nose
breather. Severe nose block may even cause respiratory
distress. Nose block is managed by instilling one or two
drops of normal saline into the nostrils 15 minutes before
feeds. Medicated nasal drops are contraindicated in
neonates.
Mucoid Vaginal Secretions

Most female babies have copious grayish white slimy
mucoid vaginal secretions due to female sex hormones.
This should not be confused with purulent vaginal
discharge.
Minor Developmental Peculiarities
Toxic Erythema (Urticaria Neonatorum)
About one-third healthy term newborn babies may
develop an erythematous rash with a central pale papule
on the second or third day of life. The rash usually starts
on the face and spreads to the trunk and extremities in
about 24 hours. The rash disappears spontaneously after
two to three days without any specific treatment. The
exact cause is not known, but it is considered as an early
marker of atopy. The scrappings from the skin lesions
often show increased number of eosinophils. The rash
should be differentiated from pyoderma and skin lesions
of congenital syphilis.
Hiccups
Tongue Tie
Most newborn babies develop hiccups especially after

the feeds. This is normal. The distention of stomach
causes irritation of the diaphragm which leads to hiccups.
They do not indicate any disease process in a newborn
baby, and the mother should be reassured regarding the
benign nature of the hiccups.
A thin frenulum under the tongue is normal and does

not need any treatment. A thick and tight fibrous
frenulum producing a notch at the tip of the tongue is
abnormal and may have to be snipped at the age of three
months. Tongue-tie seldom interferes with sucking or
speech development of the child.
Disorders due to Transplacental

Passage of Hormones
Nonretractable Prepuce
Term babies of both sexes may develop engorgement of

the breasts on the third or fourth day due to effect of
transplacentally transferred progesterone and estrogens.
The hypertrophy of the breast may last for a few days to
several weeks, but it disappears spontaneously. Local
massage, fomentation and temptation to express the milk
may lead to complications.
The prepuce is normally nonretractable in all male

newborn babies, and it should not be diagnosed as
phimosis. The mother should be advised against forcible retraction of the foreskin.
Mongolian Blue Spots
Almost all newborn babies of African and Asian origin
have irregular blue patches of skin pigmentation espe-
Newborn Care
65
cially over the sacral area and buttocks. These patches

have no relationship with Down syndrome, and they
invariably disappear by the age of 6 to 18 months.
date babies. Dryness of skin occurs due to the paucity of

amniotic fluid. Application of an emollient cream or oil
provides relief.
Congenital Teeth
Subconjunctival Hemorrhage
Some newborn babies may be born with one or two lower

incisor teeth. They do not interfere with feeding, but
cause considerable anxiety among the parents and
relatives due to the mistaken cultural belief that they are
a bad omen. The loose teeth may be extracted as a
safeguard against the risk of aspiration.
In some babies semilunar spots of subconjunctival

hemorrhage may be seen over the outer canthus of the
eye. They are seen in babies born by vaginal delivery
following vertex presentation. The hemorrhage gets
resorbed after a few days.
Milia
The spear-shaped xiphisternal cartilage may stand out

prominently in some babies, and it is not indicative of
any disease process.
Yellow white pinhead-sized papules on the nose are seen

in practically all babies. They occur due to the retention
of sebum and disappear spontaneously.
Prominent Xiphisternum
BIBLIOGRAPHY
1.
Excessive Scales and Peeling of Skin

Dry scaly skin with peeling and increased transverse skin
creases is seen in post-term and some term small-for-
Singh M. Common neonatal problems and their

management. Indian Practitioner 1970;23:65.
2. Singh M, Krishnamoorthy KS, Sinclair S, et al. Some
developmental characteristics in the newborn. Indian
Pediatr 1970;7:378.
3.5 Management of Low Birth Weight Babies

Vinod K Paul, Ashok K Deorari, Meharban Singh
INTRODUCTION
The average birth weight of a newborn baby in our
country is around 2800 to 3000 g. A neonate who weighs
less than 2500 g at birth is a low birth weight baby (LBW).
In India, over 30 percent infants are born LBW.
Nearly 80 percent of neonatal deaths and 50 percent
of infant deaths occur among the LBW neonates. Even
after recovering from neonatal complications, some LBW
babies are prone to develop malnutrition, recurrent
infections, and neurodevelopmental handicaps. There is
emerging evidence that LBW or growth-retarded
neonates are more prone to manifest diabetes mellitus,
hypertension and coronary artery disease in later life.
Therefore, LBW is a key risk factor for adverse outcome
in life.
The newborn baby may be LBW because of prematurity or intrauterine growth retardation (IUGR). A baby
born before 37 weeks of gestation is called a preterm baby.
Fetal size and weight are directly linked to gestation.

Therefore, it is obvious that if the delivery takes place
prematurely, the baby is likely to be small. Approximately one-third of LBW neonates in our country are
preterm. The second situation that leads to LBW is IUGR.
The gestation may be full term or preterm, but the baby
is undernourished, undersized and, therefore, LBW. Such
a baby is also called a small-for-date (SFD) baby. Twothirds of our LBW neonates fall in this category. At times,
an LBW neonate may be both preterm as well as SFD.
Etiology
Poor nutritional status of the mother and frequent
pregnancies are the major causes of IUGR. Mothers with
a weight of less than 40 kg and a height of less than
145 cm often give birth to SFD babies. Insufficient
nutritional intake during pregnancy also has an adverse
effect on fetal growth. Maternal hypertension,

preeclampsia, postmaturity, frequent pregnancies,
multiple pregnancy, anemia, malaria and tobacco use are
other causes of IUGR. Chronic maternal diseases of heart,
kidneys, lungs or liver may also lead to IUGR.
Preterm labor occurs in teenage mothers and in the
setting of low maternal weight, cervical incompetence,
antepartum hemorrhage, previous fetal loss, previous
preterm delivery. Sometimes, preterm labor is medically
induced for the sake of the baby as in the case of Rhisoimmunization or maternal diabetes mellitus. The
cause of a majority of preterm deliveries, however,
remains unknown.
How to recognize Two Types of LBW Neonates?
It is desirable and of practical relevance to make clinical
distinction between the two types of LBW babies. A
preterm baby is diagnosed on the basis of the period of
gestation calculated from the last menstrual cycle of the
mother. If it is less than 37 completed weeks, the baby is
designated as preterm. Preterm babies also have distinct
physical and neurological features which help in their
recognition. The deep skin creases over the soles are
present only over the anterior one-third. The external ear
or the pinna is soft and devoid of cartilage, and it does
not recoil back promptly on being folded. In males, the
scrotum does not have rugae and testes may not be
descended into the scrotum. In female infants, the labia
are widely separated and do not cover the labia minora,
resulting in the prominent appearance of the clitoris. The
back of the preterm babies has abundant growth of fine
hair called lanugo.
Small-for-dates neonates have an emaciated look and
loose folds of skin because of lack of subcutaneous tissue.
These are particularly prominent over the buttocks and
the thighs. They look alert and often plethoric. In SFD
babies, the head circumference exceeds the chest
circumference by more than 3 cm. The SFD babies are
often full term or borderline term in gestation. When their
birth weight is plotted on the intrauterine growth chart,
it falls below the tenth centile.
Problems of LBW Neonates
Preterm Babies
The basic underlying feature of the preterm LBW infant
is immaturity of their organ systems. They may not
establish respiration satisfactorily at birth and develop
asphyxia necessitating expert resuscitation. All newborn
babies keep themselves warm by active metabolism in

the brown fat. The preterm babies lack adequate stores
of brown fat and are, therefore, vulnerable to become
hypothermic at the usual ambient temperatures unless
specific measures are taken to keep them warm. Preterm
neonates less than 34 weeks of gestation do not have
coordinated sucking and swallowing movements.
Therefore, they are unable to suck at the breast and are
liable to get choked. Preterm infants, especially those less
than 30 weeks of gestation may not tolerate enteral feeds
initially because of immaturity of gut. Infants born before
34 weeks of gestation have immature lungs which do
not expand well afterbirth and are, therefore, unable to
perform the function of gas exchange. They develop
respiratory distress syndrome (RDS) characterized by
rapid and labored respirations, indrawing of the chest,
grunting and cyanosis. Because of the immature respiratory control mechanisms, these babies also have a
tendency to manifest apneic spells. These infants have
immature vascular beds around the cerebral ventricles.
The delicate vessels may rupture and cause intraventricular hemorrhage (IVH). Immature metabolic pathways
of preterm infants predispose them to the development
hypoglycemia, metabolic acidosis, and hyperbilirubinemia. Infection is another major problem among
preterm babies and indeed an important cause of
mortality. These babies do not have efficient humoral,
cellular and mucosal immune mechanisms to protect
themselves against infections. Besides, interventions such
as needle pricks and intravenous lines, especially in the
setting of a contaminated environment, predispose them
to develop potentially fatal bacterial infections. Preterm
infants may develop blindness due to retinopathy of prematurity (ROP) as a result of hyperoxia due to unmonitored oxygen therapy.
Small-for-date (SFD) Babies
The neonatal complications in SFD babies occur due to
in utero undernutrition and hypoxia. The stress of labor
may lead to fetal distress, meconium passage in utero and
birth asphyxia. Respiratory distress may occur due to
meconium aspiration syndrome. Due to chronic fetal
malnutrition, they also lack adequate brown fat stores.
This predisposes them to develop hypothermia. They are
also prone to develop hypoglycemia because of
insufficient glycogen stores. Like preterm babies, they
are also vulnerable to develop neonatal sepsis. SFD
infants are more likely to have congenital malformations
as compared to their normal counterparts.
Newborn Care
Management
Delivery of LBW Babies
Ideally, the delivery of an anticipated LBW baby should
be conducted in a hospital. Premature labor as well as
IUGR are indications for referral of the pregnant mother
to a center with well-equipped facilities. The in utero
transfer of a low weight fetus is far more desirable, convenient and safe than the transport of a LBW baby
afterbirth. Delivery should be conducted by trained
health professionals, at least one of them should be wellversed with the art of neonatal resuscitation. Resuscitation equipment like suction catheters, bag and mask,
oxygen cylinder, laryngoscope, etc. should be kept ready
beforehand. Baby must be provided warmth from a heat
source like a heater, or a lamp with 200 W bulb to prevent
hypothermia.
The Place of Care
An LBW newborn with a birth weight of 1800 g or above,
or a gestation of 34 weeks or more can be managed at
home by the mother and the family under the supervision
of a health worker or a family physician. The following
infants should be hospitalized for care:
i. birth weight of less than 1800 g
ii. gestation of less than 34 weeks
iii. neonate who is not able to take feeds from the breast
or by katori-spoon (irrespective of birth weight and
gestation)
iv. a sick neonate (irrespective of the birth weight or
gestation).
Keeping the LBW Babies Warm
Provision of warmth to prevent hypothermia is one of
the cardinal principles of newborn care. A baby under
cold stress wastes energy and oxygen in trying to maintain temperature. Hypothermia can lead to hypoglycemia, bleeding diathesis, pulmonary hemorrhage,
acidosis, apnea, respiratory failure, shock and even death.
All this is entirely preventable through the following
simple measures.
First and foremost, the mother herself is a source of
warmth for the baby. It is of immense help to nurse the
baby next to the mother, in between the breasts over the
chest, in Kangaroo positioin, day and night. Further, the
room where an LBW baby is nursed should be kept warm
(temperature between 28oC to 30oC in all weathers). This
67
temperature is slightly uncomfortable for adults, but this

discomfort should be accepted for the sake of the baby.
While in summer months no extra effort is required to
maintain this temperature, in winter a room heater or
any other warming device may have to be used. The baby
should be clothed well. Two or three layers of clothes
are generally required. If the room is not warm enough,
woollen sweater should also be put on. Feet should be
covered with socks, hands with mittens and head with a
cap. Besides, a blanket should be used to cover the baby.
The temperature regulation of the baby is satisfactory
when the trunk feels warm to touch, while the soles and
the palms are pink and warm. In early stages of
hypothermia, the trunk is warm, but the soles and palms
are cold to touch. This is not normal and baby requires
additional warmth immediately to prevent cold stress
and its adverse consequences.
In the hospital apart from the above methods,
overhead radiant warmer or incubator may be used to
keep the baby warm. Regular monitoring of axillary or
skin temperature with a low-reading thermometer (30oC40oC) should be carried out in all the hospitalized babies.
Nutrition and Fluids
Birth weight, gestation, presence or absence of sickness
and individual feeding effort of the baby determine the
decision as to how a LBW neonate be provided with
fluids and nutrition (Table 3.5.1). Ultimate goal is to meet
both these needs from direct and exclusive breastfeeding.
Neonates weighing less than 1200 g or a gestation of
less than 30 weeks, or those having sickness should
receive IV fluids initially. Enteral feeds should be introduced gradually by gavage as the babys acute problems
begin to settle. In due course, the baby is shifted to katorispoon feeds, and then the direct breastfeeds.
Infants weighing 1200 to 1800 g (or 3034 weeks
gestation) and not having any significant illness should
be put on gavage feeds initially. In a couple of days, it
should be possible to shift them to katori-spoon feeds, and
then gradually to breastfeeds.
In order to promote lactation and enable the baby to
learn sucking, all babies on gavage or katori-spoon feeds
should be put on the breast before each feed for 5 to 10
minutes. With improvement in their overall condition,
the infants would start meeting a part and, later on all of
their nutritional needs from direct breastfeeding. Breast
milk is the best milk for a LBW baby.

TABLE 3.5.1: Guidelines for the modes to provide fluids and
nutrients to LBW babies
Age
Birth weight
Gestation
Initial
After 13 days
Categories of neonates
<1200 gm
<30 weeks
1200-1800
30-34 weeks
Intravenous
fluids. Try
gavage feeds
if not sick
Gavage
Gavage
Katori-spoon
>1800
> 34 weeks
Breastfeeding.
If unsatisfactory give
katori-spoon
feeds
Breast
Later (24 weeks) Katori-spoon
Breast
Breast
After some more

time (46 weeks)
Breast
Breast
Breast
Note:
1. For gavage and katori-spoon feeds, use expressed breast
milk only. Start with small volume, and gradually buildup.
2. When the baby is on gavage or katori-spoon feeds, it is
important that he is put on the breast before every feed.
Although the baby may not obtain much milk, it will help
promote lactation and enable the baby to learn how to
suck.
3. When shifting a baby from one mode of feeding to
another, be very careful. Introduce the new mode for only
some of the feeds to begin with and then build-up
gradually.
4. The feeding of every baby should be individualized. The
above recommendations should only serve as broad
guidelines.
Most LBW babies weighing more than 1800 g or over

34 weeks of gestation are able to feed directly from the
breast. However, some of them may not be able to do so
satisfactorily during the first few days of life. During this
period, the feeds may be provided with a katori-spoon.
Breast milk is the ideal food for a LBW baby. It is
well to remember that the breast milk of the mother of
the LBW baby contains appropriately higher content of
protein and calories and is uniquely suited to provide
near optimum nutrition to her LBW baby. The milk is
thus not only species specific, it is baby specific. If lactation is inadequate in spite of best efforts, the baby should
be carefully evaluated for supplementary feeding with
top milk. Feeding with a substitute milk other than breast
milk should be reserved essentially for the hospitalized
babies and resorted to for the minimum necessary period
until breast milk feeding can be ensured. Any formula

providing (per dl) about 2 g protein (whey-dominant),
4.0 g fat (containing polyunsaturated fatty acids and
medium chain triglycerides), and 10 to 12 g of carbohydrate (as lactose and maltodextrins) and 70 to 80
kilocalories is quite suitable. If it is not possible to afford
a formula milk, any milk obtained for household use may
be fed to the baby without dilution.
It is emphasized that the decision to feed a substitute
milk other than breast milk is a very major decision and
must not be taken lightly. Only when all avenues for
obtaining breast milk are exhausted, should one resort
to this choice as an interim and unavoidable choice.
Amount and Frequency of Enteral Feeds
For infants on gavage or katori-spoon feeds, total daily
requirements can be estimated from the table on the fluid
requirements (Table 3.5.2). In a stable, growing LBW baby
daily intake of feeds should be gradually built up to 180
to 200 ml/kg. LBW babies should be fed every 2 hours
starting at 2 hours of age. Two hourly feeds are also
applicable to LBW receiving direct breastfeeding. LBW
babies may take longer on the breast as compared to their
normal weight counterparts.
TABLE 3.5.2: Fluid requirements of neonates
(ml per kg body weight)
Day of life
Birth weight
>1500 g
1000 to 1500 g
<1000 g
60
80
100
75
95
115
90
110
130
105
125
145
120
140
160
135
155
175
7 onwards
150
170
190
Note:
1. On the first day the fluid requirements range from 60 to
100 ml/kg, (the difference between the three categories
being 20 ml/kg each).
2. The daily increment in all groups is around 15 ml per kg till
day 7.
3. Extra 20 to 30 ml/kg fluid should be added for infants
nursed under a radiant warmer. For those receiving
phototherapy add extra 10 to 15 ml/kg fluid.
4. These are general guidelines, fluid therapy of every baby
should be individualized.
Newborn Care
Technique of Feeding
Gavage feeds For gavage feeding, Fr 5 polythene feeding
catheter is used for nasogastric or orogastric placement.
For nasogastric insertion, the catheter is measured from
the external nares to the tragus of the ear, and from there
to the ansiform cartilage, and marked. This length of the
tube should be inserted through the nose. For the
orogastric catheter the distance between angle of the
mouth to tragus and then to the ansiform cartilage is used
for insertion. During nasogastric or orogastric insertion,
the head is slightly raised and a wet (not lubricated)
catheter is gently passed through the nose (nasogastric)
or mouth (orogastric) down through the esophagus to
the stomach. Its position is verified by aspirating the
gastric contents, and by injecting air and auscultating
over the epigastric region. At the time of feeding, the
outer end of the tube is attached to a 10 or 20 ml syringe
(without plunger) and milk is allowed to trickle by
gravity. At the end, about 2 ml of sterile water should be
injected to rinse the tube. The baby should be placed in
the right lateral position for 15 to 20 minutes to avoid
regurgitation. There is no need to burp a gavage-fed baby.
The polythene nasogastric or orogastric tube may be
inserted before every feed or left in situ for 2 to 3 days.
While pulling out a feeding tube, it must be kept pinched
and pulled out gently while applying constant negative
pressure with a syringe to avoid trickling of gastric
contents into the trachea.
Gavage feeding may be risky in very small babies.
They have a small capacity of stomach and the gut may
not be ready to tolerate feeds. Stasis may also result from
paralytic ileus due to autonomic immaturity. Thus,
gavage-fed preterm babies are candidates for regurgitation, aspiration and necrotizing enterocolitis (NEC).
Before every feed, the abdominal girth (just above the
umbilical stump) should be measured. If the abdominal
girth increases by more than 2 cm from the baseline, the
baby should be evaluated carefully for any illness. The
enteral feeds may have to be suspended till the
abdominal distention improves.
Katori-spoon feeds Feeding with a spoon (or a similar
device such as paladai') and katori (or any other receptacle such as a cup) has been found to be safe in LBW
babies. This mode of feeding is a bridge between gavage
feeding and direct breastfeeding. It is based on the
premise that neonates with a gestation of 30 to 32 weeks
or more are in a position to swallow the feeds satis-
69
factorily even though they may not have coordinated

sucking efforts. The required amount of expressed breast
milk is taken in a katori. The baby is placed in a semiupright posture with a napkin around the neck to mop
up the spillage. The spoon is filled with milk, a little short
of the brim, placed at the lips of the baby in the corner of
mouth. The baby will actively swallow the milk. The
process is repeated till the required amount has been fed.
With paladai the tapering snout is placed at the angle of
the mouth and milk is allowed to be trickled gradually
as the baby swallows it.
If the baby does not actively accept and swallow the
feed, try to arouse the baby with a gentle stimulation. If
he or she is still sluggish, do not insist on this method. It
is better to switch back to gavage feeds till the baby is
better prepared.
Breastfeeding The method of breastfeeding is essentially
the same as for the normal weight babies. LBW babies
may be slow in sucking and take longer time to feed.
Assessment of Adequacy of Nutrition
The key measure of optimal feeding is the weight pattern
of the baby. A LBW baby loses up to 1 to 2 percent weight
everyday amounting to 10 to 15 percent cumulative
weight loss during the first week of life. Birth weight is
regained between 10th and 14th day. All babies start
gaining weight by the second week of life at a rate of
about 15 to 20 g per day (12% of birth weight). It is
important to note that the SFD-LBW babies who are
otherwise healthy should not have any appreciable
weight loss at all, and they should start gaining weight
early. It is desirable to weigh all LBW babies at the
postnatal age of 2 weeks (to check regaining of the birth
weight), 4 weeks (to ascertain a weight gain of at least
200300 g) and then every month. Hospitalized LBW
babies should be weighed everyday on an accurate
weighing scale.
Excessive weight loss, delay in regaining birth weight
and poor weight gain are suggestive of inadequate
feeding, cold stress, excessive insensible water loss or
systemic illness (like anemia, sepsis, late metabolic
acidosis, etc.).
Nutritional Supplements
All LBW babies should receive intramuscular vitamin K
1.0 mg at birth. Vitamin A and D are required in doses of
1000 IU and 400 IU everyday, respectively, from 2 weeks

of age. At 8 weeks of age, iron supplements should be
started in a dose of 2 mg/kg/day. Very low birth babies
(<1500 g, <32-wk gestation) need vitamin E, calcium and
phosphorus supplementation till 37 weeks.
written note covering the antenatal, intranatal and

neonatal details along with the baby.
Prognosis
The cornerstone of care of the newborn infants, more so

for the LBW babies, is anticipation and early detection
of complications. This is achieved by careful monitoring
of the babies. Clinical monitoring is the most important
and practical method. It involves periodic evaluation for
signs of illness. These include lethargy, refusal to feed,
hypothermia, respiratory distress, grunt, apnea,
abnormal weight gain pattern, jaundice over soles and
palms, abdominal distention, feed intolerance, cyanosis,
pallor, sclerema, seizures and bleeding. A baby who
shows anyone or more of the above signs/symptoms
should be immediately referred for hospitalization for
prompt management of the specific complications by a
neonatologist.
Mortality of LBW babies is inversely related to the

gestation and birth weight, and directly to the severity
of illness and complications. Because of functional
immaturity of various body organs, the preterm babies
do rather poorly than the corresponding weight SFD
babies in the immediate neonatal period. Adequacy of
management at birth also makes a major difference. The
LBW who experiences significant birth asphyxia or
develops hypothermia soon afterbirth is seriously
compromised, no matter what heroic measures are instituted later on.
Long-term outcome of LBW infant depends upon gestation, birth weight and nature and severity of complications. In general, over 90 percent of LBW babies who
survive the newborn period have no neurodevelopmental handicaps. Optimal and effective care of the LBW
neonates is thus a highly rewarding experience.
Vaccination of LBW Babies
BIBLIOGRAPHY
Early Detection of Sickness and

Management of Complications
If the LBW baby is not sick, the vaccination schedule is

the same as for the normal babies. BCG, OPV and HBV
should be given at the time of discharge.
1.
Transport of a Sick LBW Baby
3.
It is essential to provide warmth during transport to

prevent cold injury. The baby should be clothed and
placed in a prewarmed basket or box, but a transport
incubator is ideal. Hot water rubber bottles may be used
as heat source. However, make sure to cap them tightly
and wrap 2 layers of towel to avoid direct contact with
the baby. Mother of the baby should also be transferred
to the hospital along with the baby as far as possible.
This will allay her anxiety and ensure breast milk feeding
of the baby. Placing the baby next to mother's body
during transport will provide the necessary warmth to
the child during the journey.
The infant should be stabilized before transport as
far as possible. A doctor or nurse should accompany the
baby, if possible. The referring doctor should send a
2.
4.
5.
6.
7.
8.
9.
American Academy of Pediatrics. Committee on

Nutrition. Nutritional needs of low birth weight infants.
Pediatrics 1985;75:76.
American Academy of Pediatrics. Pediatric Nutrition
Handbook 1993.
Arora NK, Paul VK, Singh M. Morbidity and mortality
in term infants with intrauterine growth retardation. J
Trop Pediatr 1987;33:186.
Jeeva Sankar M, Agarwal R, Mishra S, Deorari AK, Paul
VK. Feeding of low birth weight infants. Indian J Ped
2008;75:459-69.
Singh M. Disorders of weight and gestation. Care of
the Newborn. Sagar Publications: New Delhi 1991;11225.
Singh S, Singh M: Birth weight to birth weight
postnatal weight pattern of preterm infants. Indian J
Pediatr 1979;46:223.
Tsang RC, Lucas A, Uauy R, et al. Nutrition Needs of
the Preterm Infant Williams and Williams: London 1993.
Tsang RC, Nichols BL. Nutrition During Infancy Hanley
and Belfus: St Louis 1997.
World Health Organization. Kangaroo mother care: a
practical guide, Department of reproductive Health and
Research, WHO, Geneva 2003.
Newborn Care
71
3.6 Common Diseases of Newborn Babies

Meharban Singh, Vinod K Paul, Ashok K Deorari
A large majority of newborn babies do not develop any
serious difficulties and they need level I or minimal
newborn care which can be provided by the mother
under the supervision of a nurse. High-risk mothers are
likely to give birth to preterm or low birth weight (LBW)
babies which are prone to suffer from a number of
disorders. Common causes of morbidity in newborn
babies include respiratory distress syndrome (RDS),
septicemia and hyperbilirubinemia. These disorders
affect 10 to 12 percent of neonates in our institution. Most
neonatal disorders and deaths are limited to preterm and
LBW babies.
Respiratory Distress Syndrome
Respiratory difficulties are encountered in 5 to 7 percent
of newborn babies, while pulmonary pathology is the
most frequent autopsy finding in the neonates. The
clinical diagnosis of respiratory distress is suspected
when the respiratory rate is more than 60 per minute in
a quiet resting baby, and there are either inspiratory costal
recessions or expiratory grunt.
Causes
The common causes of RDS in newborn babies include
pneumonia, meconium aspiration syndrome, transient
tachypnea of the newborn, hyaline membrane disease
(HMD) and congenital malformations of respiratory and
cardiovascular systems. The infant should be assessed
for degree of distress, severity of intercostal recessions,
cyanosis, activity or alertness, nature of cry, feeding
behavior and status of peripheral circulation.
Meconium Aspiration Syndrome (MAS)
Meconium is passed in utero by 10 to 15 percent of infants,
and it suggests that the fetus may have suffered from an
asphyxial episode. The baby may be asphyxiated at birth
and may be covered with meconium. The yellow staining
of the cord, skin and nails suggests that the baby had
been soaked in meconium for several hours. The presence
of thick particulate matter (pea-souped appearance of
amniotic fluid) is associated with increased risk of MAS.
When management of the meconium-stained baby

is unsatisfactory at birth, there is a potential risk of
development of MAS. The baby is often asphyxiated at
birth and develops progressive respiratory distress soon
afterbirth. There is marked inspiratory intercostal
recessions and expiratory grunt. The chest may be overinflated or barrel-shaped due to obstructive emphysema.
The chest radiogaph shows bilateral coarse, irregular
densities with patches of obstructive emphysema. The
management is mostly supportive by maintaining
thermoneutral environment, adequate hydration and
oxygenation. There is no therapeutic utility of either
routine antibiotics or corticosteroids. All efforts should
be made to prevent morbidity due to MAS by avoiding
delay in the delivery of such babies and by ensuring
prompt and effective endotracheal suction of nonvigrous
baby at birth.
Transient Tachypnea of the Newborn (TTNB)
Transient tachypnea of the newborn (TTNB) is characterized by the development of rapid shallow breathing
in a baby at birth or few hours later. The condition is
more common in term babies born by cesarean section.
The respiratory rate may vary from 60 to 100 per minute
while intercostal recessions are either absent or minimal.
The baby remains alert and active and maintains good
color. The condition occurs due to failure of drainage of
amniotic fluid through the lymphatics leading to reduced
lung compliance. A skiagram of the chest shows linear
streakings at both hila due to dilated lymphatics and
presence of fluid in the interlobar fissure. The condition
resolves spontaneously without any specific therapy
within two to three days of life. Some infants may require
administration of 40 percent oxygen to maintain good
color.
Hyaline Membrane Disease
(Idiopathic Respiratory Distress Syndrome)
Hyaline membrane disease (HMD) is the most common
cause of respiratory morbidity in preterm babies. It affects
10 to 15 percent of preterm babies in India though its

incidence is relatively higher in the West. The condition
occurs due to a lack of pulmonary surfactant because of
the immaturity of the lungs. When surface-active
material is deficient in the alveoli, there is alveolar
collapse during expiration. Apart from prematurity, the
production of surfactant may be compromised by
damage to type II alveolar cells due to birth asphyxia,
acidosis, hypothermia, antepartum hemorrhage and
shock. Infants delivered by emergency cesarean section
are predisposed to develop HMD due to greater chances
of perinatal hypoxia.
The pulmonary immaturity of the fetal lungs can be
assessed by determination of lecithin/sphingomyelin
ratio in the amniotic fluid. Lecithin/sphingomyelin
(L/S) ratio of 2 or more is suggestive of adequate lung
maturity, while a ratio of less than 1.5 is often associated
with HMD. Amniotic fluid shake test is a simple
bedside test for assessment of lung maturity. Estimation
of phosphotidyl glycerol is a more specific indicator of
lung maturity (especially in diabetic mothers), and its
absence is invariably associated with development of
HMD.
Clinical Features
Hyaline membrane disease is characterized by a triad of
tachypnea, expiratory grunt and inspiratory retractions
in a prematurely born asphyxiated infant. The symptoms
may begin at birth or within 6 hours of delivery. There is
gradual worsening of retractions, grunting and cyanosis.
During the next 24 to 48 hours, the course of disease is
relentlessly progressive and may be complicated by
patent ductus arteriosus (PDA). A gastric aspirate shake
test is usually negative. The skiagram of the chest shows
the air bronchogram extending beyond the left cardiac
border followed by diffuse opaque appearance due to
solid lungs.
Management
Premature labor should be arrested by appropriate
tocolytic therapy to gain pulmonary maturity. The
induction of labor should be delayed as far as possible
till pulmonary maturity is confirmed by the results of
amniotic fluid L/S ratio or level of phosphatidyl glycerol.
When premature labor below 34 weeks of gestation is
unavoidable, the mother should be administered
betamethasone 12 mg IM every 24 hours for two doses
or dexamethasone 6 mg intramuscularly four doses at
an interval of every 12 hours.
The infant should be nursed in a thermoneutral

environment and administered oxygen through a head
box. An intravenous line should be established to
maintain fluid and electrolyte balance, for the correction
of acidosis and administration of drugs. Intratracheal
administration of synthetic surfactant is associated with
improved survival and reduced risk of complications.
Arterial oxygen saturation should be monitored with the
help of a pulse oximeter. When arterial oxygen saturation
cannot be maintained above 90 percent despite providing oxygen in the head box at a concentration of
40 percent, the infant should be provided continuous
positive airway pressure (CPAP) through silastic nasal
prongs. When CPAP is also ineffective to maintain
adequate oxygenation, the baby is managed by intermittent positive-pressure ventilation (IPPV). The acidbase parameters and blood gases should be monitored
frequently to correct acidosis and hypoxia or hyperoxia.
Unmonitored high concentrations of oxygen in preterm
babies may lead to retinopathy of prematurity (ROP) due
to oxygen toxicity. Antibiotics are administered
whenever there is suspicion of superadded bacterial
infection. The management of HMD demands excellent
supportive care by trained nurses and the availability of
high technology to monitor and manage the hypoxia due
to ineffective ventilation. The case fatality rate due to
HMD is related to the quality of neonatal care and varies
between 25 and 50 percent.
Congenital Malformations
Respiratory distress in the newborn may occur due to a
number of congenital malformations of pulmonary
system or due to congestive heart failure because of
congenital heart disease. The common respiratory
malformations include choanal atresia, Pierre Robin
syndrome, esophageal atresia with tracheoesophageal
fistula, diaphragmatic hernia and vascular rings.
Congenital and postnatal pneumonia is an important
cause of RDS and is discussed under neonatal sepsis.
Neonatal Sepsis
(Septicemia, Pneumonia and Meningitis)
Systemic bacterial infections of newborn infants are
termed neonatal sepsis. This is a generic term which
incorporates neonatal septicemia, pneumonia, meningitis
and urinary tract infections which may manifest clinically
in isolation or in different combinations. They are the
most common cause of neonatal deaths in India. Low
Newborn Care
birth weight is an important underlying condition. In
neonatal septicemia, the infant has overwhelming
bacteremia with poor localization of infection into any
particular organ system. The clinical manifestations are
characteristic albeit nonspecific. Pneumonia manifests as
respiratory distress. Meningitis is often silent clinically
with a clinical picture dominated by manifestations of
associated septicemia. Appearance of excessive highpitched crying, fever, seizures, blank look and bulging
anterior fontanelle are suggestive of meningitis.
Neonatal sepsis can be divided into two subtypes
depending upon whether the onset of symptoms is
during the first 72 hours of life or later. Early-onset infections are caused by organisms prevalent in the genital
tract or in the labor room and maternity operation theater.
It often manifests as pneumonia causing respiratory
distress. The predisposing factors for early-onset sepsis/
pneumonia include prolonged premature rupture of
membranes (PPROM), foul smelling liquor, multiple per
vaginal examinations, maternal fever, difficult or
prolonged labor and aspiration of meconium.
Late-onset septicemia is caused by the organisms
thriving in the external environments of homes or
hospitals. The infection is often transmitted through the
hands of the care providers. The onset of symptoms is
usually delayed beyond 72 hours afterbirth and the
presentation is that of septicemia, pneumonia or
meningitis. The predisposing causes of late-onset sepsis
include: lack of breast milk feeds, superficial infections
(pyoderma, umbilical sepsis), aspiration of feeds,
disruption of skin integrity with needle pricks and use
of intravenous fluids. These factors enhance the chances
of entry of organisms into the body systems of neonates
who are much less immunocompetent as compared to
older children and adults. The common organisms
responsible for neonatal septicemia and pneumonia
include Escherichia coli and Staphylococcus epidermidis and
S. aureus. In hospitals Klebsiella pneumoniae is an important
etiological agent.
Clinical Features
The newborn baby has a limited ability to respond to a
number of insults resulting in identical stereotyped
manifestations due to a variety of conditions. The manifestations of neonatal septicemia are often vague and
nonspecific demanding high index of suspicion for its
early diagnosis. Any alteration in the established feeding
behavior is the most characteristic early feature. The baby
73
who had been active and sucking normally, gradually

or suddenly becomes lethargic, inactive, unresponsive
and refuses to suck. The infant may appear pale with
grayish circumoral cyanosis and a vacant look. Hypothermia is a common manifestation of septicemia in
preterm babies, while term babies may manifest with
fever, especially in association with gram-positive infections and meningitis. Diarrhea, vomiting and abdominal
distention may occur. Jaundice and hepatosplenomegaly
may be present. Episodes of apneic spells with cyanosis
may be the sole manifestation of septicemia in preterm
babies.
The additional localizing features may appear depending upon the spread of infection to different systems
and organs of the baby. The clinical manifestations of
pneumonia include tachypnea, chest retractions, grunting, cyanosis and apneic spells in addition to inactivity
and poor feeding. Cough is unusual. Findings on auscultation of chest are nonspecific and noncontributory.
Diagnosis
Septic screening should be done to support the clinical
suspicion of infection before the institution of specific
antibacterial therapy. The reliable markers of neonatal
septicemia include leukopenia (less than 5000 per cu
mm), elevated band neutrophils (more than 20%), raised
micro-ESR (more than 15 mm) and positive C-reactive
protein (more than 8 mg per ml). Blood culture and CSF
examination are mandatory before initiating specific
antibacterial therapy. A skiagram of the chest should be
taken in all cases. It may show scattered or localized
opacities suggestive of patchy consolidation. Blood
should be examined for glucose, bilirubin, urea and
electrolytes. In all infants born following PPROM (more
than 24 hours) or those developing respiratory distress
soon after-birth, gastric aspirate should be collected in a
heparinized tube and examined under the microscope
after staining with Leishman's stain. The presence of
more than 5 neutrophils per high power field or when
their number exceeds three times the number of the
epithelial cells, is suggestive of intrauterine or congenital
pneumonia. A bacterial culture should be obtained from
liquor amnii (or cervical swab), gastric aspirate, throat,
umbilical stump and blood.
Management
The infant should be managed in a thermoneutral
environment and started on intravenous infusion.

Hypoglycemia, anemia and shock should be appropriately managed. Fresh blood or fresh frozen plasma is
useful to improve defense mechanisms by providing
opsonins, complement and polymorphonuclear leukocytes. Specific antibacterial therapy should be instituted
through intravenous route. The choice of antibiotics
depends upon the prevalence of bacterial flora and their
sensitivity pattern against available antibiotics. In a
community-acquired neonatal septicemia, a combination
of ampicillin or benzyl penicillin with gentamicin is
appropriate. In hospital-acquired neonatal septicemia,
the logical initial choice would be a combination of
cloxacillin with aminoglycoside such as gentamicin or
amikacin. When response to this antibiotic combination
is unsatisfactory or there is an associated meningitis,
ampicillin is substituted by a third generation cephalosporin such as cefotaxime. When the etiologic agent is
identified, the antibacterial therapy can be made highly
specific. For instance, septicemia due to Pseudomonas
aeruginosa is best managed by ceftazidime or piperacillin
and in resistant staphylococcal infection, amoxycillin
with clavulinic acid or vancomycin may be considered.
Listeriosis is best managed with ampicillin.
Exchange blood transfusion is recommended in
critically sick neonates having sclerema, disseminated
intravascular coagulopathy (DIC) or hyperbilirubinemia.
There is no role of intravenous immunoglobulins in
neonatal sepsis. The prognosis depends upon the weight
and maturity of the infant, nature of the etiologic agent
and quality of specific and supportive therapy. The
presence of underlying congenital malformations like
meningomyelocele, tracheoesophageal fistula and
surgical procedure adversely affect the outcome. The
reported case fatality rates due to neonatal septicemia in
various studies from India range between 15 and 20
percent. Therefore, it is essential that all efforts should
be made to prevent the occurrence of bacterial infections
in newborn babies by adopting strict aseptic rituals and
routines.
Prevention of Infections
Newborn babies especially those prematurely born are
at an increased risk of developing bacterial infections and
despite aggressive management septicemia has a high
case fatality rate. It is far more cost-effective to prevent
nosocomial infections rather than to treat them with
expensive antibiotics and high quality supportive care.
The following protocols for prevention of infections
should be strictly followed in the nursery.
1. Handwashing and thorough scrubbing with soap and

water up to elbows for at least 2 minutes, gowning
and change of shoes are mandatory before entry to
the nursery. Rings, bangles and wristwatch should
be removed before hand-washing. Strict and
obsessive handwashing (for 20 seconds) and use of
antiseptic lotion in-between handling of babies
should be ensured. The hands should be dried with
either a disposable paper napkin (or reusable
autoclaved minitowel) or hand dryer.
2. Babies should be fed early and exclusively with
expressed breast milk (or breastfeed) without any
prelacteal feeds. Careful attention should be paid to
the hygiene of the katori and spoon. The use of a
feeding bottle and pacifier are condemned.
3. The umbilical stump should be left open. Local
application of triple dye or spirit reduces colonization.
4. All procedures in the nursery should be performed
after wearing mask and gloves. Unnecessary invasive
interventions such as needle pricks and setting up of
intravenous lines should be kept to the barest
minimum. The use of stock solution of heparinized
saline for rinsing of intravenous lines is a dangerous
practice and should be replaced by flushing with a
single-use normal saline ampule. There should be no
compromise in the use of disposables. Barrier nursing
should be ensured.
5. Strict housekeeping routines for washing, disinfection, cleaning of cots/incubators, etc. should be
ensured, and these policy guidelines should be
available in the form of a manual in the nursery.
6. The use of prophylactic antibiotics for prevention of
nosocomial infections is strongly condemned. They
are not only useless but dangerous due to the
potential risk of emergence of resistant strains of
bacteria.
Neonatal Jaundice
Jaundice is a relatively common physical abnormality in
a newborn baby during the first week of life. Clinical
jaundice manifests as yellowness of the skin of the face
when the serum bilirubin level exceeds 5 mg/dl. As the
degree of jaundice increases, there is a cephalopedal
progression of yellowness of the skin. When the trunk of
the baby is distinctly yellow stained, the serum bilirubin
level is likely to range between 10 and 15 mg/dl. The
yellow staining of the palms and soles is ominous and
indicates that the serum bilirubin level has exceeded
Newborn Care
TABLE 3.6.1: Causes of pathological jaundice
1. Idiopathic
2. Prematurity
3. ABO-incompatibility (ABO-HDN*)
4. Rh-isoimmunization (Rh-HDN*)
5. G-6-PD deficiency
6. Septicemia
7. Breast milk jaundice
8. Hypothyroidism
75
limits of intensity and age of disappearance besides the

exclusion of pathologic causes. Physiological jaundice
occurs due to relative polycythemia with reduced
lifespan of neonatal red blood cells, hepatic immaturity
(regarding uptake, conjugation and excretion of bilirubin)
and exaggerated enterohepatic circulation of bilirubin.
The mother must be reassured regarding the benign
nature of physiological jaundice and her fears regarding
infection or hepatitis should be allayed. She should be
advised to breastfeed the baby frequently, but there is
no need to advise extra glucose water.
9. Neonatal hepatitis (intrauterine infections)

10. Metabolic disorders
Hemolytic Disease of the Newborn (HDN)
* HDNHemolytic disease of the newborn
Hemolytic disease of the newborn (HDN) due to blood

group incompatibility between the mother and fetus is
the most common cause of hyperbilirubinemia in the
newborn baby. The incompatibility may exist among
Rhesus, ABO or minor blood group systems.
15 mg/dl. All newborn babies must be examined twice

a day during the first week of life to assess the onset,
severity and age of disappearance of jaundice.
Causes of Jaundice
The important causes of pathological jaundice in
newborn babies are given in Table 3.6.1. About 5 percent of newborn babies develop pathological jaundice
or hyperbilirubinemia. The onset of jaundice within 24
hours of age, its marked intensity as evidenced by yellow
staining of the palms and soles and its persistence beyond
two weeks of age are suggestive of pathological jaundice.
Investigations should be performed to identify possible
cause of pathological jaundice and appropriately
managed.
Physiological Jaundice
About 60 to 70 percent of healthy newborn babies are
likely to develop physiological jaundice which may cause
undue anxiety to the parents. Physiological jaundice
appears between 24 and 72 hours of age, its maximum
intensity is seen on the 4th to 5th days of life, and the
peak serum bilirubin level does not exceed 15 mg/dl.
This type of jaundice usually disappears before 14 days
of life and does not need any specific therapy. In preterm
babies, the peak of physiological jaundice is seen a little
later, and peak bilirubin level may be higher and jaundice
takes relatively longer time to disappear. The diagnosis
of physiological jaundice cannot be made by examining
the baby at one point of time because it depends upon a
characteristic time table of jaundice, taking into
consideration the time of onset of jaundice, maximal
Rhesus Hemolytic Disease of

the Newborn (Rh-HDN)
When an Rh-negative mother is carrying an Rh-positive
fetus, the passage of fetal red blood cells into the maternal
circulation may invoke an antibody response by the
maternal immunological system. Enough anti-D
antibodies are not produced during the first pregnancy,
but each subsequent pregnancy with Rh-positive fetus
leads to increasing antibody production. The Rhsensitization of the other may also occur by amniocentesis, external version, abortion and stillbirths. The
anti-D antibodies being IgG in type, they readily
crossover to the fetus through the placenta and destroy
D-positive fetal red blood cells. The Rh isoimmunization
can be suspected during antenatal period by identifying
the blood group of the mother and estimating the titer of
anti-D antibodies by indirect Coombs test.
There is a wide spectrum of clinical manifestations
of erythroblastosis due to Rh-HDN, ranging from a
normal baby to a stillborn baby with hydrops fetalis.
There is increasing severity of the disease with each
subsequent pregnancy. The newborn baby may be
anemic at birth and has hepatosplenomegaly. Jaundice
usually appears within 24 hours of age and rapidly
increases in intensity. In a severely affected baby, the
clinical picture is characterized by severe anemia, gross
hepatosplenomegaly and generalized anasarca (hydrops
fetalis), and the baby may die in utero.

If the mother is Rh-negative, cord blood should be
collected for Rh and ABO typing, direct Coombs test,
hemoglobin, reticulocyte count, peripheral blood smear
and serum bilirubin. The positive direct Coombs test in
a Rh-positive baby clinches the diagnosis of Rh-HDN.
In the affected baby, the serum bilirubin should be
monitored every 6 to 12 hours depending upon the rate
of rise of bilirubin.
Rhesus isoimmunization can be effectively prevented by prophylactic administration of anti-D immunoglobulins in an unsensitized Rh-negative woman
within 72 hours of delivery in the following situations:
1. Delivery of an Rh-positive baby
2. Abortion or stillbirth of Rh-positive conception
3. Following procedures having increased risk of
fetomaternal hemorrhage such as amniocentesis and
external version.
The dose of anti-D immunoglobulin varies. The antiD immunoglobulin should only be given to the mother
whose indirect Coombs' test is negative.
ABO Hemolytic Disease of the Newborn (ABO-HDN)
The ABO hemolytic disease of the newborn usually
occurs when mother is O group and her baby is either A
or B group. Fetomaternal ABO incompatibility exists in
about 25 percent of pregnancies, but the hemolytic
disease develops in only 10 percent of these incompatible neonates. Unlike Rh-HDN, the history of increasing
severity of disease in subsequent pregnancies is generally
not present in ABO-HDN.
The diagnosis of ABO-HDN is suspected by early
onset of jaundice in A or B group baby of an O group
mother. The ABO-HDN is a relatively milder disease as
compared to Rh-HDN. The anemia is usually absent or
mild, and there may be mild hepatosplenomegaly. The
direct Coombs test is usually negative or weakly positive.
Blood examination may show reticulocytosis, microspherocytosis and increased fragility of red blood cells.
The diagnosis is confirmed by the demonstration of high
titer of IgG hemolysins in maternal blood against the
baby's blood group.
Septicemia
Jaundice is an important manifestation of bacterial infection in newborn babies and occurs due to hemolysis and
hepatitis. The clinical picture is usually dominated by
systemic features of septicemia and the occurrence of

jaundice after the age of three days. The direct reacting
or conjugated bilirubin is often elevated to 2.0 mg/dl or
more, and jaundice often persists beyond 14 days of life.
Glucose-6-PhosphateDehydrogenase Deficiency
The incidence of G-6-PD deficiency varies between 5 and
20 percent among different ethnic groups in India.
Deficiency is limited to male babies as the condition is
inherited as X-linked recessive. The hemolysis may occur
spontaneously or following exposure to certain drugs
and infections. The clinical picture is characterized by
the sudden and dramatic appearance of unconjugated
hyperbilirubinemia requiring exchange blood transfusion.
Persistent Neonatal Jaundice
Neonatal jaundice whether physiological or pathological,
usually disappears by 2 weeks of age. The important
causes of persistent neonatal jaundice are illustrated in
Table 3.6.2. Hyperbilirubinemia may be predominantly
unconjugated or there may be significant elevation of
direct reacting or conjugated bilirubin. The elevation of
conjugated bilirubin is usually characterized by clay
colored stools, and high colored urine staining the
napkins. It must be remembered that most conditions
producing hyperbilirubinemia during the first week of
life are associated with the elevation of unconjugated
bilirubin. Despite deep jaundice, the urine in such babies
is normal colored and does not contain any bile pigments
or urobilin.
TABLE 3.6.2: Causes of persistent neonatal jaundice
Unconjugated hyperbilirubinemia
1. Breast milk jaundice
2. Hypothyroidism
3. Crigler-Najjar syndrome
4. Intestinal obstruction or stasis
5. Ongoing hemolysis (Rh, ABO)
Conjugated hyperbilirubinemia (cholestasis)
1. Neonatal hepatitis
2. Extrahepatic biliary atresia
3. Inborn errors of metabolism
4. Total parenteral nutrition
Newborn Care
Pathogenesis of Kernicterus
Jaundice in a newborn baby is a serious condition because
unconjugated hyperbilirubinemia may cause bilirubin
encephalopathy or kernicterus. The occurrence of
kernicterus is related to complex interaction between the
level of unconjugated bilirubin which is lipid soluble,
gestational maturity of the infant and integrity of the
blood-brain barrier. It is generally believed that
unconjugated bilirubin level of more than 20 mg/dl due
to any cause may lead to kernicterus in a newborn baby.
However, it is well-known that a preterm infant may
develop brain damage at a relatively lower serum
bilirubin level, while some term babies may tolerate
serum bilirubin concentration of up to 30 mg/dl without
any kernicterus. Adequate levels of serum proteins are
essential for effective binding of bilirubin to prevent its
leakage into the interstitial and intracellular compartments. When bilirubin binding sites in the albumin are
blocked by other anions like hydrogen (acidosis), free
fatty acids, (hypoglycemia and hypothermia) and certain
drugs like salicylates, sulfonamides and sodium
benzoate, kernicterus may occur at lower serum bilirubin
levels. Perinatal distress factors such as hypoxia,
hypothermia, hypoglycemia, acidosis, birth injury and
septicemia may damage the integrity of the blood-brain
barrier, and predispose the infant to develop bilirubin
encephalopathy at a relatively lower serum bilirubin
levels.
77
preparation of vitamin K in high doses is known to

aggravate hemolysis and may predispose to the
development of kernicterus. Administration of phenobarbitone during the last week of pregnancy in an Rhisoimmunized mother or during first three days of life
in any infant suspected to have Rh-HDN and cephalhematoma may reduce the severity of jaundice by
enhancing maturation of hepatic microsomal enzymes
like Y-acceptor proteins and glucuronyl transferase in
the liver. Its therapeutic utility, howerver, is limited
especially in preterm babies. High dose intravenous
immunoglobulin (0.5-1.0 gm/kg) in Rh-iso-immunized
babies is known to decrease need of exchange blood
transfusion and duration of phototherapy.
Phototherapy
Phototherapy or exposure to light is known to cause
photoisomerization of bilirubin to more polar, watersoluble, harmless compounds which are readily excreted
in the bile, feces and urine. Phototherapy units with blue
or white tubes or halogen lamps are useful for preventing
rapid rise in serum bilirubin levels (Fig. 3.6.1). The naked
infant is exposed under phototherapy unit which is kept
at a distance of about 45 cm from the baby's skin. During
exposure to light, the eyes must be effectively shielded
to prevent retinal damage. The position of the infant
should be changed frequently so that the maximal area
of the skin is exposed to light. The infant is kept under
the light round-the-clock and taken out only for feeding
Management
Hyperbilirubinemia should be considered as a medical
emergency, and all attempts must be made to ensure that
serum bilirubin levels are kept within safe limits.
Exchange blood transfusion remains the most effective
and reliable method of lowering serum bilirubin when
it approaches critical levels. Other supportive measures
are useful to prevent excessive rise of serum bilirubin.
Supportive Measures
Early feeding and the maintenance of adequate hydration
are useful to prevent hyperbilirubinemia. Hypoxia,
hypothermia, hypoglycemia and acidosis should be
prevented and if they occur they should be promptly
managed. Septicemia should be treated with appropriate
antibiotics. When cephalhematoma is associated with
critical hyperbilirubinemia, it should be aspirated or
drained. The administration of a water-soluble
Figure 3.6.1: Compact fluorescent light phototherapy units (top

both sides) and fibreoptic cold light below the baby for giving
intense phototherapy for jaundice. Note eyes are effectively
covered to prevent retinal damage

or change of wet napkins. Most preterm babies are placed
under phototherapy when their serum bilirubin
approaches 10 to 12 mg/dl, and term babies are given
phototherapy when their serum bilirubin approaches
15 mg/dl. Appropriate charts are available which are
based on serum bilirubin levels, postnatal age of the
infant and birth weight of the child, to provide more
reliable indications for phototherapy and exchange blood
transfusion. During phototherapy the infant should be
closely watched for hydration status, temperature, degree
of jaundice and anemia by frequent blood examination.
Phototherapy is by and large safe but may produce loose
greenish stools, dehydration, hypothermia, or hyperthermia, and skin rash. During phototherapy, the clinical
evaluation of the severity of jaundice becomes unreliable
because the infant's skin gets bleached under light.
Exchange Blood Transfusion
If despite phototherapy and other supportive measures,
the bilirubin level is approaching 20 mg/dl, exchange
blood transfusion is mandatory to prevent brain damage.
The indications for exchange blood transfusion are listed
in Table 3.6.3. However, in an individual infant, the
decision for exchange blood transfusion should not be
based merely on the level of unconjugated serum
bilirubin but other important factors like gestational
maturity, postnatal age, presence or absence of perinatal
distress factors, and cause of jaundice should also be
taken into consideration. Double volume (160 ml/kg
blood) exchange blood transfusion is performed through
umbilical vein.
BIBLIOGRAPHY
1.
Arya LS, Singh M. Gastric aspirate shake test as a

predictor of hyaline membrane disease. Indian J Med Res
1979;70:444.
2. Deorari AK, Chellani H, Carlin JB, Greenwood P, Prasad
MS, Satyavani A, et al. Clinico-epidemiological profile
and predictors of severe illness in young infants
(<60 days) reporting to a hospital in North India. Indian
Pediatrics 2007;44:739-48.
TABLE 3.6.3: Indications for exchange

blood transfusion
Early indications in infants with Rh-HDN
1. Cord hemoglobin of 10 g/dl or less
2. Cord bilirubin of 5 mg/dl or more
3. Unconjugated serum bilirubin of more than 10 mg/dl
within 24 hours or rate of rise of more than 0.5 mg/dl
per hour
Jaundice due to any cause
1. Exchange at lower bilirubin levels in the presence of
perinatal distress factors (Asphyxia, respiratory distress,
sepsis, hypothermia, etc.)
2. Unconjugated serum bilirubin of 20 mg/dl or more in a
term baby
3. In preterm babies, serum bilirubin of more than 1.0 mg/
100 g weight of the infant (i.e., 10 mg/dl for 1000 g and
15 mg/dl for 1500 g and so on)
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Diamond I. Kernicterus. Revised concepts of pathogenesis and management. Pediatrics 1966;38:539.

Gluck L, Kulovich HV, Borer RC, et al. Diagnosis of the
respiratory distress syndrome by amniocentesis. Am J
Obstet Gynecol 1997;109:440.
Gottstein R, Cooke RW. Systematic review of intravenous
immunoglobulin in hemolytic disease of the newborn.
Arch Dis Child Fetal Neonatal 2003;88:F6-F10.
Jeeva Sankar M, Agarwal R, Deorari AK, Paul VK. Sepsis
in the newborn. Indian J of Pediatrics 2008;76:261-66.
Kishore K, Deorari AK, Singh M, et al. Early-onset neonatal sepsis: Vertical transmission from maternal genital
tract. Indian Pediatr 1987;24:45.
Mishra S, Agarwal R, Deorari AK, Paul VK. Jaundice in
the newborns. Indian J of Pediatr 2008;75:157-63.
Newman TB, Maisels MJ. Bilirubin and brain damage:
what do we do now? Pediatrics 1989;83:1062.
Paul VK, Singh M. Diagnosis and treatment of neonatal
sepsis. Indian Pediatr 1986;23:1023.
Singh M. Some practical aspects of neonatal jaundice.
Indian J Pediatr 1977;44:220.
Starr SE. Antimicrobial therapy of bacterial sepsis in the
newborn. J Pediatr 1985;106:1043.
4.1 Growth and Development: Basic Concepts: AB Desai, Dilip Mukherjee ......................................................................................... 80
4.2 GrowthBirth to Puberty: KN Agarwal, DK Agarwal, SK Upadhyay ................................................................................................. 83
4.3 Physical Growth and Sexual Development in Adolescence: KN Agarwal, DK Agarwal, SK Upadhyay ....................................... 96
4.4 Development: KN Agarwal, DK Agarwal, SK Upadhyay ..................................................................................................................... 105
4.5 Failure to Thrive: Madhulika Kabra, PSN Menon ................................................................................................................................ 111
4.1 Growth and Development: Basic Concepts

AB Desai, Dilip Mukherjee
Growth and development begin at conception and end
at maturity. They are unique characteristics of children
and any obstacle in this process at any stage can possibly
result in aberration of growth and/or development.
Frequently, the terms growth and development are used
together. In the normal child they progress together, and
are interdependent. Growth is defined as an increase in
the size of an individual due to increase in number and
size of the cells, resulting in an overall increase. This
increase can be seen, appreciated and measured
accurately.
ASSESSMENT OF GROWTH
Growth can be measured in terms of:
i. Nutritional anthropometry (weight, height, circumference of head, chest, abdomen and pelvis)
ii. Assessment of tissue growth (skin fold thickness and
measurement of muscle mass)
iii. Bone age (radiological by appearance and fusion
of the various epiphyseal centers)
iv. Dental age
v. Biochemical and histological means.
For day-to-day work anthropometry is the simplest
tool.
Nutritional Anthropometry
This is the technique of measuring somatic growth.
Length
Until 24 or 36 months of age, length in recumbency is
measured using an infantometer (See Chapter 2.2 on
Physical Examination for details). The length is recorded
in centimeters upto one decimal point.
Height
After the age of 2 years, standing height is recorded by a
stadiometer. The details have been provided in the
Chapter 2.2 on Physical Examination. Detecto weighing
scales fixed with anthropometric rods are in common
use. For community survey, portable type of anthropometric rods are also used. For recording stature (height),
the subject should remove his/her socks and shoes and

stand perfectly straight with arms relaxed by his/her sides
and ankles and knees together. Before measurement starts,
a gentle pressure may be applied over the spine with one
hand while other hand holds the anthropometric rod. The
subjects head is positioned in Frankfort plane.
Sitting Height
For recording sitting height, the subject is made to sit on
a table or other convenient hard surface so that his/her
head lies in Frankfort plane. The back should be straight,
thighs horizontal and comfortably positioned. The feet
should be supported on the foot board and hands should
rest comfortably on the subjects lap. To ensure that the
subject's back is fully extended, the observer may run
his/her index finger up the spine applying pressure to
the lumbar and sacral regions, causing the subject to sit
up a reflex action. The head board should be lowered
and made to touch the head of the subject and reading
should be recorded to the nearest completed unit.
Body Proportions
The total body length is divided in two segments. The
upper segment is from head to pubic symphysis and
lower segment from pubic symphysis to the toes. The
U/L segment ratio is 1.7:1 at birth. By 6 to 7 years, it
reaches 1:1. If the ratio is infantile after 1 year of age, it
suggests short limb dwarfism due to bone disorders such
as rickets and hypothyroidism.
Weight
It is the commonest and important anthropometric
measurement. The weighing scales best suited are those
which are designed on balance arm principle. The details
of measurement have been provided in Chapter 2.2 on
Physical Examination. Accuracy up to 0.1 kg is quite
acceptable. For smaller babies, machines of more
accuracy are required as 0.1 kg forms a higher percentage of total body weight. More recently, many electronic
weighing scales giving accuracy up to 0.01 kg have been
made available.

The weighing scales should be checked for
accuracy using known weight from time to time. The
beam scales are better instruments for all purposes rather
than spring weighing scales, i.e. bathroom scales, as the
spring may get expanded due to repeated use, may get
rusted and variation of temperature may give false
reading.
In Japan special type of weighing scales are devised
which in addition to the weight of an individual also note
Body Mass Index and amount of subcutaneous fat.
Head Circumference
The details of measuring head circumference has been
given in Chapter 2.2 on Physical Examination. It should
be recorded to the nearest 0.1cm.
Midarm Circumference (MAC)
The details have been provided in the Chapter 2 on
Physical Examination. It should be kept in mind, that
upper arm circumference can be measured both in flexed
and extended positions and also either at the maximum
circumference of biceps muscle or mid-point, as the
difference between the two is negligible.
Chest Circumference
The chest circumference for boys, prepubertal girls and
men can be recorded at the level of xiphisternal junction
during normal breathing. It is recorded to the nearest
0.1 cm.
81
can be used to distinguish between malnutrition of recent

origin, i.e. wasting and malnutrition due to a considerable
period of months. In chronic malnutrition the child is
stunted with the weight for age and height for age being
low. In acute malnutrition, height for age is normal but
weight for age is low (wasting). Thus, the weight and height
measurements together are useful in understanding the
dynamics of malnutrition. In nutritional short stature the
weight/height is equal; the child may pass off as a normal
child of lower age if the chronological age is not known.
These have been discussed in the chapter on Protein-energy
malnutrition.
Quackstick
Quakers midarm circumference measuring stick is a
height measuring rod, calibrated in MAC rather than
height; values of 80 percent MAC for height are marked
on the stick at corresponding height levels. If a child is
found taller than his/her arm circumference level on the
stick, he/she is considered malnourished. The quackstick
was devised in Mexico and has since been adapted in
Africa and India.
Midarm/Head Circumference Ratio
It is a simple and useful criterion for detection of
malnutrition. A ratio 0.280 to 0.314 indicates early malnutrition, 0.250 to 0.279 moderate, and less than 0.249
denotes severe malnutrition.
Age Independent Anthropometry

Quetlets Index
Midarm Circumference (MAC)
As the midarm circumference is relatively constant
between 16.5 cm to 17.5 cm in 1 to 5 years of age, this
measurement may be considered as an age independent
variable up to 5 years of age. Any child whose MAC is
less than 12.5 cm up to 5 years of age, is considered
malnourished. Shakirs tape also measures the MAC. A
bangle of 4 cm in diameter, used in field studies is not a
reliable method (Bangle test).
Weight for Height
The degree of wasting can be measured by comparing the
childs weight with expected weight for a healthy child of
the same height. Combinations of these measurements
have been used to distinguish different types of
malnutrition. Waterlow suggested that weight for height
It is based on the relationship between weight and height

and is expressed as weight (kg)/Height (cm) 100.
Normal value varies from 0.14 to 0.16. In gross
malnutrition, it is less than 0.14. It is a quite reliable ratio
for assessing malnutrition.
Mid-upper Arm/Height Ratio
It is also a very good indicator of nutritional status. A
ratio of less than 0.29 indicates gross malnutrition, while
the normal value ranges from 0.32 to 0.33.
Body Mass Index (BMI)
BMI =
Weight (kg)
_________________
Height2(m2)

This is similar to Quetlets index except that the values
are in SI units. BMI values can be used to draw standardized percentile curves in children and adolescents. It is
specially useful for defining obesity. BMI values above
95th percentile for age are usually used to define obesity.
Ponderal Index (PI)
PI =
Height (cm)
______________________________________
Cube root of body weight (kg)
This is another index similar to BMI and is often used

in defining newborn with intrauterine growth retardation (IUGR).
caliper is applied at the marked level and reading is

recorded to 0.1 mm.
Bone Age or Skeletal Maturity
Appearance and fusion of various epiphyseal centers
follow a definite sequence related to chronologic age from
birth to maturity. Radiological examination of left wrist
and elbow is usually considered for bone age assessment.
X-ray of the lower end of femur, and talus is used for the
assessment of maturity of new-born babies. The details
of appearance and fusion of various centers is given in
subsequent sections.
Dental Development
Tissue Growth
This measurement is done for special purposes and is
not used in routine clinical practice. It is measured with
a special caliper.
Triceps Skinfold Thickness
The skinfold is picked up over the posterior surface of
the triceps muscle, 1 cm above the mark on a vertical
line passing upward between bony point identified for
taking measurement, maintaining a pressure of 10 g/
mm2 on the caliper and freeing the skinfold from the
underlying muscle with left hand between thumb, index
and middle finger and holding caliper with the other
hand. The reading is recorded to the nearest 0.1 mm.
Subscapular Skinfold Thickness
The subject stands as for the triceps skinfold with
shoulder and arm relaxed. The inferior angle of scapula
is located by running finger on medial border of scapula
downward, till inferior angle is reached. The skin is
pinched up immediately below the inferior angle either
in vertical line or slightly downward and reading is
recorded to the nearest 0.1 mm maintaining pressure of
caliper as before.
Biceps Skinfold Thickness
For recording biceps, the child is made to stand erect,
facing observer with arm on side and palm facing
forward. The skinfold is picked up over the belly of biceps
and 1 cm above the line marked for the upper arm
circumference and triceps skinfold on a vertical line
joining antecubital fossa to the head of humerus. The
Eruption of teeth follow a definite sequence. Eruption of

temporary or deciduous teeth begins at about
6 months with eruption of upper or lower central incisors,
followed by lateral incisor. By one year of age 4 to 8 teeth
are present. The permanent teeth begin to erupt at 6 years.
Details of dental development are provided in
subsequent chapters.
GROWTH STUDIES AND PERCENTILES
While discussing growth, various terms which are used
must also be understood.
Cross-sectional Study
This is a very convenient, easy, less time consuming and
economical method to study growth. For example,
children of each age group in large number are collected, their weights are recorded and an average is found
out. These groups of children are studied just once.
Linear or Longitudinal Study
In this type of study, the same child is measured from
birth to maturity at yearly or previously decided regular
intervals. It is difficult to study very large number of
children in this fashion and hence, the linear studies have
comparatively less subjects in number. The longitudinal
study helps us to determine the growth velocity.
Concept of Percentiles
While making various calculations, the use of terms like
mean or average and standard deviation (SD) is well
known. While expressing the growth the term percentile
or centile is often used. This may be explained in a simple

way, e.g. the height of 100, one year old normal children is
not exactly the same. They are arranged in such a way
that the shortest is number one and the tallest is number
100. Rows of children are thus made. The mean of each
number is worked out. The child at number 1 is one
percentile, number 10 is 10th centile, number 50 is 50th
centile and so on. The child on 10th centile on height
chart means that 9 children are less in height and 90
children are more in height. The 50th centile is the median
value and is also termed the standard value. Accepted
range for normal is between 3rd and 97th percentiles.
The standard deviation (SD) charts are based on
distribution of data above and below a mean value. The
average normal range falls above and below 2 SD,
expressed as 2 SD. + 1 SD is equal to 84 centile and-1 SD
is equal to 16th centile. + 2 SD corresponds to 97th centile
and - 2 SD corresponds to 3rd centile. The mean SD
curves are useful for quantifying the degree of retardation
exactly.
charts are separate for boys and girls. The recently

developed Indian standards are provided in subsequent
sections.
Velocity Growth Charts
These charts are developed by long-term longitudinal
studies and are known as incremental charts. They show
the rate of change which could be due to chronic illness
or growth hormone deficiency. Different countries may
use their own growth charts. In Great Britain, Tanner's
growth charts are used. In India, Agarwal et al have
prepared the charts based on studies on affluent Indian
children.
BIBLIOGRAPHY
1.
2.
Growth Charts
Growth chart is the most important tool in assessment
of growth of an individual child. A standard chart
contains weight for age, height for age and weight for
height. The head circumference is included for first 3
years of life. They depict mean, standard deviation (SD)
or percentile values at each age.
World Health Organization (WHO) has accepted
National Center for Health Statistics (NCHS) USA, charts
as the international standard for growth for the first 3
years of life. The growth of the healthy and wellnourished children is represented in these charts. The
83
3.
4.
5.
6.
7.
Agarwal DK, Agarwal KN, Upadhyay SK, Mittal R,

Prakash R, Rai S. Physical and sexual growth pattern of
affluent Indian children from 5 to 18 years of age. Indian
Pediar 1992;29:120383.
Agarwal KN. Physical growth in Indian affluent
children (Birth to 6 years). Indian Pediatr 1994;31: 377
413.
Falknar F, Tanner JM (Eds). Human Growth, 2nd edn, 3
vol. New York: Planum. 1986.
Mukherjee D, Nair MKC. Growth and development.
Growth and Development 1st edn. IAP, 1997.
Tanner JM. Growth at Adolescence, 2nd edn. Oxford:
Blackwell Scientific Publication 1962.
Tanner JM. Physical growth and development. In :Forfar
JO, Arneil GC (Eds): Textbook of Pediatrics, 2nd edn.
London : Churchill Livingstone 1978;249303.
Tanner JM, Whitehouse RH, Camerson N et al. Assessment of Skeletal Maturity and Prediction of Adult Height,
2nd edn. London: Academic Press. 1983.
4.2 GrowthBirth to Puberty

DEFINITION
Growth and development in human beings at the moment
of conception and are continuous processes, until the
epiphyses (growing ends of bones) fuse and growth in
height ceases. The term growth denotes increase in size or
body mass; and development is the emerging and expanding
capacities of an individual to provide progressively greater
faculties in functions, i.e. acquisition of a variety of

competencies for optimal functioning in a social milieu.
The growth, measures show how body grows, i.e.
length (growth in stature), skull circumference (brain
growth) and weight (bone and muscle mass) increase
rapidly in early childhood-first three years of life( the
most active growth period). Therefore, regular measurements of length (best indicator of physical growth) and

skull circumference (indicator of brain growth) are
important to detect growth failure (Figs 4.2.1 and 4.2.2;
Table 4.2.1).
TABLE 4.2.1: Growth pattern in infant and

early childhood
Length gain being the best indicator of growth
Length gain
Measurement at age
At birth
Birth to 3 months
36 months
69 months
912 months
3.5 cm/month
2.0 cm/month
1.5 cm/month
1.3 cm/month
3 months
9 months
12 months
24 months
50 cm
60 cm
70 cm
74-75 cm
86-87 cm
By 3rd year (36th month length is 93 cm). At 4th year approaches

100 cm.
Weight
Weight at birth 3.03.5 kg, there is loss of around 810 percent
in first 810 days by 1215th days it approaches the birth weight.
Weight gain
Measurement at age
2 weeks to 3
months
36 months
25 g/day
20 g/day
69 months
15 g/day
912 months
12 g/day
Doubles birth weight

by 56 months
Trebles (3 times) at 1 year of
age
Quadruples (four times) at
2 years of age. Five time by
3 years of age and 6 times by
5 years of age
By the time infant wt. doubles birth weight~ 5-6 months; fat in
body trebles (25% of the total body weight) thus almost 1.5 kg
body weight at 6 months is fat, while during 6-12 months-fat
deposit is 500 g, only.
Skull(Head Circumference): Indicates Brain Growth
Growth in head circumference (cm): In normal full term child
Age
Head circumference
At birth
3 months
6 months
9 months
12 months
2 years
5 years
12 years
34-35
40
42-43
44-45
46-47
48
50.3
52 cm
Increment is 2 cm/mo in first 3 mo; 1 cm/mo between 3 to 6 mo;

0.5 cm/mo between 9-12 mo. Thereafter gain in head circumference is very slow, only 5 cm after first birth day to 12 years of
age.
Head Circumference (HC) in Preterm
Gestation weeks
HC cm
26
24.0
27
25.6
30
27.6
32
29.6
34
31.6
36
33.0
Postnatal growth, i.e. increase in length/height, skull

circumference and weight, stretches from i) Conception:
Intrauterine growth period to infancy (the most rapid
growth period. Brain growth is very rapid from 20 weeks
of gestation, and continues until 20 months of age, It is
around 67%, of the adult size at birth and 90%, on the
first birthday (Fig 4.2.3; Tables 4.2.1 and 4.2.6). These
cerebellum (meaning Little Brain in Latin, it plays a big
part in the integration of sensory perception and motor output)
reaches adult size by 18 months of age.
Growth in Preschool and School Years
This rapid early childhood growth is followed by a long
phase of slow juvenile growth the height gain is: in early
school Years, by 3-5 years of age the height increment is 68 cm/year and weight gain is 2 kg / year. Later in school
age 6 to 10 years in girls and 6- 12 years in boys
(Prepubescent) 5-6 cm per year and weight 3-3.5 kg per
year, until pubescence sets in (Table 4.2.2 and Figs 4.2.4
and 4.2.5).
Growth in Adolescence
The morphological and physiological changes during
Adolescent Growth Spurt involve nearly all organs of
the body. These changes do not begin at the same age
point or take the same length of time in all individuals to
reach completion. During Puberty somatic as well as
skeletal growth is related to sexual development (sexual
maturity rating by Tanner 1962), as adolescent growth is
initiated and controlled by the sex hormones. Thus for
assessment of their growth means for height, weight,
BMI, skin fold thickness etc. in relation to sexual maturity
are more relevant than those obtained for chronological
age (Agarwal et al Indian Pediatrics, 2001).
Around 10-12 years in girls and 12-15 years in boys
there is initiation of puberty- adolescent growth spurt
lasting for 2.5 to 3.0 years. In this phase girls gain 25-26
cm and boys 28-30 cm in height (Tables 4.2.2, 4.2.3 and
Fig. 4.2.4 and 4.2.5). The muscles, heart, liver, and kidney
follow the same growth pattern. The lymphoid tissue
achieves peak growth in prepubertal period 6 to 9 years
with a steady decline thereafter. The reproductive organs
show the most rapid growth in size and function along
with body growth (somatic) with onset of puberty.
85
Figure 4.2.1: Height, weight and head circumference for boys from 0-36 months (Percentiles)
(Redesigned by Agarwal KN, Agarwal DK, Bansal AK for the Indian Academy of Pediatrics. From-Agarwal DK, Agarwal KN.
Physical growth in Indian affluent children (Birth6 years). Indian Pediatr 1994;31:377-413
Figure 4.2.2: Height, weight for girls from 0-36 months (Percentiles)
(Redesigned by Agarwal KN, Agarwal DK, Bansal AK for the Indian Academy of Pediatrics. From-Agarwal DK, Agarwal KN.
Upadhyay SK, Mittal R, Prakash R, Rai S. Physical and social growth pattern of affluent Indian children from 5-18 years of age.
Indian Pediatr 1992,29:1203-1282 (Birth6 years). Indian Pediatr 1992
87
classification of malnutrition since mid 1970s (50th

percentile taken as 100%).
NCHS1963-1974. CDC growth charts. (International
growth reference on American children)
British children- Tanner et al 1966
Dutch-V an-Wieringen 1964-66.
Other European Growth standards: Czechoslovakia;
Denmark; Hungary; Norway and Sweden.
AsianChina, Japan, Hongkong, Thailand, Taiwan
and India (These growth curves are very similar).
Infact every country has national growth standard.
Individual childs growth potential for height is related to

the mid parental height (MPH) the calculations are as
follows
Although worlds children appear to follow a similar

growth pattern, still there are variations due to ethnic,
geographical, and regional factors giving differences in
velocity of growth and adult stature. Therefore, Indian
Academy of Pediatrics (IAP) Growth Monitoring
Guidelines consensus committee in Sept 2006,
recommended to use affluent children data collected by
Agarwal et al 1992 and 1994 see Indian Pediatr March
2007 pp 187-197 as standard for Indian childrens growth
assessment. To identify children: with growth deviation,
i.e., under nutrition and over nutrition and with conditions
that manifest through abnormal growth.
Fathers height-13 + Mothers height

MPH for boys (cm)= ___________________________________________________
2
Growth Curves
Figure 4.2.3: Increase in head circumference in late gestation

and first 2 years of life. The period of maximum brain growth is
also plotted
Adult Stature
Or = average of parents height 6.5 cm

Mothers height + 13 + Fathers height
MPH for boys (cm) = ___________________________________________________
2
Or = average of parents + 6.5 cm
Growth Monitoring- Why?

Growth is a fundamental characteristic of childhood
Despite being influenced by many factors, it remains
remarkably predictable
Normal growth is an indicator of optimum health
Deviation from the normal pattern is indicative of a
pathological process
Periodic assessment facilitates early detection of
growth faltering which may be the first manifestation
of an infection/disease.
There were several growth standards to measure
children, e.g.
Staurt Meredith Charts 1940 (Harvard standard
1929-39). Used in Indian Academy Pediatrics
Distance growth curves (Percentile growth curves)- the

term refers to the position of an individual child on a
given reference distribution. The percentiles are
calculated for 3rd, l0th, 25th, 50th, 75th and 97th etc
values. The observations between 3rd and 97th
percentiles include 94% children; this also represents
children with mean: + 2 SD. The 50th percentile (median
value) is similar to mean, if there is Gaussian distribution.
For any age 50th percentile indicates that for the given
parameter 50% children are taller and 50% shorter than
the boy/girl under measurement.
As recommended by the lAP growth curves and
tables with percentile distributions for height, weight and
skull circumference are given for boys as well as girls for
birth to 3 years of life (Figs 4.2.1 and 4.2.2), and height
and weight for 2-18 years for boys and 2-17 years for
girls (Figs 4.2.4 and 4.2.5 and Tables 4.2.2 and 4.2.3).
Measure childs height/weight or skull circumference
then put your scale or pencil on the age of the child and
mark this parameter on the curve and note in which
percentile the measured parameters fall.

TABLE 4.2.2: Height or length percentile (in cm) for Boys and Girls:
Birth to 18 years of age (Indian affluent and NCHS data)
Indian affluent
percentiles
Boys
Age
NCHS
percentiles
Girls
Boys
3rd
50th
97th
3rd
50th
97th
47.6
56.3
62.5
66.8
70.1
75.6
80.1
84.0
87.3
90.2
92.8
95.3
97.9
100.7
103.9
106.1
108.5
110.8
113.3
115.6
118.0
120.3
122.7
125.1
127.5
129.9
132.4
134.
137.4
140.0
142.6
145.2
148.0
150.8
153.6
156.6
159.6
162.7
161.0
50.4
59.4
65.9
70.6
74.3
80.7
86.0
90.5
94.4
97.7
100.8
103.7
106.2
110.0
113.6
117.3
119.7
121.6
123.6
125.7
128.2
130.8
133.6
136.6
139.6
142.7
145.8
148.9
152.0
154.9
157.6
160.2
162.5
164.6
166.3
167.7
168.7
169.3
169.8
53.2
63.8
70.8
75.4
78.8
84.9
90.5
95.9
100.8
105.2
109.3
113.1
116.4
119.5
122.2
128.4
130.8
133.2
135.8
138.5
141.4
144.5
147.7
151.0
154.3
157.5
160.8
163.9
166.9
169.7
172.3
174.7
176.8
178.5
179.8
180.7
181.2
181.1
181.6
47.5
55.8
61.6
65.6
68.6
73.8
78.2
82.0
85.3
88.3
91.2
94.1
97.2
100.6
104.5
104.5
107.1
109.7
112.3
115.0
117.8
120.6
123.4
126.1
128.8
131.4
133.9
136.3
138.5
140.6
142.4
144.1
145.5
146.6
147.5
148.0
148.3
50.3
59.1
65.5
70.0
73.5
79.8
85.0
89.9
93.3
96.7
99.8
102.9
106.0
109.3
113.1
114.5
117.4
120.3
123.2
126.2
129.2
132.3
135.2
138.1
140.9
143.5
146.0
148.3
150.4
152.2
153.8
155.1
156.0
156.6
156.8
156.5
157.0
53.1
62.9
69.7
74.5
78.0
84.4
90.2
95.3
99.9
104.0
107.6
110.9
113.8
116.4
118.7
126.0
129.3
132.8
136.4
139.8
143.1
146.2
149.0
151.7
154.2
156.5
158.5
160.4
162.1
163.5
164.7
165.8
166.5
167.1
167.4
167.6
168.0
Birth
3
6
9
12
18
24
30
36
42
48
54
60
66
72
6.5
7.0
7.5
8.0
8.5
9.0
9.5
10.0
10.5
11.0
11.5
12.0
12.5
13.0
13.5
14.0
14.5
15.0
15.5
16.0
16.5
17.0
17.5
18.0
Girls
3rd
50th
97th
3rd
50th
97th
46.2
56.1
62.8
67.4
71.0
76.7
81.3
85.8
89.9
91.5
94.9
98.2
101.3
104.2
107.0
109.6
112.1
114.1
116.9
119.2
121.5
123.7
126.0
128.3
130.6
133.0
135.5
138.1
140.9
143.8
147.0
150.4
153.8
157.1
160.0
162.3
163.9
164.5
164.4
50.5
61.1
67.8
72.3
76.1
82.4
87.6
92.3
96.5
99.1
102.9
106.6
109.9
113.1
116.1
119.0
121.7
124.4
127.0
129.6
132.2
134.8
137.5
140.3
143.3
146.4
149.7
153.0
156.5
159.9
163.1
166.2
169.0
171.5
173.5
175.2
176.2
176.7
176.8
54.8
66.1
72.9
77.3
81.2
88.1
94.0
98.7
103.2
106.7
111.0
114.9
118.6
122.0
125.2
128.3
131.3
134.2
137.0
139.9
142.8
145.9
149.0
152.3
155.9
154.7
163.8
167.9
172.0
175.9
179.2
182.0
184.2
185.8
187.1
188.0
188.6
189.0
189.2
45.8
54.9
61.0
65.3
69.0
75.1
80.3
84.9
88.8
90.6
94.0
97.2
10..1
102.8
105.4
107.9
110.3
112.6
115.0
117.5
120.0
122.6
125.4
128.5
131.7
135.2
138.7
141.9
144.6
146.5
147.8
148.6
149.1
149.5
149.9
150.4
151.1
49.9
59.5
65.9
70.4
74.3
80.9
86.5
91.3
95.6
97.9
101.6
105.1
108.4
111.6
114.6
117.6
120.6
123.5
126.4
129.3
132.2
135.2
138.3
141.5
144.8
148.2
151.5
154.6
157.1
159.0
160.4
161.2
161.8
162.1
162.4
162.4
163.1
53.9
64.2
70.9
75.6
79.6
86.7
92.6
97.7
102.3
105.3
109.2
113.0
116.7
120.3
123.9
127.4
130.9
134.3
137.7
141.1
144.5
147.8
151.2
154.5
157.8
161.2
164.4
167.2
169.7
171.6
172.6
173.9
174.5
174.8
175.0
175.0
175.0
(Source: Data from (1) Agarwal DK et al. Physical and sexual growth pattern of affluent Indian children from 5 to 18 years of age.
Indian Pediatr 29:120382, 1992, (2) Agarwal DK et al. Physical growth in Indian affluent children (Birth to 6 years). Indian Pediatr
21:377413, 1994. and (3) Hamill PVV et al. NCHS growth curves for children Birth18 years. National Center for Health Statistics,
Publ. No. DHS 8781650, 1977. Hyattsville MD,USA)
Figure 4.2.4: Percentiles for height (cm) and weight (kg) (Boys 2-18 years)
Data source Agarwal et al. Indian Pediatrics 1992 and 1994
89
Figure 4.2.5: IAP growth curve: Percentiles for height (cm) and weight (kg) (Girls 2-17 years)
Data Agarwal et al. Indian Pediatrics, 1992 and 1994
91
TABLE 4.2.3: Weight (kg) Percentiles of Boys and Girls : Birth to 18 years (Indian affluent and NCHS data)
Indian affluent
percentiles
Boys
3rd
2.5
4.8
6.2
7.2
7.8
8.9
9.8
10.6
11.3
11.9
12.5
13.1
13.8
14.5
15.3
15.7
16.2
16.8
17.5
18.2
19.2
19.9
20.9
21.9
22.9
24.1
25.3
26.7
28.1
29.6
31.2
32.9
34.6
36.5
38.5
40.6
42.8
45.2
47.6
50th
3.1
5.7
7.4
8.5
9.3
10.7
11.9
12.9
13.8
14.6
15.4
16.2
17.1
18.1
19.2
20.0
21.0
22.0
22.6
23.5
24.4
25.6
27.0
28.7
30.6
32.7
34.8
37.1
39.4
41.8
44.1
46.3
48.6
50.5
52.4
54.0
55.5
57.2
58.6
Age
NCHS
percentiles
Girls
97th
4.0
6.7
8.6
10.1
11.2
13.1
14.7
16.0
17.2
18.3
19.3
20.3
21.5
22.7
24.2
27.7
29.7
31.6
33.5
35.5
37.7
40.1
42.7
45.4
48.2
51.1
54.1
57.1
60.0
63.0
65.9
68.7
71.4
73.9
76.3
78.5
80.5
82.2
83.6
3rd
2.5
4.5
5.9
6.8
7.5
8.6
9.4
10.1
10.8
11.3
11.9
12.6
13.4
14.4
15.7
14.4
14.8
15.3
15.9
16.4
17.1
18.3
19.5
20.9
22.3
23.7
25.1
26.5
27.9
29.3
30.7
32.1
33.4
34.6
35.7
36.7
37.6
50th
3.2
5.4
7.0
8.1
9.0
10.4
11.6
12.6
13.5
14.3
15.1
15.9
16.8
17.8
18.9
18.3
19.0
19.9
20.8
22.0
23.5
25.1
26.9
28.9
30.9
32.9
35.0
37.1
39.1
41.0
42.7
44.3
45.7
46.8
47.7
48.2
48.4
Boys
97th
3.9
6.6
8.4
9.6
10.5
12.2
13.7
15.2
16.7
18.0
19.4
20.6
21.9
23.1
24.3
25.4
27.5
29.8
32.3
34.9
37.7
40.5
43.4
46.4
49.3
52.2
55.1
57.9
60.7
63.2
65.7
67.9
70.0
71.8
73.3
74.3
75.6
Birth
3
6
9
12
18
24
30
36
42
48
54
60
66
72
6.5
7.0
7.5
8.0
8.5
9.0
9.5
10.0
10.5
11.0
11.5
12.0
12.5
13.0
13.5
14.0
14.5
15.0
15.5
16.0
16.5
17.0
17.5
18.0
3rd
2.5
4.2
6.0
7.4
8.2
9.3
10.1
10.9
11.8
12.4
13.1
13.9
14.7
15.5
16.3
17.1
17.9
18.7
19.5
20.2
21.0
21.8
22.7
23.7
24.8
26.1
27.6
29.3
31.2
33.4
35.9
38.4
40.9
43.4
45.7
47.8
49.6
51.0
52.0
50th
3.3
6.0
7.8
9.2
10.2
11.5
12.6
13.7
14.7
15.7
16.7
17.7
18.7
19.7
20.7
21.7
22.9
24.0
25.3
26.7
28.1
29.7
31.4
33.3
35.3
37.5
39.8
42.3
45.0
47.8
50.8
53.8
56.7
59.5
62.1
64.4
66.3
67.8
68.9
Girls
97th
4.2
7.6
9.7
11.1
12.2
13.8
15.0
16.2
17.5
19.3
20.5
21.8
23.2
24.7
26.2
27.9
29.8
31.8
34.1
36.5
39.2
42.1
45.2
48.4
51.7
51.1
58.7
62.3
65.9
69.5
73.2
76.7
80.1
83.4
86.4
89.2
91.6
93.7
95.3
3rd
2.3
4.0
5.6
6.7
7.6
8.6
9.6
10.5
11.3
12.1
12.8
13.4
14.0
14.6
15.3
15.9
16.7
17.4
18.3
19.2
20.2
21.3
22.5
23.8
25.2
26.7
28.3
30.0
31.7
33.5
35.2
36.8
38.3
39.7
40.8
41.6
42.3
50th
3.2
5.4
7.2
8.6
9.5
10.8
11.9
12.9
13.9
15.1
16.0
16.8
17.7
18.6
19.5
20.6
21.8
23.3
24.8
26.6
28.5
30.5
32.5
34.7
37.0
39.2
41.5
43.8
46.1
48.3
50.3
52.1
53.7
55.0
55.9
56.4
56.7
97th
3.9
6.9
8.9
10.4
11.5
13.0
14.3
15.7
17.0
19.1
20.4
21.6
22.9
24.3
25.8
27.6
29.7
32.2
35.0
38.0
41.3
44.7
48.2
51.8
55.3
58.7
62.0
65.1
68.0
70.7
73.0
75.1
76.8
78.2
79.1
79.7
80.0
(Source: Data from (1) Agarwal DK et al. Physical and sexual growth pattern of affluent Indian children from 5 to 18 years of age.
Indian Pediatr 29:120382, 1992, (2) Agarwal DK et al. Physical growth in Indian affluent children (Birth to 6 years). Indian Pediatr
21:377413, 1994. and (3) Hamill PVV et al. NCHS growth curves for children Birth18 years. National Center for Health Statistics,
Publ. No. DHS 8781650, 1977. Hyattsville MD,USA)

TABLE 4.2.4: BMI (Mean +SD) and Percentiles for Indian Boys
Age (Years)
5
6
7
8
9
10
11
12
13
14
15
16
17
18
97
358
501
585
701
1135
1476
1652
1591
1433
1093
771
361
87
Mean
14.4
14.8
15.0
15.2
15.6
16.1
16.6
17.1
17.7
18.2
19.2
19.7
20.1
20.4
Percentiles
SD
1.31
1.34
1.57
1.83
2.09
2.42
2.71
2.72
3.03
2.90
3.12
3.09
2.83
3.36
10
25
50
75
85
95
12.4
13.0
13.0
12.9
12.9
13.2
13.3
13.6
14.0
14.5
15.4
15.8
16.3
15.7
12.8
13.4
13.5
13.3
13.4
13.6
13.8
14.2
14.5
15.1
15.9
16.5
16.9
16.8
13.5
13.9
14.0
14.0
14.2
14.5
14.7
15.2
15.5
16.3
16.9
17.4
17.8
17.8
14.4
14.7
14.8
14.8
15.1
15.4
15.8
16.4
17.1
17.7
18.4
19.1
19.7
20.0
15.0
15.4
15.7
15.9
16.4
17.0
17.6
18.3
19.0
19.6
20.5
21.1
21.5
22.5
15.6
15.9
16.4
17.0
17.3
18.5
19.1
19.8
20.4
21.1
22.0
22.7
24.4
23.6
17.0
17.8
18.8
19.7
21.0
22.1
23.4
23.8
25.3
25.3
27.3
27.6
26.8
28.0
N = Number of children.
TABLE 4.2.5: BMI mean (+ SD) and percentiles for Indian Girls
Age (Years)
5
6
7
8
9
10
11
12
13
14
15
16
17
18
254
449
596
640
784
933
906
893
782
627
383
27
119
27
Mean
14.4
14.5
15.0
15.7
15.7
16.7
17.5
18.4
19.2
19.7
20.0
20.5
20.3
20.9
Percentiles
SD
1.5
1.7
1.9
2.32
2.5
6.6
3.1
3.2
3.6
3.2
3.3
3.2
3.1
3.2
10
25
50
75
85
95
12.3
12.4
12.5
12.8
12.5
13.0
13.5
13.9
14.6
15.4
15.9
15.9
16.6
16.9
12.7
12.9
12.9
13.2
13.1
13.6
14.1
14.6
15.3
16.0
16.5
16.6
16.9
11.9
13.5
13.5
13.5
13.9
14.0
14.6
15.2
15.9
16.7
17.3
17.7
18.1
18.3
18.3
14.3
14.3
14.6
14.9
15.1
16.1
16.9
17.8
18.6
19.0
19.3
20.0
20.1
20.0
15.2
15.3
15.7
16.5
16.8
18.2
19.0
20.1
21.0
21.4
22.0
22.4
22.0
23.0
15.7
16.0
16.6
18.0
18.0
19.9
20.6
21.9
22.6
23.0
23.6
23.1
23.0
23.2
18.3
18.8
19.7
21.4
21.7
23.2
24.5
25.7
27.1
27.4
27.7
27.4
25.9
N = Number of children.
Methods to measure height, weight and skull circumference

are discussed in other chapters.
The human growth velocity is measured as gains in
length, skull circumference and weight this is most rapid
during 3 months (3rd trimester) of gestation and 4-5
months after birth, than at any other age. Deceleration
in growth continues throughout childhood. In mid
childhood particularly in boys there is growth spurt term
adenarche this is related to androgens released from the

adrenal cortex. By the onset of puberty girls average 140
cm and boys around 150 cm (due to 2 extra years of
growth before the pubertal growth).
Growth velocity (the height velocity) is the rate
growth over a fixed time interval. The velocity must
oscillate closer to the 50th centile (if < 3rd percentile slow
growth; if> 90th percentile rapid growth- both are
Figure 4.2.6: IAP growth curve: Percentiles for body mass index (BMI) (boys 2-18 years)
Prepared from Indian Pediatrics 1994;p-377 and 2001;p-1217 (DK Agarwal, AK Bansal and KN Agarwal)
93
Figure 4.2.7: IAP growth curve: Percentiles for body mass index (BMI) (girls 2-17 years)
Prepared from Indian Pediatrics 1994;p-377 and 2001;p-1217 (DK Agarwal, AK Bansal and KN Agarwal)
abnormal). The velocity change is the earliest evidence of

alteration in growth rate as compared to distance growth
curve. Thus a doctor can suspect disease/nutrition
deprivation/behavioral problem if the velocity falls.
Body growth: The growth is cephalocaudal in directionheadneckarmstrunk and legs. It is also distoproxi-
mal, i.e. trunk-arms become functional before-hands fingers (pincer grasp).

Body Mass Index (BMI; kg/m2) the ratio of weight in kg to
the square of height in meters is a good indicator of
energy reserves and diagnoses obesity and under
nutrition (Tables 4.2.4 and 4.2.5; Figs 4.2.6 and 4.2.7 for
95
TABLE 4.2.6: Percentile for Head, Chest and Midarm

circumferences in (cm) of Boys and Girls between birth-72
months of age
3rd
Boys
50th
97th
Age (month)
3rd
Girls
50th
97th
34.8
39.8
42.8
44.4
45.3
46.6
47.6
48.4
49.0
49.4
49.7
50.0
50.3
50.7
51.2
36.7
41.9
44.9
46.5
47.4
48.7
49.7
50.5
51.1
51.6
52.1
52.6
53.1
53.8
54.6
Birth
3
6
9
12
18
24
30
36
42
48
54
60
66
72
33.0
37.6
40.3
41.8
42.7
43.8
44.6
45.2
45.6
45.8
46.0
46.2
46.5
47.0
47.8
34.6
39.5
42.4
44.1
45.0
46.2
47.2
47.8
48.2
48.5
48.7
49.1
49.5
50.2
51.2
36.5
41.1
44.0
45.6
46.5
48.0
49.1
50.0
50.8
51.4
51.9
52.5
53.0
53.7
54.6
32.6
38.4
42.0
44.1
45.4
47.4
49.0
50.2
51.1
51.8
52.4
53.1
53.8
54.7
55.9
34.8
42.1
46.5
48.9
50.2
52.2
53.7
55.0
55.9
56.7
57.7
58.3
59.1
60.2
61.6
Birth
3
6
9
12
18
24
30
36
42
48
54
60
66
72
30.3
35.7
38.9
40.8
41.8
43.3
44.4
45.1
45.7
46.1
46.6
47.1
47.8
48.8
50.3
32.4
38.0
41.6
43.7
45.0
46.9
48.4
49.4
50.2
50.9
51.4
52.1
52.9
54.0
55.4
34.8
41.3
45.2
47.4
48.7
50.7
52.4
53.5
54.4
55.9
56.8
57.7
58.6
59.5
60.6
Birth
3
6
9
12
18
24
30
36
42
48
54
60
66
72
8.4
9.5
10.4
11.1
11.7
12.6
13.2
13.5
13.6
13.6
13.6
13.7
13.8
14.2
14.8
9.9
12.2
13.5
14.1
14.3
14.7
15.0
15.2
15.4
15.7
15.8
16.0
16.2
16.4
16.7
11.1
13.7
15.2
15.9
16.2
16.7
17.1
17.4
17.8
18.1
18.3
18.6
18.8
18.9
19.1
Head
;
33.2
38.0
40.8
42.4
43.3
44.6
45.5
46.2
46.6
46.9
47.0
47.2
47.4
47.6
48.1
Chest
30.9
36.2
39.4
41.3
42.4
44.1
45.4
46.3
47.0
47.5
48.0
48.5
49.2
50.1
51.4
Midarm circumferences
8.9
10.0
10.8
11.4
11.9
12.6
13.2
13.6
13.9
14.0
14.1
14.2
14.2
14.3
14.4
9.8
12.3
13.7
14.3
14.5
14.8
15.0
15.2
15.4
15.6
15.8
16.0
16.2
16.5
16.7
1.3
14.2
15.7
16.4
16.6
17.0
17.2
17.5
17.8
18.1
18.4
18.7
19.0
19.4
19.8
(Source: Agarwal DK, Agarwal KN. Indian Pediatrics 31:377:

413,1994)
Figure 4.2.8: Surface area nomogram modified from the data

of E Boyd by CD West (Source: Nelsons Textbook of
Paediatrics, 12th edition 1983. WB Saunders and Co.)
affluent Indian children). Children with BMI >95th

percentile for age and sex are obese and those <5 th
percentile are thin. BMI is sex and age specific in children
and changes as they grow older.
Ponderal Index: (kg/m3) the main clinical application is
in the new born period. PI< 2.0 suggests symmetrical
IUGR (retarded fetal growth).

Body Proportions
The body proportion can be assessed by measuring lower
body segment (L) by taking length from symphysis pubis
to the floor. The upper segment is obtained by subtracting
lower segment from height of the child. The ratio of upper
to lower segment is 1.7 at birth; 1.3 at 3 year of age and
1.0 at 7 years of age. Higher U/L ratio may indicate shortlimbed dwarfism or bone disorders such as rickets.
There are racial differences in body proportions:
a. Africans have longer legs and arms, narrower hips
as compared to shoulders.
b. Chinese have longer arms to legs and broader hips.
c. Japanese have larger trunk to legs.
d. Indians and Europeans are similar.
e. In spite of similar environment, Afro-Americans are
taller than Americans but Asians are shorter than
Europeans.
Mid-arm circumference: Measured mid way between
acromian and olecranon processes (left upper arm). It
increases from 9.8 at birth to 14.5 cm at 1 year of age.
Between 1-5 years there is increase from 14.8 to 16.2 cm
(Table 4.2.6). For this age period of 1-5 years >13.5 cm is
taken as normal children with 12.5-13.4 cm are having
mild to moderate undernutrition and those <12.4 as
severe under nutrition.
Chest circumference: It can be recorded at the level of nipples.

It overtakes head circumference by 8-10 months of age
(Table 4.2.6).
Body surface area: In pediatric practice, the growth
parameters of height and weight are used to calculate
Body surface area useful in calculating fluids and drug
doses (Fig. 4.2.8).
BIBLIOGRAPHY
1. Agarwal DK, Agarwal KN, Upadhyay SK et al. Physical
and sexual growth pattern of affluent Indian children
from 5 to 18 years of age. Indian Pediatr 1992;29:1203
82.
2. Agarwal DK, Agarwal KN. Physical growth in Indian
affluent children (Birth6 years). Indian Pediatr 1994;
31:377413.
3. Agarwal KN, Saxena A, Bansal AK, Agarwal DK. Physical
growth in adolescence. Indian Pediatr 2001; 38:1217-35.
4. Hamill PVV, Johnson CL, Red RV et al. NCHS growth
curves for children, Birth18 years. Hyattsville MD,
National Center for Health Statistics. Publication number
DHS 1997;8781650.
5. Khadilkar VV, Khadilkar AV, Choudhury P, Agarwal
KN, Ugra D, Shah NK. IAP Growth monitoring
guidelines for children from birth to 18 years. Indian
Pediatr 2007; 44:187-97.
4.3 Physical Growth and

Sexual Development in Adolescence
The morphological and physiological changes during
Adolescent Growth Spurt involve nearly all organs of
the body. These changes do not begin at the same age
point or take the same length of time in all individuals to
reach completion. During Puberty somatic as well as
skeletal growth is related to sexual development (Sexual
maturity rating by Tanner, 1962 and Marshall and Tanner
1985), as adolescent growth is initiated and controlled
by the sex hormones. Thus for assessment of their growth
means for height, weight (Tables 4.3.1 and 4.3.2), BMI
(Table 4.3.3) skin fold thickness etc in relation to sexual
maturity are more relevant than those obtained for

chronological age (Figs 4.3.1 and 4.3.2).
This chapter discusses pattern of physical growth and
sexual development during adolescent growth spurt. The
reasons for earlier initiation of Puberty and completion
of adolescent growth in girls as compared to boys are
discussed. It also presents the growth tables relevant in
assessment of growth during pre adolescence (as
initiation of puberty has big age range) and adolescence
based on Indian affluent children growth data by
Agarwal et al 1992, 1994, 2001 and 2007.
97
TABLE 4.3.1: Showing weight and height percentiles in relation to genital development and age in boys
Age (yrs)
10
25
50
75
90
97
Number
Genital development stage (SMR)

10
Wt.
23.0
25.3
Ht.
128.2
130.8
11
Wt.
24.5
27.0
Ht.
130.7
134.7
12
Wt.
26.1
28.1
Ht.
133.8
137.3
13
Wt.
28.2
30.2
Ht.
136.5
141.0
14
Wt.
31.4
32.2
Ht.
142.4
145.7
27.5
135.5
29.4
138.5
31.0
141.7
32.5
145.0
35.0
148.6
31.1
139.7
32.6
142.4
34.9
145.5
36.5
149.0
38.9
153.4
35.3
144.6
37.0
146.8
39.9
150.0
41.5
152.2
42.5
156.6
40.8
148.5
42.9
151.0
46.3
154.5
52.2
156.0
49.0
159.9
48.2
151.3
51.0
155.3
55.8
159.3
61.2
160.6
62.1
166.6
259

10
Wt.
23.8
26.2
Ht.
127.8
134.6
11
Wt.
28.4
29.7
Ht.
134.2
139.6
12
Wt.
28.7
32.4
Ht.
139.6
143.4
13
Wt.
30.4
32.7
Ht.
141.5
142.2
14
Wt.
32.8
34.7
Ht.
145.7
149.3
15
Wt.
37.2
38.0
Ht.
152.5
152.5
16
Wt.
39.6
41.8
Ht.
154.6
157.0
28.9
137.8
32.8
143.6
35.4
148.2
35.8
149.5
38.2
153.5
42.0
156.1
44.1
157.4
34.7
145.6
36.4
148.0
39.0
152.2
39.9
154.1
42.8
157.8
46.1
161.1
50.2
162.0
40.2
151.8
41.8
153.1
44.2
156.4
45.6
158.5
48.6
161.8
51.3
166.0
55.3
165.6
45.4
155.1
46.7
158.5
50.6
160.5
51.7
162.1
54.4
165.6
61.6
169.3
63.7
172.8
49.1
159.1
50.9
163.0
59.4
163.0
61.9
166.9
64.8
169.1
77.0
172.7
71.9
179.6

11
Wt.
27.9
35.8
Ht.
138.8
147.4
12
Wt.
32.1
35.1
Ht.
143.0
148.4
13.
Wt.
33.8
36.8
Ht.
147.0
151.5
14
Wt.
34.8
38.5
Ht.
148.5
154.0
15
Wt.
39.2
41.7
Ht.
154.0
157.0
16
Wt.
41.8
43.5
Ht.
156.7
159.0
17
Wt.
43.9
45.7
Ht.
160.3
161.0
39.7
150.9
38.4
153.1
41.1
156.0
42.5
158.0
45.2
161.0
47.8
162.5
48.4
164.1
43.2
156.4
43.0
157.9
45.6
160.2
47.7
162.6
50.8
165.5
52.6
166.5
55.1
167.8
49.0
161.3
47.7
162.5
51.1
165.0
52.7
167.5
56.5
169.3
60.2
171.5
62.9
173.7
54.3
163.0
54.1
167.0
59.4
168.5
58.9
171.2
65.7
172.8
69.5
175.0
68.6
177.5
58.6
166.0
61.0
168.9
71.1
172.6
68.6
174.8
75.2
176.3
76.6
178.9
76.2
184.3

13
Wt.
39.3
41.3
Ht.
152.9
157.6
14
Wt.
40.5
42.9
Ht.
153.7
158.0
15
Wt.
41.6
44.0
Ht.
156.5
159.2
16
Wt.
42.5
45.4
Ht.
157.9
160.2
17
Wt.
44.8
47.1
Ht.
160.3
162.0
18
Wt.
43.9
46.5
Ht.
157.5
163.8
45.8
160.5
46.8
162.0
47.3
163.5
50.0
164.7
52.3
165.4
51.7
166.5
50.5
164.9
52.0
166.0
52.3
167.0
55.0
168.9
57.1
169.3
58.3
170.0
57.2
169.1
57.7
170.7
59.6
171.5
62.5
173.5
63.1
173.3
64.5
173.0
65.7
173.0
65.8
174.1
69.2
174.5
70.5
177.2
70.9
176.5
74.7
177.9
71.3
177.4
77.3
178.2
77.9
179.4
82.3
181.5
80.6
181.0
84.9
183.2
(Source: Indian Pediatrics 2001;38:1217-35)
480
518
287
91
64
165
366
467
311
116
45
28
156
430
555
407
210
68
80
316
461
420
259
75

TABLE 4.3.2: Showing weight and height percentiles in relation to breast development and age in girls percentiles
Age (yrs)
10
25
50
75
90
97
Breast development stage (SMR)

10
Wt.
23.0
26.4
Ht.
127.7
131.5
11
Wt.
24.5
26.7
Ht.
131.1
134.3
12
Wt.
25.8
27.2
Ht.
134.9
137.6
13
Wt.
27.0
29.1
Ht.
139.9
141.3
29.3
135.4
29.0
137.7
29.9
140.0
30.7
144.9
32.3
139.4
32.2
142.5
33.2
144.5
36.1
149.5
36.5
143.9
36.8
146.2
37.4
149.1
41.0
153.7
42.3
147.3
42.1
149.7
43.0
152.6
46.8
161.0
49.9
151.0
50.6
154.7
48.7
157.7
50.9
165.2
383

10
Wt.
29.0
31.2
Ht.
134.9
138.5
11
Wt.
30.1
32.4
Ht.
138.0
140.0
12
Wt.
30.9
33.6
Ht.
140.0
143.5
13
Wt.
32.0
33.5
Ht.
141.5
145.0
14
Wt.
32.4
34.2
Ht.
144.0
145.8
15
Wt.
34.8
37.8
Ht.
146.5
149.0
16
Wt.
36.2
37.2
Ht.
147.1
148.9
33.1
141.0
34.8
143.2
35.9
146.0
36.3
148.0
38.8
150.0
39.1
150.6
38.2
152.0
37.6
144.3
38.8
147.0
39.4
150.2
40.0
151.9
42.9
154.2
43.0
155.0
43.0
155.2
43.0
147.5
43.5
150.5
44.5
153.5
45.0
156.7
47.0
157.0
46.5
157.3
46.8
158.4
48.9
150.5
48.3
154.5
51.2
157.3
50.6
160.1
52.1
161.7
48.2
162.7
52.6
163.5
53.0
153.7
56.2
157.1
57.2
162.0
60.6
163.3
58.3
164.5
53.2
164.9
55.2
168.3
131

11
Wt.
29.9
35.5
Ht.
138.2
142.7
12
Wt.
34.4
37.8
Ht.
142.7
145.3
13.
Wt.
33.4
37.6
Ht.
144.0
146.2
14
Wt.
35.7
38.0
Ht.
145.1
146.5
15
Wt.
35.7
38.7
Ht.
146.2
148.2
16
Wt.
38.2
39.5
Ht.
147.1
148.7
17
Wt.
37.4
39.7
Ht.
148.0
149.3
39.3
147.0
40.2
148.5
40.5
150.1
40.9
150.5
42.3
152.0
43.5
152.7
43.0
152.0
43.6
150.3
44.5
152.0
44.3
153.3
44.4
154.5
45.8
155.0
48.0
156.0
47.7
155.5
49.6
154.5
49.3
156.0
49.6
157.1
50.3
157.7
50.4
159.0
53.3
159.9
51.5
159.0
54.9
156.3
53.9
159.3
55.3
160.6
55.3
161.6
56.0
161.7
57.3
163.0
54.2
165.0
58.7
161.7
59.1
161.9
64.3
164.2
63.6
167.0
64.5
167.7
66.4
167.1
59.3
166.8
115

12
Wt.
39.0
42.7
Ht.
142.8
147.5
13
Wt.
39.4
42.0
Ht.
143.0
147.5
14
Wt.
37.1
41.5
Ht.
145.6
147.8
15
Wt.
36.5
41.5
Ht.
146.2
148.1
16
Wt.
38.4
41.8
Ht.
147.1
148.2
17
Wt.
41.2
43.4
47.3
149.8
45.7
150.5
45.4
151.5
44.9
151.5
46.4
152.8
48.0
52.8
152.6
51.8
155.1
51.4
155.0
49.9
156.0
50.5
156.6
53.2
58.6
156.8
59.3
160.5
57.3
159.5
58.5
160.8
58.0
159.9
57.7
63.3
161.1
66.2
163.8
65.0
162.2
66.2
164.5
64.8
163.0
62.8
66.1
163.2
71.5
167.8
73.2
165.6
72.4
168.0
75.2
166.9
77.0
(Source: Indian Pediatrics 2001;38:1217-35)
Number
353
195
53
316
330
242
143
71
34
244
304
264
142
89
33
88
178
189
187
148
60
99
TABLE 4.3.3: Showing Body Mass Index (BMI) in adolescents in relation to sexual development and age
BMI percentiles kg/m2
Age
yrs
5
15
50
85
90
95
15
50
85
90
95
G
B
SMR. 2
13.4
13.0
14.2
13.7
16.5
15.4
20.1
17.6
20.7
17.9
21.7
18.7
SMR. 3
10
G
B
13.7
13.5
14.6
14.3
16.7
15.9
20.2
18.7
21.0
20.0
22.6
21.5
14.7
13.7
15.6
14.7
18.0
16.1
21.5
18.9
22.6
19.4
23.8
20.1
11
G
B
13.3
13.5
14.2
14.4
15.8
15.9
18.9
19.1
20.2
20.2
22.5
21.6
14.9
14.1
15.8
15.0
18.0
16.6
1.2
19.0
22.2
19.8
24.1
21.3
12
G
B
13.4
13.6
14.2
14.4
15.8
16.2
18.9
19.5
19.5
20.8
20.8
22.4
14.7
14.2
15.6
15.2
17.6
16.7
20.8
19.8
21.9
20.9
24.3
23.5
13
G
B
13.3
14.0
14.2
14.7
15.4
16.4
18.3
21.1
19.6
22.3
21.4
24.5
14.5
14.0
15.3
14.9
17.4
16.8
20.1
20.2
21.4
20.7
23.3
23.2
14
G
B
15.1
15.7
17.9
21.0
21.8
23.2
SMR-4
SMR-5
11
G
B
16.1
16.7
19.0
23.0
23.6
24.9
12
G
B
15.1
14.5
16.9
15.6
19.2
17.0
22.1
19.8
23.0
20.9
24.3
22.3
17.0
19.2
22.5
25.7
26.9
27.8
13
G
B
15.6
14.9
16.6
15.7
18.9
17.8
21.8
21.1
22.6
21.9
24.9
44.4
17.0
15.5
18.6
16.9
21.6
18.7
25.2
21.7
26.3
22.6
27.8
23.7
14
G
B
15.5
14.7
16.5
15.8
18.8
17.7
21.9
20.8
23.0
21.7
24.3
23.8
16.8
15.4
18.4
16.4
21.2
18.6
24.5
22.3
26.2
23.5
27.7
25.2
15
G
B
16.0
15.4
16.9
16.4
19.0
18.4
22.3
22.0
23.5
23.7
25.2
25.7
16.5
15.5
17.8
16.5
20.7
18.9
25.1
22.3
25.8
23.9
26.7
25.8
16
G
B
16.1
15.9
17.2
16.9
19.6
18.9
23.1
22.7
24.5
23.9
25.9
25.3
16.5
15.8
17.5
17.1
21.2
19.3
24.9
22.7
26.7
23.8
28.1
26.0
17
G
B
16.5
16.2
17.1
17.1
19.5
19.3
21.6
22.3
22.1
23.4
23.2
25.5
16.7
16.2
18.2
17.3
21.3
20.1
24.2
23.0
25.3
23.9
26.3
26.2
SMR = Sexual maturity rating; G = Girls and B = Boys.

Indian Pediatr 2001;38:1217.35.
STAGES OF PUBERTAL DEVELOPMENT
Puberty Encompasses
Clinically identifiable stage in development of secondary

sexual characteristics for girls and boys are summarized
below. The values in parentheses give mean age of
appearance or % of adolescents (Indian affluent data)
having appearance in that stage.
These features in girls and boys help to rate the sexual
maturity, once this is done it is easier to assess growth of
the individual adolescent in relation to SMR and age.
Somatic Growth and Sexual Development

1.
2.
3.
4.
Adolescent growth spurt

Development of secondary sexual characteristics.
Attainment of fertility.
Establishment of individual sexual identity.
Timing for Puberty onset has wide variability Girls
8-12 years and Boys9-14 years of age.
100
A. Development of Breast and Pubic Hair in Girls

Sexual maturity
Stages (SMR)
1.
2.
3.
4.
5.
Breast
Pubic hair (Mean age = 13.6 yr)
Preadolescent
Bud stage and papilla elevated
as small mould (10.2 yr)
Areola enlarged no contour separation (11.6 yr)
Areola and papilla form secondary mound (13.6 yr)
Mature nipple projects, areola part
of general breast contour( 15.6 yr)
Preadolescent
Sparse lightly pigmented straight
around medial border of labia (22%)
Darker, more and curl + (92%)
Coarse curly abundant (98.8%)
Adult feminine triangle spread
to medial surface of thigh (100%)
B. Development of Genitals and Pubic Hair in Boys

SMR
1.
2.
3.
4.
5.
Penis
Scrotum and testes
Pubic hair
Preadolescent
Slight or no pigmented
enlargement (11.3 yr)
Longer (12.8 yr)
Larger, glans +
breadth increased (14.1 yr)
Adult size (16.4 yr)
Testes <4 ml
Enlarged darker scrotum
Pigmented
Testes 6-8 ml
Testes 10-12 ml
scrotum dark
Testes 12 ml
None
Scanty long slightly (60%)
Puberty Growth Spurt -related to

Adrenal Steroids
There is increase in general growth rate of skeleton, muscle
mass and viscera.
During adolescent growth spurtthis growth in girls
is evident shortly before the appearance of mammary
budding. The budding of breast (Thelarche) is due to
secretion of ovarian estradiol. Estradiol stimulates
growth hormone secretion; the growth velocity is
doubled (Peak Height Velocity). The adrenal androgens
initiate pubic/axillary hair growth and the onset of
apocrine sweat production, though facilitated by the
estrogen. The peak height velocity (maximum body
growth9-10 cm/year) is at Tanner stages II and III of
mammary gland development. It is at this level of sexual
maturity in girls the menarche is attained. The growth
in the post menarchial period is limited as girls can gain
5-6 cm in linear growth, only. Thus the maximum gain
in height is pre-menarchial in Tanner stages II-III.
In boys the first evidence of adolescent growth spurt
is noted with increase in testicular volume over 4 ml. The
peak height velocity (10.5 cm/year) approaches at the
testicular volumes of 10-12 ml (Tanner stages III and IV).
Dark, small, curling + (97%)

Resemble adult type but less in
quantity and curls (99%)
Spread to medial surface of thigh,
Facial hair- 14.8 yr.
Testosterone is poor stimulator of the growth hormone

(both are synergistic); large quantity of testosterone must
collect to initiate growth hormone secretion. Therefore in
boys growth spurt and sexual development is delayed by
2 years. This gives advantage to boys for extra period for
growth. Testosterone is converted to Dihydrotestosterone
by 5 reductase. Both hormones induce growth of the
external genitals and pubic hair.
Achievements in Physical Growth during Puberty
a. Average duration of growth is 2.5 to 3 years.
b. Total gain in height: Boys average = 27-29 cm;
Girls = 24-26 cm.
At 10.5 yearsBoys and girls have similar height.
11.0-12.5 yearsGirls have higher mean height by 2
cm.
14.0 yearsBoys are taller by 5 cm
16.0 yearsBoys are taller by 12 cm.
c. Average Peak height velocity (PHV): is observed
in SMR-2 (breast stage-2); while in boys it is observed
in SMR-3. Boys have PHV of 10.5 cm/year around
G-3 to G-4 stages of sexual development. In Girls PHV
is comparatively lower 9.0 cm/year in B-2 to B-3 stage
of SMR. There is no relationship in normal boys and
101
Figure 4.3.1
girls between PHV and final height. Finally early and

late maturing end Up at exactly the same height. Total
weight gain during adolescence is around 1/4 of the
adult weight (around 25 to 30 kg). Peak weight
velocity is preceded by PHV. Early maturing are more
fatty and muscular, the late matures fattier.
d. Those undernourished also gain same height in
adolescence but do not show any PHV. During
adolescence early life stunting is not corrected. The
growth pattern in an undernourished adolescent is
summarized below (Agarwal 1986-92; ICMR report):
Height gain was similar to affluent Indian children
in adolescent growth spurt.
No age period could be identified for peak height
velocity.
Weight gain was 38% of the affluent Indian.

Deficit of early life in height was not corrected
during adolescent growth spurt
Rapid growth of undernourished adolescents has
been associated with hypertension.
Boys had delayed maturation of genitals by 1.54
yr.; pubic hair by 0.82-yr and axially hair by 0.65yr testicular vol was similar.
Girls had delayed breast development by
2.19 years.
Menarche was delayed by 0.82 year.
Growth is accelerated in obese children, generally they are
tall, and bone age is advanced but commensurate with
height age.
102
Figures 4.3.1 and 4.3.2: Shows genital development according to Tanner (Tanner 1962, Growth at adolescence 2nd Ed. Blackwell
Oxford). The height and weight data for affluent Indian children (Indian Pediatr 29:1203-82, 1992) in relation to genital development
are presented graphically, M = Mean, represents mean of all the children measured at a particular age; 2 to 5 lines, correspond
to means of children measured in the genital development stage for that age. To find the average height of a boy 14 years of age
in genital development stage 3, the value is 156.5 cm, but for stage 4 for the same age the value will be 161.5 cm. Therefore,
during the adolescent period growth is to be correlated with sexual development rather than age
Sexual Dimorphism
The growth and body composition is regulated by the sex
hormones. Shoulder growth is more in boys while girls have
more hip growth (wide hip). Boys have more growth for all
other measurements except for hip width as compared to
girls.
Boys as well as girls both start puberty with similar fat

and lean body mass content. The gain in lean body mass
is almost twice in boys as compared to the girls. Therefore
girls have more fat; finally it approaches around 25% of
total body weight as compared to 18% in boys. Boys who
are more active in sports also need more oxygen. Therefore

they have more Red Blood Cell mass (higher hemoglobin
as compared to girls) in order to provide oxygen.
Bone growth: Bone growth (bone mineral density): 50% of
the bone growth completes during first month of life to
puberty onset. b) 30% in puberty and remaining 20% in
late adolescence to adulthood. Therefore almost 50% of
the bone growth occurs during adolescence (period 2.5 to
3 years).
Brain growth: MRI studies show that the Maximum brain
growth related to organization and planning occurs in
older children in the rear of the brain- linked more to
language learning and spatial understanding. Thus brain
development continues.
Metabolic changes: Onset of puberty immediately raises
the demand on nutritional needs. During peak periods
of growth nutritional requirements are increased. These
correlate with sexual maturity rating (SMR) being highest
in SMR 2 and 3. The heart rate slows down and settles at
adult rate of 62-82/min. The blood pressure increases
and normal level 110-120 systolic and 60 to 80 diastolic
is achieved. The basal metabolic rate is high. The rate,
depth and type of respiration settle at 15-20/min. The
tidal volume increases to 1000 to 1500 ml/day.
Hematological values match the adult values.
Dietary requirements for adolescent growth: Energy-around
136500 Kcal as total cost of adolescent growth spurt. Peak
need in girls with budding of breast (SMR II and III) in
boys with testicular enlargement (SMR-III and IV) 2200
and 3000 Kcal respectively/day.
Protein 12-14% of energyFor Boys 0.34 g/cm of height
and girls 0.28 g/cm of height.
Fat < 30% of the total energy need. 7% saturated, 10%
polysaturated and 10% mono saturated fat. Cholesterol
ideally <200 mg/day.
During adolescence the early life lesions of
Atherosclerosis begin to accelerate 400 g of Folic acid
is recommended. Other B complex vitamins are
important to maintain cellular energy metabolism.
Vitamin D for Calcium absorption, etc.
ii. for social pressure to reach cultural ideals of

thinnessexcessive dieting, e.g. anorexia nervosa1% (more in girls) and bulimia-can lead to
renal failure, irregular heart rate, bone marrow
hypoplasia, osteoporosis and dental erosion.
b. Intensive physical training alters hypothalamicpituitary axis in adolescent girlsmenstrual
functions and reduced bone density.
Over Weight and Obese Diagnosis in
Indian Adolescents (Table 4.3.4)
The BMI values for Indian children 5-18 yr boys and girls
(Indian Pediatrics 200 IP 1220) are lower than the
NCHSWHO reference data WHO 1995 Physical Status
p 475. The supporting data also do not have sufficient
follow-up in India to show that those at extremes have
similar later life health consequences as seen in USA. It
was observed that BMI was closely similar for different
ages in the same sexual maturity rating. Thus suggesting
that during adolescence SMR related BMI will be a better
index to assess thinness (<5th centile); overweight and
obesity (> 85% and >95% centile, respectively).
The percentage of such children likely to be higher
in adolescence, if the sex maturity related criteria (SMR) of
diagnosis are used (use of BMI tables in relation to SMR).
Besides weight for age and sex and BMI the other
useful measurements are waist/ hip ration and skin fold
measurements.
TABLE 4.3.4: Showing BMI kg/m2 cut off for overweight

and obesity in relation to sexual maturity (SMR) for boys
(B) and girls (G) (Developed from the data in Indian
Pediatrics 2001; by Agarwal et al)
SMR
2
Adolescent BehaviorImplications for

Growth and Health
a. Extremes of nutrition intake:
i. Overeating resulting in overweight and obesity;
103
Overweight (>85%)
Obese (>95%)
19
22
19
21
19
20
21
23
22
25
22
24
22
26
25
27
104
TABLE 4.3.5: Age of appearance and fusion of ossification

centers. The following table gives the age of appearance
of ossification centers. The figures in the main head are
in years and indicates maximum age at which centers are
expected to appear. Figure in parenthesis indicate mean
age in months of appearance of these centers (Courtesy
Dr SK Bhargava and G Mehrotra)
Bone
Carpal bones
Capitate
Hamate
Triquetral
Lunate
Scaphoid
Trapezium
Trapezoid
Pisiform
Metacarpals
2nd
3rd
4th
5th
1st
Wrist
Radius
Ulna
Shoulders
Coracoid
Acromion
Elbow
Radius
Medial epicondyle
Lateral epicondyle
Trochlea
Capitulum
Ulna
Hip and Knee
Distal end of femur
Proximal tibia
Femur head
Greater trochanter
Lesser trochanter
Patella
IIiac crest
Shoulder
Clavicles
(medial end)
Humerus-upper end
Greater tuberosity
Appearance
Males
Females
Fusion
Males Females
0.5 (2 m)
1.0 (2 m)
4.0 (30 m)
6.0 (42 m)
8.0 (66 m)
7.0 (67 m)
7.1 (69 m)
13.0
1.0 (2 m)
1.0 (2 m)
3.0 (21 m)
5.0 (34 m)
5.0 (51 m)
6.6 (47 m)
6.6 (49 m)
10.0
1.7 (18 m)
1.7 (20 m)
1.7 (23 m)
1.7 (26 m)
4.1 (32 m)
1.6 (12 m)
1.6 (13 m)
1.6 (15 m)
1.6 (16 m)
2.0 (18 m)
17.0
17.0
16.4
16.4
17.0
14.9
14.8
14.9
14.9
14.9
1.7
7.4
3.5
6.5
17.4
17.4
16.4
15.8
TABLE 4.3.6: Eruption and maturation of deciduous and

permanent dentition
Eruption
Root completed
Maxillary
Central Incisors
Lateral Incisors
Canine
First Molar
Second Molar
7 months
9 months
18 months
14 months
24 months
1 month
2 years
8 years
2 years
5 years
Mandibular
Central Incisors
Lateral Incisors
Canine
First Molar
Second Molar
6 months
7 months
10 months
12 months
20 months
1 year
1 year
8 years
2 years
3 years
Maxillary
Central Incisor
Lateral Incisor
Canine
I Premolar
II Premolar
I Molar
II Molar
III Molar
7 to 8 years
8 to 9 years
11 to 12 years
10 to 11 years
11 to 12 years
6 to 7 years
6 to 12 years
17 to 21 years
10 years
11 years
13 to 15 years
12 to 13 years
11 to 13 years
10 to 11 years
12 to 14 years
18 to 25 years
Mandibular
Central Incisor
Lateral Incisor
Canine
I Premolar
II Premolar
I Molar
II Molar
III Molar
6 to 7 years
7 to 8 years
9 to 10 years
10 to 12 years
11 to 12 years
6 to 7 years
11 to 13 years
17 to 21 years
9 years
10 years
12 to 14 years
12 to 13 years
13 to 14 years
9 to 10 years
14 to 15 years
18 to 25 years
Deciduous Teeth
Permanent Dentition
5.6
14.0
13.0
12.0
18.0
18.0
17.0
17.6
6.2
7.4
6.2
7.9
0.5
10.4
3.5
5.6
7.5
7.6
0.5
8.6
16.2
16.2
16.0
16.0
16.0
16.4
14.5
14.3
13.0
13.0
13.0
14.0
at birth
at birth
1.0 (4 m)
2.0
12.0
5.0(46 m)
16.0
at birth
at birth
1.0 (4 m)
16.0
17.0
20.0
15.0
16.0
20.0
17.0
17.0
25.0
25.0
0.5
3.5
0.5
2.9
06.0
17.5
05.0
16.5
3.0 (29 m),

16.0
BONE AGE
Bone age is better correlated with onset of secondary sex
characters in children, with delayed puberty than
chronological age. It is closely correlated with menarche. Skeletal maturation is more advanced in girls than
boys of same chronological age. Table 4.3.5 gives the age
of appearance and fusion of various ossification centers.
Bone Age Assessment
1. In full-term at birth, following classification centers
are present as evidenced by X-rays of feet and knee:
i. Distal end of femur
ii. Proximal end of tibia
iii. Head of humerus
2.
3.
4.
5.
iv. Calcaneus
v. Talus
vi. Cuboid
By first birth day (X-ray hand and wrist)
i. Humerus upper end around 6 months (Age 3 to 9
months on X-ray of shoulder)
ii. Carpal centers usually appear by 2 months of age:
Two carpal centers are present at one year of age.
One additional center appears each year. Thus, 7
carpal centers are usually present at 6 years of age.
Third year of life: Metacarpals and phalangeal epiphyseal centers are radiologically demonstrable.
8 to 12 years: Distal ulnar epiphysis appears in most
girls by 8 to 9 years and in boys by 10 to 12 years.
12 to 16 years (X-ray of elbow and hip)
Elbow: Distal end of ulna
Lesser trochanter 12 years
Hip : Iliac crest
16 years
DENTAL AGE
At birth neither the maxillary nor the mandibular
alveolar process is well developed. Occasionally, a natal
tooth is present although the first primary teeth normally
do not erupt until approximately 6 months of age. The
natal tooth that is seen, may be prematurely erupted
normal tooth or an extra or supernumerary tooth. Dental
105
age, as judged by gingival eruption of teeth, is closely

correlated with skeletal age. Recently it has been shown
that the timing of tooth formation, rather than eruption,
provides a more reliable index of dental maturity.
Furthermore, eruption times are restricted to less than
30 months and after 6 years of age. Table 4.3.6 gives
reference to dental age and dental root development
(Indian Pediatrics 2003, 130 and 2004, 1031).
BIBLIOGRAPHY
1. Agarwal DK, Agarwal KN. Physical growth in affluent
Indian Children (birth-6 years). Indian Pediatr 1994;
31:377-413.
. Agarwal KN, Agarwal DK, Seth A. The Growth-infancy
to adolescence (2nd edn). CBS Publisher and Distributor,
New Delhi, 2007.
3. Agarwal KN, Agarwal DK, Upadhaya SK, Mittal R,
Prakash R, Rai S. Physical and sexual growth pattern of
affluent. Indian children from 5-18 years of age. Indian
Pediatr 1992; 29:1203-82.
4. Agarwal KN, Saxena A, Bansal AK, Agarwal DK. Physical
growth assessment in Adolescence.
5. Dentition-Indian Pediatr (2003;40:124-129 and 2004,
41:1031-1034).
6. Marshall WA, Tanner JM. Puberty. In Human Growth
(2nd edn). Falkner F, Tanner JM (Editors).
7. Tanner JM. Growth in adolescence (2nd ed). 1962.
Blackwell Scientific Publication Oxford.
4.4 Development
INTRODUCTION
Development refers to qualitative and quantitative
changes and acquisition of a variety of competencies
for functioning optimally in a social milieu. Further,
development is a continuous process from birth to
maturity. It depends on maturation and myelination
of brain; unless that has occurred, no amount of
practice can make the child learn that skill. It may be
stressed that, besides 10 percent prevalence of
developmental delay, the early identification of such
problems remains difficult. Although severe disorders
can be recognized in infancy, it is unusual to diagnose
speech impairment, hyperactivity or emotional
disorders before the age of 3 or 4 years, and learning
disabilities are rarely recognized before children start

their schooling. If one can diagnose developmental
delay in early stages of growth, the intervention can
reduce long-term sequel.
Developmental delay is said to exist, if the child does
not reach developmental milestones at the expected age,
i.e. broad variation among normal children. Although
the delay may occur from a biological factor such as
chromosomal disorder or an environmental factor such
as maternal depression, the primary model for pathogenesis of developmental delay is a transectional one,
with the process of development viewed as an interaction
between the child and environment, in which each can
have profound effect on other.
106
BRAIN GROWTH AND DEVELOPMENT

Brain growth is important to receive stimuli and take
body functions, the process of brain growth and
acquisition of developmental processes is summarized
below.
Process of Brain Growth
In the ectodermnotochord develops to form a
neural grooveNEURAL tube (cavity with overlying
neural crest)18 to 24 days
Error: results in spina bifida, anencephaly, etc.
Few weeks after conception to cellular level thru
adolescenceBrain continues to grow and myelinate
a. Cells inside the tube form CNS (central nervous
system) and
b. Cells outside and the ectodermANS (autonomic
nervous system).
Process of Myelination
Sensory and motor areas within first month to first
year of life- training and practice is effective only after
myelination.
Maximum myelination, occurs by 6 years of life.
Prefrontal cortex is not myelinated until close to
adolescence.
Developmental Profile
1. Early brain stem and cordBirth-light reflex, startle
reflex, Babinski reflex, reflex movement, reflex birth
cry and grasp reflex.
2. Visual, auditory, tactile, mobility, language and
manual competences
3. Brain stem and early sub cortical areas2.5 months
4. Midbrain and sub cortical areas7 months
5. Initial cortex12 months
6. Early cortex18 months
7. Primitive cortex36 months
8. Sophisticated cortex72 months.
Skill Achievements
Gross motor
Fine motor
Language
Cognitive
Self help
Social
The developmental pattern from birth to first birthday

is given in Figure 4.4.1.
Developmental Surveillance
The first part of development is head control, which is
observed in ventral suspension, prone and supine
position. The remaining phases of development can be
observed either in sitting or standing position. The areas
of observation of behavior development include gross
motor activity, fine motor and vision, hearing and speech
and social behavior and play. Besides one has also to
observe the acquisition of sphincter control. Normal
development is given in Table 4.4.1 for the developmental
abilities at various ages. (See Chapter 4.2 para 1).
ASSESSMENT OF NORMAL DEVELOPMENT
The developmental history and physical findings should
be compared with the achievements listed for normal
children. For preterm one must take their corrected age
into account. If one finds any warning sign' take note of
the points in history/physical examination and define
the type of impairment, disability or any handicap. The
children may be observed for their activities as follows:
Preschool Age
i. Play, climbing stairs, speech, hand (for adaptive
behavior), feeding.
ii. Posture, walking, play and manipulation with
toys (tests for vision).
iii. Performance: Understanding, matching color,
concentration, visual acuity.
iv. Comprehension of language: To point to body
parts, objects in books, to pick named toys and
accept commands appropriate to age.
School Age
i. Test for reading, arithmetic functions like +, , ,
, writing name, age, address, drawing a picture;
to test application, concentration and organizational skills.
ii. Test deafness, physical examination.
iii. Vision by 3 to 5 years age of 6/6 (adult) capability.
iv. Intelligence assessment.
The various tests which can be used for developmental screening are outlined below:
Figure 4.4.1: Showing growth and development in first 2 years of life
107
108

TABLE 4.4.1: Developmental abilities and warning signs at various ages
AREAS
Personal social
6 weeks old
Smiles, coos
responsively
Language
hearings and speech
Adaptive
Gross
motor
Warning
signs
Stills to mother's
voice, startles
at sudden noice
Follows face
90 stares
intently
Primitive
reflexes +head
in line with trunk
when lifted
* None is elicited
*Abnormal Moro's
*Persistent squint
6 to 9 months old
6 month enjoys bath,
playing boo and
chew on items.
9 months show
objects to mother,
mirror image
6 month. Responds
to own name.
Speaks ma, da.
9 month. Mama,
dada (Double syllable)
Understands 'No'
6 to 7 months Change
grasp palmar to
index. Transfers
objects hand to
mouth.
9 months Pincer grasp
foot regard. Fixes
pellet of paper,
follows fallen
object
6 months bears some

wt on legs, rolling
over, in prone
head up.
wt.of hands
7 months Crawls and
pulls to stand
*Slow social responses

*Absence of
babble
*Persistence of
hand Pats regard.
*Abnormal
voluntary hand grasp.
*Persistent
primitive
reflexes
12 months old
Comes when called,
finds hidden
objects, waves byebye, gives toys on
request
Understands
some words, uses
'mama, dada'
with meaning
'No'
Throws objects,
watches them fall,
picks up crumbs
from floor. Pincer
grasp, shakes head,
Bangs two bricks
together
Shuffling gait
like a bear.
Cruises round
holding on to
furniture. Walks
one hand held,
pivots when sitting
*No tunefull babble

*Hold objects
close to eyes.
*Immature gait
*No sitting
Points to 3
body parts.
Obeys single
commands. Says
6 words. Jargons
echoes, speech
Neat pincer
picking of threads
pins. Scribbles
using fisted
grasp. Turns 2 or
more pages at a
time. Builds
tower of 34 (2.5 cm)
cubes
Walks well,
Carries toys.
Climb stairs.
Climbs into
chair
*Drools no words
*Absent pincer
grasp
*Does not walk
Phrases of 23
words, gives
name, 50 words+,
naming games,
Has inner
language
Turns one page at

a time, Imitates a
straight line in
both vertical and
horizontal and a
circle, unscrews
lids, makes tower of
68 cubes
Pushes tricycle
with feet, walks
downstairs 2
feet per tread,
Runs, kicks ball
jumps on the
spot
*No speech
*Unsteady on
feet
Stands on one
leg for a few
seconds. Peddles
tricycle, stairs
adult style for
ascent, jumps of
bottom step
*No phrases
* Persistent daytime wetting/
soiling
*clumsy
18 months old
Cup: Lifts-drinks-and
puts down. Self spoon
feeding. Pulls at
dirty nappy. Does
dusting, sweeping
2 to 2 years
Plays alone, tantrums,
demanding. Day by day,
puts on shoes, socks
and pants. Turns door
handles. Uses spoon and
fork
3 to 3 years
Goes toilet unassisted,
dresses/undresses with
minimum assistance,
Knows some nursery
rhymes, handles knife
and fork, plays with
peers
Gives full name,

sex. Counts to
10, 35 word
sentences
Mature pen grasp,

copies + and 0
Correctly matches
2 or more colors.
Threads large
beads. Makes tower of 9
Contd...
109
Contd...
AREAS
Personal social
4 to 5 years
Wipes own bottom.
Eats using knife and
fork, dresses-except
for tie and laces,
imaginative play,
plays in groups, shares
toys, obeys rules
Language
hearings and speech
Adaptive
Gross
motor
Warning
signs
Gives
address/age/
telephone no.,
Counts up to 10 by
4 years, 20 by 5 years
knows 3 coins,
grammatical speech
asks meaning of
abstract words
Matches 4 colors,
Copies cross,
square and by 5 a
triangle. Draws a
recognizable man
4 years climbs trees

and ladder, enjoys
ball games.
5 years hops, skip
jump off 3 steps,
catches a ball
*Socially isolated.
*Unintelligible
or ungrammatic
speech.
*Unable to tell
name or address
Tests of General Intelligence

i. Stanford Binet Intelligence Scale
ii. Wechsler Intelligence Scale for Children
iii. Goodenough Draw a man test
range of developmental skills containing 125 items

(DDST-II).
GeseII Development Schedule
This scale provides three complementary tools for assessing the developmental status of children, i.e. the motor
scale, the mental scale and infant behavior record.
Gesell was the pioneer in behavior development assessment of children. The scale provides an estimate in 4
major areas of development, i.e. motor, adaptive,
language and personal social. In the first year of life,
development is estimated on weekly intervals starting
from 4 to 52 weeks, then every 3 monthly intervals till 2
years and at 6 monthly intervals till 5 years of age.
The scale provides an estimate of DQ (developmental
quotient) for each area separately as well as the overall
DQ.
Maturity age
DQ = 100
Chronological age
A child having DQ below the two-thirds or threefourths ratio (DQ between 6575) is considered at risk of
developmental delay.
This scale has a clinical diagnostic orientation. It is
more concerned with the diagnosis and evaluation of
abnormalities than with the measurement of attainment
of various milestones. Hence, it is more satisfactorily
applicable to handicapped children rather than some of
the other tests.
Denver Development Screening Test (DDST)
DDST has been the most extensively used screening
test. Recently, it has been revised to cover broad
Bayleys Scale of Infant Development
Phataks Baroda Screening Test

Test items are arranged according to age. The test has
been validated at various Indian centers such as the Child
Development Unit of KEM Hospital, Pune, Child
Development Unit, University of Baroda, and the All India
Institute of Medical Sciences, New Delhi.
Trivandrum Development Screening Chart
This test developed at Trivandrum is summarized in Table
4.4.2. This is a simplified version of the Baroda
development screeing test.
Identification of Risk Factors for
Developmental Delay
To identify child at risk for developmental delay the
pediatricians have to listen very carefully the history given
by parents, followed by detailed physical examination
and certain screening laboratory tests for metabolic
disorders. The risk factors which could suggest for
more closer, surveillance are given in Tables 4.4.3
and 4.4.4.
110
TABLE 4.4.2: Trivandrum development screening test

Test item
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
Social smile
Eyes follow pen/pencil
Holds head steady
Rolls from back to stomach
Turns head to sound to bell/rattle
Transfers objects hand to hand
Raises self to sitting position
Standing up by furniture
Fine prehension pellet
Pat a cake
Walks with help
Throws ball
Walks alone
Says two words
Walks backwards
Walks upstairs with help
Points to parts of a doll (3 parts)
3rd
97th
0.1
1.1
1.1
2.7
3.0
4.1
5.8
6.3
6.7
6.7
7.7
9.5
9.9
11.2
11.2
12.2
15.3
2.7
3.9
3.8
10.0
5.8
7.0
11.0
11.0
10.9
12.7
13.0
16.7
17.9
19.1
19.5
24.4
24.3
(Nair MKC, et al. Indian Pediatrics: 1991;28:86972)
TABLE 4.4.3: Risk factors for developmental delay that can

be identified in the history taking
Prenatal maternal factors: Acute or chronic illness (e.g., human
immunodeficiency virus infection, use of drugs or alcohol, toxemia,
previous miscarriage or stillbirth.
Perinatal factors: Obstetrical complications, prematurity, low birth
weight, multiple gestation.
Neonatal factors: Neurologic events (seizures or intraventricular
hemorrhage), sepsis or meningitis, severe hyperbilirubinemia and
hypoxia due to respiratory compromise.
Postnatal factors: Seizures, sepsis or meningitis, recurrent otitis
media, poor feeding, poor growth, exposure to lead or other toxins.
Factors in the family history: Developmental delay, deafness,
blindness, chromosomal abnormalities.
Factors in the social history: History of abuse or neglect, limited
social or financial support, teenage parent, single parent, mentally
retarded parent, stressful life full of unhappy events (e.g., divorce,
death or unemployment of parent).
TABLE 4.4.4: Risk factors for developmental delay that can

be identified in the physical examination
Abnormal growth, e.g. height or weight <5th percentile or head
circumference <5th or >90th percentile.
Major congenital anomalies, e.g. spina bifida or midline defects.
Minor congenital anomalies, e.g. hypertelorism, hirsutism or
micrognathia.
Neurocutaneous lesions, e.g. neurofibromatosis or caf au lait
spots.
Abnormal optical findings, e.g. esotropia, exotropia, cataracts, or
poor visual tracking.
Abnormal findings in ears, e.g. unusual shape, placement or
recurrent acute or serious otitis.
Visceral abnormalities, e.g. hepatosplenomegaly.
Skeletal abnormalities e.g, brittle bones or dwarfism.
Neurologic abnormalities, e.g. lack of alertness, abnormal
reflexes, hypertonia or hypotonia or asymmetric finding.
Disorders of Development
1. Impairment: An abnormality of body function or
structure: Mild backwardness, delayed speech and
language, clumsiness and specific learning disabilities, e.g. reading, writing, spelling.
2. Disability: Reduced ability to perform a task or function.
3. Handicap: A continuing impairment or disability of
body, intellect or personality, e.g. mental retardation,
severe learning difficulty, cerebral palsy, autism,
deafness, blindness or poor vision.
4. Presence of soft neurological signs: Poor, fine motor
coordination as assessed by finger tapping, toe
tapping, stringing beads, etc.
111
4.5 Failure to Thrive

Madhulika Kabra, PSN Menon
Failure to thrive (FTT) is a common and often perplexing concern for parents and pediatricians. Pathophysiologically, FTT is a state of caloric insufficiency
without an apparent etiology. It is a descriptive term
rather than a diagnosis and is used for children whose
attained weight or rate of weight gain, is significantly
below their age and sex matched controls. Though
primarily weight is affected, linear growth and head
circumference may also get affected, if the insult is
prolonged and severe. By definition, FTT is sustained
weight loss, failure to gain weight or a persistent fall in
weight from the child's normal centile (Fig. 4.5.1). This
definition excludes transient weight loss associated with
acute illness.
There is lack of consensus about anthropometric
criteria for FTT. Commonly used criteria are shown in
(Table 4.5.1) . Important points to remember are:
1. Label of FTT should not be given, based on a
single observation, i.e. failure to gain weight or weight
loss should be observed over a period of time.
2. Usually children less than 3 years or maximum up to
5 years are included in this definition.
TABLE 4.5.1: Definition of failure to thrive1
Attained growth
Weight <3rd percentile on NCHS growth chart
Weight for height <5th percentile on NCHS growth
Weight 20% or more below ideal weight for height.
Triceps skinfold thickness < 5 mm
chart
Rate of growth
Depressed rate of weight gain
< 20 g/d from 0 to 3 months of age
< 15 g/d from 3 to 6 months of age
Fall-off from previously established growth curve
Downward crossing of >2 major percentiles on NCHS

growth chart
Documented weight loss
NCHSNational Center for Health Statistics

1Hank DA, Jeisel SH. Failure to thrive. Pediatr Clin North Am
1998;35:1187-1205.
Figure 4.5.1: Failure to thrive: A: weight loss, B: static

weight, C: Fall-off in weight gain
3. Small size alone is not an adequate criterion for

confirming FTT, as constitutional and genetic factors
may result in short stature.
ETIOLOGY
The standard classification of dividing the causes of FTT
as organic and non-organic, probably is not very appropriate. Whether the condition is primarily organic or nonorganic in origin, all children who fail to thrive, suffer
the physical and psychological consequences of
malnutrition and are at a significant risk for long-term
physical and psychodevelopmental sequelae. Table 4.5.2
summarizes the causes of FTT.
Organic diseases are responsible for less than 20
percent of cases with FTT. lt should be recognized that
environmental deprivation can coexist with and
complicate organic FTT. For example, a child with
cerebral palsy, or multiple congenital malformations is
likely to be environmentally deprived due to lack of care.
Organic causes of FTT are most commonly gastrointestinal or neurologic.
DIAGNOSIS
History and physical examination are the mainstay for
diagnosis of FTT. It should be emphasised that, extensive
laboratory investigations have no role in the diagnosis
112

TABLE 4.5.2: Causes of inadequate weight gain1
Inadequate intake
unless assessment suggests a probable organic cause and

localizes the pathology to a particular system.
Poverty
History
Misperceptions about diet and feeding practices
Inadequate breast-milk production
Errors in formula reconstitution
ldeally, both parents should be present during the

interview and parent-child and parent-parent interaction must be critically assessed.
Dysfunctional parent-child interaction
Behavioral feeding problem
Routine Antenatal, Natal and Perinatal History
Neglect
Child abuse
Apart from the details of pregnancy, delivery and perinatal details, some points need special mention.
Was the child born of unplanned pregnancy? Did the
parents consider medical termination of pregnancy?
Children born of unplanned pregnancy tend to be
emotionally deprived.
Was it a preterm delivery? If growth parameters are
not corrected for gestational age, these children may
be erroneously labelled as FTT.
Intrauterine growth retardation (IUGR) is another risk
factor for FTT. Symmetrical IUGR children have a
worse prognosis in this regard.
History suggestive of exposure to intrauterine
infections.
Mechanical problems with sucking, swallowing, feeding
Primary neurological diseases
Chromosomal abnormality
Prenatal insult
Systemic disease resulting in anorexia/food refusal
Calorie wasting
Persistent vomiting
Gastroesophageal reflux
Gastrointestinal obstruction
Rumination
Metabolic problems
Increased intracranial pressure
Malabsorption and/or chronic diarrhea
Primary gastrointestinal diseases
Cystic fibrosis
Infections
Endocrinopathies
Structural problems
Renal losses
Diabetes mellitus
Renal tubular acidosis
Increased caloric requirements
Congenital heart disease
Chronic respiratory disease
Neoplasm
Hyperthyroidism
Chronic or recurrent infection
Altered growth potential/regulation
Prenatal insult
Chromosomal abnormality
Endocrinopathies
1Hank
DA, Jeisel SH. Failure to thrive. Pediatr Clin North Am

1998;35:1187-1205.
Growth Data
Evaluation of growth pattern is the most important aspect
of evaluation. Review child's present and past growth
parameters. This is only possible if parents have maintained a 'Road to health' card or previous growth status is
known. Undocumented weight loss may not help in diagnosis. In situations where previous record is not available, it is advisable to follow the child for weight gain.
Dietary History
A detailed dietary history, both past and present should
be elicited to evaluate caloric and protein intake.
Detailed Social and Family History
A detailed social and family history provides useful clues
for diagnosis of non-organic failure to thrive. Following
factors need special evaluation:
1. Lack of support systems: relatives and friends.
2. Financial constraints.
3. Psychiatric problems/drug abuse in family.
4. Marital problems, parental discord.
5. Serious illness or death in family.

Detailed Evaluation of Developmental Milestones
Physical examination Physical examination should be
thorough and complete. Detailed anthropometry should
include length/height, weight, head circumference,
upper/lower segment ratio, skinfold thickness and
midarm circumference.
Routine and thorough general and systemic examination is a must, as it gives clues to do specific diagnosis and investigations.
Detailed neurodevelopmental assessment should be
performed.
Specific behavior patterns should be looked for. These
may give a positive clue for non-organic FTT. These
include unusual watchfulness, decreased vocalization, lack of cuddliness, head banging, rocking
movements and rumination.
Signs of abuse and neglect.
Signs of vitamin and nutrient deficiencies should be
looked for.
Laboratory Investigations
In most instances, a detailed general and systemic examination will help in ruling out an organic cause for FTT.
Detailed laboratory investigations are indicated only
if the history and physical examination suggest that an
organic cause is responsible for FTT and to localize the
systems involved. A battery of routine investigations
should be avoided because they are unproductive in most
instances, expensive, may be misleading and diverting
attention. The following investigations are considered
adequate for initial evaluation:
Complete blood count with ESR.
Urine and stool examination.
Urine culture and sensitivity.
Tuberculin test.
Blood urea and serum creatinine.
Radiological investigations are not routinely indicated, unless the child needs evaluation for tuberculosis
or physical abuse. Determination of bone age may be
required in some cases. More invasive diagnostic procedures are called for, when a specific diagnosis is suspected.
MANAGEMENT
The major goals of management are nutritional rehabilitation, treating an organic cause if detected and addres-
113
sing psychosocial and developmental issues involved.

Individual management of these have been discussed in
detail in subsequent chapters.
The first decision that one has to take is, whether the
child requires hospitalization or not. Indications for hospitalization are as follows:
1. Weight for height less than 70 percent of the median
2. Detailed evaluation for a suspected organic disorder
3. Suspected abuse/neglect
4. Non-response to outpatient management.
Diet
An experienced dietician should always be involved
in planning and supervising diet. Unless there is a
strong suspicion of an organic cause, one should
proceed directly for a two weeks trial feeding. Daily
monitoring during this period is extremely important.
Nutrition monitoring record includes daily weight
and total calories consumed during last 24 hours
against expected. Every effort should be made to feed
the child orally. If oral feeding is inadequate, tube
feeding may be tried for short periods.
Help of a child psychologist may be sought, if indicated. Organization of a program of intensive
environmental stimulation and affection is also
needed. Every attempt should be made to see that
parents are actively involved in the management.
At the end of two weeks of trial feeding, the child
is reassessed. A good intake during the feeding trial, and
a good response in terms of weight gain, suggest that
the primary problem was nutritional deprivation usually
associated with emotional deprivation. Further management of the child who fails to respond to the feeding trial,
is shown in Figure 4.5.2. It is perfectly justified to
undertake detailed investigations in the child with FTT
who fails to respond to a two weeks trial of feeding.
However, by this time, the physician usually has an idea
of the diagnostic possibilities, and he/she can tailor the
investigations accordingly.
PROGNOSIS
It may be tentatively concluded, that for most children
with FTT in infancy and early childhood, the outlook for
linear, ponderal and brain growth recovery is good,
provided appropriately aggressive hyperalimentation is
provided. The outlook for complete intellectual, behavioral and educational recovery is variable and less certain.
114
Figure 4.5.2: Schematic diagram showing evaluation of FTT; (GIgastrointestinal, GERgastroesophageal reflux,
RTArenal tubular acidosis, CRFchronic renal failure, CNScentral nervous system)
BIBLIOGRAPHY
1. Maggioni A, Lifshitz F. Nutritional management of failure
to thrive. Pediatr Clin North Am 1995;42:791-810.
2. Marcovitch H. Failure to thrive. Br Med J 1994;108:35.
3. Overby KJ. Failure to thrive. In Rudolph AM (Ed),
Rudolph's Pediatrics 20th edn. Stamford, Connecticut;
Appleton and Lange, 1996;3-9.
4. Suri M, Kabra M, Aggarwal A, Verma IC. Failure to thrive.

Indian J Pediatr, CME programme 1994;8.
5. The American Board of Pediatrics-Programme for
Renewal of Certification in Pediatrics. Failure of Thrive.
Supplement to Pediatrics in Review 1993.
5.1 Infant and Young Child Feeding: RK Anand, SP Srivastava ........................................................................................................... 116
5.2 Breastfeeding and Weaning: RK Anand, SP Srivastava, Arun Gupta, JP Dadhich ........................................................................ 122
116
5.1 Infant and Young Child Feeding

RK Anand, SP Srivastava
All children have three important needs to help achieve
their full potentiala feeling that they are loved, that
their stomachs are supplied with wholesome food, and
that they have freedom from infection. Enough evidence
is on record to show that a child who feels loved and is
well-nourished, has a rather low risk of getting serious
infections.
over and above the basal rate of metabolism due to the

digestion and assimilation of food. A school-going child
spends about 12 percent of total energy for growth, 25
percent for physical activity, 50 percent for basal
metabolism, 5 percent for TEF and about 8 percent as
fecal loss due to unabsorbed fat.
Energy Requirements
Nutrient Requirements
For children to be well-nourished, they need energy from
a wide variety of nutrients to lead a healthy and happy
life. Basic knowledge about the so called macronutrients
as well as micronutrients is essential to provide the right
type of food in sufficient quantities in health and disease.
While adequate food is important throughout childhood,
it is crucial during the first 5 years of a child's life,
particularly so, in the first 3 years when rapid growth
occurs, and the child is entirely dependent on her mother
and family for food.
Macronutrients and Micronutrients
The macronutrients like proteins, carbohydrates, fats,
fiber and water are required in large or gram quantities
to meet that daily optimum needs for energy and normal
functioning of the system. The micronutrients like
calcium, iron, zinc, iodine, sodium, potassium and
vitamins, though needed in small (milligram or microgram) quantities, are equally important for fulfilling
several physiological needs of the body.
In children, measurement of what healthy, well-growing

children actually eat, is mostly used for assessing the
energy requirements.
A comparison of energy requirement of infants as
elucidated in the FAO/WHO/UNU Expert Report of
1985 and the earlier FAO/WHO Report reveals that
infants need less energy than what was earlier thought
of (Table 5.1.1). The Indian Council for Medical Research
(ICMR) agrees with the revised estimates. It has also been
observed that the required energy intake of breastfed
children is lower then that of formula-fed babies. Based
on these reports as well as studies which show that
infants can grow normally on exclusive breastfeeding for
6 months of age, it is suggested that there need not be an
undue haste to add foods, other than breast milk until
that age.
The energy needs between 1 to 18 years are computed from energy needs per kg body weight of well-to-do
Indian children. As a rough estimate, a one-year-old
infant needs 1,000 calories daily. This is about half of
what most mothers eat. After the age of 1 year, an
approximation to the minimum energy needs can be
Energy
The child needs energy for: (i) growth, (ii) for daily
physical activities like crawling, walking and playing,
and (iii) catch-up growth following infections. Hence,
child needs to be offered an extra meal while recovering
from an infection. Even when a baby is at rest, energy is
required for basal metabolism to maintain essential
physiological functions like breathing, which go on round
the clock for as long as the individual remains alive.
Energy expenditure also takes place due to thermogenic
effect of food (TEF). This is due to increase in metabolism
TABLE 5.1.1: Recommended energy

requirements for infants
Intake (cal/kg)
Estimates
(1973)
Estimates
(1985)
03
120
116
36
115
99
Age
(months)
69
110
95
912
112
101
Infant Feeding 117

TABLE 5.1.2: Recommended additional energy and protein
requirements during pregnancy and lactation
Group
Daily additional
requirement of
calories (cal)
Daily additional
requirement of
protein (g)
Pregnant
300
15
06 months
550
25
612 months
400
18
Lactating women
made by adding 100 calories for every year of the life, e.g.
a child of 5 years needs at least 1,400 calories each day. It
is advised that for malnourished children, the
recommended intakes for the actual age should be used,
and no adjustments for actual body weight should be
made.
The pregnant and lactating mother needs extra
energy, while she makes all efforts to adequately meet
the nutritional needs of her fetus and later her breastfeeding baby. Therefore, it is important to provide extra
calories to such a mother (Table 5.1.2).
Recommended Dietary Allowances (RDA) and
Nutrient Requirements
Twenty-four amino acids have been identified so far, for

the synthesis of proteins within the body. Eight of these
cannot be synthesized and hence must be supplied in
adequate amounts from outside. These 8 (nine for infants)
are called essential amino acids. They are: leucine,
isoleucine, lysine, methionine, phenylalanine, threonine,
tryptophan and valine. Two amino acids are considered
semi-essential, because they are synthesized by the body
at rates inadequate to support the growth in children.
These are arginine and histidine. Histidine is the ninth
amino acid essential for infants, besides the eight
mentioned above. Low birth weight (LBW) babies need
to be supplied arginine, cystine and taurine as well. For
them, these three are also essential.
Proteins are needed by the body for growth, for repair
and maintenance of body tissue, maintenance of osmotic
pressure, catalytic functions through enzymes, protection
through immunoglobulins and interferon, hormonal role
as with insulin, transport through hemoglobin and
albumin, provision of energy when calorie intake is not
adequate, and during pregnancy and lactation for
synthesis of fetal tissue proteins and milk proteins (Table
5.1.2). Protein foods may also carry other important
nutrients such as vitamins and minerals.
Recommended dietary allowances are the amount of

nutrients present in habitual diets consumed by a given
population and also the level that would cover the
requirement of most of the individuals in that population.
This must not be blindly applied to the nutrient
requirements of an individual. The needs of an individual
vary widely. Nutrient requirement is the amount of
absorbed nutrient that is essential to fulfill the
physiological functions in a particular individual.
Recommended dietary allowances (RDA) does not refer
to this individual need. Hence, it should be used for
population-based studies. However, it may be used as a
reference while evaluating the adequacy of the diet of
an individual. In this connection, it may be noted that
we do come across children with normal growth who
appear healthy and happy even though they were not
consuming nutrients as per the recommended dietary
allowances.
A protein is said to be biologically complete if it contains

all the essential amino acids in amounts needed by the
human body. Protein from egg and human milk satisfies
this criteria and serves as a reference for defining the
quality of other proteins. The proteins in animal foods
compare well with egg protein. Hence, such foods are
considered to be sources of good quality protein. For this
reason, vegetable proteins are said to be of poorer quality
than animal proteins because they lack one or more
essential amino acids in them. However, it is important
to note that when two or more vegetarian foods are mixed
together in such a way that the deficient amino acid in
one is supplemented by the other, it becomes a complete
food. Hence, it is possible to obtain a high-grade protein
at low cost, from a mixed vegetarian diet of cereals, pulses
and legumes.
Protein
Estimated Protein Requirement (Table 5.1.3)
Proteins are complex organic nitrogenous compounds

made available from food. Each gram of protein provides
4 kcal of energy. Proteins are made-up of amino acids.
The energy requirements of a child come from proteins,

carbohydrates and fats. All calculations of protein
requirement are done in a situation where energy
Protein Quality
118

TABLE 5.1.3: Estimated protein requirements
(g/kg) of infants
Age (months)
Daily requirement (g/kg)
03
2.3
36
1.85
69
1.65
912
1.50
requirements of the child are met. If this condition is not

fulfilled, estimates of protein requirement will be wrong
since a part of proteins will be utilized to provide energy.
Fat
Fat in the diet is a source of essential fatty acids (EFA)
which are required for proper membrane function and
prostaglandin synthesis. The Indian diets which are
cereal based are bulky. The bulk presents a problem for
young children because of their small stomach. Fats help
in overcoming this problem. They improve the calorie
intake by enhancing the energy density of foods. Fats
also improve the palatability of diets. They are important
for the absorption of fat soluble vitamins like vitamin A.
Dietary fat may be derived from two sources namely,
visible fat and invisible fat. Visible fats are found in fatty
parts of animals, liver, egg yolk and the fat in milk.
Vegetable sources of visible fats are coconut, nuts and
various vegetable oils. Analysis of foods has revealed that
cereals and pulses in the Indian diet may contribute
significantly to dietary fat intake as invisible fat. It is
estimated that such a diet based only on cereals and
pulses without any fat can meet more than 50 percent of
the individuals essential fatty acids requirement.
Fats are made-up of fatty acids which include
saturated fatty acids like palmitic and stearic, monounsaturated fatty acids like oleic and polyunsaturated
fatty acids like linoleic and linolenic. The latter two
cannot be synthesized in the body and have to be
supplied through dietary fat. Dietary fats with an equal
proportion of saturated, monounsaturated and polyunsaturated fatty acids components are considered
desirable. Adequately breastfed infants receive nearly
70 g fat per day of which about 10 percent is linoleic and
1 percent linolenic acid. Breast milk meets all the essentials
fatty acids needs of such infants. In this context, the
superiority of breast milk over cow and buffalo milk must
be emphasized since the former contains large chain
polyunsaturated fatty acids which are biologically more
potent. Infants who have been weaned completely or

partially should be given enough vegetable oil with high
linoleic acid content to meet their essentials fatty acids
requirements. Fats like ghee, hydrogenated fats and
coconut oil are comparatively saturated and are poor
source of essentials fatty acids. Other edible oils are better
sources of essentials fatty acids . Cotton seed, corn,
sunflower, soy-bean and safflower oils contain 50 to
70 percent essentials fatty acids, whereas groundnut has
25 percent essentials fatty acids.
Studies relating fat intake to cardiovascular disease
and obesity suggest that an intake of fat as an energy
source beyond one-third of total calories, is undesirable.
Since in India, almost 10 to 15 percent of this can be
derived from invisible fat, visible fat intake should be
restricted accordingly.
Carbohydrates
Carbohydrates are the third important source of energy.
In fact, they supply almost half of the bodys energy
requirement. They are classified as follows:
Monosaccharides
(e.g., glucose, fructose, galactose)
These cannot be hydrolyzed into any further simpler
form.
Disaccharides
(e.g., sucrose, lactose, maltose)
They yield 2 molecules of same or different monosaccharide on hydrolysis.
Sucrose = Glucose + Fructose
Lactose = Glucose + Galactose
Maltose = Glucose + Glucose
Oligosaccharides
Oligosaccharides (dextrins) yield 3 to 6 monosaccharide
units on hydrolysis.
Polysaccharides
(e.g., starch, dextrins, glycogen, cellulose)
These yield more than 6 monosaccharide units on hydrolysis.
The carbohydrates are ingested in above forms and
are oxidized as glucose (dextrose). It is advisable to have
more of complex carbohydrates i.e., polysaccharides or
Infant Feeding 119

starches in the diet rather than simple carbohydrates i.e.,
sugars including sucrose. Thus, the amount of sugar in
the diet should be restricted, right from an early age.
Cellulose is the indigestible component of carbohydrate in the diet with scarcely any nutritive value. It
mainly contributes to dietary fiber. Complex carbohydrates supply enough fiber. Intake of highly refined foods
containing little fiber, leads to constipation and other
intestinal disorders. Thus, wholewheat flour preparations are better than those made from refined flour.
Requirement for Minerals and Trace Elements
Macrominerals
Calcium and phosphorus are required for the formation
of bones and teeth, and calcium in ionic form is important for transmission of nerve impulses. Phosphorus is
an important constituent of nucleic acid and phospholipid compounds. The desirable ratio of Ca:P is 1:1 in
most cases except during infancy where the ratio should
be 1:1.5.
Infants require about 500 mg of calcium per day.
Children between 1 to 9, 10 to 15 and 16 to 18 years
require 400, 600 and 500 mg, of calcium, respectively.
The best sources of calcium are human and animal milk
and the bones of small fish. Millet and ragi are also good
sources, the latter being especially valued for its calcium
content which is about 344 mg per 100 g. Leafy vegetables
like amaranth, fenugreek (methi) and drumstick leaves
are also rich sources. The Indian diet is adequate in
phosphorus, and no dietary recommendations are
suggested. Magnesium is a component of cells and is
essential for various metabolic reactions. Its deficiency
leads to neuromuscular dysfunction. The Indian diet is
adequate in magnesium, and no specific recommendations are made.
Currently, there are no specific recommendations for
dietary intake of sodium and potassium. However, there
is need for fixing limits in view of evidence that high
sodium intake may be related to hypertension. In general,
children should be offered foods containing low sodium
from an early age. Later, fast foods containing high
amount of sodium should be avoided.
Trace Elements (Microminerals)
They are needed in very small amounts but are vital for
life. They include iron and copper, essential for blood
formation; iodine to prevent goiter and hypothyroidism,
zinc for quicker healing of wounds, and manganese, cobalt

and selenium for growth and general health.
Iron
An average adult male has about 4.0 g and an adult female
about 3.0 g of iron in the body. Seventy percent of iron in
the body is in the form of hemoglobin. Storage iron
constitutes about 26 percent of the body iron.
Iron is needed in the diet to replace the iron lost in
the stools and urine and through the skin. There is considerable loss during menstruation and during delivery.
The requirement is higher during period of rapid growth
and during pregnancy. An intake of 20 to 30 mg a day is
adequate for older children and adults. During
pregnancy, although menstrual related iron losses are
nil, an additional 1000 mg iron is required for the fetus,
the placenta and the increased maternal blood volume,
especially during the second and last trimester.
Infants, children and adolescents require iron for their
expanding red cell mass and growing body tissue. In a
normal infant, two-thirds of body iron is present in red
blood cells. During the first 2 months of life, there is a
marked increase in iron stores due to a fall in hematocrit.
These stores are subsequently mobilized to supply iron
for growth needs and to replace losses. Hence during
this period, there is a minimal requirement for dietary
iron. By about 6 months, the iron stores decrease
significantly, and the infant needs a generous dietary
intake of iron. Breast milk contains a low amount of iron.
However, since the bioavailability of iron from breast
milk is very high, the iron requirements of breastfed
infants are fulfilled during the first 6 months of life. After
this, complementary foods must be added to meet the
increased demand for iron. By 1 to 2 years, children start
eating the family food, which in our country is predominantly cereal and pulse based. Iron absorption from this
diet is low.
There are several dietary factors influencing the
absorption of iron. The amount of iron that a person
absorbs depends on: (i) The total amount of iron in the
meal, (ii) The type of iron in the food, (iii) Other foods in
the meal, (iv) Amount of iron that the person needs.
There are two types of iron in food: (i) heme iron
found in meat, liver, chicken and fish. About 15 to 35
percent of this is absorbed, and (ii) nonheme iron. This
is found in plants, legumes, cereals, eggs and milk. Less
than 5 percent of this is absorbed.
120
The other foods taken with a meal can increase or

decrease the amount of nonheme iron that is absorbed,
such as foods rich in vitamin C, e.g. guavas, oranges,
lemons, tomatoes and foods which contain heme iron
such as liver, meat, chicken or fish. Fermented and germinated foods also increase absorption. Tea and coffee
and phytates in wheat and maize hinder absorption. Iron
absorption is very high in pregnant women especially
when they are anemic. Dried fish, meat, liver and egg
are good sources of iron. Green leafy vegetables and
cereals too are relatively good sources.
Low overall dietary intake is an important factor
responsible for low iron intake. Increasing the dietary
intake to meet the calorie needs increases the dietary
intake of iron by about one-third. Infections interfere with
food intake and the absorption of iron. Blood loss due to
gastrointestinal disorders and parasitic worms is an
important cause of iron deficiency anemia.
Iodine
Iodine is secreted by the thyroid gland. Vegetables grown
on iodine rich soil and sea foods are good sources of
iodine. Iodine is essential for normal growth and
development. The amount of iodine available in the body
is about 15 to 20 mg, of which 70 to 80 percent is trapped
in the thyroid. The normal daily requirements are about
100 to 150 mg. Iodine deficiency is a major public health
problem in India. An estimated 167 million people are
at risk for iodine deficiency disorders in India, out of
which 54 million have goiter and over 8 million have
neurologic handicaps. The government is encouraging
the common salt to be iodated to cut-down the high
incidence of iodine deficiency disorders in the country.
Zinc
Zinc is available from a wide variety of dietary sources.
Human breast milk contains a special zinc-binding ligand
which increases the bioavailability of zinc for the infant.
The body needs about 4 to 6 mg of zinc per day.
Important sources are meat, chicken, fish, cereals and
legumes. There is sufficient zinc in our food and so
supplements of zinc are not necessary. Severe zinc deficiency can cause growth retardation, anorexia, hypogonadism, persistent diarrhea and poor wound healing.
Fluoride
Fluoride is a mineral which is important for bones and
teeth. It makes bones harder and prevents tooth decay.
However, too much fluoride can cause discoloration of

teeth and make bones weaker, thereby resulting in
deformities. Fluorosis occurs in endemic form in parts
of Andhra Pradesh and Punjab because of high fluoride
content in water and soil.
Requirements for Vitamins
Vitamins are organic nutrients needed by the body in small
amounts. They are classified as:
i. Fat-soluble vitaminsA, D, E, K
ii. Water-soluble vitaminslike thiamine (B1), riboflavin (B2), folic acid, vitamin B12, vitamin C
Water-soluble vitamins are not stored in the body
except for some storage of folic acid and vitamin B12 in
liver and the surplus is excreted in the urine. Extra doses
of such vitamins are therefore not required. Fat-soluble
vitamins are stored in the body and excess of these may
lead to toxicity.
Vitamins do not themselves yield energy, but they
enable the body to use other nutrients. Each vitamin has
a specific function to perform and deficiency of any particular vitamin may lead to specific deficiency disorder.
Vitamin A
Vitamin A is necessary for the normal functioning of the
eyes including the ability to see in the dark. Deficiency
of vitamin A is associated with increased infections and
protein energy malnutrition. Deficiency leads to loss of
vision and eventually to blindness. Colostrum i.e., the
first milk after childbirth is rich in vitamin A.
Breastfeeding prevents vitamin A deficiency up to 6
months of age.
There are two forms of vitamin A in foods. Retinol is
found only in animal foods. Carotene is found mainly in
yellow or green plant foods. The body changes much of
the carotene to retinol. Six molecules of carotene make
one molecule of retinol.
Vitamin A is present in the fatty parts of several
animal foods. The liver oil of certain fish like cod, halibut
and shark are very rich in vitamin A. Many vegetables
too are a good source of vitamin A, because they contain
-carotene which is converted into vitamin A in the body.
-carotene is important1 mg of -carotene yields 0.5
mg of retinol. Only 50 percent of the -carotene in food
is absorbed, therefore 1 unit of -carotene yields only
0.25 mg of retinol. About 50 g of common fresh leafy
vegetables a day, or 100 g of mango or 200 g of papaya
will provide an adequate quantity of this vitamin. Fresh
Infant Feeding 121

vegetables contain more carotene than stale ones. The
vitamin A lost while cooking is not so great, but frying
destroys 70 percent of it. On an average, there is a 50
percent loss in storage and cooking, as is practised in
Indian homes. Young children require about 300 mg
retinol per day. Vitamin A can be stored in the liver, and
the body can build-up a store which can be used in times
when vitamin A is lacking in the diet.
Important sources of vitamin A, i.e. (retinol) include
breast milk, animal milk, liver from animals, fish, eggs,
butter, ghee, and cottage cheese.
Important sources as carotene include red palm oil,
orange and yellow fruits such as mangoes, papayas and
oranges, vegetables such as carrot, pumpkin, dark green
leafy vegetables, tomato, yellow maize, and yellow banana.
Sources: Milk and milk products, egg, liver, leafy vegetables, wheat, millet and pulses.
Folic Acid
Folic acid is important in the multiplication and maturation of red blood cells, and its deficiency results in certain
types of anemia. It is credited with preventing neurological
defects in fetus. The intake of folic acid is low among riceeating population. The daily requirement is 25 to 100 mg,
but pregnant women require 150 to 300 mg.
Sources: Fresh green vegetables, liver, kidney, fish and
pulses. Cereals contain 5 to 12 mg per 100 g, and pulses
contain 23 to 70 mg per 100 g. Leafy vegetables contain 50
mg per 100 g.
Vitamin D
Vitamin D plays an important role in the absorption of
calcium and phosphorus from the intestine and in the
formation of bones and teeth. Vitamin D needs are greatest
at time of rapid growth, i.e., in infants and young children,
adolescents and pregnant women.
Sources: Fish liver oil is the richest natural source of
vitamin D. It is also found in liver, egg yolk and milk, to
a small extent. However, vitamin D is formed in the body
by the action of sunlight on certain chemicals in the skin.
This can be an adequate source, and it is important that
children are allowed to play in the sun. An infant and the
mother too, should be exposed to the sun and should not
be overclothed while doing so. Only five minutes exposure
to sunlight per day for persons with fair skin is sufficient
to meet the daily requirement of vitamin D. Adults, infants
and children, pregnant and lactating women and premature babies need 100 IU, 200 IU, 400 IU and 500 IU, per
day, respectively.
Thiamine (Vitamin B1)
Sources: Thiamine is found in meat, poultry, fish, liver,
whole grain cereals, legumes, oil-seeds, milk and egg.
Deficiency can lead to beri-beri. This deficiency disease
has become quite rare now.
Riboflavin (Vitamin B2)
The daily requirement of riboflavin is 0.6 mg per 1000
calories. The average loss during cooking is about
30 percent. Its deficiency leads to cracked lips and corners
of mouth and rough skin.
Vitamin B12 (Cyanocobalamin)

Like folic acid, vitamin B12 is also involved in the maturation of cells, and deficiency results in megaloblastic
anemia.
Sources: Animal foods like milk, meat and liver.
Vegetables do not contain B12, but the vitamin may be
provided by molds and yeasts, often in association with
plant foods.
Vitamin C (Ascorbic Acid)
Vitamin C helps body to use calcium and other nutrients
to build bones and blood vessels. It helps the body to absorb
nonheme iron. Vitamin C is very susceptible to destruction
by exposure to light, heat and drying. The daily
requirement is about 50 mg, allowing for a 50 percent loss
while cooking. Vitamin C helps in the absorption of iron.
Sources: Fresh fruits and vegetables are good sources.
Guava is particularly rich in vitamin C. Other rich sources
are citrus fruits. Amla is the richest source, but is rather
astringent and not easily acceptable to children. Other
sources are fresh potatoes with skin, plantains and cooking
bananas, fresh milk and breast milk. Dry pulses do not
contain vitamin C, but germinating pulses are rich sources.
About 80 percent of the vitamin is formed in the grain and
15 percent in the sprout. The best source of vitamin C for
the infant is breast milk.
Storage of leafy vegetables at room temperature
destroys 35 percent of the vitamin, and about 12 percent is
destroyed under refrigeration.
122
General Guidelines about Infant and

Young Child Feeding
Ideal infant feeding comprises exclusive breastfeeding for

6 months, followed by sequential addition of semi-solid
and solid foods to complement (not replace) breast milk,
till the child is gradually able to eat normal family food
after one year. The latter period when other foods are added
is also referred to as weaning. The term weaning does not
denote termination of breastfeeding.
Appropriate feeding is crucial for the healthy growth
and development of the infant. However, lack of confidence
and widespread ignorance and misconceptions frequently
result in improper management of infant feeding. The
prominent areas of concern include discarding or minimal
feeding of colostrum to the newborn baby, exclusive
breastfeeding in only 46 percent babies in the first 6 months
of life, unnecessary utilization of commercial infant milk
foods and animal milks, early termination of breastfeeding
and premature or delayed introduction of semi-solids
which may be contaminated, low in caloric density and
fed less frequently. These inept feeding practices directly
or indirectly, contribute substantially to infections, illness,
malnutrition and mortality in infants.
Following are the salient practical guidelines for
optimal infant and young child feeding.
Provide extra helping of family food and some green

vegetables to the pregnant and lactating mother.
Discuss with the pregnant mother and her family,
about the importance of breastfeeding and dangers
of bottle-feeding.
Prefer delivery in a baby-friendly hospital (see
page 137).
Put the baby to the breast soon after delivery (see
page 130).
Encourage intake of colostrum as first and subsequent feeds.
Avoid prelacteal feeds like water, glucose water,
honey water, (janam ghutti) or artificial milk.
Practise exclusive breastfeeding (give no other
food or fluids including water) for 6 months of life.
Breastfeed as often as the baby wants.
Ensure proper positioning while breastfeeding (with
enough breast in baby's mouth so that the infant is
beastfeeding and not nipple feeding).
Allow the baby to empty one breast before offering
the other for suckling. Do not time the feed.
Add mashed fruits and homemade cereals after 6
months, while breastfeeding is continued for 2 years
or more.
5.2 Breastfeeding and Weaning

RK Anand, SP Srivastava, Arun Gupta, JP Dadhich
BREASTFEEDING
It is now well-understood that breastmilk is the ideal milk
for both rich and poor babies, that colostrum is essential
for the newborn, that bottle-feeding is dangerous, that
complementary foods must be added after 6 months of
age while breastfeeding is continued for two years or
beyond, and that we must ensure that nutrition of the
lactating mother is well taken care of.
Anxiety associated with the unfounded fears of
lactation failure (the inability to produce milk) and of
milk insufficiency (the inadequacy of breastmilk for
meeting the nutritional needs of the normal infant) is the
most common reason for mothers failing to initiate
breastfeeding within one hour of birth, maintenance of

exclusive breastfeeding for the first six months,
interrupting breastfeeding prematurely, or beginning
complementary feeding, before it is nutritionally
required. The mother wrongly perceives that she is not
getting enough milk. In fact this perception is universal
and is the most common reason for non-exclusive
breastfeeding. All mothers need help from health
workersespecially with her first baby. The health
worker must be well-equipped to convince the mother
about the importance of breastfeeding and skilled enough
to counsel and support her when she has any difficulty in
breastfeeding.
Infant Feeding 123

Antiviral factor
Antistreptococcal factor
Para-amino benzoic acid (PABA).
Figure 5.2.1: Breastfeeding is central

(Courtesy: Baumslag)
Advantages of Breastfeeding to the Child

More and more people are now appreciating that
breastfeeding is central to growth monitoring, immunization programs, nutrition, diarrheal disease prevention
and family planning programs, all of which are related to
each other (Fig. 5.2.1).
Complete Nutrition
The human brain and the child has to grow very fast in
the first two years of life. Breast milk provides complete
nutrition for first 6 months and continues to be an
important source of nutrition in the second year of life.
It contains the most suitable protein and fat rich in essential fatty acidslinoleic acid and linolenic acid for the
baby in right quantities, has more lactose than other
milks, offers enough vitamins, iron and water, and has
the correct proportion of salt, calcium and phosphate.
The special enzyme lipase in the breast milk helps in
proper digestion of fat.
The presence of these factors help the breastfed child

to have less diarrhea than artificially fed babies, less
incidence of necrotizing enterocolitis (NEC), and fewer
respiratory and middle ear infections. The bifidus factor
helps a special bacteria called Lactobacillus bifidus to grow
in the baby's intestine which in turn prevents other
harmful bacteria from growing and causing diarrhea.
Lactoferrin in breast milk binds iron which prevents the
growth of some harmful iron feeding bacteria. High
concentration of PABA in breast milk may protect the child
from getting malaria. The bile salt stimulated lipase, kills
Giardia lamblia and Entamoeba histolytica. It is estimated
that exclusive breastfeeding for six months with
appropriate complementary feeding in addition to
breastfeeding could prevent the deaths of an additional
1.3 million infants each year.
The other advantages include:
Counters risk of allergic disorders like asthma and
eczema.
Cancer (lymphoma) risk is reduced.
Configuration of jaw is better because of the mechanism of suckling at the breast.
Caries in teeth are less common.
Coronary artery disease risk and incidence of obesity,
type-2 diabetes and hypertension in later life is
reduced.
Clever children: Premature babies who were breastfed,
turned out to be more intelligent than the artificially
fed.
Cot death or sudden infant death syndrome risk is
probably reduced in breastfed babies.
Cover Against Infection

Human milk has following anti-infective factors which
protect the child from several serious bacterial and viral
infections
Immunoglobulins especially secretory IgA
Lactoferrin
Lysozymes
Complements
Interferon
Lactoperoxidase
Cells (T and B lymphocytes and macrophages)
Bifidus factor
Advantages to the Mother

1. Convenient
2. Cheaper than artificial milkall it costs the family is
the little extra food needed by the mother.
3. Cancer risk of breast and ovary and risk of osteoporosis
in later life is reduced.
4. Contraction of the uterus when the baby is put to breast
soon after delivery assists in expulsion of placenta
and minimizes risk of postpartum bleeding.
5. Contours of body come back to normal due to utilization of fat reserves laid down during pregnancy and
124
due to involution of uterus. Thus, a woman who

breastfeeds regains her figure faster, compared to a
woman who does not breastfed. Pregnancy alters the
shape of the breastswhether a woman breastfeeds
or not. If she wears a well-fitting brassiere, her breasts
will have a good shape.
6. Calming effect: For many women, breastfeeding
provides a sense of calm and satisfaction, which is
probably related to the helpful hormonal changes
while breastfeeding.
Advantages to Both Mother and Child
1. Comforting body-contact between the mother and child
while breastfeeding facilitates a close loving bond
between the mother and her baby.
2. Child spacing: As long as a mother remains amenorrheic (bleeding before 56th postpartum day being
ignored) and breastfeeds exclusively, she gets 98
percent protection from pregnancy in the first six
months due to production of appropriate hormones.
However, it is advised to use other family planning
methods acceptable to the couple.
3. Considered beneficial for diabetic mother and for the
reduced risk of diabetes in children.
Comparison of Human Milk and Cows Milk

This is summarized in Table 5.2.1.
Anatomy and Physiology of
Breastfeeding (Fig. 5.2.2)
The breast consists of gland tissue (alveoli), supporting
tissue and fat. The alveoli make the milk, which goes
along milk ducts towards the nipple. Under the areola,
these ducts widen to form the lactiferous sinuses where
milk collects. Therefore, enough of the areola should be
offered to the breastfeeding baby.
Every time the baby suckles at the breast, he or she
stimulates the nerve endings in the nipple. These nerves
carry messages to the anterior pituitary which synthesizes prolactin. Prolactin stimulates gland cells in the
breast to secrete milk. As the baby continues to suckle,
sensory nerves help secrete oxytocin from the posterior
pituitary. Oxytocin contracts the muscle cells around the
alveoli, resulting in squeezing out or ejecting the milk
from the nipple. The oxytocin reflex is dependent on the
mothers state of mind and it may be cut-off in a mother
who worries and doubts whether she could feed her baby.
Preparation for Successful Breastfeeding
Motivate the Mother before Birth
Cost Benefits
Breastfeeding provides economic as well as ecological
benefits to the family, the nation and the health sector.
The expectant mother and her close relatives including

the husband, should be informed about the advantages of
Global Support for Breastfeeding

The global support for breastfeeding remains ongoing and
strong. According to the World Health Organization
(WHO), well over two-thirds of under-five child deaths,
which are often associatated with inappropriate feeding
practices occur during the first year of life. Under normal
circumstances, infants who are not breastfed are 5 times
more likely to die from pneumonia and 14 times more
likely to die from diarrhea, than infants who are
exclusively breastfed for the first 6 months. Protection that
breast milk confers is all the more important in environments without safe water supply and sanitation. The child
survival series published in july 2003 in the Lancet gives
additional evidence-based support for the importance of
breastfeeding. It reconfirms that breastfeeding is the single
most important preventive intervention, capable of saving
more than a million additional lives annually.
Figure 5.2.2: Anatomy of the breast (Courtesy King)
Infant Feeding 125

TABLE 5.2.1: Comparison of human milk and cows milk
Parameter
Human
Cows
Bacterial
contamination
None
Likely
Antibodies
Leukocytes
Lactoferrin
Bifidus factor
Others
Not active
1%
0.5%
4% (too much)
3% (too much)
Enough for growing

brain
Enough for brain,
retina and bile acid
conjugation
Not enough
Virtually absent
4% (average)
4%
Enough unsaturated
Too much
saturated
Enough for growing

brain
Enough
Not enough
Anti-infective
substances
Protein
Total
Casein
Amino acids
Cystine
Taurine
Fat
Total
Saturation of
fatty acids
Linoleic acid
(essential)
Cholesterol
and the need for breastfeeding. The breasts should be

examined, and the mother reassured that the size of the
breasts and shape of nipples, flat or short whatsoever,
have no relation to lactation performance. Ask the mother
to rub the nipple and press the areola on either side of
the nipple. This makes most nipples stand out and appear
longer. Let her then gently try and pull the areola and
the nipple to form a teat. If the nipple pulls out easily, it
is protractile and normal. Many nipples which look flat
or short, pull out or protract well and do not cause any
problem, while other nipples which do not protract well
develop during pregnancy and improve more after
delivery when the baby suckles and stretches them.
If a nipple does not pull out but goes deeper, it is
inverted. A simple technique has been described to help
mothers with retracted nipples breastfeed by applying
negative suction through a plastic syringe. The nozzle
end of the syringe is cut. The plunger is withdrawn from
its usual position and inserted through the cut end.
Negative suction is then applied via the new open end
kept over the nipple and the adjacent areola. Once the
nipple protracts out, the syringe is removed and the baby
is put to breast with enough areola in the mouth. When
repeated before each breastfeed for a few days, the nipple
become protractile in most cases.
Not enough
Lipase to digest fat Present
None
Lactose
7% (enough)
3-4% (not
enough)
Salts (mEq/l)
Sodium
Chloride
Potassium
6.5 (correct amount)

12 (correct amount)
14 (correct amount)
25 (too much)
29 (too much)
35 (too much)
Minerals (mg/l)
Calcium
Phosphate
350 (correct amount)

150 (correct amount)
1,400 (too much)

900 (too much)
Iron
Small amount, but

well-absorbed
(enough)
Small amount,
poorly absorbed
(not enough)
Vitamin
Enough
Extra needed
Note Infant milk powder or formula is similar to cows milk. The

expensive brands are modified so that they are more like human
milk. However, the quality of protein and fat can never equal that
of breast milk, and no formula can contain all anti-infective
substances. Also, if the formula is mixed incorrectly, it can either
cause severe malnutrition or obesity and hypernatremia due to too
concentrated feeds.
(Courtesy King)
Select the Right Place for Delivery

It is important to choose such a hospital for delivery where
breastfeeding is supported. Such hospitals are now called
baby-friendly (see page 133).
Avoid Unnecessary Use of Drugs Prior to Delivery
While it is important to reduce a womans physical discomfort, the indiscriminate or excessive use of sedatives,
analgesics and anesthetics may prevent the mother
establishing a close contact with her infant immediately
after delivery and diminish the newborn infant's suckling
capabilities. Episiotomy, unless really indicated, must be
avoided.
Initiate Breastfeeding Soon after Delivery
After a normal delivery, most babies want to suckle
during the first half or one hour after they are born. The
baby should be given to the mother to be held as soon as
he/she is born. This also helps her to establish the bond
with her baby and to provide colostrum to the newborn.
126
In cesarean delivery, the baby starts breastfeeding as soon

as the anesthetic effects are over. As the mother is on her
back, the baby is placed on pillow(s) raised to the level of
the mothers breast for convenient positioning of the baby
on to the breast.
Give Colostrum and Avoid Prelacteal Feeds
Sit with the mother within 24 hours after delivery. Tell her
about colostrum which is produced in small amount but
is enough to meet all the needs of the baby in the first few
days. Colostrum is thicker and yellower than later milk.
Feeding this is important immunologically (since it is rich
in antibodies and protective substances), nutritionally (to
provide vitamins and minerals) and developmentally (to
ensure maturation of intestinal mucosa). Giving colostrum
has also been called the first immunization of the child.
Compared to that, the mature milk (which appears within
2 weeks of birth) is thin. In the beginning of a breastfeed,
foremilk is rich in proteins, lactose, vitamins, minerals
and water while towards the end of the feed (hindmilk) it
has more fat and is rich in energy.
A vast majority of newborns in our country are not
given colostrum but receive prelacteal feeds (feeds given
before the free flow of milk from the breasts) such as honey,
sugar, glucose, water and artificial milk. This should be
discouraged in a sympathetic manner by minimizing
conflict with traditional beliefs. Colostrum is all the food
needed at this timeno supplements are necessary. A
baby is born with enough water in the body to last several
days if necessary. Many babies lose a little weight in the
first week, but this is normal. If prelacteal feeds are given,
the baby does not suckle adequately from the breast as his
or her stomach gets full. Then he or she shall not get
colostrum. Such feeds may also be contaminated. Allergies
are more common in babies given artificial milk including
powder milk in the first months of life. If these feeds are
given with a feeding bottle, the baby may get used to the
nipple of the bottle and may not make the necessary effort
to suckle and empty the breast. This either results in
breastfeeding failure or may cause engorgement or even
infection of breast.
Figure 5.2.3: Suckling in good position. Baby is unwrapped, is

close to the mother, chin touches the breast, mouth is wide
open, lower lip is everted, and much of the areola is in the
mouth. Baby takes slow deep sucks and causes no pain to
the mother (Courtesy King)
Recommend Demand Feeding

The baby must be breastfed as often as he/she wants.
Frequent suckling and emptying of breasts increase milk
production and help to prevent problems like engorgement.
In the initial days, babies have irregular feeding intervals.
They may feed 6 to 12, or as many as 18 times in 24-hour
period. This frequent feeding is likely to settle into more
predictable routine as lactation is established.
Continue Each Feed as Long as Baby Wants
For the baby to get hindmilk as well, allow the baby to
suckle from one breast until the baby releases the nipple
spontaneously. Then the other breast should be offered. If
the baby is not interested, start from the other breast the
next time to keep the milk flowing.
Do Not Wash the Nipple before and after Every Feed
Frequent washing especially with soap, removes the
natural oil from the breast making the skin dry and more
easily damaged. A daily bath is all that is needed to keep
the breasts clean.
Help the Baby Suckle in a Good Position
Caution Mother in Advance about Breast Engorgement
The mother must offer enough of the areola into the babys
mouth so that the tongue can express the milk from the
lactiferous sinuses (Fig. 5.2.3). Mother can breastfeed while
lying down so long enough of the areola is in the babies
mouth.
After the first 3 to 4 days, some mothers may develop

painful engorged breasts. The best way to prevent the same
is to let the baby suckle as often and as soon after birth as
possible. If engorgement persists, relieve it by expressing
milk from the breasts. If health workers help to establish
Infant Feeding 127

exclusive breasfeeding, many problems like mastitis and
sore nipples can be prevented.
THE IMPORTANCE OF EXCLUSIVE BREASTFEEDING
Anything less than exclusive breastfeeding for 6 months
of an infants life greatly increases her chances of
infection and death, even among well-to-do families.
Unfortunately, only 46 percent women exclusively
breastfeed their babies during first 6 months and only
about 26% babies begin breastfeeding within one hour
after birth. Even at age 0 to 1 month, many mothers give
water or other supplements. Breast milk has enough water
in it to meet the hydration requirements, even under
extremely hot (up to 42C) and dry (relative humidity 9
13%) summer conditions of the country.
Exclusively breastfed babies grow rapidly in initial
stages and then may slow down normally at about 3 or 4
months. This so-called faltering is part of a normal
growth curve for such breastfed babies and has been
rightly labeled as pseudofaltering. Exclusive breastfeeding should be continued in such babies for 6 months.
BREASTFEEDING BEYOND INFANCY FOR
TWO YEARS OR BEYOND
It is recommended that breastfeeding, in addition to the
complementary foods be continued for 2 years or more .
The observed malnutrition in some prolonged (beyond 12
to 18 months age) partially breastfed children is not due
to consumption of breast milk per se, but is primarily due
to inadequate quantity and quality of the complementary
foods.
Breast milk can act as a cheap and vital source of good
quality proteins, fat, calcium, vitamins and anti-infective
factors beyond the first year of age. It has the highest energy
density of all foods commonly consumed in this age group
in the developing countries and can still provide one-third
of all the energy and protein requirements that a child
needs during the second year of life. Further, the protective
effect of breastfeeding at this stage is likely to be critical for
the survival of malnourished children. Additionally,
breastfeeding, by extending the duration of amenorrhea
following childbirth reduces fertility. Longer intervals
between births can enable mother to provide better care
and attention to the child.
green leafy vegetables. There is no need to avoid any

specific food. However, use of excessive caffeine, tobacco,
and alcohol is not desirable.
Important Practical Considerations
Related to the Infant
Adequacy of Breast Milk
A breastfed infant is consuming sufficient milk if he or
she is gaining weight checked at periodic intervals on the
same weighing scale, urinates six times or more a day
with colorless or light yellow urine and is feeding and
sleeping well. Some breastfed babies, however, demand
feeds frequently in the first weeks, at times even after 1/2
to 1 hour while sleeping for 3 to 5 hours at other times.
This is physiological and does not indicate milk
insufficiency.
Stool Frequency
Active, healthy, breastfed babies passing urine normally
may pass frequent watery or frothy motions. This is not
diarrhea and does not need any treatment. At times these
motions are green. Stool examination in some of them may
also show presence of reducing substance. This can also
be normal. No medicine needs to be given and
breastfeeding should be continued. In contrast, a few
breastfed babies evacuate the bowel only every alternate
or third day, but the stool is soft in consistency. This is
also normal and should not be treated as constipation.
Crying
Crying is one of the most common reasons of adding
artificial milk when it is not required. There are many
other reasons for crying in an infant which must be considered like passage of urine or stools, need for more body
contact, illness, infantile colic, etc.
Multiple Births
Breastfeeding of twins presents no problem. However, we
should ensure that a mother who is not well-nourished
gets adequate nutrition. The situation is obviously more
demanding for triplets.
Low-birth Weight (LBW) Infants
Diet of Lactating Mother

A lactating woman should be advised to eat an extra
helping of the family food and regular consumption of
Mothers milk is the best food for the LBW babies. The
borderline term and growth retarded LBW babies can
suckle fairly well at the breast and should be fed on
128
demand. However, LBW and other high-risk infants who

cannot suckle should be given expressed breast milk in
preference to formula feeds with a small glass, cup and
spoon, tubes, paladai, etc. The child should be put directly
to the breast as soon as possible. Some of these babies may
also need artificial milk. Avoid giving it through a feeding
bottle.
Illnesses in the Infant
Breast milk is the most easily digestible food for an ill
baby. Feeding human milk is actually beneficial in common
infantile ailments including diarrhea and acute
respiratory infections. Breastfeeding, therefore, must be
ensured during such illnesses. The child may suckle less
vigorously or for a shorter time and should receive the
feeds at more frequent intervals. However, breastfeeding
and for that matter, any type of feeding may have to be
temporarily stopped in critically ill infants.
Cleft Lip or Palate
With a cleft of the lips or gums, there is usually no problem. If the cleft involves the palate, suckling becomes
difficult. Some babies need to be fed the expressed breast
milk through a tube or from a cup until they are able to
suckle well enough at the breast.
Suckling for Comfort
Babies suckle not only out of hunger but also for pleasure
and comfort. They suck on anything that goes into their
mouthstheir fingers, a piece of cloth, their thumb, etc.
This does not necessarily mean that they are hungry.
Vitamin Supplementation
Full-term exclusively breastfed infants do not require any
supplementation. If a mother is malnourished with
multiple deficiencies, her diet should be improved and
multivitamin drops may be given to her baby.
Important Practical Considerations
Related to the Mother
about her ability to produce enough milk can interfere

with the let-down reflex. In such a situation, the mother
produces enough milk, but the milk does not flow down.
Also, inadequate suckling by the infant due to
inappropriate feeding technique, e.g. improper positioning
and other difficulties related to breastfeeding that go
unresolved for lack of proper guidance and support can
also lead to insufficient milk.
Frequent suckling in proper position is the secret of
successful breastfeeding. Often, the supplementary feeds
that were introduced because of unfounded fears about
the quality and quantity of breast milk contribute directly
to decreased milk secretion. To help such a mother to
increase her milk supply, it may be helpful to hospitalize
her for about a week, while she is helped to improve the
feeding technique and build up the milk supply. Metoclopramide (10 to 15 mg three times a day) may be given for
10 days to two months to increase the milk supply. If the
mother uses a bottle for feeding the baby, that must be
stopped. The mechanisms of suckling from the breast and
sucking from the nipple of a bottle are different. A child, if
used to bottle, might not make any necessary effort required
to breastfeed. If essential, supplementary milk may be given
after breastfeeding (and not between two breastfeeds) in a
small glass or with a cup and spoon, until the mothers
milk supply becomes sufficient again.
Engorgement of Breasts
When the milk first comes into the breasts, they feel hard
and painfully full. The best way to prevent this
engorgement is to let the baby suckle as often and as soon
after birth as possible.
To treat engorgement, act as soon as it develops. Use
warm compresses on the breast. Allow the baby to suckle
as far as possible. If the baby cannot get hold of an engorged
breast, help the mother to express milk. Hand expression
is preferable to a pump. After expressing some milk, help
the mother to put the baby to breast. Milk should be
expressed as often as necessary to make the breasts
comfortable.
Not Enough Milk
Blocked Duct, Mastitis and Breast Abscess
Some mothers wrongly perceive that they are not getting

enough breast milk. If the baby is passing a light colored
urine on exclusive breastfeeding, reassure such a mother
that her baby was getting enough milk from her. Doubting
If a milk duct becomes blocked, a painful lump forms.

Gently massage the lump towards the nipple to try and
unblock the duct. Continue feeding the baby from the
breast.
Infant Feeding 129

If a blocked duct is not cleared, the breast tissue may
become infected, and the breast itself becomes tender and
swollen. If untreated, an abscess develops. Encourage the
mother to continue breastfeeding the baby. If suckling is
painful, help her to express her milk every 3 hours. Warm
compresses help to relieve pain. If mother develops fever,
chills and bodyache, she may need a full course of
antibiotics or drainage of the abscess if required.
Sore Nipples
If the baby does not take enough breast into the mouth,
mother can get sore nipples. To prevent it, make sure that
the baby suckles in a good position. To treat sore nipples,
do not stop breastfeeding but correct the suckling position.
Do not put any cream on the nipples and do not wash
them with soap. If the baby has oral thrush, treat it and
apply the same medicine on the mothers nipple. Exposure
of breast to air, or leaving a little creamy hindmilk on the
nipples helps healing. If suckling is impossible for a day
or two, express the milk and feed the baby from a cup.
Thin or Watery Milk
Breast milk is normally thinner and more watery than
cow's or buffalo's milk. The foremilk, which at the start of
a breastfeed is thin, is rich in protein, lactose, vitamins,
minerals and water. It contains less fat, while hindmilk,
near the end of a feed is thicker and rich in fat. Babies need
both foremilk and hindmilk and therefore must be allowed
to suckle from one side for as long as they want before
they are offered the other breast. Babies allowed such
freedom often get satisfied by suckling only from one side.
They must be offered the other breast for the next feed.
Maternal Malnutrition
Mothers with mild to moderate chronic malnutrition can
fully breastfeed their infants. If the mother's diet is poor in
vitamins and minerals, these must be supplied. Only with
severe malnutrition or under famine conditions, a woman
may produce a smaller amount of milk. In an undernourished mother, the milk is made at the expense of her
own body tissue. So, she must be provided with enough
food. The notion that mothers need to drink more milk or
eat more to produce enough breastmilk is not correct.
Menstruation and Pregnancy
Mother can feed during menstruation and half way
through pregnancy. If she is eating well, breastfeeding
can continue all through the pregnancy.
Maternal Illness
Most maternal illnesses do not require discontinuation of
breastfeeding. It is recommended even with mastitis, breast
abscess and other infectious illnesses including urinary
tract infection, tuberculosis, hepatitis, typhoid and
leprosy.
As far as the question of HIV and infant feeding is
concerned, the general principle is that in all populations,
irrespective of HIV infection rates, breastfeeding should
continue to be protected, promoted and supported. About
the risk of parent-to-child transmission of HIV, the risk is
reported to be less in exclusively breastfed or exclusively
artificially fed babies compared to those on mixed feeding.
Factors which affect the mother-to-child transmission are: recent
infection with HIV, severity of HIV infection, infection with
other sexually transmitted diseases, obstetric procedures,
duration of breastfeeding, type of feeding, i.e., exclusive
breastfeeding, exclusive artificial feeding or mixed feeding,
condition of the breasts and condition of the babys mouth.
Evidence is now available to suggest that breast problems
like sore nipples or mastitis can double the transmission
risks. To reduce this risk, mother may choose to breastfeed
exclusively and stop breastfeeding after six months, or to
avoid breastfeeding altogether. In India where majority of
babies are mixed fed, achieving either is a challenge.
Prevention of breast problems is critical, not only in HIVpositive mothers but in general population as well to
enhance HIV free survival. This can only be achieved with
skilled assistance to mothers to ensure that the baby
suckles in a correct position to prevent such problems.
However, not breastfeeding has many disadvantages,
both for the mother and her baby. Infants who do not
receive breast milk at all may have 14 times risk of dying
from diarrhea compared to exclusively breastfed babies.
In India with IMR of about 57 per thousand, current
thinking is that safe (preventing breast problems and
additional antiretroviral drugs ) exclusive breastfeeding
for the first six months would be the best strategy. The UN
Guidelines for Health Care Managers and Policy Makers
2003 state that if formula feeding is not affordable, feasible,
acceptable, accessible or safe, exclusive breastfeeding is
recommended. National AIDS Control Organization
(NACO) offers antiretroviral drugs for the mother within
4 hours before the baby is delivered and the baby is also
given nivarapine.
Keeping yourself updated on this very complex issue
and a fast changing scenario would be very useful. Women
need access to infant feeding counseling and skilled
130
assistance to help them to decide the best way to feed their

children in their situation and support them in their
choices.
In infections like typhoid, the mother makes specific
antibodies against the infective agent in her breast milk
to protect her baby.
Physically incapacitating systemic illnesses in the
mother may prevent or necessitate discontinuation of
breastfeeding. In the absence of an attendant, it may be
safe to keep the baby away from a psychotic mother. In
such situations, wherever feasible, the breasts should be
emptied frequently to maintain lactation.
Drug Therapy
Majority of the commonly used drugs are compatible with
safe breastfeeding. However, lactating women should
preferably take drugs during or immediately after
breastfeeding to avoid the period of maximum concentration in the blood and milk. Only a few drugs necessitate discontinuation of breastfeeding like anticancer and
antithyroid drugs, radioactive preparations, gold salts,
lithium, etc.
Mother Employed outside the Home
Mother employed outside the home should initiate
breastfeeding like all the mothers and she should take
care not to introduce a bottle feed, just to get the baby
used to it. If the child gets used to the bottle, it may
mean the end of a successful breastfeeding experience for
the mother. If a mother cannot take her baby with her to
breastfeed at work, she can express her milk by hand and
leave it for a helper to feed the baby in her absence. The
expressed breast milk (EBM) should be given to the baby
from a clean small glass or a cup. Feeding bottles should
not be used because they are hard to clean, and their use
makes the baby less eager to suckle at the breast. The EBM
can be stored at room temperature for up to 6 hours and
up to 24 hours if kept refrigerated. If the milk separates, it
can be shaken up. It remains good for use.
NONHUMAN MILK (BREAST MILK SUBSTITUTES)
Occasionally, artificial milk may have to be given to
adopted babies or those who have lost their mothers or
such infants who have been hooked to bottle-feeding and
have stopped breastfeeding completely since long. In such
cases, liquid milk consumed by the family should be
utilized and powder milk (commercial infant milk food)
should be discouraged. There is less risk of overdilution

and contamination with liquid boiled milk than with
powder milk. Child is given three parts of pure cows milk
and 1 part of water for the first 2 months. Then undiluted
milk is given. Part of excessive fat from pure buffalos milk
should be removed by separating the cream from milk
after boiling and cooling it. A teaspoon of sugar is added
to 4 ounces (120 ml) of the feed.
Aim at five, 4 hourly feeds. Starts with an ounce
(30 ml) per kg of weight per feed. For instance, if the
baby weighs 4 kg, give 4 ounces of milk 4 hourly
omitting the midnight feed.
If powder milk is used, the proportion should be one
level measure of infant milk powder to 1 ounce (30 ml)
of water. Companies have also started marketing various
follow-on milk formulas to be given after the age of 6
months. There is no need to use these at all.
Infants who are solely on artificial milk need additional plain water supplementation.
Bottle-feeding should be avoided because it is difficult to keep the bottle clean. With a little patience, even a
LBW newborn baby can be taught to take the milk from
a small glass or a spoon, particularly the long spouted
spoons (paladai, jhinook, bondla, gokhari). These are
convenient to hold and easy to clean. If a bottle is used,
make sure that the baby gets a boiled bottle for each feed.
INFANTS MILK SUBSTITUTES ACT 1992
Realizing that aggressive marketing of infant foods and
feeding bottles leads to decline in breastfeeding, the
World Health Assembly in 1981 passed an International
Code of Marketing of Breast Milk Substitutes. In 1992,
the Government of India passed The Infant Milk Substitutes, Feeding Bottles and Infant Foods (Regulation of
Production, Supply and Distribution) Act, 1992.
The Act does not allow advertisement of infant milk
substitutes powder or feeding bottle. No display of
placards or posters of baby foods or feeding bottles is
allowed in the hospitals. Incentives or inducement to
mothers or health workers for promoting the sale of
products under the Act is prohibited. The labeling on the
tin and educational material dealing with prenatal or
postnatal care or with infant feeding must include details
outlined in the Act. Those violating the Act can be fined or
imprisoned. The Act is now further strengthened by the
Infant Milk Substitute Feeding Bottles and Infant Feeds
(Regulation of Production, Supply and Distribution)
Amendent Act, 2003. This document has been reproduced
Infant Feeding 131

in the annexure. The Act does not allow advertisement of
infant milk substitutes powder or infant foods or feeding
bottles. In fact no baby food can be promoted for children
under the age two.
Those violating the Act can be fined or imprisoned.
Following are some example of the violations of the Act.
Promotion of any baby food and feeding bottles by
what ever name for children up to two years
Advertising of baby foods or feeding bottles by any
means of television, newspapers, magazines, journals,
through SMS, emails, radio, pamphlets etc.
Distributing the product or samples of these to any
person.
Contacting pregnant or lactating mothers by any
person in a hospital, residence, marketplace, or by
sending pamphlets, posters etc.
Providing gifts and samples to the mother and
healthcare providers, use of tied sales by providing
free consumer products like soap/bowls with these
products.
Distributing information and education material to
mothers, families etc.
(But educational material can be given to a health
professional like doctors, nurses provided it has
information prescribed in caluse 7 of the IMS Act, 2003.
The education material should have only factual
information and should not promote the products)
Tins, cartons and accompanied leaflets of these
products having picture of mothers or babies, cartoons
or any other such images.
Display of placard, posters in a hospital, nursing

home, chemist shop, etc. for promoting these products
Sponsoring hoardings of these products for hospitals
and chemist shops.
Making payments to doctors, nurses for promoting
these products.
Demonstrating mother or their family members how
to feed these products. However a doctor can
demonstrate this to the mother.
Giving gifts to doctors, nurses or their associations.
Giving funds to associations like IAP, IMA, NNF, etc.
for organising seminars, meetings, conferences,
contests, educational courses or sponsoring projects,
research, tours or article in medical journals.
Fixing commission of employees on the basis of volume
of sales of these products.
ADDITION OF SEMISOLID AND SOLID FOODS
(COMPLEMENTARY FEEDING)
Getting the baby accustomed to other foods besides breast
milk (or other milk) is termed weaning. Some wrongly
interpret it as weaning the baby away from the breast.
Complementary feeding is a better term them weaning
(Fig. 5.2.4).
Importance of Appropriate Addition
After 6 months of age, while breastfeeding is being
continued, addition of other foods is essential to prevent
growth faltering. Delayed introduction of additional foods
Figure 5.2.4: Optimal infant and young child feeding
132
in an exclusively breastfed infant, results in malnutrition.

Improper introduction of these foods is fraught with
dangers of: (i) diarrhea due to infection from unhygienic
preparation, (ii) malnutrition related to inadequate calorie
intake due to low frequency of feeding and low calorie
density of additional foods.
Timing of Introduction of Semisolids
Semisolid foods to complement breast milk should be
introduced after 6 months of age. The individual decision
should be guided by the growth performance and
physiological maturation of the infant, but they should
never be started before completion of 4 months. To
minimize any interference with the normal course of
breastfeeding, semisolid foods should preferably be given
between breastfeeds.
encouraged. The bulk of the weaning food can be reduced

by malting of grains/cereals.
Frequency, Amount and Consistency of FeedingBroad
Age-related Guidelines
Infants vary grossly in the amount that they require and
eat. Therefore, in general, mother should be advised to
prepare and offer a mixed nourishing diet based on the
usual family foods and leave it to the baby to take as much
as is desired. The child's general activity and growth, as
judged by the family and the health worker and confirmed
by weighing as often as possibledepending on the
facilities, is good evidence of adequate food intake.
However, the following broad feeding guidelines can be
offered:
Six to Nine Months
Continuation of Breastfeeding
Initially, breast milk forms main food of the baby and the
weaning diet is extra. Later, even when more semisolid
food is added, breast milk still continues to remain an
important component of the infant's diet. Breastfeeding
should be continued for 2 years or more.
Feeding Guidelines
Formulate additional foods from the usual family diet.
The weaning foods in a thickened but mashed, i.e. softened
form, and variety should be attempted. Use of commercial
weaning foods should be avoided as far as possible.
Family pot feedinggiving the family food in a mashed
form, and providing something extra like oil/fat and green
vegetables is best, since it is economical, saves time and
the infant grows up accustomed to the traditional foods.
Enhancing Nutritive Value
The nutritive value of these foods should be enhanced by
enrichment of the staple cereals with pulses (for proteins)
oil/fat and sugar for increasing calorie density and green
vegetables for vitamins, especially, A, B and C, and iron.
Advantage should be derived from the usual diet pattern
of a mixture of cereals and pulses (idli, dosa, pongal, khichri,
missi roti, etc.) by addition of some oil/fat/sugar and green
vegetables. Dilution of weaning diet and use of watery
gruel and lentil or rice water should be strongly discouraged. Use of animal milk, milk products, fruits, eggs, fish
or meat, if culturally acceptable and affordable, should be
After 6 months, one can start with cereal based porridge

(suji, wheat flour, ground rice, ragi, millet, etc.) enriched with
oil/fat and/or animal milk if possible, or mashed fruits
like banana or other seasonal fruits like papaya, mango,
etc. One or two teaspoonfuls are enough to start with, and
the quantity and frequency should be increased gradually.
The baby at the end of this phase should be consuming
half a cup of food.
Gradually the baby should be used to feeding from the
family pot (mashed rice with dal; khichri; egg, meat and fish
if culturally acceptable; a little chappati softened in dal or
milk; dahi; mashed vegetables; fruits, etc. enriched with
some oil/fat and green vegetables). They need four to five
weaning meals a day, in addition to regular breastfeeding.
Nine to Twelve Months
At about 9 months, babies can start chewing on soft food.
The food at this time does not need to be mashed but, can
be chopped or pounded. A variety of household foods
should be given four to five times a day and the quantity
gradually increased. By about one year, young children
should be eating foods cooked for the family but at least
four to five times a day. A child of one to two years needs
about half the food that the mother eats.
Preparation and Storage of Weaning Foods
Careful hygienic preparation and storage of weaning
foods is crucial to prevent contamination. The hands
should be thoroughly washed with soap and water before
Infant Feeding 133

preparation and feeding, and the cooking place and
utensils must be clean. The foods should be preferably
fresh, cooked or boiled well and if feasible, prepared
immediately before they are to be eaten. If food has been
kept for over two hours, it is desirable to reheat it thoroughly
until it boils, before consumption.
Encourage breastfeeding on demand.

Give no artificial teats or pacifier like dummies or
soothers to breastfeeding infants.
Foster the establishment of breastfeeding support
groups and refer mother to them on discharge from the
hospital or clinic.
Feeding during and after Common Illnesses
Hospitals which practice the ten steps to successful

breastfeeding are given public recognition and are given
a plaque that they can put by their front entrance
designating them as baby-friendly. Country level
guidelines for achieving baby-friendly hospital status
have been developed. Assisted by the Government,
UNICEF and WHO, a National Task Force has been formed
with representatives from Indian Medical Association,
Association of Obstetricians, Pediatricians, Nurses and
Hospital Administrators, Breastfeeding Promotion
Network of India (BPNI) and Association for Consumers
Action on Safety and Health (ACASH). More and more
hospitals are now being given this status.
The concept of supporting mothers to breastfeed is
important. However, promotion of breastfeeding alone is
not enough to make a hospital baby-friendly. This should
also include practices which will make hospitals safe and
friendly for newborns and their mothers such as:
i. Safer and mother-friendly delivery practices,
ii. Proper care of the umbilical cord,
iii. Warming and temperature regulation of newborn
after birth,
iv. Early diagnosis and management of conditions
such as absence of spontaneous breathing, aspiration, sepsis, hypoglycemia, etc.
Feeding should continue during ailments like diarrhea,

respiratory infections, etc. unless the medical condition of
the child contradicts it. Restriction or dilution of food
should be discouraged. Despite anorexia, the infant can
be coaxed to eat small quantities but more frequently, i.e.
after every 2 to 3 hours. After illness, the child should be
provided more than the usual diet to regain the weight
lost.
BABY-FRIENDLY HOSPITAL INITIATIVE (BFHI)
It is now being increasingly recognized that while mothers
want to breastfeed, certain hospitals and health workers
lag behind in their support to the mother. This support is
being provided through the concept of BFHI.
Baby-friendly hospital initiative is a global effort with
hospitals to provide support to the mother before, during
and after delivery so that she has a joyful breastfeeding
experience. These hospitals must fully practise all ten of
the ten steps to successful breastfeeding given in a joint
WHO/UNICEF document.
Ten Steps to Successful Breastfeeding
Every facility providing maternity services and care for
newborn infants should:
Have a written breastfeeding policy that is routinely
communicated to all health care staff.
Train all health care staff in skills necessary to implement this policy.
Inform all pregnant women about the benefits and
management of breastfeeding.
Help mothers initiate breastfeeding within half-hour
of birth.
Show mothers how to breastfeed, and how to maintain lactation, even if they should be separated from
their infants.
Give newborn infants no food or drink other than
breast milk, unless medically indicated.
Practice rooming-inallow mothers and infants to
remain together 24 hours a day.
National Guidelines on Infant and

Young Child Feeding
The Government of India has issued a set of guidelines for
the promotion of optimal feeding practices of infants and
young children. These are available from the website of
the Ministry of Women and Child Development. The
contents of this chapter are in line with the spirit of the
national guidelines.
BIBLIOGRAPHY
1.
Anand RK, Kumta NB, Kushwaha KP, Gupta A (Eds).

The Science of infant feeding. Jaypee Brothers: New Delhi,
2002.
2. Baumslag N, Putney PG. Breastfeeding: The Passport to
life. NGO Committee on UNICEF, New York, 1989.
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3. Breastfeeding promotion network of india (2006). Joint

statement on infant and young child feeding.
www.bpni.org Accessed on June 17,2008.
4. Ghosh S. Nutrition and Child Care. Jaypee Brothers:
New Delhi, 1997.
5. Gupta A, Rohde Jon E. Infant and young child undernutrition:Where lies the solution ? Economic and political
weekly. December 4, 2004.
6. Kesaree N, Banapurmath CR, Banapurmath S, Shamanur
K. Treatment of inverted nipples using a disposable
syringe. J Hum Lact 1993;9:2729.

King FS, Anand RK. Helping Mothers to Breastfeed.
Association for consumers action on safety and health:
Mumbai, 1994.
8. National family health survey. http://www.nfhsindia.
org/nfhsz.html.Accessed on June 17,2008.
9. Sachdev HPS. Infant feedingmajor practical considerations. In Sachdev HPS, Choudhary P (Eds): Nutrition in
Pediatrics. Department of Pediatrics, Maulana Azad
Medical College: New Delhi, 1994;79128.
7.
6.1 Protein Energy Malnutrition Meenakshi N Mehta .................................................................................................................................... 136

6.2 Water Soluble Vitamins: B Complex Vitamins Shashi N Vani .............................................................................................................. 163
6.3 Fat Soluble Vitamins Panna Choudhury .................................................................................................................................................. 166
6.4 Trace Elements B Bhandari ...................................................................................................................................................................... 171
6.5 Child and Adolescent School Health Education Sushil Madan ............................................................................................................ 176
136
136
IAP
IAP Textbook
Textbook of
of Pediatrics
Pediatrics
6.1 Protein Energy Malnutrition

Meenakshi N Mehta
Underlying every other condition is malnutrition, due to both
calorie and protein deficiency. Though poverty is the main
contributing cause, it is greatly aggravated by lack of proper
dietary knowledge.
INTRODUCTION
Protein energy malnutrition (PEM) and growth
retardation are probably the most widespread health and
nutritional problems of the developing countries,
including India. UNICEFs report The Progress for
Children identifies that in the developing world 146
million children under five years are under weight,
predisposing them to serious complications from
common childhood illnesses. Consequently protein
energy malnutrition is the most deadly form of
malnutrition. It is estimated that it is the primary or
associated cause of around half of the nearly 11 million,
i.e. 5.6 million annual deaths each year or 30,000 each
day in children under five years. Maternal and child
undernutrition is the underlying cause of 3.5 million
deaths, 35 percent of the disease burden in children
younger than 5 years and 11 percent of total global
DALYs (disability adjusted life year). As per the estimates
stunting, severe wasting and intrauterine growth
restriction together were responsible for 2.2 million
deaths and 21 percent of DALYs, for children younger
than 5 years. Not only these deaths are preventable, but
these needless deaths on regular basis is a humanitarian
disaster that cannot be allowed to continue UNICEF
says A recent update using data from 2001 and DALY
approach confirmed that undernurition/protein energy
malnutrition remains the single leading cause of health
loss in the world today Child underweight for age
accounts for 8.7 percent of the total disease burden in
people living in low and middle income countries,
mainly those of South Asia and sub-Saharan Africa.
Eighty percent of the worlds undernourished children
live in just 20 countries. Of an estimated 178 million
children aged younger than 5 years who are stunted (i.e.
have height for age Z score of less than2), most live in
sub-Saharan Africa and South Central Asia. 160 million
(90%) stunted children live in just 36 countries and make
up 46 percent of the 348 million children in those
countries About 55 million children are wasted (i.e. have

a weight for height Z score of less than2) of whom 19
million have severe wasting (weight for height Z score
of less than3) or severe acute malnutrition (weight for
height Z score of 3 or associated edema) Although
nutritional deficiencies are epidemic throughout
developing world South Asia (Bhutan, Maldives,
Afghanistan, Sri Lanka, Bangladesh, Pakistan, India and
Nepal) is home to more than half the total number of
underweight children, most of who live in India. With a
rate of 46 percent, the levels of children underweight in
South Asia are staggering. Three countries, India,
Bangladesh and Pakistan account for half the worlds
UW children, despite having just 29 percent of the
developing worlds under five population. In South Asia
other forms of undernutrition have persisted 44 percent
of U5 are stunted and 15 percent wasted. In many
countries a chronically poor diet and lack of access to
safe sanitation is compounded by gender discrimination.
South Asia is the only region in which girls are more
likely to be underweight than boys. In India, one out of
every three adult women is underweight and therefore
at risk of delivering low birth babies. After the
World Summit for Children in 1990 announced key
requirements for improving child health with a crucial
focus on nutrition, the UN incorporated these nutritional
aims into its first Millennium Development Goal (MDG
1: to eradicate extreme poverty). A target for MDG 1 is
to reduce by half, between 1990 and 2015, the proportion
of people who suffer from hunger which is to be
measured by assessing the percentage of children under
five years who are underweight.
DEFINITION
WHO defined PEM as range of pathological conditions
arising from coincidental lack in varying proportions of
proteins and calories , occurring most frequently in
infants and young children and commonly associated
with infection. The extent of weight loss and growth rate
varies with severity of PEM, i.e. in the early stages, there
is failure to maintain weight or growth rate, but as it
becomes progressive, there is loss of weight associated
with loss of subcutaneous fat and muscle mass with
Nutrition
dysfunction of many vital organs which lead to a variety
of clinical features. With increasing severity, there is
increasing failure in the homeostatic mechanisms of the
body and damage to the immune defences which may
result in infections, shock and death. In Nelsons
Textbook of Pediatrics XVI ed., Heird William has used
the word undernutrition for malnutrition interchangeably; however he has coined a new name Severe
Childhood Under nutrition for Protein Energy
Malnutrition. His argument is that under/malnutrition
is a result of inadequate dietary intake of single nutrient,
energy and/or protein, whereas PEM is usually
accompanied by deficiencies of other nutrients and the
term severe childhood undernutrition more accurately
describes the condition. But in the next paragraph it is
mentioned that this is a spectrum ranging from mild
undernutrition resulting in some decrease in length for
age and/or weight for age through severe forms of
undernutrition resulting in more marked deficits in
weight for age and length for age as well as wasting. Use
of term Severe Childhood Undernutrition for milder
variety of PEM is misleading and unjustifiable, since mild
is opposite to severe. Hence the conventional term PEM
seems to be more appropriate. If at all, we may call it
Energy Protein Malnutrition (EPM) to denote PEM, as
energy deficiency is much common than protein
deficiency and the incidence of energy deficiency is 10
to 15 times higher compared to protein deficiency in the
children suffering from PEM.
MAGNITUDE OF THE PROBLEM
Despite all time high Indias economic growth,
improving literacy and even declining infant mortality,
India continues to have the dubious distinction of being
among the worst off in the world: a high percentage of
malnourished children (Fig. 6.1.1). The last National
Family Health (NFHS) survey data released in 2007
showed that 45 percent of Indian children are under
weight and 70 percent are anemic. Of the underweight
children (0-59 months) 19.8 percent were wasted and 48
percent stunted, 43 percent are from rural area and 33.7
percent from urban area. Indian children are twice as
likely to be malnourished as even those in subSaharan
Africa and five times more likely to be than children in
China. Even with its remarkable economic programs,
Indias malnutrition levels in the last 7 years since the
last NFH survey have not been getting any better. As
per geographic focus, malnutrition in India is concen-
137
Figure 6.1.1: Morbidity and mortality
trated in a relatively small number of states, districts and

villages. A recent World Bank report noted that five states
account for about 80 percent of malnourished children.
A follow-on mapping study has identified the districts
where problem is most severe. The incidence of PEM is
higher in nutritionally vulnerable groups: young children
and women during pregnancy and lactation, as the
calorie and protein requirements are larger, relative to
their size than in older children and adults. Evidence
shows that most of the damage caused by malnutrition
happens either when child is in the womb or in the first
two years of life. Most of the impairment to brain
development and future productivity in these early
months of life is irreversible. As per the last NFH survey,
the most common age of PEM is between 6 months and
2 years and around 50 to 60 percent children are malnourished by 2 years; stunting is a major problem and
was observed in almost half of children. About 6,600
under five children die everyday of malnutrition in India.
PEM accounts for death in about 7 percent of cases and
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is underlying cause of death in 46 percent cases below 5

years of age. Majority of PEM (60-70%) is of mild to
moderate degrees and is severe in only 2 to 5 percent of
cases.
Apart from weight for age, other indicators like height
for age, and weight for height are also used to assess the
nutritional status of the children. In Z score classification,
children below 2 standard deviation (SD) are classified
as malnourished.
ECOLOGY/ETIOLOGY OF MALNUTRITION
Protein energy malnutrition (PEM) is the result of a
complex interplay of interacting and related factors in
the individual, family and community. Inadequate
dietary intake and disease are immediate determinants
of PEM. Disease may affect PEM by various mechanisms.
Conversely, PEM may increase susceptibility to and
severity of infections. The causes in individual are
anorexia, increased losses from intestine, malabsorption
and micronutrient deficiency disease, infectious diseases,
inadequate intakes of breast milk, early weaning from
breast, late weaning and inadequate access to food. The
familial causes are maternal illiteracy, poor knowledge
and practices of child rearing, maternal malnutrition,
large number of under 5 children, abrupt or early
weaning from breast, poverty, overcrowding, poor living
and sanitary conditions, unemployment, alcoholism or
debt. The community causes include national poverty,
poor educational status, inadequate medical facilities,
cultural practices and beliefs, marginalizing of girls and
women, natural and man-made disasters, poor rainfall
Figure 6.1.3: Socioeconomical and biological

determinants of PEM
Figure 6.1.4: Socioeconomical milieu of PEM
Figure 6.1.2: Ecology of PEM
or excess rain, or poor facilities for storage and transport,

and hoarding and black marketing. The community and
national causes have direct impact on the family and
individual child. Thus, PEM is an end result of many
ecological problems (Figs 6.1.2 to 6.1.6). Occasionally, the
terms primary malnutrition and secondary malnutrition
are used to denote the etiology. These terms refer
respectively, to malnutrition resulting from inadequate
food intake and malnutrition resulting from increased
nutrient needs, decreased nutrient absorption, and/or
increased nutrient losses. Both primary and secondary
Nutrition
Figure 6.1.5: Mortality related to bottle feeding
139
foods to feed infants, whom the parents believe to be at

risk for milk allergies and also in families who believe in
fad diets. Many cases are associated with rice milk diet,
a product that is very low in protein content.
In addition, PEM has been noted in chronically ill
patients in neonatal or pediatric intensive care unit as
well as among patients with burns, HIV, cystic fibrosis,
failure to thrive, chronic diarrhea syndromes, malignancies, bone marrow transplantation and inborn errors
of metabolism.14
Malnutrition does not only affect children in
developing countries. In more developed areas of the
world the prevalence of obesity in childhood is increasing
rapidly and in Europe in 2004, there were an estimated
14 million overweight children, 3 million of who were
obese .This trend has also been seen in India as well in
economically well to do families the school going
children have been found to be overweight due to faulty
food habitsconsumption of junk foods of high
carbohydrate and fat contentburgers, pizzas, chips,
popcorn, batatawadas, samosas, sweets, chocolates,
etc. aerated beverages like Coke, Thumbs up and
sweetened synthetic fruit juices. Fruity, etc. compounded
by TV culture, video games, computer with decreased
physical activity and thus increase of anabolism.
PATHOPHYSIOLOGY OF PEM
Figure 6.1.6: Relation of morbidity due to milk tin foods

resulting into severe PEM
malnutrition occur in developing as well as developed

countries; malnourished children often present with
gastroenteritis, pneumonia.
In dealing with the problem of PEM, certain common
myths need to be dispelled, for it is not poverty and lack
of food alone that cause malnutrition. In fact, in the
richest 20 percent of Indias population, more than 1 in 4
children are underweight and nearly 2 out of 3 anemic.
In the developed nations like USA, PEM has been
reported in families who use unusual and inadequate
Many of the manifestations of PEM represent adaptive

responses to inadequate energy and/or protein intakes.
In the face of inadequate intakes, activity and energy
expenditure decrease. However, despite these adaptive
responses fat stores are mobilized to meet the ongoing,
albeit lower, energy requirement. Once these stores are
depleted, protein catabolism must provide the ongoing
substrates for maintaining basal metabolism. In the etiopathogenesis of PEM, there has always been a vigorous
debate. Why is it that among children destined to become
malnourished some develop kwashiorkor while others
develop marasmus? What are the determinants? Several
insults have been proposed as principal causes of
kwashiorkor including dietary protein deficiency,
aflatoxin in food as well as diarrhea, impaired renal
function, decreased Na + , K + ATPase activity, and
depressed cellular protein synthesis reinforced by
infection. The latest theory proposes that kwashiorkor
arises from excessive noxious insults, resulting in the
generation of sufficient reactive oxidative free radicals
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to exceed the hosts antioxidant capacity. Children with

kwashiorkor, when compared with marasmic or normal
controls have greater concentrations of biomarkers of
oxidative stress and damage as well as lower blood
concentrations of antioxidants. Furthermore, clinical
resolution of kwashiorkor coincides with the return to
normal of these markers. This proposal is supported by
low plasma concentrations of methionine, a dietary
precursor of cysteine, which is needed for synthesis of
the major antioxidant factor glutathione. This possibility
also is supported by lower rates of glutathione synthesis
in children with edematous compared to non edematous
PEM.
CLINICAL MANIFESTATIONS
The clinical manifestations of malnutrition depend on
the severity and duration of nutritional deprivation, the
age of the undernourished subject, relative lack of
different proximate principals of food and micronutrients
and the presence or absence of associated infections.
Nutritional marasmus and kwashiorkor are two different
extreme forms of a continuous process of malnutrition.
Nutritional marasmus results from predominant energy
deficiency whereas kwashiorkor is due to predominant
protein deficiency though some energy deficiency may
co-exist. As per Gopalan a well known nutritionist, the
dietary background of children suffering from
kwashiorkor and marasmus may well be the same; the
difference is of adaptation to deficiency. As per this
adaptation theory marasmus is an extreme degree of
adaptation to prolonged inadequacy of energy in the diet,
whereas kwashiorkor is due to adaptation failure or
dysadaptation to two situations; first, continued prolongation of the stress of malnutrition and second, sudden
precipitation or aggravation by a fulminant infection such
as measles, diarrhoeal episode, pneumonia or pertussis.
Further he explains that relatively mild effect of
adaptation may lead to nutritional dwarfism.
Occasionally, patients who are initially marasmic may
develop edema due to protein loss when the individual
is known as marasmic kwashiorkor. In clinical practice,
such extremes account only for a small proportion of
cases of malnutrition. Malnutrition can be compared to
an iceberg; while only tip of the iceberg, i.e. the severe
forms are seen above the surface of the water, those
hidden under the surface constitute a vast majority of
children suffering from mild and moderate forms of PEM
which remain hidden in the community. Since they are
Figure 6.1.7: The Iceberg of malnutrition
not brought for any medical attention they are at a highrisk of deterioration and progress to severe forms if
uncared for prolonged period (Fig. 6.1.7) A majority have
mild to moderate deficiency with varied clinical
manifestations, and this range is known as protein energy
malnutrition (PEM). Besides these specific syndromes,
protein energy deficiency impairs resistance to infection
and is consequently associated with high morbidity and
mortality rates, especially among toddlers in poorly
nourished communities. Mild degrees of protein energy
deficiency, leads to growth retardation rather than frank
malnutrition: this may be associated with some degree
of retardation in mental development.
CLINICAL FEATURES
Protein energy malnutrition (PEM) is most common in
under 5 children, with peak incidence between 6 months
to 3 years. Artificially fed babies usually from lower
socioeconomic status develop PEM below 6 months of
age. They are usually associated with infection also. Initial
response to nutritional deprivation is of two types:
1. Dynamic children: The infants remain active but fail
to gain weight and later length, and
2. Sedentary children: The children who maintain their
growth initially by limiting their activities. But
ultimately they also fail to grow. About two-thirds of
children with PEM do not present with clinical signs
and are diagnosed by anthropometry. However,
children with long standing nutritional deprivation
fail to develop any of the following manifestations:
depigmented lusterless haireasily pluckable. Skull
circumference gets arrested. Other features of chronic
PEM may be glossitis, stomatitis, gingivitis, pallor,
thin lusterless skin, wasting, edema, vitamin A
deficiency, rickets, parotid enlargement, etc.
These children may manifest as prekwashiorkor,
kwashiorkor, marasmus, marasmic kwashiorkor, and
nutritional dwarfism.
Nutrition
141
Marasmus
Marasmus can develop in the first months of life, and
will result, if mothers milk supply is insufficient, as a
result of which the mother feeds the baby with diluted
buffalos , cows, goats or even tin milk, and very little
or no other food is offered. Hence common age of
occurrence is 0 to 2 years, but it can occur at a later age
also. Marasmus is characterized by failure to gain weight
and irritability, followed by weight loss and listlessness
until emaciation results. Marasmus is diagnosed by gross
loss of subcutaneous fat and the infant seems to have
only skin and bones. There is conspicuous absence of
edema. Growth retardation is severe and obvious. The
head appears disproportionately large with very little
hair and if cut does not grow back easily. Weight is less
than 60 percent of expected weight.
The ribs are visible and the costchondral junctions
look prominent because of loss of subcutaneous tissue.
The child is conscious, alert but apathetic. In extreme
cases, the child is disinterested in surroundings and sits
listless for long hours. The facial pads of the fat are last
to go, and when that happens, the child looks like a
wisened old man. Usually, there is moderate anemia, but
may be associated with vitamin deficiencies, infections
and infestations and electrolyte balance with diarrheal
instances. In the early stages, the childs appetite is good
and readily accepts what is offered. However, in
advanced stages, there is loss of appetite and it requires
a lot of tact and patience to coax the child to eat. Infants
are often constipated but may have starvation diarrhea
with frequent, small stools containing mucus. The
abdomen may be distended or flat, with the intestinal
pattern readily visible. There is muscle atrophy and
resultant hypotonia. As the condition progresses, the
temperature usually becomes sub normal and pulse
slows (Fig. 6.1.8).
Kwashiorkor
The word kwashiorkor was suggested by Dr Cicely
Williams in early 1930s. It is an African word which
means the disease that occurs when the child is
displaced from the breast by another child. The age
incidence is later than that of marasmus and this
condition is uncommon under the age of 1 year
Kwashiorkor may initially present with vague
manifestations that include lethargy, apathy and/or
irritability. When advanced there is lack of growth, lack
Figure 6.1.8: Marasmus
of stamina, loss of muscle tissue, increased susceptibility

to infections, vomiting, diarrhea, anorexia, flabby
subcutaneous tissues and edema. The edema usually
develops early and may mask the failure to gain weight.
It is often present in internal organs before it is recognized
in the face and limbs.
Edema is characteristically pitting. It usually occurs
first above the ankles and is detected by pressing firmly
over the lower third of the medial surface of the tibia,
rarely fullness of dorsum of the feet or puffiness round
the eyes, occurs even earlier. In later stages, the whole
face, hands and body may be edematous, but ascites is
rarely due to kwashiorkor alone. Edema is mainly due
to tissue wasting, together with low plasma osmotic
pressure caused by low serum albumin level. The child
is listless, lethargic, apathetic and miserable, his moaning
cry is characteristic. The hair changes are variable. Hair
may be thin, dry, brittle and lusterless. These become
straight and hypo pigmentedbecome grayish-white or
reddish-brown. During recovery, the growing part of the
hair gets approximately pigmented, and gives
appearance of Flag. The skin changes are not constant
and manifestations are known as dermatosis. Skin
becomes darkened in irritated areas but in contrast to
pellagra, it does not occur in areas exposed to sunlight.
Depigmentation may occur after desquamation in these
areas, or it may be generalized. The skin lesions appear
as large areas of erythema, followed by hyperpigmentation. The skin becomes dry and hyperkeratotic. The
epidermis peels off in large scales, exposing a raw area
underneath which is prone to infection. It resembles old
paint flaking off the surface of the wood. The lesions are
moist, common on areas exposed to continuous pressure
and irritation. In severe cases petchiae or ecchymoses
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CLASSIFICATION OF PROTEIN ENERGY
MALNUTRITION (PEM)
Protein energy malnutrition (PEM) is a generalized
syndrome complex, and it is very difficult to classify it
using a single parameter. A large number of
classifications using anthropometric, clinical, and
biochemical parameters have been proposed.
Gomezs Classification
Figure 6.1.9: Kwashiorkorextensive dermatosis
may appear. Alternate areas of hypo and hyperpigmentation give a resemblance to pavement and is known as
pavement dermatosis. Similarly, the various skin
changes are sometimes seen in a particular mosaic form,
giving the name of mosaic dermatosis. Liver may be
enlarged and fatty, there may be associated infections in
the form of diarrhea, respiratory infections or urinary
tract infections and vitamin deficienciesvitamin A
thiamine, riboflavin and niacin. Eventually, there is
stupor, coma and death (Fig 6.1.9).
This is the first proposed classification based on weight

for age.
Standard weight for age measurement used was
Harvard growth standard, 50th centile being 100 percent.
Weight of the child
Grade
90-110% of standard
Normal
75-90% of standard
1st degree malnutrition (mild)
60-74% of standard
IInd degree malnutrition

(moderate)
Less than 60% of

standard
IIIrd degree malnutrition

(severe)
Jellifes Classification
Marasmic Kwashiorkor
Children with severe muscle and fat wasting, but with
presence of edema are called marasmic kwashiorkor.
This syndrome is seen in children with those who have
marasmus, but suddenly develop edema due to increased
deficiency of protein than before. Thus the clinical
features are those of both marasmus and kwashiorkor.
Anemia may be moderate, and one or more vitamin
deficiencies may be evident (Fig. 6.1.10). The usual
differentiating features of marasmus and kwashiorkor
are summarized in Table 6.1.1.
Nutritional grade
Percentage of standard weight for

age (50th centile of Harvard standard)
Normal
More than 90 percent
Grade I
8090 percent
Grade II
7079 percent
Grade III
6069 percent
Grade IV
Less than 60 percent
Classification Based on National Centre for Health

Statistics (NCHS) (USA) Standards
Figure 6.1.10: Marasmic Kwashiorkor
Indices
Nomenclature
for deficit of
index
Cut-off points for defining

malnutrition
% of refe- Z or SD score
rence
from reference
median
median
Weight for
height
Height for age
Wasting
< 80
<2
Stunting
< 90
<2
Weight for age
Underweight
< 80
<2
Nutrition
143
TABLE 6.1.1: The principal differentiating features of protein energy malnutrition (PEM)
Marasmus
Kwashiorkor
03 years
13 years
1. Edema
None
* Lower legs, sometimes face or generalized.
2. Wasting
*Gross loss of subcutaneous fat

All skin and bone
Sometimes hidden, sometimes fat blubbery.
3. Muscle wasting
Obvious
Sometimes hidden
4. Growth retardation
Obvious
Sometimes hidden
5. Mental changes
Usually apathetic quiet
Usually irritable moaning, also apathetic.
1. Appetite
Usually good
Usually poor
2. Diarrhea
Often (past or present)
Often (past or present)
3. Skin changes
Seldom
Oftendiffuse depigmentation occasional

flaky paint or enamel dermatosis
4. Hair changes
Seldom
Often sparse, straight silky, dyspigmentation,

gray or reddish
1. Serum albumin
Usually normal (or low)
* Low
2. Urinary urea per g creatinine
Usually normal (or low)
* Low
3. Urinary hydroxyproline
per g creatinine
* Low
* Low
4. Serum essential
amino acid index
* Low
* Low
5. Anemia
Uncommon
* Common
6. Liver biopsy
* Normal or atrophic
* Fatty changes
A. Usual age
B. Essential features
C. Variable features
D. Biochemistry/pathology
*These are the most characteristic or useful distinguishing features.
Classification Suggested by FAO/WHO

Expert Committee
Nutritional
status
Under weight
Nutritional dwarfism
Marasmus
Kwashiorkor
Body Weight
as % Standard
for age
Edema
8060
<60
<60
8060
<60
0
0
0
+/++
+
IAP Classification
Deficit in
Weight for
Height
Minimal
Minimal
++
+/++
++
Nutrition Subcommittee of the Indian Academy of

Pediatrics 1972, using the standard value (100%) as 50th
percentile of Harvard growth standard.
Nutritional grade
Percentage of standard weight for age
Normal
Grade I
Grade II
Grade III
Grade IV
More than 80 percent

7180%
6170%
5160%
< 50% or less
Add (K) for presence of edema
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Waterlow Classification
Normal
Wasted
Stunted
Weight/Age (%)
100
70
70
Weight/Height (%)
100
70
100
Height/Age (%)
100
100
84
Interpretation of Indicators
Weight/Height = Weight of the child/Weight of a
normal child of same height 100
Height/Age =
Length or Height of the child/

Length or Height of a normal child
at same age 100
Nutritional status
Stunting %
of Height/Age
Wasting %
of Weight/Height
Normal
> 95
> 90
Mildy impaired
87.595
8090
Moderately impaired
8087.5
7080
Severely impaired
< 80
< 70
Arnolds Classification
(Based on Midarm Circumference-MAC) or
(Mid-upper Arm Circumference-MUAC)
Nutritional Status
MAC (cm)
a. Normal
b. Mild to moderate PEM
c. Severe PEM
13.5 and above

12.513.4
12.4 or less.
Wellcome Trust Classification

Weight for age
(% of expected)
Edema
Clinical type of PEM
< 80
Absent
Under weight
6080
Present
Kwashiorkor
< 60
Absent
Marasmus
< 60
Present
NUTRITIONAL ANTHROPOMETRY
It is a valuable index of assessment of nutritional status
of children and mothers. Among the most studied are
weight, length/height arm circumference, skinfold
thickness, chest circumference and head circumference.
Acute vs chronic deficiency: These parameters no doubt

are the most useful and easily used procedures currently
available for field surveillance. Weight and arm
circumference are affected within a short duration of
inadequate nutrient intake and ill-health, while height
and head circumference do not change so rapidly. A
slowing in the rate of growth indicated by poor gain in
height would take 6 months to manifest itself while a
slowing of weight gain or loss can be demonstrated
within a month. A child can loose weight but not height.
Anthropometric parameters can be classified into 2
main groups, the age dependent and age independent
(used when childs age is not known) criteria.
Age Dependent Criteria
Weight for age: Serial weighing and recording of weight
for age charts is the most useful and commonly used
method for monitoring and supervising growth as it is
the most sensitive method for identifying those with
nutrition and health problems. Weighing is a quick and
easy task both for the medical as well as the paramedical
health workers the only necessary tools being weighing
scales and charts. The weight can be expressed as:
(i) percentage of the median value as suggested by
Gomez et al. Normal more than 90 percent, Grade III
below 60 percent of the expected weight for age. In India,
Indian Academy of Pediatrics has suggested that the limit
of normal be lowered to 80 percent and that various
grades be defined accordingly: Normal > 80 percent,
Grade I: 80 to 70 percent, Grade II: 70 to 60 percent, Grade
III: 60 to 50 percent, and Grade IV: < 50 percent.
It can be expressed by use of median and standard
deviation values or as the percentage so the reference
data where the median value is 50th percentile. This
method is employed to chart the upper and lower lines
of the Road to Health on the growth chart. In these
charts the upper line is equal to the 50th percentile of the
weight for boys, the lower line being the 3rd centile for
girls.
Height for age: Compares a childs height with the
expected height/length for a healthy reference child of
the same age. It is not useful for early diagnosis of
malnutrition as changes in height occur relatively slowly
compared to changes in weight.
Age Independent Criteria
Mid-upper arm circumference (MUAC) or midarm
Circumference (MAC): Between 1 to 5 years, the MUAC is
Nutrition
relatively constant between 16.5 to 17.5 cm. Any child in
this group whose MUAC is less than 12.5 cm is classified
as undernourished. MUAC is a useful method of
screening large number of children during nutritional
emergencies but is less useful in long-term growth
monitoring programs.
Weight for height: The degree of wasting can be assessed
by comparing the childs weight with the expected
weight of a healthy child of same height. Combinations
of these measurements have been suggested sometimes
to distinguish types of malnutrition. For example,
Waterlow proposed that weight/height allows one to
distinguish between children who have suffered
malnutrition in the past from those who are currently
experiencing malnutrition. In chronic malnutrition, the
child is stunted, i.e. his weight for age and height for
age are low. In acute malnutrition, however, his height
for age is appropriate, but he is wasted (low weight for
height and age) Thus, weight and height measurements
together are useful to understand the dynamics of
malnutrition, distinguishing between current malnutrition and long-term or chronic malnutrition.
Quackstick: Quackers Midarm circumference measuring
stick is a height measuring rod calibrated in MUAC
rather than height, values of 80 percent of expected
MUAC for height are marked on the stick at corresponding heights levels and the child is made to stand in
front of this stick. His nutritional status is easily read as
50, 60, 70, or 80 percent of the standard. If a child is taller
than his circumference level on the stick, he is considered
malnourished. The quackstick originally designed in
Mexico, has been adapted in Africa and India after local
modifications (Fig. 6.1.11).
Mid arm circumference to head circumference ratio: A ratio
of 0.280-0.314 indicates mild malnutrition, 0.250 to 0.279
moderate PEM, and less than 0.249 severe PEM.
Midarm/height ratio: Less than 0.29 indicates gross
malnutrition (normal0.32 to 0.33).
Chest/head circumference ratio: Chest circumference
becomes equal to head circumference at 1 year, and after
2 years, it becomes more than head circumference. In
PEM, it is still smaller than head circumference beyond
2 years of age.
Skin fold thickness: It is an indicator of availability of caloric
stores in the form of subcutaneous fat. Sites for
measurements are usually the triceps and subscapular
145
region. Type of instrument used is skin caliper of

Harpenden and Best type. Its normal value is present in
Tanners chart and measurements below 90 percent of
the standard are considered subnormal (80-90% mild,
60-80% moderate and less than 60% severe malnutrition).
Mid-thigh and calf circumference: Standards for mid thigh
and calf circumference have been developed. The values
are typically low in weaning retardation of weight gain.
THE GROWTH CHART
While the reliability of a single anthropometric
measurement may be a suspect and difficult to interpret
because of existing wide variations in any population
and may also lack adequate predictive value, measurements at regular intervals permit systematic assessment
of a childs growth. The idea of monitoring the growth
of the individual child on a long-term basis which would
be useful in the provision of child health care, gave rise
to the concept of growth chart, pioneered by Morely
in 1959 as result of long -term study of child growth in
Imesi-West Nigeria. The growth chart has been prepared
on the principle of regular monthly weighing of the child
under 5 to 6 years. The childs weight is plotted every
month against his or her age, giving a weight for age
grapha growth curve. Since Morleys original
suggestion and design over last 40 years, various
modifications have been made and these growth cards
are printed in various languages and are used in about
80 countries all over the world (Figs 6.1.12 and 6.1.13).
MULTIPLE NUTRITIONAL DEFICIENCIES
As the nutritional deficiencies are generally multiple,
anemia due to deficiencies of iron, vitamin B12 or folate
or protein may be associated. Thus the anemia may be
hypochromic microcytic, macrocytic, rarely megaloblastic or normocytic normochromic. Deficiencies of vitamin
B-complex factors, especially ariboflavinosis, are not
unusual. Vitamin A deficiency manifesting as
keratomalacia, reported in 10 to 20 percent of cases of
kwashiorkor can result in xerophthalmia, leading to
blindness. Vitamin C deficiency may become severe to
develop frank scurvy, which manifests in as painful
jointswith restricted movements, subperiosteal
hemorrhages, ecchymoses at pressure points and rarely
even bleeding gums. Since growth gets arrested in severe
PEM, rickets may become manifest when the child starts
growing with nutritional rehabilitation.
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Figure 6.1.11: Quacstickmodified for Indian children
Mineral Content
Potassium: The total body potassium may be markedly
decreased in PEM. The loss is due partly to the cellular
breakdown but more so by the loss in diarrheal stools.
Potassium being mainly an intracellular ion, its deficits
has an impact on the cellular metabolism particularly in
the organs like muscles, kidneys and pancreas.
Other electrolytes: There is also deficit of total body
sodium, calcium, phosphorus, magnesium and chloride.
The body sodium is 93 percent of the expected values
There is significant loss of magnesium from the cells as
confirmed by muscle biopsy and histochemical studies.
Serum magnesium levels are significantly low in children

with moderate and severe malnutrition and in children
with marked linear growth retardation.
Protein Energy Malnutrition (PEM) and
Endocrine Glands
Growth hormone secretion may be raised, so also the
plasma cortisol levels. Insulin levels are reduced both in
marasmus as well as kwashiorkor. Thyroid stimulating
hormone (TSH) of pituitary is elevated, T3 levels are
decreased and T4 levels are increased in PEM but
markedly decreased in marasmus and kwashiorkor.
Nutrition
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Figure 6.1.12: Prototype of growth chart (Full open)
Infection and Immunity in Protein Energy

Malnutrition (PEM)
Infectious disease nearly worsens when malnutrition is
present and conversely malnutrition usually weakens
resistance to various infections which are more serious
in a malnourished host than in a well nourished child.
These effects are synergistic and result in strikingly high
mortality rate among toddlers and under five children

in developing countries. The vast majority of children
with PEM have recurrent infections and present with
episodes of acute infections or a chronic insidious
infection which may go undetected unless carefully
looked for. Thus, recurrent infection of gastrointestinal
tract particularly diarrheal diseases, lower respiratory
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Figure 6.1.13: Prototype of growth chart (front and reverse sides)
tract like pneumonia are very common and have high

morbidity. Measles is usually a preceding illness.
Tuberculosis must be always ruled out and intestinal
parasitosis like ascariasis, hookworm, and giardiasis are
commonly present. In endemic regions malaria must also
be considered. All these infections impair nutritional

status and contribute to high mortality or in less serious
states to growth retardation and frank malnutrition.
Urinary tract infection often goes undetected and hence
must be ruled out. Occasionally septicemia especially in
Nutrition
infants and toddlers may be the cause of high morbidity
and mortality in developing countries.
Regarding humoral immunity IgG, IgM, and
secretory IgA blood concentrations are not significantly
affected in mild and moderate form of PEM and show a
good response when challenged with bacterial and viral
vaccines, but is depressed in severe forms of PEM with
infections. The cell mediated immunity (CMI) is
definitely impaired in all grades of malnutritions except
in Grade I. It is severely impaired in Grades III and IV
PEM and kwashiorkor. This explains a high incidence of
gram-negative bacterial infections and serious morbidity
and high mortality to viral infection like herpes simplex
and measles. It is because of the depressed CMI that the
tuberculin skin test is often negative in marasmus and
kwashiorkor in spite of active tuberculosis. Following
dietary treatment of four to six weeks, the CMI might
improve and the skin test may become positive. Serum
C reactive protein and C3 complement are depressed in
severe malnutrition but rise in presence of infections and
thus behave as acute phase reactants.
COMPLICATIONS
The complications of PEM are usually seen with severe
malnutrition. They are dehydration, hypothermia,
hypoglycemia, infections, anemia, xerophthalmia,
congestive heart failure, hypomagnesemia, hypocalcemia, zinc, copper, chromium and manganese
deficiency and deficiencies of other vitamins.
CONSEQUENCES OF PEM
Why should we be concerned about PEM? Malnourished
children are more susceptible to disease, have a reduced
capacity to learn and are much more likely to drop out
of school. Once in the job market their productivity is
low. For the economy as a whole, this translates into
losses of nearly 3 percent of GDP. All this places Indias
large young populationthe basis of its much awaited
demographic dividend at a growing disadvantage in
todays globalizing world.
The evidence suggests that Undernutrition has
pervasive effects on immediate health and survival as
well as on subsequent performance. These include not
only acute effects on morbidity and mortality but also
long term effects on cognitive and social development,
physical work capacity, productivity, and economic
growth.31 The magnitude of both the acute and the longer
term effects is considerable. Prospective studies suggests
149
severely underweight children (< 60% of reference

weight for age) have more than an 8 fold greater risk of
mortality than normally nourished children, that
moderately underweight children (60-69% of reference
weight for age) 4 to 5 fold greater risk, and that even
mildly underweight children (70-79% of reference weight
for age have 2 to 3 fold greater risk. The high prevalence
of mortality, even in children with mild and moderate
undernutrition, suggests that more than fifty percent of
child deaths may be caused directly or indirectly by
undernurition. Survivors of undernurition have deficits
in height and weight that persist beyond adolescence into
adulthood. These may be accompanied by deficit in
frame size as well as muscle circumference and strength.
The implications of these deficits with respect to the work
capacity of both men and women and to womens
reproductive performance are obvious. Survivors of PEM
also have deficits in cognitive function and school
performance than normally nourished children from the
same background. These deficits are related to the
severity of PEM and can be decreased probably by a
combination of dietary and behavioral interventions,
coupled with improvements to the overall quality of the
home and/or school environment. Such interventions
appear to be much more effective if instituted in early
life.
MANAGEMENT
The management of PEM depends on nutritional status,
degree of hypermetabolism, expected duration of illness
and associated complications. The goals are to minimize
weight loss, to maintain body mass and to encourage
body mass repletion or growth.
The principles of management are as follows:
1. The patient is evaluated with regard to the severity
of proteinenergy malnutrition, presence or absence
of associated systemic infections, other associated
nutritional deficits such as vitamin deficiencies or
anemia and associated fluid and electrolyte
disturbances.
2. The intake of food is promoted by all available means.
Locally available and culturally acceptable foods,
which the family can afford, are advised.
3. Complications of malnutrition and sequelae are
prevented by careful surveillance and prompt
remedial action.
4. Possible epidemiological factors for malnutrition are
considered and attempt is made to eliminate these as
far as possible.
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Mild to moderate PEM is best managed at home.

Majority of cases of severe PEM are associated with some
of the complications listed above and hence are best
managed in hospital. The indications for hospitalization
are hypothermia, infection, fluid and electrolyte
imbalance, convulsions, unconsciousness, xerophthalmia, severe dermatosis, extreme weight deficit, bleeding,
marked hepatomegaly, jaundice, purpura, raised liver
enzymes, severe anemia and cardiac failure, persistent
vomiting, severe anorexia, distended tender abdomen
and age less than one year.
Domiciliary Management
It is for mild to moderate PEM and those uncomplicated
severe PEM who have fairly good appetite, normal body
temperature, who are conscious and active and without
evidence of serious infection. These children are managed
at home by parents under observation and supervision.
They are monitored through weekly visits by
paramedicals or visits to the hospital or at a nutritional
rehabilitation center every week. The main goal of
treatment is to provide adequate calories for dual
purpose, to replace losses and to build-up nutrition and
to promote growth. Caution must be taken to gradually
build-up the calories and proteins. The energy
recommended is 120 to 150 kcl/day and protein 2 to
3 g/kg/day of high biological value. Both of these should
be based on locally available and affordable food sources,
commonly consumed by the family. The common foods
advocated are double or triple mixes of cereals and pulses
like dal, rice, khichadi, seasonal green leafy and yellow
orange vegetables, root vegetables, sugar, jaggery, milk
and milk products, if family could afford nuts like
groundnuts. Empasis must be laid on adding enough oil/
vanaspati ghee/butter to the diet, to increase calories and
palatability. Parents are educated to prepare suitable
diets from these food sources, liquid, semisolid or solid
depending on the acceptability and appetite of the child.
Frequent small feeds with calories and proteins
distributed proportionately are encouraged rather than
1 or 2 major bulky meals. Non-vegetarian articles like
egg, fish, chicken, meat, etc. are allowed for those whose
cultural and religious practices permit them. Parents are
educated about hygienic way of preparation and
handling of food, use of safe and clean drinking water
and importance of personal hygiene. Some basic advice
is also given, for management of diarrhea by oral
rehydration solution (ORS), immediate attention for
treatment of common infestations and infections and

appropriate management of anemia by oral iron and folic
acid supplements and associated vitamin deficiencies.13
To promote growth, zinc supplements are given when
positive nutrition balance starts occurring and child
manifests with increase in weight gain. Due attention
should be given to check and advise proper
immunization.
Severe Malnutrition
The best approach to the management of severe
malnutrition has been a controversial topic for many
years especially in circumstances where resources are
limited in terms of shortage of staff, medical supplies
and the budget. The encouraging reports of the
management of uncomplicated severe malnutrition using
simple, ready to use therapeutic foods with community
based care is worthwhile. This has immediate advantage
of easier access for rural populations, promoting earlier
intervention in the course of disease, improving coverage
rates and preventing nosocomial infections. The limited
hospital staff can focus on complicated cases that require
inpatient care. The risk of death rises progressively with
worsening nutritional status. More than 80 percent of
malnutrition associated deaths occur in children with
mild to moderate malnutrition as these greatly
outnumber children with malnutrition. This indicates
that, in addition to dealing with severe malnutrition, it
is vital to intervene in children with mild and moderate
malnutrition to have a greater effect on child survival.
Case fatality rates in children with severe malnutrition have remained unchanged at 20 to 30 percent
over the past five decades. Even in the 1990s, death as
high as 60 percent has been reported for children with
edematous malnutrition. Infection, including diarrhea
with accompanying water and electrolyte disturbances
is common in severely malnourished children and
been found to be the worst prognostic factor.
According to the World Health Organization a death
rate of >20 percent is considered unacceptable in the
management of severely malnourished children, 11 to
20 percent is poor, 5 to 10 percent is moderate, 1 to
4 percent is good, and < 1 percent is excellent.
Appropriate feeding micronutrients supplementation,
broad spectrum antibiotic therapy, less use of intravenous fluids for rehydration and careful management
of complications are factors that can reduce death,
morbidity and cost of treating these children.1 Based
Nutrition
upon these factors, WHO has prepared guidelines for
the inpatient case management of severe malnutrition.
Severe malnutrition is defined in these guidelines as
the presence of severe wasting (< 70 % weight for
height or 3 SD and/or edema). Not all severely
malnourished children need hospitalization. However,
since majority of the severely malnourished children,
have some complications, they need hospitalization
for critical care and intense monitoring.
The hospital management consists of 3 phases:
1. Resuscitation: lasts for 6 to 24 hours.
2. Acute phase: 1 day to 1 week+
3. Rehabilitation: Through second and third week to
6 weeks. The period of phases especially the first two
phases may vary depending on the condition of the
child when brought for medical attention.
WHO has suggested guidelines for the inpatient
treatment of severely malnourished children, the general
principles are as follows:
Phase of Resuscitation/Stabilization and
Treatment of Complications
Dehydration
Assessment of dehydration is difficult due to wasting
and edema. However, dry oral mucosa, acidotic
breathing, oliguria, absence of tears and peripheral
circulatory failure are most reliable signs. The amount
of fluid and sodium should not exceed 75 percent of the
allowances calculated on the basis of weight and age
(because of reduced capacity to excrete water and
inability to excrete sodium). Additional fluid can be given
if needed. Fluid deficit and maintenance fluids are
calculated. Deficit fluid volume is replaced by 5 percent
dextrose in N/2 saline in 6 to 8 hours, and maintenance
fluid volume is given as Isolyte P over 16 hours. If child
has shock, Ringers lactate 30 ml/kg or 20 ml/kg of 0.45
percent saline (1/2) in dextrose is given in 1 hour, then
70 ml/kg of Ringers lactate or 10 ml/kg in 1 hour of
glucose saline for two hours. If shock does not improve
then 10 ml/kg of plasma is infused. Potassium is added
in infusion in dosage of 2 to 3 mEq/kg (maximum dose
40 mEq/L) when a flow of urine is observed. In mild
dehydration, ORS (oral rehydration salt-WHO-sodium
chloride 3.5 g, potassium chloride 1.5 g, sodium citrate
2.9 g, glucose 20 g) should be given. Severely malnourished children with dehydration may not tolerate this
high sodium low potassium ORS. For them special
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rehydration solution for malnutrition ResoMal 5 ml/kg

every 30 minutes may be given. Assume all children with
watery diarrhea, may have dehydration; give (i) ResoMal
5 ml/kg every 30 minutes for 2 hours orally or by
nasogastric tube (ii) 5 to 10 ml /kg/h for next 4 to 10
hours, exact amount determined by ongoing losses; (iii)
initiate re-feeding with low calorie formula. Some of the
children may require ORS by intragastric tube. Ongoing
loss of water in stool is provided at 10 ml/kg/stool. Once
child is stable and he is able to accept oral feeds, milk
based therapeutic nutrition is started.
Correct Electrolyte Imbalance
All severely malnourished children usually have
potassium and magnesium deficiencies which may take
at least 2 weeks to correct. Give:
A. Extra potassium 2 to 4 mmol/kg/day
B. Extra magnesium 0.3 to 0.6 mmol/kg/day
C. Restrict salt, do not use diuretics
D. When rehydrating give low sodium rehydration fluid
(e.g. ResoMolcontains 45 mmol Na, 40 mmol K and
3 mmol/Mg/l). The extra potassium and magnesium
can be prepared in a liquid form and added directly
to feeds during preparation. Make a 10 percent stock
solution of potassium chloride (100 g KCl in 1 liter of
water) and 1.5 percent solution of zinc acetate (15 ml
zinc acetate in one liter of water). For milk feeds add
22.5 ml of the stock KCl solution instead of 20 ml of
electrolyte/mineral solution to 1000 ml of feed. Give
50 percent magnesium sulfate intramuscularly once
0.3 ml/kg to a maximum of 2 ml.
Hypothermia: It is common in marasmus and is usually a
manifestation of infection, hypoglycemia or severe
energy deficit. Child is kept in warm room well covered
close to mother and is given frequent feeds and antibiotics
for infection. If the axillary temperature is <35oC take
rectal temperature using a low reading thermometer, if
below 35.5C (95 oF) feed straight away (or start
rehydration if needed).
Hypoglycemia: (Blood sugar less than 50 mg/dl)/ It is
again more common in marasmus with hypothermia,
septicemia and coma. It requires 10 percent glucose 1 to
2 ml/kg in bolus followed by 10 percent dextrose in
N/5 saline in maintenance dose for 24 hours. Use of 50
percent dextrose is not recommended. Alternatively, if
10 percent intravenous glucose is not available give
10 percent sucrose solution (1 rounded teaspoon of sugar
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GENERAL PRINCIPLES FOR ROUTINE CARE
Rehabilitation
Steps
Stabilization
Phase
Day 12
Day 27+
Week 26
1. Hypoglycemia
...........................
2. Hypothermia
...........................
3. Dehydration
...........................
4. Electrolytes
.......................................................................................................................
5. Infection
.....................................................................................
6. Micronutrients
........................... No iron ............................................. With iron .................
7. Cautious feeding
.....................................................................................
8. Rebuild tissues
................................
9. Sensory stimulation
.......................................................................................................................
10. Prepare follow-up
.......................................................................................................................
in 3.5 tablespoonfuls water) orally or by nasogastric tube.

Then feed every 30 minutes for 2 hours, giving one
quarter of the 2-hour feed each time. Give antibiotics and
continue 2 hourly feeds, day and night. As hypoglycemia
and hypothermia usually occur together and are signs
of infection, check for hypoglycemia whenever
hypothermia is found. Frequent feeding is important in
both condition.
Infection: Diagnosis of fulminant infection is made by high
index of suspicion or in the presence of hypothermia,
apathy, convulsion or come. Antimicrobials (broad
spectrum) are started immediately while awaiting culture
reports. Gastric aspirate examination and culture, X-ray
chest and Mantoux test are done to diagnose pulmonary
tuberculosis. Blood film for malaria may be required. If
child has no complications, cotrimoxazole 5 ml orally
twice daily for 5 days (2.5 ml if weight <4 kg) (5 ml is
equivalent to 40 mg TMF + 200 mg SMX) or if the child
is severely ill, has complications give intravenous
ampicillin (50 mg/kg/6 hourly for two days) then oral
amoxicillin for 5 days or continue ampicillin for 5 days.
Add gentamicin 7.5 mg/kg IM/IV for once. If no
improvement within 48 hours add chlorophenicol 25
mg/kg/IM/IV for 5 days or appropriate antibiotic, if

specific infections are identified. If anorexia persists after
5 days course, antibiotics are continued for full 10 days.
If no/poor response, reassess the child fully. Some
experts routinely give metronidazole 7.5 mg 8 hourly for
7 days to hasten intestinal repair of mucosa and reduce
the risk of potential anaerobic infection.
HIV/AIDS: In children with HIV/AIDS, good recovery
from malnutrition is possible though it may take longer
and treatment failures may be common. Lactose
intolerance occurs in severe HIV related chronic diarrhea.
Treatment should be same as for HIV negative children.
Anemia: If hemoglobin is less than 5 g/dl, small packed
cells transfusion (5-10 ml/kg) is given. In children with
impending cardiac failure, partial exchange transfusion
(10-20 ml/kg) may be quite beneficial. Whole blood
transfusion (10 ml/kg) has been recommended for
severely ill-malnourished children Iron supplementation
for anemia is withheld for first 1 to 2 weeks to allow
transferrin regeneration and to permit resolution of
infection. Iron may interfere with the proteins host
defense mechanisms. There is also concern that free iron
during the early phase of treatment, may exacerbate
Nutrition
oxidant damage, precipitating infections (malaria, clinical
kwashiorkor, or marasmic kwashiorkor in a child with
clinical marasmus.
Xerophthalmia: Vitamin A, 2 lac units aqueous preparation
should be given to all severely malnourished children
on days 1, 2 and 28th in children above 1 year of age or if
infant below 1 year or weight less than 10 kg, half of
above dose is given. If the infant is between 0 to 6 months
50,000 units are given.
Congestive heart failure is most common after 3 days of
acute phase usually in kwashiorkor. Oxygen inhalation
and diuretics are helpful.
Hypocalcaemia: Requires correction by calcium gluconate
IV 1 to 2 ml/kg or calcium lactate powder 3 g/day orally.
Zinc deficiency: Dose of zinc is 2 mg/kg/day. In presence
of diarrhea 10 mg/day in infants < 6 months is recommended 20 mg/day in older children for 10 to 14 days.
Other vitamins: Appropriate vitamins should be supplied
with 10 ml, MVI1-2 ml daily in drip and later orally
plus vitamin K 1-5 mg weekly.
Copper, chromium and manganese deficiency: Dose of copper
is 20 ug/kg/day, that of chromium is 0.20 ug/kg/day
and manganese is 10 ug/kg/day.
Although the phases of resuscitation and acute phases
are divided separately, quite often the medical treatment
started during the phase of resuscitation continues into
acute phase. The acute phase also may be prolonged to 2
to 3 weeks instead of 1 week as suggested.
Dietary Management of Severe PEM
Initial Phase
At no other place the golden rule of go slow- rather than
hurry is appropriate than in the dietary intervention of
severely malnourished children. In the initial
stabilization phase a cautious approach is required
because of the childs fragile physiological state and
reduced homeostatic capacity. Feeding should be
designed to provide just sufficient energy protein to
maintain basic physiological processes. The regime
recommended is one that provides near maintenance
requirement, i.e. approximately 80 cal/kg/day and
0.7 g protein/kg/day with the calculation being based
on actual rather than expected weights. The second rule
is to offer small amount of feeds of low osmolarity and
low lactose at frequent intervals to avoid the incidence
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of vomiting, hypoglycemia and hypothermia. The intake

can be gradually stepped up so that by the end of first
week the child is able to take approximately 100 cal/
kg/day and 1 g protein/kg/day. Some authorities,
suggest 100 kcal/kg/day and 1 to 1.5 g of proteins/kg/
day. If the child is breastfed, continue to breastfeed but
give starter formula (milk based formulas containing
75 kcal/100 ml (0.9 g protein/100 ml) which will be
satisfactory for most children. Very weak children may
be fed by spoon, dropper or syringe. A recommended
schedule in which volume is gradually increased and
feeding frequency gradually decreased is:
Days
Frequency
Vol/kg/feed
Vol/kg/day
12
2 hourly
11 ml
130 ml
35
3 hourly
16 ml
130 ml
67 +
4 hourly
22 ml
130 ml
For children with a good appetite and no edema this

schedule can be completed in 2 to 3 days (e.g. 24 hours
at each level). Severely malnourished children often have
refusal to feed and hence forced feeding by intragastric
tube has to be resorted to. Rarely, children with
intractable diarrhea may have to be given total parental
nutrition. Milk is the most common nutritional liquid
food and is also well tolerated, except by children with
secondary disaccharide (lactose) intolerance. Fluid
volume is usually calculated at approximately 130 ml/
kg/day. This may be divided into 2 hourly feeds in the
first week and 3 hourly thereafter, the calorie content of
milk can be increased by adding oil as follows:
Composition of Enriched Milk
Component
1. Cows milk (300 ml)
2. Sugar (85 g)
3. Vegetable oil (30 g)
Total
Energy (Cal)
Protein (gm)
198
340
270
9.6
808
9.6
The amount of water added to this formulation would

depend on the desired concentration of calories and
proteins required and state of hydration of the individual
patient since milk is the only fluid offered to the child. If
the volume is made up to 1000 ml then 120 ml/kg/day
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of diluted formula (milk) should provide 96 calories/

kg/day and 1.1 g protein/kg/day. Coconut oil is the
recommended oil as it is supposed to provide medium
chain triglycerides (MCT); other oils are equally effective
besides coconut oil is not culturally used by all
communities for feeding. Dietary LC-PUFA (long chain
polyunsaturated fatty acids) have been known to
improve intestinal repair in severe protein energy
malnutrition, therefore its quantitative and qualitative
supply should be considered.
In children with lactose (disaccharide intolerance, any
of the following preparations can be tried. In mild lactose
intolerance, milk need not be omitted completely but the
lactose content can be decreased by fortifying with other
articles of diet like rice. For severe grade, lactose may
have to be completely eliminated and replaced by other
articles as shown below:
Phase of High Energy Feeding
Diet for Lactose Intolerance (of Varying Severity)

Name (g)
Constituents
Calories Proteins
Low lactose diet

1. Dried skimmed
Milk
Skimmed milk 60 g
400
20
79
Sucrose 12 g
Vegetable oil 15 g
2. Milk + rice
Milk 75 ml
Rice 5 g
Sugar 25 g
Lactose free diet

Rice 50 g
710
10
Glucose 45 g
egg-1
Oil 30 g
2. Cereal pulse
Rice 50 g
After the child passes through the initial phase and shows
signs of improvement, tolerates the prescribed diet, one
can then gradually increase the calorie intake to
approximately 150 to 180 cal/kg/day. The amount of
milk could be gradually decreased and the intake of
semisolid/solids increased. The protein intake
recommended during phase is in the range of 1.5 to 2 g/
kg/day. High energy foods that can be offered are:
Energy Rich Foods
Water 100 ml
1. Rice-egg
Alternately, fresh curds also have been very well

tolerated by lactose intolerant children. Curd plain or
curd-rice is traditionally eaten by most communities, and
is easy to prepare and feed. It can be given even to an
young infant in homogeneously mashed and mixed form.
WHO has recommended milk-based formulas
namely, starter F-75 containing 75 cal/100 ml and 0.9 g
protein/100 ml in the initial feeding schedule and then
gradually increasing to F-100 and F-135 supplying 100
and 135 calories/100 ml of feed respectively for catchup
growth. These formulas are mainly based on the use of
dried skimmed milk or dried whole milk and the use of
these formulas is limited because of the economic
constraints of the less advantaged communities of India
where the problem of PEM is most common. Refer
Appendices for details.
715
9.2
Green gram pulse 25 g

Jaggery 50 g
Name
Rice 25 g
715
12.5
720
26
Soybean 25 g
Glucose 50 g
500
2. Sooji (Rawa)
Kheer
Toned milk 750 ml

Sugar 100 g
Sooji 25 g
Oil 5 g
1432
28.4
3. Hyderabad
mix
Whole wheat 40 g
Bengal gram 16 g
Groundnuts 10 g
Jaggery 20 g
330/86
11.3/86
4. Shakti Ahar
Roasted wheat 40 g
Roasted gram 20 g
Roasted peanut 10 g
Jaggery 30 g
390
11.4
Oil 35 g
Chicken gruel
Chicken 100 g
Glucose 40 g
Oil 50 g
Water 1000 ml
Calories/ Proteins/
100 gm 100 gm
1. Besan mix/
Bengal gram flour
ladoo/Panjiri wheat flour
Jaggery, ghee
(1 part of each)
Oil 25 g
3. Soya rice gruel
Ingredients
Nutrition
Transfer of Family Type Diet or
Phase of Rehabilitation 19
Once the child is able to tolerate a high dose of therapeutic
nutrition and has started gaining weight, he or she may
be offered solid/semisolid family foods containing
cereals, pulses, vegetables rich in calories and
quantitatively appropriate Bengal gram, groundnuts,
and dark green leafy vegetables should be added to
regular family foods. Oils, sugar and fruits should also
be given and minerals and vitamins could be continued
for 5 to 6 weeks. Parents could be given nutrition
education with emphasis that nutritionally adequate diet
need not be expensive and special foods need not be
purchased or cooked. The diet prescribed for the child
should be such that the family can provide within their
limited income, can be easily cooked at home, does not
perish easily, is culturally acceptable, as well as locally
available.
Discharge from hospital: No definite guidelines can be
provided as criteria vary from hospital to hospital.
Prolonged hospitalization is associated with the risks of
acquiring a nosocomial infection while premature
discharge may result in incomplete recovery. Discharge
can be contemplated once the acute problems are over,
appetite has returned and oral intake is adequate.
Discharge criteria based on attainment of certain
anthropometric indices, e.g. 80 percent of weight or 75
percent of weight for age, though described in literature
are difficult to attain as it means prolonged hospital stay
which in itself may be associated with considerable
morbidity and mortality risk in developing countries.
Provide Sensory Stimulation and
Emotional Support
In severe malnutrition there is delayed mental and
behavioral development provide:
A. Tender loving care during recovery and follow-up.
B. A cheerful stimulating environment
C. Structured play therapy 15 to 30 minutes/day
D. Physical activity as soon as well enough
E. Maternal involvement when possible (e.g.
comforting, feeding, bathing, play).
Assessment of Recovery and Follow-up
Recovery can be assessed by: Improvement of general
condition, alertness, smile.
155
1. Return of appetite
2. Gain in weight 50 to 70 g/day.
3. Disappearance of edema (7-10 days) and
hepatomegaly.
4. Rise in serum albumin over the first 2 weeks of
therapy.
Recovery is complete when the child reaches his or
her standard weight which usually takes 6 to 8 weeks.
Follow-up of such children is essential because, mortality
rates of 10 to 30 percent have been reported after
discharge from hospital. Continued supervision is
necessary, till the expected weight for height has been
achieved.
PROGNOSIS
Mortality rates in severe PEM vary between 10 and 30
percent. The causes of deaths are same which determine
hospitalization. Long-term sequelae of PEM are
irreversible stunting and mental impairment.
PREVENTION OF PEM
PEM is a socioeconomic disease of multifactorial origin.
As seen here; its prevention requires a coordinated
approach of many disciplines such as nutrition,
agriculture, food technology, health administration,
health education and strong political commitment.
The Indian Academy of Pediatrics has come with
recommendation on infant feeding which is crucial for
optimum growth and health of our children.
Following actions are qualitative, and may be taken
as guidelines at family and community level to prevent
PEM (Fig. 6.1.14).
1. Protection, promotion and support for exclusive
breastfeeding, right from birth to 6 months of life
2. Correct infant and child rearing practices.
3. To impose no restriction on feeding during illness.
4. Supplementary feeding with energy dense semisolid
foods from 6 months, along with extended breastfeeding up to 2 years of age. Gradually, increasing
the number, frequency and the amount of family
foods so that baby is able to take all by 1 year of age.
Appetite is a central component in the decision
making process and skills used by care givers to
determine when and how much to feed their infants.
Chronic anorexia and illness are among problems
among infants and children in developing countries.
Chronic anorexia is associated with parentchild
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vi. Universal immunization program (UIP)
vii. National control programs, e.g. control of
diarrheal diseases (CDD),
Acute respiratory infections (ARI), malaria, anemia,
etc.
National Nutrition Programs
Figure 6.1.14: Prevention of PEM
interaction, characterized by unclear messages,

premature termination of feeding, inconsistent meal
times and limited food availability. This leads to poor
and appetite behavior development in children.
Similarly, a diet which is monotonous, and nonnutritious or filling up by liquids, e.g. fruit juice leads
to growth failure and poor appetite should be
discouraged. An active parent-child interaction,
motivation and response to queries of child, tasteful
and diversified diet of good quality and quantity,
good food hygiene, health care including
breastfeeding and care during illness and adequate
feeding time are some of the measures to enhance
the acceptance of the food by a child.
5. Integrated health care package of appropriate
feeding, immunization, ORS (Oral rehydration salt)
for ADD (Acute diarrheal disorders), periodic
deworming and early diagnosis and treatment of
illnesses.
6. Special nutritional and health care to women before
pregnancy, while pregnant and lactating mothers.
Following actions are required at community level:
i. Supplementary feeding program
ii. Agricultural development.
iii. Education and environmental sanitation
iv. Population control
v. Nutritional intervention programs
Following programs already exist at national level to

prevent PEM:
1. Applied nutrition program
2. School lunch program
3. National goiter control program
4. Cash program in nutrition (special feeding programs
for 0 to 3 years, school feeding programs for 3 to 5
years, prophylaxis against blindness.
5. Integrated child development services (ICDS)
These programs need special attention to make
appropriate feeding of the young child a national
movement.
Intensified nutrition action in 20 countries where 80
percent of undernourished children live, can lead to
achievement of the 1st MDG and greatly increase the
chances of achieving goals for child and maternal
mortality. (MDGs 4 and 5). Nutrition should be a priority
at national and sub national levels because it is central
for human, social and economic development. In
addition to health and nutrition interventions, economic
and social policy addressing poverty, trade and
agriculture that have been associated with rapid
improvement in nutritional status should be
implemented. Nutrition resources should not be used to
support actions unlikely to be effective in the context of
country or local realities. Interventions with proven
effectiveness that are selected by countries should be
rapidly implemented at scale There is reservoir of
important experience and expertise in individual
countries about how to build commitment, develop and
monitor nutrition programs, move towards acting at
scale, reform or phase out ineffective programs and other
challenges. This resource needs to be formalized, shared
and used as the basis for setting priorities in problem
serving research for nutrition.
Recent evidence, indicates that if high impact
interventions such as breastfeeding, complementary
feeding and vitamin A and zinc supplementation are
scaled up, they will have a synergistic impact on growth
and development, as well as survival. Even countries
Nutrition
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Figure 6.1.15: The time to act is now
with low per capita incomes can make significant

progress if appropriate policies are matched by political
will. The priority of nutrition interventions must be
children under 2 years old, when they are most
vulnerable to disease and mortality. Early childhood
offers a window of opportunity; nutrition related
interventions during this period have the greatest impact.
In addition, interventions need to focus on women
before they become pregnant, while pregnant, when
lactating through antenatal care and other
opportunities, because mothers deprived of good
nutrition are likely to give birth to underweight babies.
The health and nutrition needs of children in complex
emergencies must remain a priority But there is, further,
an urgent need to focus on the major causes of death
and undernurition in silent emergenciesoutside
camps, in stable environment and in communities
affected by HIV/AIDS, particularly in Southern Africa.

As the World Bank advocates, nutrition needs to be
repositioned in national development if the MDGs are
to be achieved. Achieving the MDG targethalving the
proportion of underweight children between 1990 and
2015 will involve effort at micro, meso, macro, and global
levels (Fig. 6.1.15) as well as parternerships among all
sectors of society.
To begin with the MDGs have been adopted by
United Nations Member Statesalready a big step
forward for children and humankind. And in the push
towards the MDGs the battle against poverty has moved
to center stage. The world is certainly capable of getting
on track to meet the MDGs on child nutrition and
health. There can be no excuses if another generation
of children is allowed to fall by the way side. The time to
act is now.
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APPENDIX 1:RECIPE FOR RESOMAL ORAL REHYDRATION SOLUTION
Ingredient
Amount
Water
2 liters
WHO-ORS
one 1 liter-packet*
Sucrose
50 g
Electrolyte/mineral solution
40 ml
3.5 g sodium chloride, 2.9 g trisodium citrate dihydrate, 1.5 g potassium chloride, 20 g glucose. ReSoMal contains approximately
45 mmol Na, mmol K and 3 mmol Mg/liter.
RECIPE FOR ELECTROLYTE/MINERAL SOLUTION*

USED IN THE PREPARATION OF ReSoMal AND MILK FEEDS
Weight the following ingredients and make up to 2500 ml. Add 20 ml of electrolyte/mineral solution to 1000 ml of milk feed.
Quantity g
Molar content of 20 ml
Potassium chloride: KCl
224
24 mmol
Tripotassium citrate: C6H5K3O7H2O
81
2 mmol
Magnesium chloride: MgCl26H2O
76
3 mmol
Zinc acetate: Zn (CH3COO)22H2O
8.2
300 mol
Copper sulphate: CuSO45H2O
1.4
45 mol
Water: make up to
2500 ml
If available, also add selenium (sodium selenate 0.028 g NaSeO410 H2O) and iodine (potassium iodine 0.012 g KI per 2500 ml).
Note: Dissolve the ingredients in cooled boiled water. Store the solution in sterilised bottles in the fridge to retard deterioration.
Discard if turns cloudy. Make fresh each month.
*If the preparation of this electrolyte/mineral solution is not possible and if pre-mixed sachets are not available, give K, Mg and Zn
separately:
Make a 10% stock solution of potassium chloride (100 g KCl in 1 liter of water) and a 1.5% solution of zinc acetate (15 g zinc acetate
in 1 litre of water).
For the oral rehydration solution, use 45 ml of the stock KCl solution instead of 40 ml electrolyte/mineral solution.
For milk feeds, add 22.5 ml of the stock KCl solution instead of 20 ml of the electrolyte/mineral solution of 1000 ml of feed.
Give the 1.5% zinc acetate solution by month 1 ml/kg/day.
Give 50% magnesium sulphate intramusculary once (0.3 ml/kg to a maximium of 2 ml).
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APPENDIX 2: RECIPE FOR F-75, F-100 AND F-135

Recipes for
F-75a,b,c
F-100d
F-135e
(Starter)
(Catch-up)
(Catch-up)
Dried skimmed milk (g)
25
80
90
Sugar (g)
100
50
65
Vegetable oil (g)
30
60
85
Electrolyte/mineral solution (ml)
20
20
27
1000 ml
1000 ml
1000ml
Energy kcal
75
100
135
Protein (g)
0.9
2.9
3.3
4.8
Water: make up to
Lactose (g)
1.3
4.2
Postassium (mmol)
4.0
6.3
7.7
Sodium (mmol)
0.6
1.9
2.2
Magnesium (mmol)
0.43
0.73
0.8
Zinc (mg)
2.0
2.3
3.0
Copper (mg)
0.25
0.25
0.34
12
10
% energy from protein

% energy from fat
36
53
5.7
Osmolarity (mOsmol/L)
413
419
508
To make up:
Using an electric blender mix the dried skimmed milk, sugar and oil with warm boiled water, add electrolyte/mineral
solution-make up to 1000 ml and blend at high speed.
If no mixer is available, mix the milk, sugar, oil and electrolyte/mineral solution to a paste, and then slowly add the warm
boiled water-make up to 1000 ml.
aComparable starter formulas can be made from 35 g whole dried milk, 100 g sugar, 20 g oil, 20 ml electrolyte/mineral and
water to 1000 ml, or with 300 ml fresh cows milk, 100g sugar, 20 ml oil, 20 ml electrolyte/mineral solution and water to
1000 ml.
bIsotonic
versions of F-75 (280 mOsmol/L) are available commercially from Nutriset in which maltodextrins replace some
of the sugar, and in which all the extra nutrients (K, Mg and micronutrients) are incorporated.
cA low osmolar cereal based F-75 (334 mOsmol/L) can be made by replacing 30 g sugar by 35 g cereal flour. Cook for 4
minutes. This may be helpful for children with osmotic diarrhea.
dComparable catch-up formulas can be made from 110 g whole dried milk, 50 g sugar, 30 g oil, 20 ml electrolyte/mineral
solution and water to 1000 ml or 880 ml fresh cows milk, 75 g sugar, 20 ml oil, 20 ml electrolyte/mineral solution and water
to 1000 ml.
eFor
use in special circumstances (see section C2 inadequate feeding)
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APPENDIX 3: F-75 FEED VOLUMES BY FEEDING FREQUENCY AND BODY WEIGHT (Columns 2, 3 and 4
are approximately 11 ml/kg/feed, 16 ml/kg/feed and 22 ml/kg/feed respectively)
Childs
weight (kg)
2-hrly
(ml/feed)
3-hrly
(ml/feed)
4- hrly
(ml/feed)
2.0
20
30
45
2.2
25
35
2.4
25
2.6
Childs
weight (kg)
2-hrly
(ml/feed)
3-hrly
(ml/feed)
4-hrly
(ml/feed)
6.0
65
100
130
50
6.2
70
100
135
40
55
6.4
70
105
140
30
45
55
6.8
75
110
150
2.8
30
45
60
7.0
75
115
155
3.0
35
50
65
7.2
80
120
160
3.2
35
55
70
7.4
80
120
160
3.4
35
55
75
7.6
85
125
165
3.6
40
60
80
7.8
85
130
170
3.8
40
60
85
8.0
90
130
175
4.0
45
65
90
8.2
90
135
180
4.2
45
70
90
8.4
90
140
185
4.4
50
70
95
8.6
95
140
190
4.6
50
75
100
8.8
95
145
200
4.8
55
80
105
9.0
100
145
200
5.0
55
80
105
9.2
100
150
200
5.2
55
85
115
9.4
105
155
205
5.4
60
90
120
9.6
105
155
210
5.6
60
90
125
9.8
110
160
215
5.8
65
95
130
10.0
110
160
220
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APPENDIX 4: STRUCTURED PLAY ACTIVITIES

Play therapy is intended to develop language skills and motor activities aided by the use of simple toys. It should take place in
a loving, relaxed and stimulating environment.
Language skills: At each play session:
Teach local songs and finger and toe games.
Get child to laugh and vocalise, repeate what (s) he says.
Describe all activities.
Teach action words with activities, e.g. bang bang as (s) he beats a drum, bye bye as (s) he waves, etc.
Teach concepts at every opportunity, examples are in italics in the text below.
Motor activities:
Every day encourage the child to perform the next motor milestone, e.g.:
Bounce the child up and down and hold under the arms so that the feet support childs weight.
Prop child up, roll toys out of reach, encourage child to crawl after them.
Hold hand and help child to walk.
When starting to walk alone, give a push-along and later a pull-along toy.
Activities with toys:
Simple toys can easily be made from readily available materials.
These toys can be used for a variety of different motor activities.
Ring on a String
Swing ring within reach and tempt child to grab it.
Suspend ring over crib and encourage child to knock it and make it swing.
Let child explore the ring, then place it a little distance from child with string stretched towards him/her and within
reach. Teach the child to retrieve the ring by pulling on the string horizontally.
Sit child on lap, then holding the string, lower the ring towards the ground. Teach child to get the ring by pulling up on
the string vertically. Also teach child to dangle the ring.
Rattle and Drum
Let the child explore rattle. Show child how to shake it saying shake shake.
Encourage child to shake the rattle by saying shake but without demonstrating.
Teach child to beat drum with shaker saying bang bang.
Roll drum out of reach and let child crawl after it, saying fetch it.
Get child to say bang bang as (s) he beats drum.
In and Out Toy with Blocks
Let child explore blocks and container. Put blocks into container and shake it, then teach child to take them out, one at a
time, saying out and give me.
Teach child to take out blocks by turning container upside down.
Teach child to hold a block in each hand and bang them together.
Let child put blocks in and out of container saying in.
Cover blocks with container saying where are they, they are under the cover. Let the child find them. Then hide them
under two and then three covers (e.g. pieces of cloth).
Turn the container upside down and teach the child to put blocks on top of the container.
Teach child to stack blocks, first stack two then gradually increase the number. Knock them down saying, up up then
down. Make a game of it.
Line up blocks horizontally, first two then more, teach child to push them along making train or car noises. In older
children teach stop and go, fast and slow and next to. After this teach to sort by colors, first two then more, and teach high
and low building. Make up games.
Posting Bottle
Put an object in the bottle, shake it and teach the child to turn bottle upside down and to take object out saying can you
get it? Then teach child to put the object in and out. Later try with several objects.
Stacking Bottle Tops
Let child play with 2 bottle tops then teach to stack them saying Im going to put one on top of the other. Later increase
the number of tops. Older children can sort tops by color and learn high and low.
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BIBLIOGRAPHY
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5. Baqui AH, Ahmed T. Diarrhoea and malnutrition in
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11. Ghosh S. The Feeding and Care of Infants and Young
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12. Gopalan C. Kwashiorkor and marasmus. Evaluation and
distinguishing features. In McLarne RA, Windowson
EM (Eds) Calorie Deficiencies. London; Churchill
Livingstone 1968;49-58.
13. Gupte S. Nutritional deficiency states. In The Short
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14. Heird WC. Food insecurity, Hunger and under nutrition
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RM, Behrman RE, Jenson HD, Stanton BF (Eds):
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15 Jellife DB. The assessment of the nutritional status of the
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16 Lopez AD, Mathers CD, Ezzati M, et al. Global and
regional burden of disease and risk factors. 2001,
Systematic analysis of population health data. Lancet 2006;
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17. Mathur GP, Kushawaha KP, Mathur S. Protein energy
malnutrition (PEM) updated. In: Gupte S (Ed) Recent
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18. McLaren DS, Burmaqn D. Nutritional Assessment. In The
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19. Mehta Meenakshi N. Nutritional management of

diarrhoeal diseases. Indian Pediatrics; 1996;32:149-57.
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21. Proceedings of the Workshop on Protein Calorie Malnutrition. Ecology and Managementnt 1975;12:57-117.
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K. Nutrition trends in India. National Institute of
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6.2 Water Soluble Vitamins:

B Complex Vitamins
Shashi N Vani
Thiamine (Vitamin B1): Anti-Beriberi
Vitamin or Aneurin
Thiamine is water and alcohol soluble, fat insoluble,
stable in slightly acidic solution and labile to heat, alkali
and sulfites.
3. Neurologic typeFeatures include vomiting tremors

and convulsions. Ptosis, nystagmus and extraocular
muscular paralysis also occur due to thiamine
deficiency. It starts in infants of 6 to 12 months age
and runs a chronic course.
Sources
Physiology
Active coenzyme form of thiamine is thiamine pyrophosphate (TPP) also called cocarboxylase, which acts in
various oxidative decarboxylations: (i) conversion of
pyruvic acid with eventual entry into Krebs cycle via
acetyl coenzyme A and that of alpha-ketoglutaric acid
with entry into Krebs cycle via succinyl coenzyme A, and
(ii) transketolase reaction in hexose monophosphate
(HMP) shunt. In thiamine deficiency, utilization of
pyruvic acid is decreased and therefore pyruvic acid and
lactic acid accumulate in the tissues.
Good sources of thiamine include yeast, unmilled cereals,

pulses, oil seeds, groundnuts.
As soon as the diagnosis of thiamine deficiency is
made, the child should receive 10 mg thiamine intravenously. In the next 5 days, he or she should be given
10 mg of vitamin twice daily followed by 10 mg daily
orally for next 6 weeks. A breastfeeding mother should
also receive thiamine therapy.
Riboflavin (B2)
Riboflavin is sparingly soluble in water, sensitive to light
and alkali and stable to heat, oxidation and acid.
Clinical Features of Deficiency

The classical deficiency syndrome of thiamineberiberi
has been eradicated from the country in older children.
It is of two types.
1. Dry beriberi affects the nervous system. Its symptoms
include irritability, fatigue, emotional disturbances,
headache, polyneuritis, calf muscle tenderness, difficulty in standing from sitting position, sluggish
tendon reflexes, reduced appetite, indigestion,
constipation, slow growth and gradual emaciation.
2. Wet beriberi is characterized by palpitation, tachycardia, dyspnea and edema.
Infantile beriberi may be of three types.
1. Cardiovascular type is characterized by tachycardia,
dyspnea, shrill cry, cyanosis and vomiting (onset
very acute).
2. Aphonic typeIt has a subacute onset, hoarse cry,
which is followed soon by aphonia. Terminal manifestations include dyspnea, puffiness and pitting
edema.
Physiology
It is a constituent of flavoprotein enzymes important in
hydrogen transfer reactions, amino acid, fatty acid and
carbohydrate metabolism and cellular respiration. It is
also a constituent of retinal pigment for light adaptation.
Symptoms confined to skin and mucosa include glossitis,
cheilosis, nasolabial dysbecia, circumcorneal vascularization and keratitis, watering of eyes, photophobia and
blurring of vision. If the pregnant mother is riboflavin
deficient, the growth and development of the fetus may
be retarded.
Sources
Good sources include milk, cheese, meat, eggs, fish, green
leafy vegetables, and whole grains.
Therapy is by administering riboflavin 3 to 10 mg
orally or 2 mg IM daily for a few days. This should be
followed by 10 mg orally daily, for about 3 weeks.
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Niacin (Nicotinamide, Nicotinic Acid,

Antipellagra Vitamin)
Niacin is water and alcohol soluble and stable to acid,
alkali, light, heat and oxidation.
Physiology
It is constituent of coenzymes I and II. Nicotinamide
adenine dinucleotide (NAD) and nicotinamide adenine
dinucleotide phosphate (NADP) are cofactors in a
number of dehydrogenase systems. L-tryptophanan
essential amino acid can be converted to niacin. This
meets parts of the requirement of this vitamin. Therefore,
deficiency is more prevalent in maize eating population.
This is characterized by 3 Ds, i.e. diarrhea, dermatitis
and dementia. Other gastrointestinal symptoms include
loss of appetite, nausea, vomiting and achlorhydria.
Other neurological manifestations are muscle weakness
and loss of memory. Dermatitis consists of pigmented,
scaly, cracked skin on those parts of the body which are
exposed to sunlight such as neck and back of hands.
Hartnups disease is a genetic transport defect of amino
acids, leading to niacin dependency.
Sources
Good sources include groundnuts, whole cereals, pulses,
meat and fish. Therapy comprises nicotinamide, 50 to
300 mg, daily in divided doses orally, given for 2 weeks,
followed by adequate supply of B-complex vitamins in
diet to bring about complete recovery.
Pyridoxine
Physiology
Pyridoxine includes a number of derivatives of pyridine
such as pyridoxine, pyridoxal and pyridoxamine.
Through its active coenzyme form (pyridoxal phosphate),
pyridoxine plays a central role in amino acid metabolism,
e.g. in transamination, decarboxylation and desulfuration.
In pyridoxine deficiency, urinary excretion of xanthurenic acid increases after tryptophan loading. Dietary
deficiency is rare. Deficiency of the vitamin results from
an inborn error of metabolism or is secondary to some
other disease. Prolonged use of isoniazid is one of the
causes of pyridoxine deficiency.

It includes hyperacusis, hyperirritability, hypochromic
anemia, nausea, vomiting and failure to thrive.
The manifestations include convulsions, normocytic
and hypochromic anemia refractory to iron therapy.
Growth retardation and gastrointestinal tract (GIT)
symptoms like diarrhea, and vomiting may occur.
Sensory neuropathy, cheilosis and glossitis are infrequent
in children.
When metabolic causes like hypoglycemia, hypocalcemia have been ruled out, we should think of vitamin
B6 deficiency, if an infant has persistent convulsions. Such
infants should receive 50 to 100 mg of pyridoxine
intravenously.
Sources
Good sources are liver, meat, fish, cereals and legumes.
Administration of 5 mg of pyridoxine IM followed
by 0.5 mg daily orally for 2 weeks causes complete
recovery.
Folate (Folic Acid, Ketoglutamic Acid, Folacin)
These are a group of related compounds containing
pteridine ring, para-aminobenzoic acid and glutamic
acid. Pteroylglutamic acid (PGA) is slightly soluble in
water and labile to heat, light and acid.
Physiology
Folates are concerned with formation and metabolism of
one carbon units: (i) participates in synthesis of purines
and pyrimidines for nucleic acid synthesis, (ii) interconversion of amino acidsglycine and serine, and
(iii) breakdown of histidine. The active form of folate is
tetrahydrofolate produced by the enzyme folate reductase
in 2 steps: Folate dihydrofolate tetrahydrofolate.
Impaired DNA synthesis in cells results in abnormalities of cell division so that the tissues affected are those
with rapid cell turnover, i.e. the intestinal mucosa and
bone marrow. Therefore, the predominant symptoms are
megaloblastic anemia and diarrhea.
Sources
Good sources are leafy vegetables, liver and eggs.
Overcooking and boiling destroys folate in food.
Nutrition
Recommended dietary allowance (RDA) is
100 microgram. Requirements increase during pregnancy
and lactation.
Vitamin B12 (Cyanocobalamin)
Vitamin B12 is slightly soluble in water, stable to heat in
neutral solution, labile in acid or alkaline ones, and
destroyed by light. Castle intrinsic factor of the stomach
is required for absorption of vitamin B12. Vitamin B12 is a
cyclical compound containing cobalt atoms. It is
converted to coenzymes such as methyl cobalamin and
5 deoxyadenosyl cobalamin in the body. These coenzymes play essential roles in the following metabolic
reactions:
1. Conversion of methyl malonyl coenzyme A to
succinyl coenzyme A. In deficiency of vitamin B12,
methyl malonyl coenzyme A accumulates in the body
and is excreted in the urine as methyl malonic acid.
2. Conversion of homocysteine to methionine in presence of tetrahydrofolate is catalyzed by an enzyme
containing methyl cobalamin as a coenzyme.
Vitamin B12 also plays important roles in nucleic acid
metabolism and protein synthesis.
Absorption, Transport and Storage
Vitamin B12 is absorbed in the lower part of the ileum by
highly specific intestinal cells. Intrinsic factor, present in
gastric juice, combines with vitamin B12 forming vitamin
B12 intrinsic factor complex that binds to specific receptor,
sites on the intestinal brush border. From here the vitamin
B12 is internalized and intrinsic factor is left behind.
Transport of vitamin B 12 in the body is by transcobalamine II and storage bound to transcobalamine I.
Deficiency of vitamin B12 leads to impaired deoxyribonucleic acid (DNA) synthesis, which further leads to
maturation arrest of cells in the bone marrow and
defective myelination of large nerve fibers in the spinal
cord and especially the long tracts of lateral and posterior
columns.
So, the hematologic manifestations involve entry into
the circulation of immature cells that are larger in size
and in the absence of concomitant iron deficiency are
adequately hemoglobinized leading to macrocytic
normochromic anemia. The neurological manifestations
due to long tract demyelination in lateral and posterior
columns is known as subacute combined degeneration.
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Sources
Good sources include foods of animal origin such as milk,
eggs, meat and liver,
Recommended dietary allowance (RDA):
Children0.2 to 1 microgram/day.
Adults1 microgram/day.
Vitamin C
It is also known as ascorbic acid and antiscorbutic
vitamin.
Important Actions
These include oxidation of tyrosine and phenyl-alanine,
conversion of proline to hydroxyproline which is necessary for collagen formation, integrity and maintenance
of ground substances, conversion of folic acid to folinic
acid, and absorption of iron.
Scurvy is usually seen between 6 months and 7 years of
age. Initial symptoms are vague and include irritability,
tachypnea, digestive disturbances and loss of appetite.
Other features of severe deficiency include:
i. Generalized tenderness, especially along the shafts
of lower limbs leading to pseudoparalysis and
characteristic frog position of limbs (semiflexed hips
and knees and outwardly turned feet).
ii. Palpable swelling along the shaft of legs due to
subperiosteal hemorrhages.
iii. Hemorrhages in gums, especially around erupted
teeth leading to spongy, swollen, bluish purple
gums.
iv. Petechiae or purpura due to bleeding in skin.
v. Hematuria, melena, subdural bleeding.
vi. Follicular hyperkeratosis and hemorrhages at root
of hair follicles.
vii. Rosary at costochondral junction and depressed
sternum.
Diagnosis
Diagnosis is made on the basis of:
i. Clinical picture
ii. Characteristic roentgenographic appearance of long
bones, ground glass appearance due to osteoporosis
and loss of trabeculae, dense white line of Frenkel
at epiphyseal ends of long bones with adjacent area
of rarefaction (fracture zone), thin cortex, signet ring
appearance of epiphyses.
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iii. laboratory tests are less satisfactory

a. Plasma vitamin C level below 0.6 mg/dl
b. Vitamin C concentration in buffy layer of
centrifuged blood
c. Vitamin C excretion in urine, after a test dose of
vitamin C given intravenously.
Sources
Good sources include fruits and juices especially citrus
fruits. Indian gooseberry is one of the richest source.
Drumstick leaves are also very good source of vitamin
C.
Differential Diagnoses
Requirement
1. Poliomyelitis: Due to pain, in scurvy the patient

assumes limited movements and frog-like posture.
So, poliomyelitis may be mimicked. Differentiation
may be done by acute pain on movements, muscle
charting and true flaccid paralysis in polio.
2. Leukemia: Due to bone tenderness, and bleeding
tendency, this may mimick scurvy. Differentiation
can be done by associated hepatosplenomegaly and
raised blood counts and presence of premature cells
in circulation.
3. Nephritis: Presence of hematuria may mimick scurvy.
Associated hypertension and urine abnormality helps
to differentiate.
4. Meningitis: Neck rigidity, fever and irritability may
confuse with meningitis. Meningeal signs help to
differentiate.
Adult 75 mg/dl, Infant 30 mg/dl, Adolescence

80 mg/dl, Pregnant women100 mg/dl, Lactating
women150 mg/dl.
Treatment
Recommended therapy is loading dose of vitamin C
500 mg orally or parenterally followed by a daily dose of
100 to 300 mg for several weeks. Clinical response occurs
rapidly, and prognosis is good, though radiological
improvement and subperiosteal swellings take time to
improve.
Prevention
Breastfeeding of infants should be encouraged. Lactating mothers should receive vitamin C supplements.
6.3 Fat Soluble Vitamins

Panna Choudhury
VITAMIN A DEFICIENCY
Vitamin A is a generic descriptor of retinoids that exhibit
qualitatively the activity of all-trans-retinol compounds.
Retinol signifies vitamin A alcohol and is found in foods
of animal origin only. Some carotenoids which are found
in plants, bacteria, algae and fungi can be converted into
retinol and are called provitamin A. The carotenoid with
the highest vitamin A activity is beta carotene. Beta
carotene yields two molecules of retinol. Retinol is
esterified in the mucosal cell with palmitic acid. Retinyl
palmitate is stored in the liver. Being fat soluble, retinol
mobilized from the liver must be bound in serum to
retinol binding protein (RBP) which is synthesized in the
liver. RBP also protects retinol from oxidation and
releases it to specific receptor sites on the surface of the
target cell. Recently, it has been suggested that RBP

synthesis may be affected in zinc deficiency.
Physiology
Vitamin A is an essential nutrient required for normal
reproduction, vision, growth, hematopoiesis and
immune competence. The key to most of these functions
is the role of vitamin A in regulating the gene expression
and cell differentiation practically for every cell in the
body. The importance of vitamin A in maintaining
integrity of epithelial tissues and functioning of the retina
for vision has been well established. Visual pigment in
rods is called rhodopsin, which is composed of a protein
called opsin and a pigment, 11-cis retinine (vitamin A).
Rhodopsin is light sensitive and when light falls on eyes,
Nutrition
rhodopsin splits and 11-cis retinine, is converted to
11-trans retinine. This initiates an electrochemical signal
to be carried to the brain, where visual images are
constructed. In vitamin A deficiency, the threshold for
stimulating rods is raised, thus, affecting the vision under
dim light.
Quantification of vitamin A is expressed in various
ways. One International unit (IU) equals 0.3 g retinol.
Rich sources of vitamin A include fish liver oils, butter,
egg, carrot, green leafy vegetables, tomato, and ripe
mangoes. Breastfeeding protects children through the
first 3 to 4 years of life in rural areas of Asia and Africa.
In India, daily intake of vitamin A as retinol equivalent
has been recommended as 350 g for infants, 400 g for
preschool children, and 600 g for school children and
adolescents.
Deficiency of vitamin A can occur from deficient diet,
decreased absorption due to chronic intestinal disorders
or reduced storage in liver diseases. There could be an
increased requirement of vitamin A in presence of
infections. Supplementation of vitamin A has been
shown to have an impact on childhood mortality. In
India, Bitot spots are seen in 0.7 percent of preschool
children with overall prevalence as 0.21 percent in all
age groups. Vitamin A deficiency is responsible for 0.04
percent of all blind cases.
Clinical Features
Ocular lesions affect the posterior segment of eye initially
with impairment of dark adaptation and night blindness.
Often the mother of the infant notices that he or she takes
considerable time to adjust to dim light or darkness
(twilight blindness). Xerosis of conjunctiva is usually the
first sign that can be seen on examination. The
conjunctiva becomes dry, lusterless, wrinkled and dirty
brown in color. These changes are most obvious in the
interpalpebral bulbar conjunctiva. Conjunctival xerosis
may lead to formation of the so called Bitot's spot which
consists of almost a triangular area, usually about the
temporal aspect of the limbus covered by a fine white
foamy or greasy substance. It is composed of heaped up
sloughed-off keratinized cells and saprophytic bacilli,
which collect on conjunctival surface. Nasal involvement
reflects more advanced deficiency. Keratomalacia is seen
in the late stage and consists of softening, necrosis and
ulceration of the cornea. Once cornea gets involved,
photophobia accompanies the clinical profile. WHO has
proposed a classification for xerophthalmia (Table 6.3.1).
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Extraocular lesions include dry, scaly skin, especially

over the outer aspect of the limbs, called follicular
hyperkeratosis, toad skin or phrynoderma. Increased
susceptibility to infections due to squamous metaplasia
of respiratory, urinary and vaginal tract epithelium; renal
and vesical calculus may occur more often in such
subjects.
TABLE 6.3.1: WHO classification for xerophthalmia
Classification
Primary signs
X1A
Conjunctival xerosis
X1B
Bitot's spots
X2
Corneal xerosis
X3A
Corneal ulceration
X3B
Keratomalacia
Secondary signs
XN
Night blindness
XF
Fundal changes
XS
Corneal scarring
Diagnosis
In the presence of clinical manifestations, diagnosis is
not difficult. In vitamin A deficiency state serum retinol
level is usually below 20 mg/dl. Conjunctival impression
cytology is a noninvasive technique that assesses vitamin
A status by detecting early losses of vitamin Adependent, mucus secreting goblet cells and early
metaplasia of the epithelium.
Treatment
Prevention of vitamin A deficiency can be achieved by
making available, 1 only the recommended daily
allowances of vitamin A to all children. According to the
National Program for Prevention of Blindness, children
in the age group 6 to 11 months should receive 100,000
IU of vitamin A orally (preferably during measles
immunization) and other children between 1 and 5 years,
should receive 200,000 IU vitamin A every six months in
the target areas. Use of vitamin A and beta carotene rich
food should be encouraged. Fortification of commonly
eaten foods with vitamin A can be an effective
prophylactic measure.
For treatment of xerophthalmia, according to WHO
guidelines, 200,000 IU vitamin should be given orally on
presentation, the following day and, whenever possible,
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1 to 4 weeks later. Infants' 6 to 12 months receive a half

dose, and infants less than 6 months one-quarter the dose,
following the same schedule. Children with wasting
malnutrition, recurrent diarrhea, pneumonia and severe
infections should also receive full treatment course of
vitamin A.
HYPERVITAMINOSIS A
Signs of toxicity may appear with massive doses or with
large doses over a large time period. Child may have
nausea, vomiting, drowsiness, papilledema and symptoms suggestive of raised intracranial tension (pseudotumor cerebri). In chronic cases, marked anorexia, failure
to thrive, alopecia, seborrheic dermatitis, hepatomegaly,
and tender bone swelling may develop. Radiographic
examination may show hyperosteosis of the shafts of long
bones. However, beta carotene ingestion is seemingly
without toxicity. With chronic high consumption, the
skin, but not the sclerae are stained yellow-orange, which
is benign and reversible.
VITAMIN D DEFICIENCY
Antirachitic properties of vitamin D are the result of small
structural changes, under the influence of ultraviolet
irradiation in a number of steroids related to cholesterol.
However, only ergosterol and 7-dehydrocholesterol have
practical importance. Ergosterol is of plant origin and on
irradiation, it transforms to Vitamin D2 (calciferol). 7dehydrocholesterol is normally present under the skin,
and on exposure to ultraviolet rays of the sunlight, it
converts to vitamin D3 or cholecalciferol. The latter is
converted to 25-hydroxycalciferol in the liver and is
further converted to 1, 25-dihydroxycholecalciferol,
which is specifically helpful in promoting synthesis
of calcium transport protein in the intestinal
wall. Parathormone controls the production of
1, 25-dihydroxycholecalciferol, the metabolically active
form of vitamin D.
Vitamin D, unlike other vitamins is not abundantly
available in foodstuffs. Rich source of vitamin D is fish
liver oil and to some extent it is available in butter and
egg. Thus, infants are more prone to vitamin D deficiency
as, natural diet of infants like milk, cereals, vegetables,
fruits are deficient in vitamin D. This gets aggravated if
there is also lack of access to sunlight. Vitamin D
deficiency also occurs in presence of malabsorption, liver
and kidney diseases. Rickets, a metabolic disorder of
growing bone leading to bony deformities, when results

from vitamin D deficiency is known as nutritional rickets.
The normal daily requirement of vitamin D for infants
and children is 200 IU. It has been estimated that only
five minutes of exposure to sunlight is sufficient to meet
the daily requirement of vitamin D. However, it should
be remembered that the effective ultraviolet rays in
sunlight are cut-off by haze, windowpane, etc.
Biochemical Changes
Vitamin D deficiency causes decreased absorption of
calcium from gut. The resulting hypocalcemia leads to
increase in parathormone secretion. This helps in release
of calcium from bone. Parathormone also reduces the
excretion of calcium by kidneys and renal tubular
reabsorption of phosphate. As a result, the serum calcium
level tends to become normal, while the serum phosphate
level falls. After sometime, this compensatory
mechanism fails and both calcium and phosphorus levels
fall. Since calcium phosphate is necessary for deposition
of calcium in growing bones, decrease in blood levels of
calcium, phosphorus or both interfere with the
calcification of the osteoid tissue. Serum alkaline
phosphatase level also gets increased due to increase in
osteoblastic activity.
Pathology of Rickets
The epiphyseal plate is a narrow well-defined strip from
where cartilage cells grow in parallel column towards
the metaphysis. After initial proliferation, the old
cartilage cells degenerate and disappear, leaving spaces
into which the blood vessels and osteoblasts of the shaft
can penetrate. Calcium is deposited in the zone of
degenerating cartilage, which is then called Zone of
preparatory calcification. In rickets, the cartilage cells
go on multiplying giving rise to a broad irregular
cartilaginous zone. The process of degeneration and
calcification becomes incomplete, leading to softness of
the bone. Rapidly growing cartilage cells particularly
affect the costochondral junctions and end of long bones.
There is also defective mineralization in the subperiosteal
bone. In long-standing cases, the bones under stress may
become deformed or even have pathological fractures.
Supplementation of vitamin D restores the normal
development of the bone with calcification starting at
the zone of preparatory calcification, which in a
radiography would be seen as a thin dense line near the
epiphysis.
Nutrition
169
lax ligaments. Deformity of the pelvis in a female, results

in difficulty during labor at a later stage. Long bones of
the legs get deformed when the child starts bearing
weight and is thus, usually seen after the age of one year.
Bending of the femur, tibia and fibula, result in bowlegs or knock-knees. Coxa vara and green stick
fractures may also occur. All deformities of bones result
in rachitic dwarfism. Dentition may be delayed and
disordered eruption of temporary teeth occurs. In
children between 8 and 18 months, permanent teeth,
which are undergoing calcification, may be affected.
Besides skeletal deformities, there is a generalized
hypotonia with delay in motor development. The
abdomen is protuberant, and generalized flabbiness of
muscles may result into visceroptosis with downward
displacement of spleen and liver.
Figure 6.3.1: Case of rickets showing widening of
wrists and beading of ribs on chest
Clinical Features
Rickets is a disease of growing bones and its incidence is
particularly high between 4 and 18 months. Skeletal
deformities are the most striking feature of rickets.
One of the early signs of rickets is craniotabes. In this
condition, on pressing occipital or posterior part of
parietal bone, a sensation like pressing a ping-pong ball
can be felt. It results from the thinning out of the inner
table of the skull due to absorption of noncalcified osteoid
tissue. Fontanel may remain wider than normal and close
late. Other early evidences of osseous changes are,
palpable enlargement of costochondral junctions, i.e.
rachitic rosary and widening of the wrists (Fig. 6.3.1) and
ankles.
Signs of advanced rickets can be easily recognized.
Bossing of skull generally starts after the age of six months.
It occurs due to heaping up of osteoid tissue in the frontal
and parietal regions so that the skull appears squarish
or box-like shape. In thorax, the sternum is pushed
forward, producing a pigeon chest. A horizontal
depression known as Harrison's groove, corresponding
to costal insertion of the diaphragm, develops. The chest
deformities decrease the lung resilience and predispose
the child to intercurrent infections. Bending of the spine
backwards (kyphosis) and laterally (scoliosis) may occur.
Pelvis may become softened and, the promontory of the
sacrum is pushed anteriorly and the acetabulae inwards,
resulting in a narrowed pelvic inlet. This is helped by
Diagnosis
The diagnosis of rickets is based on the clinical features,
biochemical findings and characteristic radiological
picture. The serum calcium level may be normal or low,
the serum phosphorus level is below 4 mg/dl, and the
serum alkaline phosphatase is usually elevated.
Radiological changes are best seen in the lower end of
radius and ulna. Skiagram of the wrist shows widening,
cupping and fraying of the epiphyses, in contrast to the
normally sharply demarcated and slightly convex
epiphyseal line (Figs 6.3.2A and B). The density of shafts
decreases with prominent trabeculae. There is an increase
in distance between concave epiphyseal line and the ends
of metacarpals. Green stick fractures, expansion of bone
ends and bending of bones may be evident on
radiographs. Some raising of the periosteum is due to
excess of osteoid lying under the periosteum.
Differential Diagnosis
Nutritional rickets should be differentiated from other
types of rickets and chondrodystrophy. Other conditions
producing bony deformities may, sometimes, need
consideration. Craniotabes and a large head apart from
rickets, occurs in hydrocephalus, congenital syphilis and
osteogenesis imperfecta. Enlargement of costochondral
junctions may also be seen in scurvy and chondrodystrophy.
Management
Vitamin D is given in a dose of 15000 g (or 600,000 IU)
orally or intramuscularly. If there is no sign of healing
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Deformities of bones are corrected by orthopedic
measures.
HYPERVITAMINOSIS D
High-dose of vitamin D given over a long period may
cause anorexia, vomiting, hypotonia, irritabiliy,
polydipsia and polyuria. There is hypercalcemia and
hypercalciuria. Radiological examination reveals evidence of metastatic calcification and osteoporosis of long
bones.
VITAMIN E DEFICIENCY
Figure 6.3.2A: Florid rickets showing cupping, fraying and

widening of metaphysis of distal end of radius and ulna
Vitamin E is a group of closely related naturally occurring fat-soluble compound of which tocopherol is
functionally the most potent. It is active as an antioxidant
and, probaby involved in the metabolism of nucleic acids.
It is widely present in most foods. One mg of alphatocopherol provides 1.5 IU activity of vitamin E. The
deficiency of vitamin E is rare. The most common causes
are diarrhea and poor intake of food. Deficiency may
result in arcflexia, ataxia, muscle weakness and
dysarthria. In premature infant, low levels of vitamin E
are associated with hemolytic anemia, hyperbilirubinemia and intraventricular hemorrhage. This responds
quickly to 5 to 25 mg of vitamin E therapy. Generally,
infants should receive 3 mg of alpha-tocopherol daily.
VITAMIN K DEFICIENCY
Figure 6.3.2B: Healing rickets showing zone of calcification at

the distal end of radius and ulna; also seen the periosteal
calcification of metaphysis
line in skiagram taken 3 to 4 weeks after therapy, the

same dose can be repeated. If there is no response within
3 to 4 weeks of the second dose, investigations for
refractory rickets should be initiated. Rickets can also be
treated with a dose of 50 to 125 g (2000 to 5000 IU) daily
for four weeks. After the healing of rickets, normal daily
requirement of vitamin D should be continued.
Vitamin K is a naphthoquinone derivate. Absence or

failure of its absorption from the intestine leads to
hypoprothrombinemia and decreased synthesis of some
coagulation factors (VII, IX and X). The normal requirement of vitamin K is met by bacterial synthesis in the
intestine. In addition, it is also found in high
concentration in a wide variety of foods and vegetables
like spinach, cabbage, peas, tomatoes, soybean and liver.
The deficiency of vitamin K can occur in malabsorption states, biliary obstruction, after oral antibiotic
therapy or in newborn before colonization of the guts.
In general, vitamin K deficiency or hypoprothrombinemia should be considered in all patients with
hemorrhagic disturbances. Hemorrhagic disease of the
newborn is one of the most common manifestations. The
bleeding is variable and can occur anywhere, though,
most common is gastrointestinal bleeding. A daily dose
of 1 to 2 mg of vitamin K orally is sufficient for treatment.
Nutrition
In severe deficiency state, 5 mg of aqueous vitamin K
can be given parenterally.
BIBLIOGRAPHY
1.
2.
Dietary Guidelines for Indians. Indian Council of Medical

Research, New Delhi, 1998.
Report. Micronutrient Deficiency Disorders in 16 Districts
171
of India, Indian Council of Medical Research, New Delhi,

2001.
3. Sommer A. Vitamin A Deficiency and its Consequences:
Field Guide to Their Detection and Control (3rd edn).
World Health Organization: Geneva, Switzerland, 1995.
4. West KP Jr: Vitamin A deficiencya pediatric priority
in tropics. In David TJ (Ed): Recent Advances in
Pediatrics. BI Churchill Livingstone: New Delhi,
1997;14:15975.
6.4 Trace Elements

B Bhandari
Minerals occur in all living tissues, some of them in such
small amounts that routine analytical methods available
in the past were unable to measure them. Minerals found
in < 0.01% of body weight are termed trace elements.
Out of 81 elements found in the human body, following
are essential (E) for humans, e.g. arsenic, bromine, carbon,
chlorine, cobalt, copper, flourine, iodine, iron,
molybdenum, nickel, manganese, nitrogen, selenium,
silicon, sodium, sulfur, phosphorus, potassium, tin,
vanadium and zinc. These are essential for growth and
maintenance of life or health. Other trace elements
constantly occur in living tissues but are non-essential
(NE), e.g. aluminium, antimony, cadmium, mercury,
germanium, rubidium, silver, lead, gold, bismuth,
titanium, zirconium, etc.
Trace elements catalyze and control biochemical
reactions. More than half of the enzymes in human bodies
have one or more of these at active sites. Some trace
elements like magnesium and calcium form complexes
with enzymes and nucleic acid and act as biological
triggers. Others are essential for enzyme activity (zinc,
copper), hormone synthesis (iodine), and vitamin
functions. Safe and adequate concentration for each
element is required in the body for optimal function.
Every trace element is potentially toxic when this range
exceeds, and deficiency occurs when it falls short of
requirement.
Trace Element Deficiency and Toxicity
Etiological factors for trace element deficiencies have
been summarized in Table 6.4.1. Excess trace elements inhibit enzyme activities, alter nucleic acid
structure and function, impair synthesis of protein, effect
TABLE 6.4.1: Etiological factors implicated in

trace elements deficiency
Primary Deficiency
Inadequate intakezinc, copper, iron, iodine
Secondary Deficiency
Genetic or inborn errors of element metabolismzinc,
copper
Total parenteral nutritioncopper, zinc, selenium, iron,
manganese
Drugs and iatrogeniccopper, zinc, iron
Environmentaliodine, selenium
Malabsorption and chronic diarrheairon, zinc, copper
Protein energy malnutritionzinc, copper
Prematurity and LBW (poor stores)iron, copper, zinc
High requirements (pregnancy, lactation, rapid growth,
viz prematurity)zinc, iron
Element interactions with other nutrients and elements
copper/zinc, iron/zinc, iron/copper, iron/manganese
Increased excretion: nephrosis, liver, cirrhosis, chelating
agents, trauma, burns, pica, hemolytic anemiazinc.
Adapted from References 3,5,7,8
cell wall permeability and lead to toxicity Table 6.4.2

summarizes functions, essentiality, effects of deficiency,
excess and sources including recommended daily
allowances (RDA) for some of the trace elements.
Diagnosis
As the signs and symptoms of deficiency except for
severe zinc deficiency, and excess of trace elements in
early period are often nonspecific, a high degree of
clinician's suspicion, knowledge and advanced laboratory facilities are required to confirm the diagnosis.
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TABLE 6.4.2: Disorders of trace elements
Trace
element
Function
Deficiency
Excess
Sources
Aluminium Binds mainly to

(NE)
albumin and transferrin
Not described
Encephalopathy,
anemia, cardiac
and bone toxicity
Cooking utensils, spinach,

food additives, tea leaves,
infant milk formula,
dialysis and intravenous
fluids, antacids
Arsenic
(E)
Not described
Diarrhea
Anemia
Cancer
Hyperkeratosis
Renal failure
Lung cancer
Dermatitis
Unknown
May be taurine and
sulfate production
from methionine
Chromium Regulation of blood
(E)
sugar, potentiates
insulin metabolism
Cobalt
(E)
Copper
(E)
Fluoride
(E)
Iodide
(E)
Iron
(E)
Impaired glucose
tolerance in PEM?
Peripheral
neuropathy
Hypothyroidism?
Widely distributed
Part of erythropoitin
Cardiomyopathy
Milk, meat and sea foods
and cyanocobalamine
Goiterogenic
Synthesis of thyroid
hormone
Transferrin
Refractory anemia
Indian childhood
Liver, oysters, fish
Hemoglobin
Osteoporosis
cirrhosis
whole grains, nuts,
Absorption of iron
Neutropenia
Wilsons disease
legumes, contaminated
Oxidative enzyme
Delayed bone age
Hemolytic anemia
water-milk stored in brass
activationtyrosinase, Ataxia
Renal dysfunction
copper utensils
catalase, uricase,
Pseudoparalysis
(Fancon-like anemia)
cytochrome oxidase, Hypercholesterolemia Acute copper poisoning
lysyl oxidase, etc.
Menkes disease
vomiting, hemolytic anemia
Defective hair
and gastric hemorrage
pigmentation
Hypothermia
Degenerative changes
in elastin of aorta
Mental deterioration
Retarded growth
Constituent of bone
Dental caries
Fluorosis
Drinking water,
and tooth
Osteoporosis
Vomiting, diarrhea,
sea foods
Abdominal pain
Toothpaste
Tetany
Endemic cretinism
Cardiovascular collapse, Iodized salt, sea
Part of T3 and T4
Simple goiter
Goiter
food, food grown in
Hypothyroidism
Maternal excess may
known goiterous areas
cause congenital hypothyroidism and goiter
Transport of oxygen
and carbondioxide
(hemoglobin and
myoglobin), part of
oxidative enzyme
cytochrome-C
and catalase
Anemia
growth failure
Impaired learning
and alertness
Hemosiderosis,
iron poisioning
Liver, meat, egg yolk,

green vegetables,
whole grains, legumes
nuts
RDA
(mg or mg/day)
0.0050.2 mg
0.0001 mg
0.050.1 mg/kg
1 ppm in water
(100 g/dl)
< 6 mo 40 g
612 mo 50 g
13 yr 70 g
46 yr 90 g
710 yr 120 g
> 11 yr 150 g
< 6 mo 6 mg
6 mo 10 yr10 mg
> 11 yr (male) 12 mg
> 11 yr (female)
15 mg
contd...
Nutrition
173
Table 6.4.2: contd...

Trace
element
Function
Deficiency
Lead
(NE)
Magnesium Constituent of bone Tetany

(E)
Enzyme activator
Muscle and nerve
irritability
Cation
Manganese Constituent of
Increased
(E)
mitochondrial super- prothrombin
oxide dismutase
and bleeding time
Structure of bone
Hypercholesterolemia
Antioxidant
MolybdeConstituent of
Cancer of esophagus
num (E)
xanthine oxidases,
Sulfate oxidase
Mercury
Toxic for many
(NE)
enzymes and RNA
Nickel
Stabilization of DNA Not known
(E)-?
and RNA
Urease-matalloprotein
contains nickel as
essential constituent
Selenium
Cofactor of
Keshan
(SE)
glutathione
cardiomyopathy
peroxidase
Kashin-Beck disease
Decreased fertility
Silicon
(E)
Vanadium
Zinc
(E)
Structure of
collagen and elastin
Not known
Part of several
enzymes
Stabilization of
membranes
Development
of taste buds
and brain
Impaired early bone

development
Not known
Failure to thrive
Anemia
Hypogonadism
Acrodermatitis
enteropathica
Reduced immunoincompetence.
Poor wound healing
Alopecia
Congenital
malformation
Decreased acuity
of taste
Excess
Sources
RDA
(mg or mg/day)
Anemia, abdominal
colic, muscular
weakness low IQ low
attention encephalopathy
Unknown
Leaden petrol lead

based paints, canned
fruits, lead toys
cosmetics
Cereals, legumes, nuts
Milk, meat
40340 mg
Encephalopathy,
pneumoconiosis,
syndrome like
Parkinson's disease
Cholestatic jaundice
Hyperuricemia
Cereals, legumes, nuts

Manganese containing
dust absorbed via
alveolus
01 yr 0.81.0 mol
112 yr 0.70.9 mol
>12 yr 0.60.8 mol
Cereals, grains, lagumes, 0.150.5 mg

green leafy vegetables
Minimatta disease
Acrodynia
Dermatitis,
nasal and pulmonary
carcinoma,
liver necrosis
Alopecia,
Vegetables, meat, water
nail deformity
lassitude,
garlic odor to
breath
Pulmonary inflammation,
granuloma and fibrosis
Not known
Food cooked in
Grains, nuts, cheese
galvanized utensils
Meat, oysters
may lead to nausea,
vomiting and diarrhea,
decrease in high
density lipoproteins,
gastric ulcer, pancreatitis,
pulmonary fibrosis,
copper deficiency
Essential(E), Nonessential(NE), Adapted from references 35
<6 months 10 g
612 months 15 g
16 yr 20 g
710 yr 30 g
> 11 yr 5075 g
012 months 5 mg
110 yr 10 mg
> 11 yr 15 mg
174
174
IAP
IAP Textbook
Textbook of
of Pediatrics
Pediatrics
Further presence of trace elements in laboratory atmosphere, glassware, water, reagents, etc. contaminate
samples unless meticulous care is taken. Currently
techniques used for trace element analysis are atomic
absorption spectrometry (AAS) and neutron activation
analysis (NAA). Sometimes estimation of enzymes dependent on these elements and outcome of therapeutic
supplementation may help in establishing diagnosis.
Zinc
Deficiency
Zinc deficiency syndrome was first discovered in the
Middle East. Cereal diets decrease its absorption due to
high phytates, fibers and phosphates as also chronic
diarrhea. Nephrosis, liver cirrhosis, hypoalbumenic
states, chelating agents, total parenteral nutrition (TPN),
trauma, burns and hemolytic anemia cause increased
excretion of zinc in urine causing deficiency. Deficiency
is also seen when body requirements are increased as in
developing fetus, pregnant women, and adolescents. Pica
in children is associated with hypozincemia. Acrodermatitis enteropathica is autosomal recessive disorder due
to failure of zinc absorption. It is characterized by growth
retardation, hypogonadism, poor appetite, eczematoid
skin lesions, alopecia and diarrhea which usually
manifest on weaning. If left untreated it progresses to
severe malnutrition, superinfection and death within 3
years. Mild subclinical zinc deficiency is frequent in
infants and children. Early clinical features of zinc
deficiency include anorexia, impaired taste and delayed
wound healing. Moderate deficiency features as seen in
West Asian dwarfs include hypogonadism, impotency,
anemia, hepatomegaly, night blindness, hyperkeratosis,
acrodermatitis, alopecia and superinfections with
bacteria or monilia due to defective T-cell function. Zinc
deficiency can lead to intrauterine growth retardation
(IUGR) and small-for-date (SFD) babies as it inhibits
growth and DNA synthesis. A strong relationship exists
between low plasma-zinc values and stunting, skin
ulceration, wasting and PEM with nutritional edema.
Diagnosis
Diagnosis can be confirmed by low zinc levels in plasma,
granulocytes, urine and sweat, latter being less reliable.
Clinical response to zinc supplementation can be
assessed in mild zinc deficiency by monitoring growth
velocity. Normal serum zinc levels in children are 66 to
194 g/10 ml. The serum levels are particularly low in

children with kwashiorkor.
Toxicity
Acute zinc toxicity leads to nausea, vomiting, abdominal
pain, diarrhea, convulsions and collapse. Chronic toxicity
which causes lethargy, anemia, neutropenia and CNS
disturbances is principally due to its competition with
copper for absorption. Inhalation of fumes leads to
respiratory distress, fever and chills (metal fume fever).
Therapy
Diet should include rich sources of zinc viz, meat, eggs,
nuts, cheese, oysters and grains. Zinc as acetate, sulfate,
gluconate, amino acid-zinc chelates and oxide have been
put to many therapeutic uses. Established uses are in
treatment of acrodermatitis enteropathica (50-150 mg/
day). Local application as cream is used in ulcer, wounds,
burns and acne. It could possibly be of use in hypogonadism, growth retardation, anemia, tremor
pigmentation syndrome pica, schizophrenia. Zinc is
widely used to reduce incidence and severity of diarrhea,
pneumonia and possibly malaria. Zinc (20 mg/day)
orally for 14 days improves morbidity and mortality in
children with diarrhea.
Copper
Normal serum levels in children are 77 to 185 mg/100
ml. Copper is a component of several enzymes which
are associated with electron transfer. Its essentiality for
proper utilization of iron has only been established
recently. Its role as an antioxidant is widely recognized.
Copper is present in whole grains, nuts, legumes, liver,
meats, etc. Copper concentrations in mothers' milk show
steady decline with lactation. It is essential for production
of red blood cells, transferrin, hemoglobin formation,
absorption of iron, and activities of tyrosinase, etc. It is
transported bound to alpha-2-globulin as ceruloplasmin.
Metallothionine, a zinc and copper binding protein
present in most human tissues is potential indicator of
copper nutritional status, while ceruloplasmin measuring
serum or plasma copper is subject to considerable
variation as an acute phase reactant protein.
Deficiency
Copper deficiency is extremely rare in well-nourished
full-term infants unless associated with gastrointestinal
Nutrition
abnormalities. It has been reported in formula-fed premature infants where copper deficiency may be presumably
due to inadequate intake for the rapidly growing infant,
or copper absorption was diminished by amount of iron
present in formula milk. Deficiency is characterized by
anemia, neutropenia, recurrent diarrhea and scurvy-like
bone changes. Deficiency is also seen in infants fed on
unfortified formula, with PEM, during prolonged
parenteral feeding and when zinc is given for several
weeks.
Toxicity
Menkes disease a X-linked recessive disorder is associated
with impaired absorption of copper. In neonate nonspecific features like hypotonia, hypothermia, seizure and
failure to thrive are seen. Kinky, pale, friable hair, severe
mental retardation and optic atrophy are constant features
which may appear later in infancy. Copper-histidine
50-150 g elemental copper/kg/24 hr used in early infancy
by subcutaneous injections prevents neuropathological
changes. Wilson's disease another genetic disorder is
characterized by choreoathetosis, mental deterioration,
liver cirrhosis, and osteoporosis due to deposition of excess
copper in various tissues. Of historical importance is the
Indian childhood cirrhosis, where copper ingested with milk,
stored and boiled in brass utensils (alloy of copper and
zinc) is deposited in liver resulting into cirrhosis. Acute
copper poisoning is characterized by metallic taste, nausea,
vomiting, gastric hemorrhage, hemolytic anemia, uremia
and jaundice.
Selenium
It acts as cofactor of glutathione peroxidase which
catalyzes the breakdown of hydrogen peroxide to
oxygen. Vegetables and meat are rich sources, provided
soil contains selenium. In Keshan province of China
where soil is deficient in selenium, children, adolescents
and women of child-bearing age develop cardiomyopathy and skeletal muscle myopathy (Keshan disease) and
osteoarthritis (Kashin-Beck disease). Excess of selenium
causes alopecia, abnormal nails, garlic odor to breath and
lassitude. It is used as antioxidant and for treatment of
seborrheic dermatitis.
Fluoride
Water, plant and animal food are sources of fluoride,
which are in turn dependent on content of fluoride in
175
the soil. It is important for structure of bone and tooth. It

prevents dental caries. When present in excess in water
and soil or ingested for longtime, they lead to calcification
of ligaments and tendons, weakness, anemia, loss of
weight and brittle bones. Mottling of teeth occur when it
is taken in excess during enamel formation (fluorosis).
This occurs when water supply contains more than 2
parts per million (ppm) of fluoride.
Magnesium
It is one of the constituents of bone and teeth. It activates
enzymes in carbohydrate metabolism and maintains
normal neuromuscular excitability. It is important intracellular cation next to potassium. Deficiency is seen in
malnutrition, malabsorption, diabetes, pancreatitis and
chronic renal failure. In newborn, hypomagnesemia is
commonly associated with hypocalcemia, and
magnesium administered may restore both calcium and
magnesium to normal values. Levels of magnesium, zinc,
copper, calcium in colostrum are higher than mature milk
of full-terms. In neonates infusion of magnesium sulfate
has been used for its neuronal protective property in
perinatal asphyxia and due to its smooth muscle relaxing
action it had been used in persistent pulmonary
hypertension, acute bronchial asthma and torsade de
points in children. Hypermagnesemia, clinically is
uncommon except in neonates born to mothers who are
receiving intravenous magnesium for pre-eclampsia.
Green leafy vegetables, nuts, legumes and cereals
are dietary sources of manganese. Since it is a constituent of cytosolic superoxide dismutase and ceruloplasmin, it is an important antioxidant micronutrient.
Severe manganese deficiency in prenatal life causes
increase in prothrombin time and bleeding. It is low in
seizure disorders. Its excess may cause syndrome akin
to Parkinson's disease. Inhalation in large quantities can
cause asthenia, leg cramps and encephalopathy.
BIBLIOGRAPHY
1. Antia EP (Ed). Trace Elements in Clinical Dietetics and
Nutrition (3rd ed). Oxford University Press: Mumbai
1989;133-36.
2. Barness LA, John SC. Nutrition. In Behrman R, Kliegman
RM, Arvin AM (Eds). Nelsons Textbook of Pediatrics
(15th edn): WB Saunders: Philadelphia 1996;141-47.
3. Bhandari B, Gupta AP, Gupta A. Breast milk mineral
content. Indian Pediatr 1985;22:23-26.
4. Bhandari B, Mehta R, Sharda B: Hepatic and serum
copper in Indian childhood cirrhosis. Indian Pediatr
1981;18:769-73.
176
176
IAP
IAP Textbook
Textbook of
of Pediatrics
Pediatrics
5.
Bhandari B. Trace Elements in human health and disease.

Quaterly Med Rev 1983;34:1-31.
6. Bhaskaram P. Zinc deficiency. Indian Pediatr 1995;32:
1153-55.
7. Buist NRM, Kennaway NG, Powell BR. In: Campbell
AGM, Mcintosh N (Eds): Textbook of Pediatrics (4th
edn). Edinburgh: Churchill Livingstone 1994;1213-15.
8. Gupta AP, Bhandari B, Gupta A, et al. Mineral content
of breast milk from North Indian Mothers giving birth
to preterm and termimplications for mineral nutrition.
J Trop Pediatr 1984;30:28688.
9. Janicki K. Drinking water and human health. In Yuregir

GT, Donma O Koyrin (Eds): Trace Elements in Health
and Disease. Qukurova Publishing: Adana 1989;2133.
10. Prasad AS. Trace Elements in Human Health and
Disease. Academy Press: New York 1976;20.
11. Prasad AS, Fitzgerald JT, Bao B, et al. Duration of
symptoms and plasma cytokine levels in patients with
the common cold treated with Zinc acetate: A randomized, double-blind placebo-controlled trial. Ann Intern
Med 2000;133:24552.
12. Sharda B, Bhandarni B. Serum zinc in protein calorie
malnutrition. Indian Pediatr 1977;14:195.
6.5 Child and Adolescent School

Health Education
Sushil Madan
A curriculum such as Life Skills and Health Education
is especially needed in developing countries like India
since there is an incerasing threat of communicable,
noncommunicable and lifestyle diseases prevalent in the
country. Lack of knowledge of diseases, preventive
health care, as well as other health issues across all
segments of society as well as absence of health and life
skills training in the Indian Education System at the
primary or secondary level makes this curriculum a dire
need.
The school-health education program was established
in 1958 with a view to stregthen younger generations.
Currently it works as a technical resource centre with
the Ministry of Education, National Centre for Educational Research and Training (NCERT), and Directorate
of Adult Education in close collaboration with the States
Health Education Department, and Universities.
However, none of the Indian schools has a system of
Health Education and Life Skill Curriculum practiced in
a systematically appropriate manner. Through school
based health education programs have been practiced
in the US, Norway nad China for mroe than 30 years, in
India they are being thought of being introduced in an
appropriate fashion only now.
Health Education and Life Skills Curriculum should
be designed to increases and create awareness of hygiene
and health among children right form their childhood
ot inculcate positive living habits and empower them to

make informed choices about their own health. Keeping
this in view Health and life Skills Education program,
the first of its kind in India, was launched in January
2004 by Udayan Care team, which followed International
Health curriculum.
The basic objectives of this curriculum should be:
i. To promote the idea of responsibility for childs
health by addressing comprehensive range of health
concerns amongst school children (6-19 years)
including (a) nutrition, growth and development,
(b) exercise and fitness, (c) disease prevention,
(d) alcholol, drug and tobacco use prevention,
(e) social and emotional health, (f) personal hygiene
of dental care, (g) consumer and environment
health, (h) safety measures and accidents, (i) conflict
resolution and prevention, (j) HIV- Aids and Family
Life Education.
ii. To instill life skills such as self-esteem, decisionmaking, goal setting, effective communication,
stress management, character building, and sensory
motor skills, ensuring they become an integral part
of each childs life and personality.
The approach followed should be as under:
a. Preparation of Life Skills and School Health
Curriculum manuals based on concerns prevalent in
school going children (6-19 years).
Nutrition
b. Training and education to School Teachers, parents,
and social Educators via manuals, workshop, and
activity books.
c. Implementation of the Curriculum, Monitoring and
feedback
Our main health concerns which impact the primary and
secondary age group of 6-19 years are
a. Nutrition, Growth and Development
b. Personal Hygiene/Cleanliness and habits/Dental
care
c. Disease prevention and immunization
d. Exercise and fitness
e. Personality Development
f. Alcohol, Tobacco and Drug Use Prevention
g. Social, Mental and Emotional Health
h. Conflict Resolution and Violence prevention for
adolescents
i. Emergencies/Safety Measures/Prevention of
accidents
j. Consumer and Environmental Health and Climate
change
k. Family Life Education and HIV/Aids Awareness
177
l. New Age Health Hazards

m. Periodic Health Check up.
NUTRITION GROWTH AND DEVELOPMENT
Adequate nutritious and healthy food is important for
proper growth and development of children and
adolescents both in health and in disease.
Offer a well balanced home cooked family diet
(Table 6.5.1). Serve a variety of textures. Avoid very
hot, icy cold or spicy food. Eating time should be a
pleasure. Any single meal should comprise of energy
foods(grains and cereals), protein foods (milk, eggs,
pulses, legumes), plenty of vegetables and fruits (rich
sources of nutrients, like vitamins and minerals and
several non-nutritional factors-fiber and phytochemicals) with sparing use of refined flour, oil, sugar
and salt which will take care of prevention of lifestyle
diseases.
Sufficient amount of milk and milk products:
Calcium is required for growth and bone
development and prevents osteoporosis. Nuts,
ragi and GLV also provide calcium.
TABLE 6.5.1: Sample meal plan

Meal time
Food group
Raw quantity
Cooked recipe
Serving
Breakfast
Milk
Sugar
Cereals (dalia, chapatti,
chirwa, oats, khakra)/egg
Panner/pulses/cheese
sprouted green gram
150-200 ml
5 gm
50 gm
Milk/coffee
1 cup
Cottage cheese with

oil and tomato/egg
Salad
One egg/cereal
20 gm
Tiffin
One fruit
One sandwich/Khakra and
vegetable or tomato and chutney
100 gm
40 gm
Lunch
Rice/Cereal/Chapati
Vegetables
Pulses
Veg salad
Curd
100 gms
100 gms
20 gms
50 gms
50 gms
Rice/Phulke 2
Veg curry
Dal
Salad
Curd
1/2 cup
1/2 cup
1/2 cup
7/8 slices
1/2 cup
Snack
Puffed rice/Groundnut
and roasted chana+ Milk
50 gms
Milk-150 ml
1 cup
Dinner
Rice/Cereal/Chapati
Vegetable
Pulses
Veg salad
Curd
100 gms
100 gms
20 gms
50 gm
50 gm
Rice/Phulka
Veg curry
Dal
Salad
1/2 cup
1/2 cup
1/2 cup
7/8 Slices
1/2 cup
*Quantity can be varied with appetite and increased with age.
178
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IAP
IAP Textbook
Textbook of
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Pediatrics
Eat fish more frequently than meat and poultry

and limit/avoid organ meats (liver, kidney, brain
etc).
Use more than one source of cooking oil. Limit
the use of ghee, butter and vanaspati.
Eat foods rich in alpha linolenic acid (legumes,
green leafy vegetables, fenugreek and mustard
seeds) to provide essential fatty acids.
Never starve the child. A child needs to eat more
during and after episodes of illness, Energy rich
cereal, pulse diets with milk and mashed
vegetables at frequent intervals help maintain
good nutritional status.
Discourage overeating to avoid obesity, risk of
high blood pressure, high cholesterol and heart
diseases and indiscriminate dieting to prevent
malnutrition.
Maintain food hygiene. Contamination is possible
before, during cooking service and storage of food.
Wash vegetables/raw foods before eating, rinse
in vinegar if possible (10 ml in half liter of water).
Avoid eating under cooked beef or pork
Prepare, eat, fresh food as far as possible
Keep cooked food covered until eaten
Protect food from dust, flies, insects, etc.
Do not use left over milk or food after half an hour
Food can be kept in the fridge for 4-8 hours.
Refrigerated foods loose just 10% of nutrients over
a years time as compared to foods stored on
shelf/outside may loose 50% of nutrients.
Consumption of unsafe foods can lead to food
poisoning / food borne diseases.
Wear footware suitable for walking and PT
separately.
Maintain good personal hygiene and keep the
cooking and food storage areas clean and safe.
Conserve maximum nutrients in fruits and
vegetables.
Consume seasonal fruits and vegetables for
vitality
Eat a combination of colored fruits and vegetables
to provide all vitamins and minerals
Highly colored fruits should be eaten to provide
phytochemicals and antioxidants
Peel skin as thin as possible-most vitamins and
minerals lie just under the skin
Wash leafy vegetables thoroughly before cutting,
never after cutting.
Cook in minimum of water in covered vessel

Do not throw leafy tops of cabbage, radish, carrots,
beetroot, and cauliflower. They are a rich source
of iron and calcium and a wealth of blood and
bones respectively.
Offer safe drinking water. Unsafe water is one of the
main causes of ill health besides air pollution. Safe
water intake can reduce the burden of communicable
diseases such as diarrhea, dysentery, cholera,
typhoid, paratyphoid and Hepatitis A by 80%.
Boiled of filtered water should be provided by
schools, rather than depend on visual cleanliness
of tap water for safety.
Watch eating: This is crucial for children and
adolescents who are easily tempted by outside foods.
Avoid junk foods comprising of refind sugar, flour
and saturated/transfats e.g. Friend potatoes,
burgers, colars, highly sweetened fruit juices, deep
fried tikkis, etc.
Avoid exotic foods: They are very expensive e.g.
Quail /EMU birds as there is no benefit as
compared to the cost.
Avoid processed foods. They contain coloring,
flavoring, and thickening agents along with
preservatives. Simple sunset yellow and tartrazine
color can cause allergy and associated symptoms
of vomiting, rashes and anaphylaxis. In addition
chances of adulteration increase.
Avoid watching television while eating. It can cause
obesity and metabolic syndrome due to excessive
eating. US have designed a television, which works
as long as the child pedals a cycle-ergo meter. Bicycles
can be used in India.
Offer favorite food along with new food in small
servings.
Do not force food on the child.
Insist on Mother / Teacher eating simultaneously.
Avoid carbonated drinks, tea, coffee and. Horlicks
before meal like lunch at school or dinner at home.
Involve the child in making salads, lemon drink
at home and school.
Grate vegetables into sauces/stews/chappatis,
etc. (Demonstration to be arranged at school).
Cut into small bits and chew each morsel 15/20
times to improve digestion.
Continue feeding during illness and more after
illness.
Nutrition
PERSONAL HYGIENE/DENTAL CARE/
CLEANLINESS AND HABITS
Simple hygiene can check deadly bacteria
Wash hands with soap and water before preparing
and serving food-before eating or feeding-child to
wash hands after coming from school or play-after
defecation and urination.
Keep finger nails clean and trimmed
Wash toys before giving to child.
Stop thumb sucking by diverting attention if present
Give bath preferably twice a day
Ask child to cover mouth and nose with handkerchief
while sneezing
Take special care of eyes/nose/ears
Vision to be checked by a doctor once a year
Wear clean clothes everyday
Do not spit or blow nose on the ground
Brush teeth twice a day for at least 2-3 minutes at a
time and flossing once a day
Rinse mouth and teeth after each meal
Comb hair daily, prevent lice infestation
Wash hair with shampoo at least twice a week
DISEASE PREVENTION AND IMMUNIZATION
Normally a child is admitted to school after primary
vaccination with; BCG, oral polio, HiB, Hepatitis B,
diphtheria, pertusis, tetanus, MMR, typhoid, Chicken
pox and Hepatitis A vaccine to take care of tuberculosis,
polio, DPT, HiB, HB, typhoid, chicken pox and
Hepatitis A. For adolescents refer to Table 6.5.2.
TABLE 6.5.2: Top up immunization of adolescents

Vaccine
Age
1. Td
Booster at 10 and 16 years
2. MMR Vaccine
One dose if not given earlier
3. Hepatitis B
Three doses (20 mcg) 0,1 and

6 months if not given earlier
4. Typhoid vaccine
VI Polysaccharide vaccine every

3 years
5. Varicella vaccine
One dose up to 13 years and

2 doses (at 4 to 8 weeks interval)
after 13 years of age if not give
earlier
6. Hepatitis A vaccine
Two doses 0 and 6 months if not

given earlier
179
Illnesses Make Life Short and Miserable

Child should remain two arms away from a sick
person to avoid catching illness.
Sick child should be told to take rest at home.
Avoid if possible over crowded places, e.g. market/
cinema halls/buses.
Avoid food given or handled by a sick person. Germs
come fre with the food.
As far as possible avoid eating outside home.
Eat home cooked food. School choldren to carry their
tiffin and water to school.
EXERCISE AND FITNESS
The energy you need to perform your work-out comes
from two primary sources:glycogen(glucose from
carbohydrate stored in the body) and stored fat. You
usually use a combination of both, to fuel your body
when you exercise. High intensity shot-term exercise
uses glycogen as its energy source. Low to moderate
exercise activity spread over a longer duration utilizes
the bodys fat reserves and strenthens muscle power.
Exercise keeps body, mind and thus health fit. Walk
to school every day. (if not too far)
Rope skipping/Cycling/Swimming are the best
exercises for the evenings/weekends for half an hour,
preferable daily.
Learn yoga that keeps you young forever and fit.
Prevent illnesses like joint pain, memory loss, with
tonic exercises and mental activities.
PERSONALITY DEVELOPMENT
Teach and prepare child and adolescent, to handle
and face the pressures pf modern day living, intense
competition, emotional challenges, rivalry, peer
pressure, etc.
Counseling and the role of an Adolescent Psychiatrist
cannot be overemphasized over here from the very
begining which would help in the Personality
development of this child and overcoming behavior,
mental problems and Psychosomatic illnesses.
ALCOHOL, TABACCO AND
DRUG ABUSE PREVENTION
Children, adolescents in particular face:
Commonly used drugs are tobacco, alcohol, cannabis
and brown sugar
180
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Pediatrics
Investigate if child loses temper easily while talking

to family members/students/teahcers and takes on
interest in personal grooming and shows poor
academic performance. There are:
Three stages of drug abuse
increasing migration from rural areas to big cities and

industrial towns has led to a large growing population
being pushed into a stage of uncertainity into a world of
competition and new challenges. This puts demand on
adaptive processes and further stress on the adolescent
population where increasing number of adolescent
population (13-19 years) appears to be involved in the
incidents of violence, sex offences, suicides and accidents
due to driving.
The hormonal changes adolescence lead to
heightened emotions. They become more emotional and
sensitive. They may go into fits of anger or pride without
understanding why it happens. Their own emotions
confuse the adolescents.
Many adolescents experience a sense of futility,
personal disorganization and aimlessness. They feel
inadequate, impersonalized and alienated and find it
difficult to adjust with the peer group. Such a disturbed
adolescent child needs counseling and advice. Problem
cases could show shyness, defiant behavior, bed wetting,
stammering, poor scholastic performance, drug
addiction, depression and hysterical convulsions.
Management
Management: Both parents and teachers can play a

supportive role in guiding the child to realize his /
her own responsiblities and taking control of his life.
Conduct more awareness drives and stop the
teenagers from getting into this habit including
smoking. Frequent counseling can be arranged with
school counselor.
Universities must admit only non-alcoholics and
nonsmokers. They must have periodical check ups
to see if an adolescent starts this habit later and take
necessary action to prevent him from repeated failure
in examinations and drop out form school/college/
sports/general activities.
SOCIAL, MENTAL AND EMOTIONAL HEALTH
In India the current high tech age and industrial
growth has led to innumerable social changes. There is
need for more education and training before placement
for a job or entry into any profession. This coupled with
Proper interview with guidance and counseling would

be essential from the pediatrician and Psychiatrist for
the Psychological turmoil. Parents cannot be blamed or
labeled guilty for hte behaviour of the adolescent. They
should be assured that adolescents have behavioral
difficulties. and the same indicate stress in them, common
in this age group. Child should be convinced by parents
or rewarded if required.
Key expectations of an adolescent from parent are:
(a) Parents interest and help (b) Listening (c) Love and
acceptance (d) Trust and (e) Autonomy/independence.
The parents should be made aware of hte expectations
which adelescents are likely to have from them. They
should back up child where necessary which gives her/
him a feeling of love.
Adolescents resent when they perceive lack of trust
by the parents. This projects parental anxiety, fears and
guilt. Adolescents get a feeling of being respected and
loved when their parents listen to them. (Adolescents
aspire to be treated as independent individuals by their
parents. Parents should grant independence gradually
rather then all at once).
The counseling to parents should take place in an
anticipatory guidance clinic.
Nutrition
CONFLICT RESOLUTION AND VIOLENCE
PREVENTION FOR ADOLESCENTS
Adolescent is the period from the beginning of sexual
maturity to the completion of physical growth,
movement from concrete to formal operational abstract
thinking and reasoning. They have difficulty in
understanding others while achieving a sense of identify
formation-self, during this period of development so they
have behavior problems which revolve around parents,
peers, self, school, employment issues and health.
Adolescents who lack parental or peer support are at
risk of psychosomatic symptoms (abdominal pain/
headache) during this stressful phase. This effect is also
reflected in social behavior.
School maladjustment is one of the first symptoms
to appear in response to alteration in development and
maturation. Teachers perception could be an efficient
screening device in this respect who could check child
behavior problems:
a. In terms of activity
b. Social Conduct
c. School Performance
Here parents are asked to report on child behavior.
Recognize the Signals
I want to run away from home

I am ashamed of my marks
I am burden on the earth
I do not want to attend school at all
I want to jump down from my house
No body loves me at all
I love to see the hanging scene in the movie Bhagat
Singh
Nothing will change if I die.
I am so angry that I feel like killing someone or myself.
I will teach my parents a lesson.
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Depression detection Technique: Trained teachers

and support staff of the institution can spot a child
what she/he does, words he/she says that can be
used as alert signs. They can help in treating children
and avoid untoward incidents.
Breaking the conspiracy of silence-Children are
secretive in nature and know what can work as guide
in their own case as well as in the case of their friends.
They know who in their group talks about death, who
plays dare games, who is keen on killing and who
will not come to school tomorrow. The catch is to
break their silence.
Triple-S Syndrome: This stands for three learning
shcools that children are subjected to these days:
School 1: Regular school; School 2: Tuition classes;
School 3: Parents at home They are instructed to obey
all the time. More space has to be given to children to
be activites, especially harmless ones, in their own
way.
All of us should learn to exercise authority in the
righteous way.
Happy Intervention triangle: It talks about changing
the form of interaction with kids. At the tip of hte
traiangle it the macro-intervention by the principal
who can make assembly meetings at school more
lively. At one end is micro intervention by teacher in
the class or in the playground who can make
classroom activity more interactive, joyous and one
that refreshes the mind. This also works as a forum
where teahers can observe and distinguish lonely kids
from others. At another end are parents, friends,
relatives and otehrs who can spend time with the
child and observe him or her in a micro environment.
They can also report on alarming signals. This is mini
micro intervention.
VULNERABILITY
Anyone can attempt suicide irrespective of their
intelligence. Each one of us can suffer form sadness/
depression and attempt suicide. However, mentally
ill are more prone to suicide but those not suffering
from the same can attempt it too. e.g. after failure in
exams or sudden discovery of a fatal illness.
In vie w of increasing violence and suicidal
tendencies amongst kids we need to build a future
strategy management for schools such as:
Do not challenge. Children who threaten are more

prone to attempt suicide than those who do not.
Hence do not challenge those who threaten to attempt
it.
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Suicideal behavior can be seen in families across
generations as depression can run in families so
proper counseling is required for parents and
children.
EMERGENCY SITUATIONS/SAFETY MEASURES/
PERVENT ACCIDENTS
They are as under:
Head and forehead injuries (Cuts/ bruises/internal)
due to fall from the terrace/balcony, while running/
playing, etc.
Slipping from staircase to entrapment of fingers in
doors at home or in the car
Injury to fingers by sharp items, poor quality toys
Swallowing of hard nuts/pins/loose parts of toys/
stray items on the floor
Burns caused by fire crackers / boiling water/tea in
the Kitchen/bathroom, etc.
Eye and ear injuries due to use of cleaning agents,
colors use in holi, etc.
Electrical shocks dur to open wires/sockets, etc.
Road accidents while crossing
Kerosene oil poisoning
Domestic/ School accidents with fall
Epileptic Convulsion, Acute asthmatic attack, comadiabetic/others, Heat stroke, Diarrhea/Vomiting,
Dehydration.
Management
Be vigilant all the time. Preventing an accident is wiser
than coping with one after the event.
Take adequate safety measures
Keep electrical sockets covered
Protect sleeping children from falling off cots with
railing/side support
Keep Kerosene/washing sode/spirit/naphthelene balls/baygon, matches and medicines out of
reach.
Avoid handling of sharp objects by children
Put safety locks on all cabinets and drawers
Secure refrigerator/dishwasher/stove/washing
machine/dryer/doors to avoid pinching of
fingers.
Keep chairs/stools away from windows to ensure
safety
Supervise in traffic/festivals and hold hands
while walking on road.
Do not leave child in the bath alone

Do not allow the child to swim alone
Do not permit children to peep out of running
vehicles
Take the child to hospital in case of emergency
immediately.
Teacher/Nurse/Mother should be trained for
immediate help and shifting to consulting room
or hospital nearby.
FAMILY LIFE EDUCATION (FLE) AND
HIV AIDS AWARENESS
There is an urgent need for informal education on
Parenting and sex education from the beginning of the
teens.
Following are the components of FLE for school
children aged 13-18 years
1. Adolescent nutrition Action Plan for the child, Kerala
has stipulated that all girls in Kerala on completion
of 18 years should aim 45 kg weight and 145 cm height
because birth wight of an infant is hte single most
important factor that determines the mental
development of a young child. Normal birth weight
of an infant has a sure edge over the low birth weight
baby born to mothers of poor nutritional status.
2. Personal hygiene Most of our school girls do not
drink water adequately not pass urine frequently in
school contributing towards silent urinary tract
infection, Poor toilet hygiene also needs immediate
attention. In many residential institutions for girls
proper menstrual hygiene including trimming of
public hair is not taught to them. They also need to
be made aware that some amount of vaginal
discharge and dysmenorrhea is within normal limits.
3. Understanding ones emotions The basis of formation
of good personality which includes a clear mind and
clear body is laid during adolescence. A person with
wholesome personality is one who has strong mental,
physical and cognitive skills which enable him/her
to behave, relate to and act effectively in the family
and the society at large.
4. The formation of good personality can surely be
influenced by the family. The family stands for all
the basic human values necessary for living usefully
and meaningfully. On one side the adolescent has the
fantasy of love and sex and parents immediate
problem is of getting him admission to Professional
college. Family life education is one acceptable mode
of introducing what is essential for adolescents to
understand and appreciate.
Nutrition
5. Awareness on HIV/Aids Family Life Education for
older children add young adults (13 - 21 years) should
have adequate emphasis on understanding and
appreciating ones own sexuality by showing parts
of body, and telling hormonal changes before and
during puberty with consequences in development.
WHAT IS HIV / AIDS ?
HIV- Human Immune Deficiency Virus infects man
alone (HIV Infects person /Carrier)
Initially multiplies rapidly-High concentration in
blood, CSF, Semen, Vaginal fluid, lesser extent in
breast milk.
Multiplies at a slower rate later and persists
throughout his/her lifetime.
Impairs functional capacity of immune system.
Clinically immunodeficient (AIDS Patient)
Is Vulnerable to TB/Pneumonia/Fungal Infection/
cancer.
MANAGEMENT
Foster each students ability to introspect on his/her
own sexual feelings and needs. Without such insight
one might not know how to avoid hurting oneself or
others.
Develop the ability to be alert and sensitive to difficult
situations where the child/student ought to think
before acting.
An adolescent becomes aware of his own/other
peoples bodiesa child can absorb attitudes towards
sex before the questioning begins.
Baby boys have erections and little girls have pleasant
feeling when they rub their thighs together or rub
their clitoris.
It is important for parents and teachers to answer
childrens queries regarding sex by explaining about
the anatomy of the body, onset of adolescence like
menstruation, breast and development of sex organs
general issues and sex abuse.
Help students to have confidence in their own
judgement and values provided by parents/teachers
who have a positive approach to sex and family life
education.
Subjects such as high risk behavior, family planning,
unplanned children, STD, etc. should be discussed
in the context of HIV/AIDS control.
It is important to ensure that adolescents have
knowledge with regard to sex, counseling, advice for
183
family planning such as contraceptive use including

condoms. A condom acts as a physical barrier and
prvents potentially infected semen or vaginal
secretions from cirect contact with the partners sex
organs/anus/mouth. Contraceptives like the pill/
IUD do not protect a woman from HIV infection. Thus
on educating and creating awareness youth can think
and act rationally thereby preventing tragedy of
unwanted pregnancy and staying healthy without
HIV/AIDS.
Crucial steps for eradication and prevention of HIV/
AIDS from the face of earth, as it will not only reduce
the burden of pediatric HIV but also overall numbers
of people infected with HIV.
a. By sex education thru plays
b. Prevention of parent to child transmission
(PPTCT) of HIV infection. This vertical transmission can be pregnancy associated or by breast
feeding.
c. Prevention thru transfusion of blood and blood
products. Blood should be screened for HIV.
d. Prevention of sharing of needles thru intravenous
drug users
e. Important to involve Junior colleges in the AIDS
Awareness Programs.
f. Avoid at all costs Unprotected Sexual Intercourse
Transmission takes place by physical contact.
Same is true for Syphilis and Gonorrhea.
g. Risk increases with multi-partner relationships.
h. Avoid Sex with commercial sex workers.
i. Avoid Sex at an early age.
j. Avoid sex (Man with Man).
k. HIV testing should be compulsory before
marriage for the couple.
Poniters for Diagnosis
Rapid loss of weight
Persistent fever and cough
Pneumonia/Tb
Swellings of lymph nodes
Diarrhoea and Oral thrush
Repeated attacks of herpes
Blood tests-Elisa (antibody 2/4 months after
Infection)
PCR (Antigen)
NEW AGE HEALTH HAZARDS
Computer hazards: Constant focusing on a particular
distance for a long period of time where eyes focus
on one point causes muscle fatigue and eye strain.
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Blinking rate drops down by a good 20-25% while

staring at a computer. Over a period of time children
tend to develop dry eyes due to this. To combat this,
it is necessary to take frequent breaks (every 30-40
minutes) where children/youth splash water on their
eyes, close their eyes for a minute and use lubricating
eye drops. To avoid Computer Vision Syndrome
(CVS) the computer screen should be below eye level.
Television watch: There is a direct co-relation between
a digital lifestyle and putting on too many pounds. It
is critical to ration a child/youths television viewing
as more the television viewing results in less fat being
burnt leading to obesity
Music blues: I Pods and other digital music players
thru head phones increase the risk of hearing loss as
they pump music directly into the ear. Anything over
80 decibels actually hurts the ear, 120 decibles leads
to instant hearing loss. It is not just the level of the
noise but also the duration. It is important to unplug
ear phones and listen to music on FM/record players
otherwise at a turned down volume or use head
phones that fit outside the ear canal.
Cell caution: Continuous use of cell phones can lead
to hearing loss and formation of benign tumor along
the auditory nerve. Electromagnetic waves from
mobile handsets are supposed to have harmful effect
on the brain, while headphones/hands free and insert
type of devices present loud noise directly at the ear
drum level; hence prolonged use should be avoided.
Sleepless nights: Getting sleep after watching TV is
difficult.Visual stimulation has a greater impact on
the brain than auditory stimulation. Children must
sleep for 8-9 hours at night to feel fresh next morning.
CONSUMER, ENVIRONMENTAL POLLUTION AND

CLIMATE CHANGE
Consumer has to face
1. Hidden Dangers of Indoor Pollution
2. Environmental Pollution and Climate Effects
Hidden dangers of indoor pollution: Chemicals are added
to our food supply, used as additives, preservatives
during food processing and storage, Cosmetics, air
freshners, computers, cleaning solutions, drugs, dyes,
household paints, light switches in cars, hair spray,
insecticides, stain removers, around us eventually
result in chemicals being inside us / in the air/ water/
soil that we breathe/drink/eat decades after their use
is ceased. Some of them may but most do not

biodegrade and they need extra metabolic enregy
expenditure to complete the detoxification process.
The current level of chemicals in food, water supply,
indoor and outdoor environment lowers out
threshold of resistance to disease and alters the bodys
metabolism causing enzyme dysfunction, nutritional
deficiencies and hormonal imbalances.
Toxins are at play in any home/work environment
in which you may find yourself with Sick building
syndrom (SBS) and cause Multiple chemical
sensitivities (MCS). It cannot be traced back to a
specific bacteria or virus. MCS results form either a
single high exposure to a particular chemical toxin
or repeated low level exposure to the thousands of
chemicals that surround us. Symptoms of MCS
include prolonged fatigue, memory difficulties,
dizziness, poor concentration, depression, anxiety,
troubled breathing, irritability, muscle and joint aches
and pains, head aches, chest pains, nausea, etc. The
list of symptoms is so large that it makes it difficult
to diagnose and differentiate from other health issues.
Environmental pollution and climate effects: Litter on city
streets and industrial waste pollutes waterways, toxic
chemicals inthe soil and ground water as it breaks
down. Light pollution defined as excess light at night
significantly increases the risk of breast cancer in
women. It also disrupts the migration pattern and
breeding cycle of many birds and animals. Smog
made of particulate matter and smoke (from petrol,
diesel, oil, coal, cooking gas) and ground level ozone
creates serious health risks for children and adults
and causes many respiratory illnesses such as chronic
bronchitis, bronchial asthma, silicosis, etc. Outbreaks
of heat waves are expected to cause spread of
infectious diseases. Drought and floods caused by
climate change impact the whole agricultural setting
which naturally means smaller harvests. It is critical
that the youth and children are made aware of the ill
effects of climate and the warming trends to reduce
CO2 emissions and global warming.
Understand climate Change: Check out Websites like
www.kidrgreen.org for more on this topic.
Prevention and Management:
Garbage management: This consists of collection,
treatment, segregation (organic and inorganic matter)
and processing of waste. Organic waste should be
returned to the earth within 24 hours. Plastic material
is separated and dealt with for recycling.
Nutrition
Drainage development: The drains should be checked
and maintained by the Municipal Corporation before
the rainy season every year. There should be no
obstruction to the flow of waste on route.
Rain water harvesting: Rain water should be conserved
on the terraces of big buildings and used for toilet
flushing and gardens. Conserve Kitchen and bath
water and reuse after treatment with oxygen for three
days.
Energy efficiency: Low energy lighting and reduced
energy consumption products such as TV, air conditioners ( with variable speed drives), CF lamps should
be used. Geysers and street lights should be switched
to solar power and solar cookers should be used for
cooking. Retrofit program can provide existing
buildings with more energy efficient products leading
to energy savings of 20-50% in the urban areas.
Bio fuel plantation: Petrochemicals used for cars, tucks
(Petrol, diesel) should be replaced by bio fuel plantation. This will be cheaper and cause less pollution
and emission reduction of CO2. Corporate Social
responsibility initiative will help largely in out
progress to mitigate global warning.
Car free days: Increasing the use of public transport
and the usage of bicycles instead of cars will curb
greenhouse gas emissions. Apart from that, physical
activity like walking and cycling will prevent obesity
and obesity related diseases. This will lead to
improved air quality and lead to better respiratory
health.
Green electricity: In Australia, UK, US green electricity
is being generated without the use of fossil fuels.
Wind, Solar, Ocean, Geo thermal and hydropower is
used instead which are renewable green sources and
hence do not release green house gasses in the process
of producing energy. Bio-mass produced by burning
garbage landfills/organic Kitchen waste is an
exception but the same can be countered by planting
vegetation which counters methane gases released
in this process.
Save and plant a tree: Trees are great for absorbing CO2
from the air. Every tree you prevent from being cut,
or that you plant, and nurture till its grown, will serve
a life time of absorbing CO2, even while it provides
beauty and shade, shelter and food, and keeps the
soil firm and healthy. Gardening and planting trees
while helping to preserve the environment is also a
good source of exercise.
185
Offsetting CO2 emissions: We must offset out remaining

CO2 emissions using CO2 allowances or credits.
Become resource savvy: Conserve energy at homes/
schools. Save water, save paper. Prevent wasteRecycle, Re-use and Refuse. Do not burn waste and
compost biodegradable waste. Keep electrical
appliances in good condition-air filters on ACs clean,
fridge coils and tube lights dust free. Depend less on
artificial aids for lighting and cooling and more on
sunlight and natural ventilation.
Youth and children to be made aware that organic
waste can be spread in thin layers not more than 5
cms in thickness and processed preferably in the
presence of plants in an area under shade.
School Teachers should take the initiative of making
nature Clubs for the children and spread the message
of climate change and foster grass root education and
activism to prepare amore proactive population for
the future. India should be seen as a part of Higher
as quoted by British Prime Minister Gordon Brown.
Prevent dengue and malaria:
Dengue and malaria are on the rise due to poor
sanitary and drainage facilities.
Need for water storage due to interrupted water
supply by Municipal corporations.
Extensive unplanned construction activities
Damp living conditions
Poor school environment
Favorable hot and humid conditions which
facilitate mosquito breeding.
Lethargic civil administration and lack of public
awareness have assured sustained dengue
transmission and malaria endemicity.
Long term vector control is the need of the day by
providing good sanitary facilities, Keeping pots
covered, spraying water bodies with pesticides
and improving the living conditions of slums and
environment since no vaccine is available till date.
Children should be made to make projects on this
to increase awareness.
HEALTH CHECK UP
Children and adolescents must have routine health
check ups by a Pediatrician for Nutrition, Growth and
Development and also be checked by ENT Specialists,
Opthalmologist for hearing, vision and dental
specialists respectively once a year. Child should also
be referred to the Pediatrician for treatment of
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physical illnesses such as diarrhea, dysentery,

pneumonia, typhoid, etc. on time.
TRAINING WORKSHOPS
Immediate need of the day is to train teachers and
supportive staff in schools both public and private with
the ultimate knowledge to spread the knowledge of
health, hygiene and life skills to primary age (6-10 years)
and family life education, HIV-AIDS and adolescent
problems to middle (11-12 years) and high school children (13-19 years). The life skills, health and curriculum
manual should be prepared in consultation with
Pediatricians, Psychiatrists. Educators and Social
Scientist. In addition simple Medical quiz should be
prepared with questions and answers which can be
discussed during question hour sessions. IAP can give
necessary support in preparation and printing of this
manual and training of teachers.
Implementation and Monitoring of the Curriculum
Teachers can teach Health and Hygiene issues along with
allied subjects. Teenage Club can be made where Family
Life Education, HIV-AIDS and Adolescent problems can
be discussed. This should work with parents, school and
community efforts in a supportive social climate. One
such successful project was carried out by Syed Amir
Group of Schools in Kolkata by the author. This can also
be carried out in conjunction with Reproductive Child
Health Program of Ministry of Health and Family
Welfare. It is important for teachers to monitor the
program and get the feedback.
CONCLUSION
Role of NGOs Creating Opportunities for Parental
Empowerment (COPE) will be the correct approach to
achieve the goals of this Curriculum along with the
parent Teacher Association.
Many programs are being carried out in School
Health Education across the world. It is critical that the
same are carried out in an orderly fashion covering all

that is required to be done according to the need of the
hour in out country. Courses pertaining to Health and
Hygiene will soon be part of the Health, Hygiene,
Immunization and Personality Development. Our
Community of Educators, Parents Students and NGOs
can work together ot create interesting, creative and
effective educational materials and follow the model of
Udayan Care if found satisfactory on monitoring.
BIBLIOGRAPHY
1. Adolescent Wellness Program by Boston Public Health,
www.bphc.org/programs.
2. Child and Adolescent School Health by School of Public
Health, sph.bjmu.educn/eng/ershao.htm.peking
University.
3. Colorado Department of Public Health and Environment:
Child, Adolescent and School Health website:
www.cdphe.state.co.us/ps/cash of 24.4.08.
4. Enhanced Health Services for High Schools,
Massachusetts Department of Public Health with Boston
Public Schools. http://www.bphc.org/programs
5. Health Action by people, Thiruvanthapuram, Published
by State Aid Cell, Thiruvanthapuram.
6. Madan S. Family Life Education for Adolescents-Why?
Indian Journal of Practical Pediatrics 1998;6:37-9.
7. Marc A Forman, William H Hetznecker, John M Dunn.
Parents as Tecahers.In Nelsons Textbook of Pediatrics
11th Ed, W B Saunders, Philadelphia 1979;2:30:61.
8. Nair MKC. Perspectives in Adolescent Care, Editorial
IAP Journal of Practical Pediatrics. Journal of Indian
Academy of Pediatrics 1998;6:7-10.
9. National Network; Health Education to be part of School
Curriculum soon: Teena Thacker, posted online.
Wednesday, March 26, 2008.
10. New Directions in Health Education. Edited by George
Campbell, Health Education and the Environment in the
Basic School Curriculum in Norway: Arne haukness,
page 117 International Health Curriculum (overview)
Publisher: Taylor and Francis 1985.
11. Udayan Care; School Health Education, Health and life
Skills for Primary Grades. Website: www.udayancare.
org/schoolhealth_education.htm
7.1 Community Pediatrics: Shashi N Vani ................................................................................................................................................. 188

7.2 National Health Programs: Shashi N Vani , Piyush Gupta ................................................................................................................ 190
7.2.1
National Rural Health Mission (NRHM) 2005-2012: Piyush Gupta ..................................................................................... 191
7.2.2
Maternal and Child Health (MCH) Programs: Shashi N Vani ............................................................................................. 193
7.2.3
Integrated Child Development Services (ICDS) Program: BNS Walia .............................................................................. 194
7.2.4
Child Survival and Safe Motherhood (CSSM) Program: BNS Walia .................................................................................. 196
7.2.5
Reproductive and Child Health (RCH) Program: BNS Walia, Shashi N Vani .................................................................... 197
7.2.6
Integrated Management of Neonatal and Childhood Illness (IMNCI) Strategy: BNS Walia .......................................... 200
7.2.7
National Programs on Immunization: A Parthasarathy, Shashi N Vani, BNS Walia .......................................................... 200
7.2.7.1
Universal Immunization Program (UIP): KM Ganessan ..................................................................................... 200
7.2.8
Acute Respiratory Infections (ARI) Control Program: Keya Lahiri, BNS Walia, Shashi N Vani ....................................... 202
7.2.9
Control of Diarrheal Disease (CDD) Program: BNS Walia, Shashi N Vani ......................................................................... 203
7.2.10 National Leprosy Eradication Program: BNS Walia ............................................................................................................. 204

7.2.11 National Vector Borne Disease Control Program (NVBDCP): Piyush Gupta ................................................................... 206
7.2.11.1 National Malaria Control Program: BNS Walia ..................................................................................................... 206
7.2.11.2 National Filaria Control Program: BNS Walia ....................................................................................................... 207
7.2.12 National AIDS and STD Control Program: BNS Walia ......................................................................................................... 207
7.2.13 Nutrition Programs: Shashi N Vani ......................................................................................................................................... 208
7.2.14 Mid-day Meal Program: HPS Sachdev ................................................................................................................................... 209
7.2.15 Anemia Control Program: Shashi N Vani ............................................................................................................................... 209
7.2.16 Control of Vitamin A Deficiency: BNS Walia ........................................................................................................................ 210
7.2.17 National Iodine Deficiency Disorders Control Program: N Kochupillai ............................................................................. 210
7.2.18 National School Health Program: BNS Walia ....................................................................................................................... 211
7.2.19 National Cancer Control Program: BNS Walia ..................................................................................................................... 211
7.2.20 National Mental Health Program (NMHP): BNS Walia ......................................................................................................... 211
7.2.21 National Program for Control of Blindness : BNS Walia .................................................................................................... 211
7.3 Community Newborn Care: Shashi N Vani ........................................................................................................................................ 212
7.4 Under Five Clinics: Ajit Kumar ............................................................................................................................................................. 215
7.5 The Girl Child: Shanti Ghosh ............................................................................................................................................................... 218
7.6 Customs and Beliefs in Child Rearing: Anil Mokashi ...................................................................................................................... 220
7.7 International Agencies and Child Health: Shashi N Vani ................................................................................................................ 225
7.8 Adoption and Care of Orphans: RD Potdar ...................................................................................................................................... 226
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7.1 Community Pediatrics

Shashi N Vani
INTRODUCTION
Pediatrics is concerned with the health of infants,
children and youth, their growth and development and
opportunities to achieve full potential as adults. Health
care of children is an essential component of pediatrics.
WHO definition of Health denotes a state of complete physical, mental and social wellbeing and not merely
an absence of disease or infirmity. This is very apt for a
child's health also and it should enable him/her to lead
a socially and economically productive life.
Study of pediatrics is not just the art and science of
the diagnosis and treatment of diseases, but also the
science for the prevention of diseases and promotion of
child's health. In the last few decades its scope has
expanded to include not only the health problems of an
individual child, but of all those in the community too.
Thus, the concept of community pediatrics has evolved.
DEFINITION
The term community pediatrics includes, the earlier disciplines known as public health, preventive pediatrics,
social pediatrics and community medicine. It focuses on
the health needs of the community as a whole. In the
modern concept, community pediatrics has been
effectively linked up with primary health care. The
foundations of the practice of community pediatrics are
based on epidemiology, biostatistics, social sciences and
organizing the health care services which include proper
planning, implementation and evaluation.
Community pediatrics includes mother and child
health care (MCH), as a very important component. It
must be remembered that mother and child's health are
interdependent on each other. Preventive pediatrics
consists of efforts to avert disease and disability, rather
than cure it.
Primary prevention: It is directed at avoiding disorders
before they begin, e.g. vaccination, clean water supply
and proper sewage disposal, etc.
Secondary prevention: It indicates recognition and
elimination of the precursors of the disease, e.g. screening programs for thyroid disorders, anemia, blindness,
etc. Screening is the search for an asymptomatic illness
in a defined population, which is usually performed for
the purpose of treatment, but is sometimes done for

counseling or research also. Ethics demand that screening
tests should not be done, unless justified by compensatory benefit and that too after obtaining informed
consent.
Tertiary prevention: It indicates the measures for
amelioration or halting of the disabilities arising from
established disease, e.g. physiotherapy to prevent contractures in patients with chronic neurological diseases.
Most successful primary preventive measures
require, understanding the cause, pathogenesis and the
natural history of diseases. For secondary and tertiary
prevention, however, determining the cause is not so
essential.
Many preventive measures such as tetanus immunization are effective only for the individual recipient.
Others are applied to the entire community, e.g. water
fluoridation, pulse polio immunization.
Thus, modern preventive medicine has been defined
as the art and science of health promotion, disease
prevention, disability limitation and rehabilitation. It
implies a more personal encounter between the individual and health professional than public health.
Social medicine: It is the study of man as a social being
in his or her total environment. The focus is on the health
of the community as a whole.
Epidemiology: It is the scientific study of factors influencing
the health, disease and the control of disease in
populations, rather than in individuals.
Why Study of Community Pediatrics is Needed?
i. Vast differences exist in the child health care
problems and services among the developed and
developing nations.
ii. Maldistribution of doctors and poor doctorpatient
ratio: Approximately, 80 percent population lives
in rural and tribal areas, whereas, 80 percent of
doctors serve the remaining 20 percent population
in urban and semi-urban areas. Thus, doctors alone
cannot cope up with the demands of the child care
from difficult rural/tribal areas.
iii. Inadequate training in pediatrics for the doctors as
well as nursing and paramedical staff does not make
Community Pediatrics
them feel confident to offer child care services in a
large community.
iv. Meagre allocation of budget for child care services,
improper prioritization and maldistribution of available funds, lack of knowledge and attitude for the
effective use of available resources, general poverty,
ignorance, traditional cultural taboos/customs, etc.
are some of the other major stumbling blocks for
provision pediatric services in developing countries.
Proper training of workers and development of
community pediatrics linked with primary health care,
offers a viable alternative for improvement of child health
services in developing countries.
Demographic Vital Statistics
Children less than 14 years of age constitute approximately 40 percent of total population. Women in the reproductive age, i.e. between 15 and 44 years of age constitute
approximately 22 percent of total population, together
they constitute about 62 to 63 percent of total population
which is a major vulnerable group.
Children less than six years age constitute approximately 17 percent of total population of which children
less than 1 year constitute 3 percent, children between
1 and 3 years of age group constitute approximately
6 percent and between 3 and 6 years constitute 8 percent
of the total population.
Infant Mortality Rate (IMR) is the most sensitive index
for assessing the quality of socioeconomic development
of a community and also reflects the quality of perinatal
care available to the community.
Incidence of low birth weight infants in India is
approximately 30 percent of total births. Vital statistics
provide an essential foundation for gauging children's
wellbeing and the level of care, nurture and resources
they receive. Some of the common indicators used are
given below:
189
Stillbirth Rate (SBR)

Number of stillbirths during the year
SBR = 1000
Number of live births + stillbirths
during the year
Perinatal Mortality Rate (PMR)
Number of stillbirths + infant deaths of
less than 7 days during the year
PMR = 1000
Number of live births + stillbirths
during the year
Neonatal Mortality Rate (NMR)
Number of infant deaths of less than
28 days during the year
NMR = 1000
Number of live births during the year
Age Specific Mortality Rate (ASMR)
Number of deaths in a particular
age group
ASMR = 1000
Midyear population of the same
age group
Under Five Mortality Rate (U5MR)(UNICEF)
Number of deaths of children less than
5 years age group
U5MR = 1000
Maternal Mortality Rate (MMR)
Crude Birth Rate (CBR)
Total number of female deaths due

to complications of pregnancy, childbirth or within 42 days of delivery from
Puerperal causes in a particular area
during a given year
MMR = 1000
Total number of live births in the
same area and year

CBR = 1000
Midyear population
(ideally, the denominator should include all the deliveries

and abortions).
Crude Death Rate (CDR)

Number of deaths during the year
CDR = 1000
Midyear population
BIBLIOGRAPHY
Infant Mortality Rate (IMR)

Number of infant deaths during the year
IMR = 1000
1. Kumar A: Role of social pediatrics in the interdisciplinary

approach to community health care. Indian Journal of
Preventive and Social Medicine 1972;3.
2. Nelson Textbook of Pediatrics, (15th edn) 1996.
3. Parks Textbook of Social and Preventive Medicine (14th
edn) 1994;327.
4. Polany L: Manual of Community Pediatrics (2nd edn),
1996.
190
7.2 National Health Programs

Shashi N Vani, Piyush Gupta
Under the Constitution of India, the subject of health
facilities, including their planning, establishment and
administration, falls under the purview of respective
governments of states of the union. However, Government of India has from time to time introduced National
Health Programs, which are either centrally sponsored,
i.e. part of expense is met by the Central Government,
or wholly funded by the Center. Though these programs
are addressed to health problems, diseases and conditions of great national concern like family planning,
AIDS control, blindness and tuberculosis control, they
suffer from numerous deficiencies in their implementation.
i. Most states have financial constraints, matching
contributions by the state often do not materialize.
ii. The staff hired under the centrally funded schemes
and the medicines available therefrom, are often the
only ones available for the total health activities of
the health services.
iii. Most of the programs do not provide for medicines
in a form suitable for child patients. Thus, anemia
prophylaxis program offers tablet of iron and folic
acid, which are unsuitable for preschool children,
in whom the anemia is very common. Similarly,
liquid preparations of rifampin or isonicotinic acid
hydrazide are not offered in the National Tuberculosis Program.
iv. The criteria for inclusion as a beneficiary of the program, often exclude children from availing of free
medicines provided in the program, e.g. sputum
positivity as a prerequisite for beneficiaries of tuberculosis control program, as only 10 percent children
suffering from tuberculosis show sputum positivity.
v. Staff training programs often neglects specific skills
required for handling children. This results in inadequate care or a complete neglect of children, e.g.
blindness control program and cancer control
program, where trained pediatric ophthalmologists
or oncologists are not employed.
vi. The vertical nature of numerous programs leads to
a set of persons performing duties related to a single
program, thus adding to transport and time costs,
so that a large part of the health budget is spent on
staff salaries, with little left for medicines, and supplies or for other essential requirements. As soon as
the latter are exhausted, the entire work force
becomes nonfunctional.
NATIONAL HEALTH PROGRAMS
The Ministry of Health, Government of India, with the
help of Central Health Council has taken several
initiatives in launching programs aimed at controlling
or eradicating diseases which cause considerable
morbidity or mortality in India. New programs are being
added and existing ones modified, in response to
changing epidemiology of disease, host or parasites. The
important National Programs are listed below:
I. National Rural Health Mission
II. National Programs Related to Mother and
Child Care
1.
2.
3.
4.
5.
Maternal and child health program (MCH)

Integrated child development services scheme (ICDS)
Child survival and safe motherhood program (CSSM)
Reproductive and child health program (RCH)
Integrated management of neonatal and childhood
illnesses (IMNCI): A strategy.
III. National Programs Related to Control of

Communicable Diseases
1.
2.
3.
4.
National program of immunization

Acute respiratory infection (ARI) control program
Diarrheal disease control program
Revised National Tuberculosis control program
(RNTCP)
5. Leprosy eradication program
6. National vector borne disease control program
(NVBDCP)
7. National AIDS control program.
IV. National Programs Related to Control of
Nutritional Deficiencies and Disorders
1. Nutritional programs
2. Mid-day meal program
3. Anemia prophylaxis program
4. Vitamin A deficiency control program
5. National iodine deficiency disorders control program.
V. National Programs Related to Control of
Noncommunicable Diseases
1.
2.
3.
4.
5.
National school health program

National cancer control program
National mental health program
National diabetes control program
National program for control of blindness.
7.2.1.
NATIONAL RURAL HEALTH

MISSION (NRHM) 2005-2012
Piyush Gupta
Recognizing the importance of health in the process of

economic and social development and improving the
quality of life of our citizens, the Government of India
launched the National Rural Health Mission of April 12,
2005. NRHM seeks to provide effective health care to
rural population throughout the country with special
focus on 18 states (Arunachal Pradesh, Assam, Bihar,
Chattisgarh, Himachal Pradesh, Jharkhand, Jammu &
Kashmir, Manipur, Mizoram, Meghalaya, Madhya
Pradesh, Nagaland, Orissa, Rajasthan, Sikkim, Tripura,
Uttaranchal and Uttar Pradesh) which have weak public
health indicators and/or weak infrastructure.
The mission adopts a synergistic approach by ralating
health to determinants of good health, viz., segments of
nutrition, sanitation, hygiene and safe drinking water. It
also aims at mainstreaming the Indian systems of
medicines to facilitate health care.
GOALS
The Goal of the Mission is to improve the availability of
and access to quality health care by people, especially
for those residing in rural areas, the poor, women and
children. Major targets are listed below:
Reduction in infant mortality rate (IMR) and Maternal
mortality ratio (MMR) by 50% from existing levels in
next 7 years.
Universal access to public health services such as
womens health, child health, water, sanitation and
hygiene, immunization, and nutrition.
Prevention and control of communicable and noncommunicable disease, including locally endemic
diseases.
191
Access to intergrated comprehensive primary health

care.
Population stabilization, gender and demographic
balance.
Revitalize local health traditions and mainstream
AYUSH.
Promotion of healthy life styles.
STRATEGIES
a. Core Strategies
i. Train and enhance capacity of Panchayati Raj
Institutions (PRIs) to own, control and manage
public health services.
ii. Promote access to improve health care at household level through the female health activist
(ASHA).
iii. Health plan for each village through Village Health
Committee of the panchayat.
iv. Strengthening sub-center through an untied fund
to enable local planning and action and more multipurpose workers (MPWs).
v. Strengthening existing PHCs and CHCs, and
provision of 30-50 bedded CHC per lakh population
for improved curative care to a normative standard
(Indian Public Health Standards defining personnel,
equipment and management standards)
vi. Preparation and implementation of an inter-sectoral
District Health Plan prepared by the District Health
Mission, including drinking water, sanitation and
hygiene and nutrition.
vii. Integrating vertical Health and Family Welfare
programs at National, State Block, and District
levels.
viii. Technical Support to National, State and District
Health Missions for public health management.
ix. Strengthening capacities for data collection,
assessment and review for evidence-based
planning, monitoring and supervision.
x. Formulation of transparent policies for deployment
and career development of human resources for
health.
xi. Developing capacities for preventive health care at
all levels for promoting healthy life styles, reduction
in consumption of tobacco and alcohol, etc.
xii. Promoting non-profit sector particularly in under
served areas.
192
b. Supplementary Strategies
i. Regulation of private sector including the informal
rural practitioners to ensure availability of quality
service to citizens at reasonable cost.
ii. Promotion of public private partnerships for
achieving public health goals.
iii. Mainstreaming AYUSH-revitalizing local health
traditions.
iv. Reorienting medical education to support rural
health issues including regulation of medical care
and medical ethics.
v. Effective and viable risk pooling and social health
insurance to provide health security to the poor by
ensuring accessible, affordable, accountable and
good quality hospital care.
c. Components
The Plan of action includes increasing public expenditure on health, reducing regional imbalance in health
infrastructure, pooling resources, integration of
organizational structures, optimization of health manpower, decentralization and district management of
health programs, community participation and
ownership of assets, induction of management and
financial personnel into district health system, and
operationalizing community health centers into
functional hospitals meeting Indian Public Health
Standards (IPHS) in each Block of the country.
The mission plans to promote access to health care to
rural household through a female health activist, ASHA.
The main components are described below:
Accredited Social Health Activists (ASHA)
Every village/large habitat will have a female Accredited
Social Health Activist (ASHA)-chosen by and accountable to the panchayatto act as the interface between
the community and the public health system. ASHA
would act as a bridge between the ANM and the village.
She will be an honorary volunteer, receiving performance-based compensation for promoting universal
immunization, referral and escort services for RCH,
construction of household toilets, and other health care
delivery programs. She will facilitate preparation and
implementation of the Village Health Plan along with
Anganwadi worker, ANM, functionaries of other
Departments, and Self Help Group members, under the
leadership of the Village Health Committee of the
Panchayat. She will be given a Drug Kit containing

generic AYUSH and allopathic formulations for common
ailments.
Other Components
i. Strengthening Community Health Centers (CHC)
for first referral.
ii. Primary Health Centers (PHC) and sub-centers.
iii. Intergrate all vertical Health and Family Welfare
Programs at District and State level merge into one
common District Health Mission (DHM) at the
District level and the State Health Mission at the
State level.
iv. Guide activities of sanitation and hygiene.
v. Strengthening disease control programs.
vi. Develop guidelines for Public-Private Partnership
(PPP) in health sector and identifying areas of
partnership, which are need based, thematic and
geographic.
vii. To examine new health financing mechanisms.
viii. Reorienting Health/Medical Education to Support
Rural Health Issues.
Timelines for Major Components
i.
ii.
iii.
iv.
v.
Preparation of Village Health Plans

ASHA at village level (with Drug Kit)
Upgrading of Rural Hospitals
Operationalizing District Planning
Mobile Medical Unit at district level
2006
2005-2008
2005-2007
2005-2007
2005-2008
6. Desired Outcomes of NRHM by 2012

i.
ii.
iii.
iv.
v.
vi.
vii.
viii.
ix.
x.
Infant mortality rate reduced to 30/1000 live births.

Maternal mortality ratio reduced to 100/100,000.
Total fertility rate reduced to 2.1.
Malaria mortality redcution rate-50% up to 2010,
additional 10% by 2012.
Kala-Azar mortality reduction rate: 100% by 2010
and sustaining elimination until 2012.
Filaria/Microfilaria reduction rate: 70% by 2010,
80% by 2012 and elimination by 2015.
Dengue mortality reduction rate : 50% by 2010 and
sustaining at that level until 2012.
Japanese encephalitis mortality reduction rate: 50%
by 2010 and sustaining at that level until 2012.
Cataract operation: Increasing to 46 lakh per year
until 2012.
Leprosy prevalence rate: Reduce from 1.8/10,000 in
2005 to less than 1/10,000 thereafter.
xi. Tuberculosis DOTS services: Maintain 85% cure rate
through entire mission period.
xii. Upgrading Community Health Centers to Indian
Public Health Standards.
xiii. Increasing utilization of First Referral Units from
less than 20 to 75%.
xiv. Engaging 250,000 female Accredited Social Health
Activists (ASHA) in 10 States.
7.2.2.
MATERNAL AND CHILD

HEALTH (MCH) PROGRAMS
Shashi N Vani
Women of the reproductive age groups and children

constitute almost 60 percent of the population. The
hazards related to pregnancy and childbirth in the former
and the frequent occurrence of nutritional and infectious
disorders in the latter, makes these groups more
vulnerable to death and disease. The term Maternal and
child health(MCH) refers to promotive, preventive
and curative health care activities for mothers and
children. These are eminently suited for inclusion in
primary health care.
Objectives of MCH:
i. To reduce maternal, infant and childhood mortality and morbidity
ii. To promote reproductive health
iii. To promote physical and psychological development of children and adolescents.
Policy Guidelines for Implementation of
MCH Programs
1. Effective use should be made of existing resources
and infrastructures available in the community.
2. The services should be delivered as close to the homes
of beneficiaries as possible.
3. Services for mothers and children should be delivered
in an integrated manner.
4. Child survival programs should serve as a sugarcoating for delivery of the family planning programs
which in general, are not popular.
5. Voluntary agencies working in the area should be
involved in providing MCH services.
Details of Services Rendered in MCH Programs
The multipurpose health workers form the backbone of
this program. They are expected to:
193
1. Record occurrence of pregnancy in their work area

on the basis of history of missed periods.
2. Screen women identified as pregnant for any of the
under mentioned Risk factors.
i. Age less than 17 years or over 35 years
ii. Height less than 145 cm
iii. Weight less than 40 kg or more than 70 kg
iv. History of bleeding in previous pregnancy
v. History of stillbirths
vi. History of cesarean section as indicated by scar in
lower mid-abdomen
3. Identify women with moderate severe anemia.
4. Administer two doses of tetanus toxoid.
5. Provide iron and folic acid tablets to pregnant women
for a period of 180 days.
The advantage of identification of at risk pregnancies is that 80 percent of total morbidity and mortality in
the group is known to occur in the 20 percent of the
pregnant women identified to be at risk by above
mentioned criteria.
Antenatal Care
The package of antenatal care for all pregnant women
consists of: screening for anemia, eclampsia and preeclampsia and multiple pregnancies. Hemoglobin
estimation is done, blood pressure recorded and fundal
height is measured.
Mothers are advised to eat more of the foods generally consumed by them. Their breasts are examined to
exclude retracted nipples. Mother is told about what
articles are required at the time of labor and for the
newborn infant on its arrival. A dialogue is initiated
regarding spacing of further births.
Intranatal Care
The program envisages delivery of infant by a trained
birth attendant. These attendants are women belonging
to the local community, who have been trained in use of
aseptic precautions, during delivery of infant, severance
of cord and subsequent care of the cord and infant. They
are trained in suction of throat mucus and in mouth to
mouth resuscitation, if required. These workers are
trained to identify infants who are ill and require referral
to an appropriate medical institution.
Education is also imparted to mothers regarding
breastfeeding, immunizations required by the infant,
family planning and general hygiene.
194
The health care of the delivered woman continues to

be supervised by the TBA at the subcenter or her house,
under the supervision of health visitor or female
multipurpose worker. Primary health care of the newborn is also undertaken by the TBA.
Care of Children
It includes the following activities to be conducted by
the female multipurpose health worker under the
supervision of the doctors at primary health center.
1. Monitoring of growth of children to detect faltering
of weight gain or malnutrition
2. Immunization against vaccination preventable
diseases
3. Treatment of common ailments as per the IMCI
guidelines
4. Referral of cases to health institutions
5. Implement national health programs
6. Impart health and nutrition education to community.
At Risk Children
In order to focus greater attention on children who are
at greater risk of disease or death, the concept of identifying and registering at risk children was enunciated.
At risk children include those who belong to any of the
under mentioned categories:
i. Birth weight less than 2.5 kg
ii. Twin births
iii. Weight below 50 percent of reference standard at
any age
iv. Difficulties in breastfeeding, bottle feeding started
below 6 months age or delay in giving supplementary foods beyond 6 months age
v. Birth order of 4 or more
vi. Death of one or both parents
vii. Recurrent illness in child or family
ICDS blocks, Anganwadi workers also help in various

MCH program tasks, especially related to detection of
malnourished children and identification of those
requiring immunization.
For every 5000 population in rural area and 3000
population in tribal area, there is a subcenter where MCH
clinics/immunization clinics are conducted on one or
more fixed days in a month. Home visits are done by
health workers according to a planned schedule. For
every such 5 or 6 subcenters totalling a population of
about 30,000, there is a primary health center (PHC)
where medical officer and health assistants conduct
curative services as well as MCH and other preventive
and promotive services.
In the recent years, for every one lakh population, an
upgraded PHC known as community health center
(CHC) has been established where some additional
health care services like anesthesia, dentistry and
pathology are made available.
Under the child survival and safe motherhood
(CSSM) program in selected districts with approximately
five lakhs population, one first referral unit (FRU) is
created where there is provision of a surgeon, an
obstetrician, a pediatrician, and an anesthetist along with
facilities of blood transfusion and operations. More
complex cases are sent either to district hospital or the
nearest teaching hospital attached to a medical college.
BIBLIOGRAPHY
1.
2.
3.
4.
Implementation of MCH Programs

Medical officer of PHC is the leader of the health team.
The services are delivered essentially through the staff
members of the PHC and subcenters comprising medical
officers, health assistants (female and male) and
multipurpose female health workers, also called as
auxiliary nurse midwives (ANM) and multipurpose male
health workers.
Trained birth attendants and village health guides
wherever available, provide support to the services. In
5.
Manual for orientation of ANM and supervisorsReproductive child health, Dept. of Family Welfare, Ministry
of Health and Family Welfare, Govt. of India, 1996.
Monograph on integrated training on national programs
for mother and child development. CTC-ICDS, Dept. of
Woman and Child Development, Govt. of India, 1992.
National Plan of Action a committment to the child, Dept.
of Woman and Child Development, Govt. of India, 1992.
Parks Textbook of Preventive and Social Medicine (14th
edn) 1994.
Polany L: Manual of Community Pediatrics (2nd edn).
1996.
7.2.3
INTEGRATED CHILD DEVELOPMENT

SERVICES (ICDS) PROGRAM
BNS Walia
The ICDS was launched in 1975 in 33 community

development (CD) blocks of the country and has now
spread to more than 4000 CD blocks. The objectives of
the scheme are outlined below:
i. To improve the nutritional and health status of
children in the age group of 0 to 6 years.
ii. To lay sound foundation of psychological, physical
and social development of the child.
iii. To reduce morbidity, mortality, malnutrition and
school drop-out rates.
iv. To impart nutrition and health education to mothers
for making them more competent in looking after
nutrition and health needs of children.
The scheme is focused for the benefit of preschool
children, and pregnant and lactating women in the
reproductive age group (15-44 years), as they constitute
most vulnerable sections of population with higher
morbidity and mortality rates. Also, foundations of health
and psychological development are laid in the first six
years of life. It is, therefore, important to utilize scarce
financial resources on this segment of population. The
package of services provided by the ICDS scheme is given
below. The expectant and lactating women are offered
health check-ups immunization against tetanus,
nutritional supplements, nutrition and health education.
Recently, health check-ups of adolescent girls have also
been included in the program. Children below the age of
36 months, are given health check-up, immunization and
nutrition supplements, whereas children between the
ages of 36 to 72 months also receive nonformal preschool
education, in addition to the above mentioned
services. The immunizations given to children include
BCG, DPT, oral poliomyelitis and measles vaccine.
Children aged five or more, also receive a booster dose of
diphtheria-tetanus toxoid. Expectant mothers receive 2
doses of tetanus toxoid during the gestation period.
In a country where almost half the population is living
below the poverty line, it is not surprising that pregnant
women and preschool children are not receiving their
caloric requirements. Though the problem is rampant in
houses of poverty stricken and landless children of Dalit
and tribal communities, it is by no means uncommon
even in well to do families, because of ignorance of proper
weaning methods for infants and preschool children. The
nutritional supplements, aim at meeting the gap of about
300 to 400 calories found in the diet of average
preschooler. These are provided in the form of preproces-
195
sed or semiprocessed foods or foods prepared on the spot

from locally available foodstuffs. Children are also
administered a dose of 200,000 international units of
vitamin A every 6 months. Iron and folic acid are also
offered for prophylaxis of anemia. Pregnant women and
nursing mothers are also given iron and folic acid tablets.
Health check-up of children includes, the record of
weight for identification of malnourished children, who
receive special attention. Antenatal care of pregnant
women and postnatal care of nursing mothers and care
of newborn infants is carried out by the female multipurpose worker of the area, under the supervision of the
health visitor. The Anganwadi worker helps them in
organization of the immunization program by
identifying children who require to be immunized and
informing families about date, time and venue where
the immunizations may be obtained.
The administrative unit for the location of an ICDS
project is a community development block in the rural
areas, a tribal development block in the tribal areas and
a slum in the urban areas.
An Anganwadi is established for a population of 1000
in rural and urban areas and 700 in tribal areas. The
Anganwadi is run by an Anganwadi worker. For a
population of 100,000 in a community development
block, 100 Anganwadi workers are employed on a part
time basis. Their work is supervised by 4 to 5 female
supervisors. The overall charge of the ICDS work in a
CD block is administered by child development project
officer (CDPO), who establishes Anganwadi centers,
maintains their supply lines, monitors the program,
arranges training programs and reports to State
Governments.
The project is monitored on the basis of monthly
reports sent by Anganwadi worker, as well as by independent teams of the Planning Commission. Numerous
benefits of the project are reported. These include raising
immunization and vitamin A coverage reduction in
prevalence of malnutrition, reduction in incidence of low
birth weight and reduction in infant and preschool
mortality.
BIBLIOGRAPHY
1.
Monograph on Integrated Training on National

Programs for Mother and Child Development CTC-ICDS,
Dept. of Women and Child Development GOI, 1990.
196
7.2.4 CHILD SURVIVAL AND SAFE

MOTHERHOOD (CSSM) PROGRAM
BNS Walia
This program was initiated in 1992. It is yet another
excercise, of renaming old programs which have existed
for several years, and repacking them with a new name.
The different components of the program are:
Advice on Breastfeeding
The topic of breastfeeding is discussed in detail in
Chapter 3 and 5. Information and education by paramedical staff and the birth attendants regarding
breastfeeding to prospective mothers is the only contribution of this program.
Care of the Newborn Infant
The main aim of child survival program is to reduce
infant mortality. Since neonatal deaths constitute almost
half of the infant mortality, it is necessary to pay attention
to such measures as they may reduce mortality. A wellthought, low cost program for the newborn infants has,
therefore, been approved for implementation though it
has yet to start functioning all over the country. A major
lacuna is the inadequate training of birth attendants and
provision of supply of sterile equipment to them.
The strategy is to:
i. Provide antenatal care to all pregnant women
ii. Ensure safe delivery services
iii. Provide basic care to all neonates
iv. Identify and refer these neonates, who are at risk.
The package of antenatal services consists of: (a)
advice on nutrition and prevention of anemia with iron
and folic acid, (b) tetanus immunization and early
identification of Pregnant women at risk so that their
labor may be conducted at a referral center.
Resuscitation
If the infant fails to cry within 15 to 20 seconds, i.e. time
taken to wipe his body and wrap him in a clean cloth,
steps should be initiated for resuscitation. They may
include clearing his throat with mucus extractor, assisted
with a ventilation bag and mask or mouth to mouth
breathing. If bag and mask are not available, take care to
blow only the air in your blown up cheek, into the infants
lung. If in spite of above described measures, the infants
heart rate remains below 60/min, an external cardiac

massage is recommended.
It is hoped that every birth shall one day be attended
by a trained birth attendant, who will cut the cord with
a sterile blade and tie it 2.5 inches from the base with a
clean twine. Supplies of cord kits can be locally assembled
and sterilized at PHC for free distribution to birth
attendants. The neonate must be protected from catching
a child by avoiding a bath, keeping the infant wellwrapped in the mothers cot and keeping the room warm.
A normal infant is put to mothers breast within an hour
of birth. No other food or water is required to be given.
Infections are the cause of a large proportion of deaths
in neonates. These can be considerably reduced by
ensuring cleanliness in delivery room, training staff in
technique of handwashing, use of sterile instruments for
cord cutting, not permitting persons who have skin or
respiratory infection to handle the infant, and not
allowing relatives to handle or feed the infant.
A dose of oral polio vaccine and BCG should be
administered to the infant, within the first week of life.
Low Birth Weight Infants
Almost 25 to 30 percent of neonates in many developing
countries, have birth weight less than 2500 gram. Weight
of neonates can be recorded by ordinary spring balances,
which are cheap and easy to carry. A red tape applied at
1800 gram mark can point to an illiterate TBA, the need
for referral whereas an orange colored tape at 2500 gram
may be used to alert the TBA to LBW of infant. The TBA
and other workers in PHC should be familiarized with
clinical features which indicate severe illness and referral
to the PHC. These are failure to feed, abdominal
distention, imperforate anus, hypothermia, failure to pass
urine for 48 hours afterbirth, fast breathing or periods of
stoppage of breathing, convulsions and jaundice reaching
up to umbilicus.
Pregnant Women
Essential Care for All
Register by 12 to 16 weeks
Antenatal check-up at least 3 times
Immunize with TT
Give IFALarge tablets to all, i.e. 1 tablet a day for
100 days
Treat those with clinical anemia: 2 tablets a day for
100 days
Deworm with mebendazole during 2nd/3rd
trimester, in areas where prevalence rates of hookworm infestation are high.
Safe and clean delivery services.
Prepare the woman for exclusive breastfeeding and
timely weaning.
Postnatal care, including advice and services for limiting and spacing births.
Early Detection of Complications
Clinical examination to detect anemia
Bleeding indicating APH (before labor) or PPH (after
delivery)
Weight gain of more than 3 kg in a month and systolic
BP of 140 mm Hg or more or diastolic BP of 90 mm
Hg or more
Fever 39C and above after delivery or after abortion
Prolonged or obstructed labor (labor pains for more
than 12 hours).
Emergency Care for those who need it
Early identification of obstetric emergencies
Provide initial management and refer to identified
referral units
Use fastest available mode of transport.
Women in the Reproductive Age Group
Counseling on:
Optimal timing and spacing of birth
Small family norms
Use and choice of contraceptives
Information on availability of:
Medical termination of pregnancy (MTP) services
and
Intrauterine devices (IUD) and sterilization
services
Provide family planning services.
BIBLIOGRAPHY
1.
Manual for orientation of ANM and supervisors

Reproductive and Child Health Dept. of Family Welfare,
Ministry of Health and Family Welfare GOI, 1996.
2. Modules of CSSM MCH division, Ministry of Health and
Family welfare, 1994.
197
7.2.5 REPRODUCTIVE AND CHILD

HEALTH (RCH) PROGRAM
The National Family Welfare Program has been renamed
in 1997, as the Reproductive and Child Health (RCH)
Program. The program envisages that men and women
make informed choices, receive counseling for responsible and health sexuality, and avail of services for
prevention of unwanted pregnancy, safe abortion and
maternity care. Also health services shall continue to be
provided, pertaining to child survival and prevention
and treatment of diseases of reproductive tract in women.
An important shift in the goals of new program is from
the malady of targetitis to providing a range of quality
services instead. The package of essential reproductive
health services recommended for implementation
includes:
i. Prevention and management of unwanted pregnancy
ii. Services to promote safe motherhood
iii. Provision of services to promote child survival
iv. Nutrition supplements for vulnerable groups
v. Prevention and treatment of reproductive tract
infections and sexually transmitted infection
vi. Reproductive health survey for adolescents
vii. Information and counseling for health and sexuality
viii. Availability of a referral system.
The additional services to be provided by the
revamped program, would necessitate retraining of staff,
and make available the equipment and supplies, supervision and support and adequate financing to make the
implementation of program, a reality.
RCH II has since been launched in 2004 with
improved strategies based on the experience gained in
the implementation of RCH I.
Contraception
Access to wider range of choices of contraceptives is wellknown to improve contraceptive use. Service providers
are expected to help clients make decisions for selecting
contraceptives that are most suitable for them. Reversible
methods of contraception are not being used to the extent
that they are desired. Safety and freedom from morbidity
caused by the method selected would ensure its
198
continued use and satisfied clients would then become

the spokes person for the program. Contraindications to
IUD insertion must be respected and patient be given
immediate medical attention, in case of any adverse
reaction.
Efforts should be made to encourage vasectomy in
preference to tubectomy, as it is a safer procedure.
Counseling of men should be carried out to dispel their
fears and anxieties regarding vasectomy.
Provision of services for medical termination of
pregnancy and safe abortion services for unwanted
pregnancies at the primary health center level, could help
to reduce illegal abortions and maternal deaths
therefrom.
Antenatal services should be provided at every clinic
and dispensary. During home visits, health workers
should identify women who have missed periods, and
once pregnancy is confirmed, at least 3 to 4 antenatal
examinations should be carried out to detect anemia,
preeclampsia, malpresentation and infection.
Advice on breastfeeding, personal hygiene, nutrition
and immunizations should be given. In the postpartum
period, family planning methods should be discussed
with the parturient lady.
Safe Delivery Services
More than 75 percent deliveries in India take place at
home, and majority of these are conducted by traditional
birth attendants. It is impossible to replace them, and
therefore, it would be worthwhile to train them to do a
clean delivery, identify pregnant women at risk,
recognize the indications for referral. Their training must
also include guidance on breastfeeding, resuscitation of
newborn and identification of danger signals in newborn
infants. Repeated training programs and continued
supervision would be required to attain desirable
standards of performance.
Postpartum Services
This program should offer services for detection and
management of infection and hemorrhage, nutrition
advice, and counseling on breastfeeding. Advice on
family planning or tubectomy if offerred during this
period, is more likely to be accepted. Timely referral and
transport should be arranged, if clinical condition
demands.
Child Survival Services

Almost, half the total deaths in children occur in the first
year of life. Prevention of infectious diseases by vaccines,
and of diarrhea and malnutrition have helped to reduce
the postneonatal mortality. Further reduction in infant
mortality rates can be expected to occur only by reduction
in prenatal and neonatal mortality. For this purpose,
better training of birth attendants and female
multipurpose workers in the care of neonates, cord care,
resuscitation, prevention of chilling of baby, identification of congenital anomalies and danger signals, would
enable referral of cases for hospitalization. Upgrading
of facilities for neonatal care at community health centers,
subdivisional hospitals and district hospitals would be
required. The pattern adopted by the Tamil Nadu state
is quite effective, without being expensive. The
resurgence of sexually transmitted diseases, may indicate
routine prophylaxis for gonococcal infection in districts,
where gonorrhea is prevalent.
Nutrition Supplements for Pregnant and
Lactating Women
These programs have been established under the
Integrated Child Development Services at the village
level, in almost half the community development blocks
in the country and benefit pregnant and lactating
women. There is need for expanding this program to
include the undernourished adolescent girls, who
should also receive iron and folic acid, in view of the
high prevalence of anemia in young women of rural
areas. Prevention and treatment of reproductive tract
infections (RTI) can affect not only womens health, but
also the outcome of delivery, child survival and HIV
transmission. Reproductive tract infections provide a
useful entry point for introduction of family planning
methods to the patients. The idea of integration of the
program of detection and treatment of RTI in the enlarged reproductive health program is, therefore, based
on sound reasoning. The need for additional supplies
and training of staff for acquisition of certain additional
skills is essential for proper implementation of the
program.
Efforts at reduction of infectious morbidity related to
RTI, should include prophylaxis against gonococcal
ophthalmia, detection and treatment of maternal syphilis
and hepatitis B immunization.
Chart 7.2.5.1
199
200
BIBLIOGRAPHY
1.
Manual for orientation of ANM and supervisors

2. Pachauri S: Defining a Reproductive Health Package for
India. South East Asia Regional Working Papers No. 4,
1995.
7.2.6 INTEGRATED MANAGEMENT OF

NEONATAL AND CHILDHOOD
ILLNESS (IMNCI)-STRATEGY
BNS Walia
About 2 million infants and young children die annually
all over the world. The tragedy is that almost 70 percent
deaths are caused by common, easily treatable illnesses
like diarrhea, pneumonia, malaria, measles and malnutrition. Majority of such patient, residing in rural area or
slum areas first come to the attention of auxiliary health
workers. It is envisaged that if these workers could be
trained in the skills required to identify and treat the
above named illnesses, the morbidity and mortality caused by these illnesses could be considerably reduced.
The WHO has coordinated these efforts and prepared
training materials and guidelines and undertaken training courses which are appropriate for use by workers of
first level outpatient health facility in developing
countries. In addition, a course has been developed to
improve drug supply situation in these facilities.
The IMNCI guidelines are based on simple clinical
signs, which have been identified as most sensitive and
specific in arriving at a clinical diagnosis, without
laboratory tests. The guidelines are presented as wall
charts in the clinics or as booklets which can serve as
handy manuals to guide the health workers.
Methodology of IMNCI
Depending on a childs age, IMNCI guidelines focus on
neonates, infants, and children upto 5 years of age. The
treatment guidelines are broadly described under the age
categories: (i) young infants upto 2 months of age; and
(ii) children age 2 months-5 years. The health worker
follows the steps of case management process as
described below:
i. Assess the young infant/child;
ii. Classify the illness;
iii. Identify treatment;
iv. Treat the young child/infant;
v. Counsel the mother; and
vi. Provide follow-up care.
A summary of this case management is presented as

color-coded charts. Chart 7.2.5.1 provides a page of these
charts. Each illness is then classified according to the color
coding, i.e. green, yellow or pink. Those in the green
classification are managed at home, those in the yellow
can be treated at the out-patient health facility while those
in pink classification need urgent referral.
If referral is decided upon, urgent treatment is given
before sending the patient away. Mothers of patients are
taught how to administer oral drugs at home, and to
increase fluid intake during diarrhea or fever. Mother is
also informed regarding which signs should be regarded
as of serious importance and should make her return to
clinic immediately and when a routine visit may be made.
Mothers are given appropriate feeding instructions and
follow-up instructions for the relevant clinical condition.
Substantial evidence has been gathered by now
regarding the effectiveness of the IMNCI approach in
reduction of childhood mortality and in improving child
care at family and community level.
The question is sometimes asked as to what is new in
this program as some of the programs like ARI and
control of diarrheal diseases did exist earlier. What is new
really, is the way the health worker is to be conveyed
this information. The guidelines help to ensures high
quality coordinated child health services. In most
developing countries, health care programs for children
include nothing more than immunization. Adoption of
this program by governments of developing countries
gives hope that the children shall survive as a result of
such efforts from the common killer diseases to benefit
from immunizations.
BIBLIOGRAPHY
1. Gove S. Integrated management of childhood illness by
outpatient health workers: Technical basis and overview.
Bulletin of the World Health Org 1997;75(suppl 1):716.
2. Lembrechts, Bryce J, Orinder U. Integrated management
of childhood illness, a summary of first experience. Bull
WHO. 1999;77(7):58293.
7.2.7 NATIONAL PROGRAMS ON

IMMUNIZATION
A Parthasarathy, Shashi N Vani, BNS Walia
7.2.7.1 UNIVERSAL IMMUNIZATION
PROGRAM (UIP)
KM Ganessan
Immunization is regarded as the greatest success story
of the 20th century. The global immunization coverage
201
has increased to over 85 percent not only in the developed countries, but also in developing countries through
successful organization of National Immunization
Programs and adoption of National Immunization
Schedules. The success gained through the 20th century,
will pave the way for introduction of several newer
vaccines in the 21st century, in the National Immunization Schedules of the respective countries.
The objectives are:

To increase immunization coverage
To improve the quality of service
To achieve self-sufficiency in vaccine production
To train health personnel
To supply cold chain equipment and establish a good
surveillance network
To ensure districtwise monitoring.
HISTORICAL PERSPECTIVES
The National Immunization Schedule
At the global level, the first ever organized immunization program, was instituted in the year 1974, under the
caption Expanded Program on Immunization (EPI) by
the World Health Organization (WHO). India adopted
EPI in 1978. While BCG, DPT, OPV, and measles for
children under five years of age and TT for pregnant
women were the targeted antigens adopted at the global
level under EPI in 1974, India adopted BCG, DPT and
Typhoid immunization in 1978 and later on, OPV in 1979.
In order to achieve certain time bound specific goals,
Universal Immunization Programs (UIP) was launched
in 1985 as an off-shoot of (EPI) with the targeted
beneficiaries, viz. Infants under one year for BCG, DPT,
OPV and measles coverage children at 1 years for DPT
and OPV Booster, children at 5 for DT and children at 10
and 16 as also pregnant women for TT. Subsequently,
Children's Vaccine Initiative (CVI) was launched at the
global level in 1991 with the objectives of improving the
quality of vaccine, exploring newer production
technologies, discovering newer vaccines and possibly
to finally develop a single vaccine vehicle incorporating
several antigens. The global program on vaccine and
immunization (GPV) was launched in 1993, at the global
level with the objective of sustaining high coverage and
developing a good global surveillance network for
vaccine preventable diseases, and evolve eradication
strategies. In India the success of UIP resulted in the
launch of child survival and safe motherhood (CSSM)
programs in 1992 and the reproductive and child health
(RCH) program in 1997, incorporating immunization as
one of the major components of the program.
An epidemiologically relevant, immunologically appropriate, technically feasible, socioculturally acceptable and

economically viable National Immunization Schedule
was evolved as the minimum needs program (MNP)
for universal coverage of children and pregnant
women.
The UIP Objectives

Universal coverage of all infants, under 5 children,
children at 10 and 16 as also pregnant women with the
recommended antigens as per the national immunization, schedule was the aim of the Universal
Immunization Program (UIP).
Achievements of UIP
High Coverage and Decline in VPDs
Annually 25 million infants and pregnant women have
been reached out. The overall immunization coverage
have gone up to nearly 90 percent for all antigens. Over
80 percent decline have been achieved for the targeted
diseases, viz. neonatal tetanus, diphtheria, pertussis,
poliomyelitis and measles.
Self-sufficiency in Vaccines
Over 21,854 PHC's and 1,32,730 subcenters are rendering
immunization services in rural area. 1500 lakh doses of
OPV, 1200 lakh doses of DPT, 1200 lakh doses of TT,
290 lakh doses of DT, 550 lakh doses of BCG and 330
lakh doses of measles vaccines are freely available
annually.
Cold Chain System
To preserve all vaccines at +2C to + 8C, the following
cold chain equipments have been supplied.
Ice Lined Refrigerators (ILR) to PHC's along with
vaccine carriers (+ 2C to + 8C) with temperature
monitoring
Walk in coolers with temperature monitoring for state
level storage
Freezers with temperature monitoring at district
stores (20C)
Walk in freezers with temperature monitoring for
large states (20C).
202
Dial thermometers have been supplied to monitor ILR

temperature. The quality of cold chain is monitored by
testing oral polio vaccine samples selected randomly
from the field. For this purpose, a new network of testing
laboratories have been setup.
Surveillance of VPDs
Effective surveillance network have also been established. The PHCs act as primary reporting units and
medical college hospitals and other major hospitals are
acting as sentinel centers. Monthly reporting including
0 reporting by the reporting units is mandatory.
Towards polio eradication strategy acute flaccid paralysis
(AFP) surveillance has been intensified through the
National Polio Surveillance Project (NPSP) through
WHO Surveillance and Assistance Surveillance Medical
Officers. Each state has got a state level immunization
officer. District immunization officers monitor the entire
program supervising the district and PHC level operation.
Targets Achieved
Neonatal tetanus elimination has been achieved by many
states. Reduction in number of cases and deaths due to
measles has since been achieved by 1992 onwards. Polio
eradication is expected to be achieved in very near future.
Pulse Polio Immunization carried out from 1995 to
2007 annually have covered over 15 crores of children
under 5, with additional doses of OPV on National
Immunization Days.
The good infrastructure established under UIP has
helped to carry out the UIP plus program namely the
CSSM. The success of CSSM has paved the way for CSSM
plus namely the Reproductive and Child Health Program
(RCH). A good rapport has been built up, with parents
and pregnant women resulting in good demand
generation. Awareness on cold chain maintenance has
increased. Sustaining high coverage has become
mandatory. Self-sufficiency of vaccine production has
encouraged introduction of newer vaccines like MMR
and Hepatitis B in the UIP in coming years. VPD eradication has become a reality. The Information Education
and Communication, (IEC) system has become effective.
The success of the program has resulted in saving an
estimated 16.8 lakh lives annually.
The current progress in UIP is the development and
implantation of a mid-term stategic (Multi-Year Plan-
MYP) with definite goals, milestones and indicators to

measure the coverage and progress, with a provision for
necessary mid-course corrections. A National Technical
Advisory Group (NTAG) was formed in August 2003.
Based on its recommendations in 2002, the Government
of India has developed our MYP for 2004 to 09.
Achievement of five specific objectives of India
Immunization Policy: availing opportunities to introduce
vaccines (like MAR/AR, JE and Hepatitis B) and to
produce an opportunity to expand wherever feasible
with other public health interventions of maternal and
child care.
BIBLIOGRAPHY
1. Basu RN: Chalenges in the final stage of polio eradication:
Ind J Ped 71: Aprl 2004:33940.
2. Biswal P: Universal immunization programme: Reduce
material 10th NCCPF meeting, New Delhi, 30th Apl 2004.
3. Ghosh A: Status of UIP in the Country. Report on
National Consultation meet on prevention of Hepatitis
B in children: NIPCCD 1998;2125.
4. John TJ, Parthasarathy A, Bhave SY: Historical Aspects
of Global Immunization Programs: IAP Guide book on
Immunization 1996;1112.
5. Sokhey J: National Immunization Program: Frontiers in
Social Pediatrics AK Patwari, HPs Sachdev (Eds). Jaypee
Brothers Medical Publishers (P) Ltd., New Delhi
1998;25365.
7.2.8 ACUTE RESPIRATORY INFECTIONS

(ARI) CONTROL PROGRAM
Keya Lahiri, BNS Walia, Shashi N Vani
Acute respiratory infections are a major cause of infant
and childhood mortality, contributing 20 to 30 percent
of the total deaths in children below 5 years of age and
15 to 30 percent of total deaths in children.
Prevalence
Patients suffering from ARI constitute 22 to 66 percent
of all pediatric outpatient cases and 12 to 45 percent of
all indoor admissions. In the urban set up, children under
the age of 5 years suffer 3 to 5 episodes of ARI in a year.
Amongst rural children, the morbidity is slightly lower.
Mortality due to ARI is higher amongst small-for-date
infants, the premature, the malnourished and when it
occurs in association with measles or pertussis.
ARI Control Program
The guidelines devised by the World Health Organization for prevention and treatment of ARI are based on
the premise that diagnosis of ARI is possible by
paramedical workers and that treatment with orally
administered antimicrobial agents is safe and effective.
The WHO protocol puts forward two signs as the
entry criteria for a possible diagnosis of pneumonia.
These are cough and difficult breathing. Presence of fever
is not essential for diagnosis. Infants under
3 months are categorized as a separate group, because
in them the gram-negative bacteria predominance as the
cause and the disease is more liable to take a serious
course. Patients belonging to this age group are treated
with antibiotics parenterally in the form of a combination
ampicillin 25 to 50 mg/kg/day and gentamicin 5.0 mg/
kg/day for a period of 7 to 10 days.
Presence of any of the under mentioned signs is
indicative of severe illness.
1. Respiratory rate more than 60/min
2. Chest indrawing in the absence of nose block.
3. Infant has stopped accepting feeds
4. Abnormally sleepy or difficult to wake
5. Hypothermia
6. Convulsions
Children aged between 3 months and 5 years: The
common causative organisms are gram-positive, e.g.
Strept. pneumoniae. Fast breathing has been noted to be a
better predictor of pneumonia than auscultatory findings.
Fast breathing is defined as respiratory rate more than
40/min in children above 1 year of age and more than
50/min in children between the ages of 3 to 12 months.
203
Presence of chest indrawing indicates serious respiratory

tract involvement.
The categorization of a case as one of pneumonia and
its severity is summarized in the Table 7.2.8.1.
BIBLIOGRAPHY
1. Basic Principles of Control of Acute Respiratory
Infections in Children in Developing Countries; a Joint
WHO / UNICEF Statement, WHO, Geneva 1986.
2. Intergrated Management of Childhood Illness: Global
status of implemention, August 1998 WHO, UNICEF,
1998.
3. Management of childhood illness is developing countries: Rationale for an integrated strategy. WHO,
UNICEF, 1998.
4. The Management of Acute Respiratory Infections in
Children: Practical Guidelines for Outpatient Care,
WHO, Geneva, 1995.
5. The role of IMCI in improving family and community
practices to support child health and development.
WHO, UNICEF 1998.
6. World Health Organization: Case Management of Acute
Respiratory Infections in Children in Developing
Countries. Document WHO/RSD/85, 15.
7.2.9 CONTROL OF DIARRHEAL DISEASE

(CDD) PROGRAM
Diarrhea is the cause of almost one-fourth of deaths in
preschool children. The experience of scientific workers
who treated cases of cholera in camps of Bangladesh
refugees in 1971 with a mortality rate of less than one
percent, provided ample proof of the effectiveness of this
TABLE 7.2.8.1: Clinical assessment and management of acute respiratory infection

Clinical signs
Classification
Treatment
Not able to drink or central cyanosis

present
Very severe pneumonia
Admit / refer oxygen IV chloramphenicol

25 mg/kg/day Assess twice daily
II
Chest indrawing
No cyanosis
Able to drink
Severe pneumonia
Admit / refer
IV Penicillin 25000 units/kg/dose, 6 hourly.
Assess once daily.
III
Resp. rate over 40/min

No chest indrawing
Pneumonia
Oral cotrimoxazol 58 mg/kg of TMP

+ 25 mg/kg/SMZ. Amoxicillin/Ampicillin
2550 mg/kg/day.
Assess once in 2 days.
No pneumonia
Treat like URI

Ask mother to return if chest
indrawing or increased respiratory rate occurs.
IV No fast breathing
No chest indrawing
Feeding well
204
low cost intervention in reduction of childhood mortality

caused by dehydration in diarrheal disease. Treatment
of dehydration caused by diarrhea was therefore
included in the child survival program with the following
objectives: to reduce diarrhea related deaths in children
under the age of 5 years by 30 percent by 1995 and by
70 percent by year 2000 AD. The strategy adopted was:
i. To train medical and other health personnel in
standard case management of diarrhea.
ii. Promote standard case management practices
amongst private practitioners.
iii. Instruct mothers in home management of diarrhea
and recognition of signs which signal immediate
medical care.
iv. Make available the oral rehydration salts (ORS)
packets free of cost, at government health facilities
at first and later through the public distribution
system.
The rational treatment of diarrhea consists in prevention of dehydration in a case of diarrhea by oral
rehydration therapy, using oral rehydration salts. The
composition of ORS is given below:
Chemical
Sodium chloride (IP)
Sodium citrate (IP)
Potassium chloride
Glucose (IP)
Quantity to be used in grams

3.5 gm
2.9 gm
1.5 gm
20.0 gm
A sachet containing the above contents is dissolved

in 1 liter of water and is kept in a clean utensil. 150 to
200 ml of solution is administered, each time a stool is
passed, depending upon whether the stool is small or
large, and upon the age of the child.
Some of ORS packets available in the market
containing a higher content of glucose, though intended
to make the solution tastier, are liable to worsen diarrhea
by osmotic effect of the sugar and therefore, should be
avoided. In case, ORS packet is not available, oral
rehydration therapy can be carried out by a home-made
solution, constituted as follows:
Common salt
Baking soda
Cane sugar
Weight
(gm)
3.5
2.5
40
Lemon
one
Household measure
3/4th of a teaspoon
1/2 teaspoon
8 level teaspoon (not
heaped)
(Supplies potassium)
Kindly note, that when cane sugar is used in place of

glucose, double the quantity of sugar is used. Other home
available solutions for prevention of dehydration, can
also be administered. These include rice water, dal water,
butter milk, soups and coconut milk. A pinch of salt is
added to each helping of 300 ml of these fluids.
Sweetened aerated drinks, fruit juices or sweetened tea
may worsen the diarrhea by their osmotic effect, and
should therefore be avoided.
Breastfeeding should be continued. If stool characteristics of the patient resemble that of lactose intolerance,
milk to be fed could be diluted with equal quantity of
water for 3 to 4 days. Others should continue to have
undiluted feeds before discharge from the PHC. The
mother should be given a few packets of ORS and
demonstrated, how to reconstitute it into a solution for
administration.
Patients who are diagnosed to be having dysentery,
are given cotrimoxazole in addition to ORS. In case of
unsatisfactory response, nalidixic acid is given for five
days. Occurrence of amebic dysentery is uncommon in
children and there is little justification for adding
metronidazole to the treatment of a dysentery case on a
routine basis.
Any program for diarrheal disease control must
include provision of potable water. Parents must also be
educated regarding storage of water and foods in clean
utensils, continuance of breastfeeding, using only freshly
prepared weaning foods and thorough washing of hands
with soap before handling foods.
7.2.10 NATIONAL LEPROSY ERADICATION

PROGRAM
BNS Walia
The National Leprosy Control Program was launched
in 1955, as a centrally aided scheme. Its focus was on
rural areas of high and moderate endemicity. In 1969 to
70, the scheme was converted into a centrally sponsored
program.
In 1981, guided by the fact, that large variations still
existed in the prevalence of the disease in different states,
the Ministry of Health and Family Welfare constituted a
working group of experts in leprosy to devise a new
strategy for eradication of leprosy. The recommendations
of the working group included conversion of the National
Leprosy Control Program into a time bound National
Leprosy Eradication Program, with specific goal to arrest
the disease activity in all leprosy cases, by 2000 AD and
screening of pre-school children and youth for early
detection of cases. A National Leprosy Eradication
Commission under the chairmanship of the Union
Minister for Health and Family Welfare for formulation
of policies, and the National Leprosy Eradication Board
under the chairmanship of the Union Health Secretary,
were constituted for monitoring the activities of the
program.
A Deputy Director General, Health Services was
given the charge of planning and implementing the
programs at the Government of India level. At the state
level, the program is supervised by a senior officer in
the Directorate of Health Services. One district leprosy
officer had been provided for districts where leprosy was
highly endemic, and one per two or three districts where
it was of moderate endemicity. The field activities have
been conducted by leprosy control units which serve a
population of 4-500,000 and comprise one medical
officer, 4 nonmedical assistants and 20 paramedical
workers.
Survey, Education and Training (SET) centers were
established for each population unit of about 25,000.
These units are located at the primary health center and
one paramedical worker is assigned to each center. It is
hoped that once the prevalence rates in leprosy-endemic
districts fall below 1 per 1000 population, the vertical
leprosy eradication program would be abolished and its
functions would be taken over by the primary health
center staff.
In the urban areas, the program is run under the
urban leprosy centers, which look after a population of
50,000/70,000 and are attached to a neighborhood
dispensary or hospital.
Reconstructive surgical facilities have been developed
at several hospitals. Operational manuals and guides
have been written and distributed to workers to ensure
delivery of services of a uniform quality.
A WHO study group on chemotherapy of leprosy in
1981, recommended the use of combined chemotherapeutic regimens for the treatment of all multibacillary
and paucibacillary patients. The former type constitute
about 25 percent of the total cases in India.
The multidrug therapy (MDT) regimen followed
under the program is given in Table 7.2.10.1.
All the antileprosy drugs are supplied free of cost to
patients from Central Government Funds. MDT has been
205
TABLE 7.2.10.1: Multidrug therapy (MDT)

regimen for leprosy
Phase
Drug
MULTI BACILLARY CASES

Intensive phase
for 14 days
Rifampicin
Clofazimine
Dapsone
Rifampicin
Dose
Administration
60 mg daily
100 mg daily
100 mg daily supervised
600 mg once
a month
Continuation phase
(for at least
Clofazimine 300 mg once
2 years)
a month
supervised
50 mg daily
unsupervised
Dapsone
100 mg daily unsupervised
PAUCI-BACILLARY CASES (PB)
Continuation phase
(minimum for 6 months)
Rifampicin 600 mg once
a month
supervised
Dapsone
100 mg daily unsupervised
found to be safe and effective as judged by decrease in

prevalence rate of cases, decline in detection rate of new
cases, and decline in deformity rates. In the 7th-five-year
plan, sample survey cum assessment units were created
in the states, for survey purposes so that the reported
data under NLEP is validated by an independent
authority.
District leprosy societies have been formed in
every district under the chairmanship of the Deputy
Commissioner. Each district is provided with a mobile
leprosy treatment unit for visits to lepers colonies for
supervision of treatment and periodic surveys.
Rehabilitation
Rehabilitation of leprosy patient included physical, social
and vocational rehabilitation. Physical rehabilitation
involves, the care of ulcers, correction of deformities and
physiotherapy. Numerous leprosy rehabilitation units,
reconstructive surgery units and hospital wards have
been established for rehabilitation of patients with
deformities. Voluntary organizations are playing a major
role in the rehabilitation field, with the guidance and
financial assistance of Ministry of Social Welfare and
several international agencies. More institutions for
vocational training of patients are required as economic,
independence is the best safeguard against social
rejection.
206
Health Education
The stigma of leprosy as a punishment for past sins, is
deeply ingrained in the Indian psyche. The notion that
leprosy is an infectious disease, which is completely
curable by available medicines without any residual
deformity, if treated at an early stage has to be propagated
widely. This is essential in order to correct the prejudices
and misconceptions of the public, as well as give the
sufferers a hope of cure, which is essential for continuing
the treatment for prolonged periods.
Research in leprosy is being promoted by ICMR and
Department of Science and Technology and is mainly
focused on trial of new treatment regimens and field trials
of vaccines for prevention of the disease.
7.2.11
NATIONAL VECTOR-BORNE
DISEASE CONTROL PROGRAM
(NVBDCP)
Piyush Gupta
National Vector-Borne Disease Control Program

(NVBDCP) initiated in 2003-04 includes the erstwhile
National Anti Malaria Program (NAMP), National Filaria
Control Program (NFCP) and Kala-azar Control
Program, and also includes programs for control of
Japanese Encephalitis (JE) and Dengue/Dengue
Hemorrhagic Fever (DHF).
7.2.11.1 NATIONAL MALARIA CONTROL
PROGRAM
BNS Walia
National Malaria Control Program has been functioning
since 1958. An expert committee recommended a revised
strategy for control of malaria which was implemented
in 1995 to 96. Special attention is to be paid to tribal areas,
epidemic prone areas and development project areas. The
seven North Eastern States having high incidence of
falciparum malaria is to be provided, with 100 percent
assistance for malaria control. In remaining states, the
program is to be operated as centrally sponsored scheme
with 50 percent funding to be contributed by the state.
Nonavailability of state contribution could result in short
falls in spray operations, decline in slide examinations
and incomplete treatment of the cases.
The objective of the program is to bring down malaria
transmission to a level, where it ceases to be a health
problem. Thereafter, PHC staff must maintain it.
PHC is the focal point of all antimalaria acitivites,

which include epidemiological surveillance by staff,
laboratory examination of blood smears of fever cases,
administration of chloroquine to all patients running
fever by health workers, spraying and antilarval
operations, surveillance, radical treatment of malaria
positive cases, and improvement of the environment.
Strategies of malaria control should include the
undermentioned essential steps: (1) survey and monitoring of incidence of malaria, and (2) use of residual
insecticide spray. The vector for filaria, Japanese B
encephalitis being the same as that of malaria and the
vector of filaria being amenable to the same insecticides
as the mosquito, the control activities against these
diseases should be integrated with the Malaria Eradication Program to avoid duplication in efforts and
expenses. The use of Japanese B encephalitis (JE) vaccine
in the areas prone to this disease has resulted in
considerable decrease in the number of reported cases
and deaths due to this disease.
The existing guidelines for vector-borne diseases
control are summarized below:
i. Spraying with appropriate insecticide in areas with
annual parasite index (API) of two or more in the
last three years.
ii. Spraying BHC in districts reporting 100 or more
cases of Japanese B encephalitis, in any year during
the last decade.
iii. Spraying DDT in PHCs reporting 10 or more cases
of kala-azar, in anyone of the last three years.
iv. Continuation of antilarval operations.
v. In addition, malathion fogging is to be undertaken
whenever an outbreak of JE or malaria is encountered.
The PHC doctor should plan intervention measures
for transmission control in a methodical fashion. The
exercise involves ascertainment of period of transmission, the vectors responsible for it, monthly
infant parasite rates, characteristics of breeding
places and susceptibility status to insecticides.
Transmission control measures include:
a. Indoor residual spray
b. Indoor/outdoor fogging
c. Antilarval measures, using chemical larvicides,
biocides, fish, fungi or nematodes.
d. Personal protection measures like bednets,
impregnated bednets, use of repellents and
gauze screening of house, should be undertaken.
Only human or mixed dwellings should be
sprayed. The formula for calculation of insecticide requirement is given below:
Name of
insecticide
Preparation of
suspension
Area to be
covered
Dosage per
sqm
DDT 50% WP
BHC 50% WP
Malathion 25%
WP
Deltamethrin
2.5% WP
1 kg/10 liter
1.5 kg/10 liter
2.0 kg/10 liter
500 sqm
500 sqm
250 sqm
1 gm
200 mg
2.0 gm
400 gm/10 liter
500 sqm
20 mg
The district malaria officers should supervise the

spraying operations.
New problems are emerging as a result of resistance of mosquitoes to insecticides. The parasites
are becoming resistant to common inexpensive
drugs. There is increased breeding of parasite at
places where irrigation and other development
projects are being implemented and migration of
malaria infected population is faster and more
frequent.
Newer strategies such as biodegradable insecticides and impregnated nets shall be introduced,
depending upon availability and affordability.
vi. Information, education and communication activities regarding the mode of spread and
prevention of vector-borne diseases, require to be
carried out on a regular basis.
BIBLIOGRAPHY
1. Training Module for Medical Officers of Primary Health
Center. Part I: Directorate of National Malaria Eradication
Program, Ministry of Health, Govt. of India, 1996.
7.2.11.2 NATIONAL FILARIA CONTROL PROGRAM
BNS Walia
The scheme has an operational component managed by
the district malaria team and the PHC staff. The research
and training component is controlled by the Director,
National Institute of Communicable Disease. The
strategy of filaria control consists of:
Antilarval measures undertaken periodically.
Administration of chemotherapeutic agents for
eradication of parasites in the host.
207
7.2.12 NATIONAL AIDS AND STD

CONTROL PROGRAM
BNS Walia
The first few cases of AIDS were described in USA in
1983. In India, the first AIDS case was recorded in 1986.
The disease has spread rapidly since last 10 years. It is
feared that, if the same rate of spread continues, by 2000
AD, India might be home to 5 million of the infected
individuals.
In response to this grave challenge, the Government
of India established the National AIDS Control Program
in 1987, under the National AIDS Control Organization
(NACO) in the Ministry of Health, Government of India.
The National AIDS Committee (NAC) and a multisectoral committee under the chairmanship of the
Minister of Health and Family Welfare and the Secretary,
Health respectively coordinate the various activities of
the program.
Similar committees have been established in all states
in the form of empowered committees, state AIDS cells
and state technical advisory committees. The latter advises
on the technical aspects of program implementation. The
NACO has established a national HIV sentinel
surveillance system consisting of (i) surveillance of HIV
infection as indicated by serum positivity (ii) surveillance
of AIDS cases, showing clinical signs and symptoms.
Surveillance of cases suffering from AIDS is now the
responsibility of all medical institutions who refer
suspected cases to the hospitals for establishing the
diagnosis and refer them to the public health authorities. The surveillance reports are sent to the states every
month and to NACO for purposes of monitoring the
program of the AIDS. Disease control activities are targetted at the three main modes of spread, which include:
i. sexual activity with multiple partners.
ii. self injection of intravenous drugs by addicts.
iii. transfusion of HIV infected blood.
The first two components which constitute risk
behaviors are tackled by information, education and
communication strategies, using media campaigns and
personal contacts.
Counseling services are provided to those who have
already acquired HIV positive status or AIDS, so that
they receive proper care and do not continue spreading
the disease. Since other sexually transmissible diseases
208
are also spread by the same behavior which leads to

spread of HIV infection; and presence of STD in an
individual increases the risk of his/her acquiring HIV
infection manifold, all the STD clinics in the country have
thus been strengthened. The diagnosis and treatment of
STD based on syndromic approach is being introduced
at PHC level. The AIDS control cell is conducting training
programs for paramedical workers and general practitioners, in order to enhance their capability for effective
STD diagnosis and treatment and for counseling.
An important component of the program is, making
available good quality condoms at reasonable prices.
HIV infected blood, causes about one-tenth of all HIV
infections in developing countries. These are totally
preventable. Encouragement of voluntary blood donation, total stoppage of sale of blood, testing of blood for
syphilis, HIV, hepatitis B and C and malaria have been
made mandatory for all blood banks. Test kits for these
infections are supplied by NACO to the blood banks.
Licensing of all blood banks in the country by the Drug
Controller, Govt. of India has been enforced. State blood
transfusion councils have been set up in all states of the
union, to supervise safe blood transfusion programs.
Numerous international donor agencies are involved
in providing financial resources, test materials and
technical know-how for the program. Non-governmental voluntary organizations are playing an important role
in the prevention and control activities initiated by
NACO.
Zonal blood testing centers have been established all
over the country, these centers receive blood samples from
affiliated blood banks and after testing samples for HIV
communicate the results to the blood banks. HIV positive
blood is discarded. Central assistance of money and
equipment is being given to states to upgrade blood bank
services. Teaching facilities for short-term training in
blood banking techniques and for training programs
leading to MD degree in blood transfusion, immunohematology are being established. 31 blood component
separation units are being set up in the country, in blood
banks which process more than 10000 units of blood
annually.
The entire program is monitored by officials
belonging to NACO by periodic visits to zonal blood
testing centers and district blood banks.
BIBLIOGRAPHY
1.
National AIDS Control Program, India, Country

Scenerio, An Update, Document prepared by NACO,
Ministry of Health and Family Welfare, 1994.
7.2.13 NUTRITION PROGRAMS

Shashi N Vani
Malnutrition is a multifaceted problem. Pregnant and
lactating women and children are at a higher risk for
undernutrition. Economically weaker sections of the
society, i.e. the rural, tribal and urban slums, are worst
affected by malnutrition.
A number of surveys and research studies have
recorded a high incidence of diet related deficiency
diseases. Common diseases due to undernutrition in
community are as follows:
Protein energy malnutrition
Nutritional anemia
Nutritional blindness
Iodine deficiency disorders (IDD)
Other disorders due to deficiency of B group vitamins
and trace elements are also not uncommon.
It is established that nutrition, immunity and infection are inter-related. Malnutrition alters immunocompetence and thus increases the risk of infection while
repeated infections tend to precipitate malnutrition,
particularly in those cases, when the nutrient intake is
marginally inadequate.
The problem of protein energy malnutrition is being
managed with the help of the following programs which
provide supplementary calories and proteins to the
beneficiaries.
Special Nutrition Program (SNP)
The main features of this program are as follows:
Children below 6 years of age are to be provided with
300 calories and 10 grams of proteins per child per
day.
Expectant and nursing mothers shall receive 500
calories and 20 grams of proteins, and severely
malnourished children 600 calories and 20 grams of
proteins, respectively.
Supply of vitamin A, iron and folic acid (IFA) tablets
in the last trimester of pregnancy.
Nowadays majority of beneficiaries have been
transferred to ICDS.
Integrated Child Development Services (ICDS) is one
of the largest supplementary nutritional programs of the
world for children less than 6 years age group and
pregnant and lactating women. Details of ICDS are
discussed later on.
Other major nutritional programs are:
Wheat-based supplementary nutrition program
(WNP)
Tamil Nadu Integrated Nutrition Project (TINP)
similar in concept to ICDS.
World Food Program (WFP)
Mid-day Meals Program (MDM)
7.2.14 MID-DAY MEAL PROGRAM

HPS Sachdev
The Midday Meal Program (MDMP), also known as the
Noon meal program, was started in 196263. Recently,
in 1995, the Government of India modified this country
wide program of nutrition support to children in primary
schools (Classes I to V).
The stated objective of the modified MDMP are:
(i) To raise the nutritional status of primary school
children, particularly those belonging to low socioeconomic groups; (ii) To improve attendance and
enrolment in schools, (iii) To prevent dropouts from
primary school. The beneficiaries of this program are
children attending primary school (6 to 11 years of age).
Children belonging to backward classes, scheduled caste
and scheduled tribe families are given priority.
The MDMP was started initially as a centrally sponsored scheme of the Government of India. However,
presently it is implemented by the State Governments
and central assistance is provided. To begin with
Employment Assurance Scheme (EAS) blocks with low
female literacy rates were included and all the districts
with District Primary Education Program (DPEP) were
given priority for implementation of scheme. One of the
school teachers on a primary school is designated as the
Organizer and is given responsibility for the implementation of the scheme.
Under the present program, the nutritional support
could be either in the form of provision of a hot meal, of
which the food grain components is 100g per child per
day for 200 school days or equivalent precooked food or
through the supply of 5 kg of wheat/rice per month per
child in a family for 10 months. The beneficiary, to be
eligible, has to attend school for 20 days in a month. The
supplementary nutrition given to each beneficiary
provides 300 calories and 8 to 12 g protein/day.
Only one or two studies have shown that the scheme
has resulted in some nutritional improvement of
beneficiaries. However, no significant improvement in
school enrolment/attendance had been documented.
209
The major bottlenecks in implementation of scheme

include frequent interruptions in the supply of raw
materials, low budget allocation per beneficiary, lack of
effective monitoring and supervision, resulting in
pilferage in the channels of distribution and wrong
identification of beneficiaries. It is also possible that
adequate amount of food offered is denied at home to
children, who receive nutrition supplements at school.
BIBLIOGRAPHY
1.
Kapil U, Bhanthi T, Nayar D: Nutrition Intervention

Programs for Promotion of Mother and Child Health in
India. Indian Practitioner 1996;1:2744.
2. Schemes of the Department of Women and Child
Development. A Synopsis. Department of Women and
Child Development, Ministry of Human Resource
Development, Government of India 1991;267.
7.2.15 ANEMIA CONTROL PROGRAM

Shashi N Vani
Poor absorption of iron from cereal diets, low iron
intakes, and hookworm infestations are the important
causes of high incidence of anemia in children and to
some extent in pregnant, lactating women. Anemia due
to iron and folic acid deficiency is known to affect up to
50 percent of Indian women in the low income group in
the second half of pregnancy, 40 to 60 percent of
preschoolers and 25 to 30 percent of women in child
bearing age. Nearly 10 percent of maternal deaths in
India are attributable to anemia.
National Nutritional Anemia Control Program
(NNACP) covers pregnant women, nursing mothers,
women acceptors to terminal methods and IUD. Target
is to cover 50 percent of total pregnant/lactating category
of women and 25 percent acceptors of terminal methods
and IUD.
Fifty percent children in age group of one to five years
have also been included in the program.
Recommended daily dose of iron and folic acid (IFA)
tablets is as follows:
Adult women: 60 mg elemental iron (equivalent to 180
mg ferrous sulfate) + 0.5 mg folic acid.
Children: 20 mg elemental iron (equivalent to 60 mg
ferrous sulfate) + 0.1 mg folic acid.
210
If the preschool children cannot swallow the tablets,

2 ml liquid should be given. Antianemia drugs are
inexpensive and distribution logistics are simpler. Iron
plus folic acid tablets should be advised for regular daily
dose, during the last trimester of pregnancy. Nausea may
occur as side effect in some cases. Two tablets/day for
three months is the normal dose given to the mothers.
Supplementation of folic acid to iron preparations
increases the birth weight of infants by 100 to 200 gm.
7.2.16 CONTROL OF VITAMIN-A

DEFICIENCY
BNS Walia
Deficiency of vitamin-A in diet can present as night
blindness, xerosis or keratomalacia, leading to loss of
sight in one or both the eyes. Vitamin-A deficiency is
reported to cause 10 percent of the cases of blindness in
India. The goal of the program was to prevent vitaminA associated blindness by the year 2000 AD. However,
it is clear that we have not achieved it.
Strategy
Since vitamin-A is capable of being stored in the liver,
from where it is released into the plasma, it is possible to
build-up stores of vitamin-A in the liver by administering
a dose of 200,000 IU of the vitamin at 6 monthly intervals.
All children between the ages of 9 months of 3 years are
administered 2 ml of vitamin-A concentrate, by
paramedical workers in the rural and slum communities,
either when they visit the health facility or at home
during the multipurpose workers home visit. Other
measures which prevent vitamin-A deficiency are:
a. Promotion of breastfeeding and feeding of colostrum.
b. Encourage the intake of green leafy vegetable and
yellow colored fruits.
c. Increase of coverage with measles vaccine, as an
attack of measles depletes vitamin-A stores.
Special attention is given to the program in areas
where some cases of xerosis or night blindness have been
detected, in areas of country with famine conditions and
during measles outbreaks. Children suffering from
cholestatic jaundice are also more liable to develop
keratomalacia. Mothers should be encouraged to
improve food intake of their children during illness and
for a few weeks after recovery.
7.2.17 NATIONAL IODINE DEFICIENCY

DISORDERS CONTROL PROGRAM
N Kochupillai
The National Goiter Control Program (NGCP) was
initiated in the sixties. The program then had the objective of surveying goiter prone regions of the country for
prevalence of endemic goiter and initiating iodation of
salt, in areas found to be endemic for goiter.
Kochupillai et al using a filter paper, cord blood spot
based strategy, showed strikingly high incidence of
neonatal chemical hypothyroidism (NCH) of 100 per
thousand births (10%) in the Tarai districts of UP. Further
studies revealed, high prevalence of cretinous and
subcretinous levels of developmental damage to the brain
of children in these regions. These findings made the
government include salt iodation in the 20 point program
of the Prime Minister in 1984. Compulsory iodation of
edible salt was introduced in UP in 1987, which resulted
in remarkable decline in incidence of NCH after
successful salt iodation in UP. Subsequent studies
conducted under the aegies of ICMR in 14 randomly
selected districts of the country, showed that endemic
goiter was widely distributed in the whole of the country
and not restricted to the Himalayan belt. Thereupon, the
Central Council for Health, approved a national policy
of universal iodation of edible salt all over India, to
eradicate nutritional iodine deficiency and related mental
retardation in the country.
The IDD control program has three components:
1. Initial survey to identify endemic areas.
2. Supply of iodized salt to the identified areas.
3. Resurvey after 5 years of continuous supply of
iodized salt to assess impact of the measures.
The district administration has been given the
responsibility of advocacy, policy implementation and
monitoring. A goiter control cell in the Salt Commissioners organization monitors the operations of
production of iodized salt, its quality and distribution.
BIBLIOGRAPHY
1.
Epidemiological survey of endemic goiter and endemic

cretinism. An ICMR TOSA force study. ICMR Publication
1989.
2. Kochupillai N, Godbole MM, Pandav CS, Karmarkar
MG, Ahuja MMS. Int Jr Med Res 1984;80:29399.
3. Kochupillai N, Pandav CS, Godbole MM, Mehta M,
Ahuja MMS: Bull WHO 1986;64:54751.
7.2.18 NATIONAL SCHOOL HEALTH

PROGRAM
211
7.2.21 NATIONAL PROGRAM FOR

CONTROL OF BLINDNESS
BNS Walia
BNS Walia
A beginning was made on this program in 1996 by

undertaking examination of school pupils, by camp
approach during 3 days on two consecutive months every
year. Doctors, dentists, teachers and paramedical workers
from the state health services were deployed for the
purpose. Students requiring specific interventions were
referred to nearby dispensaries/hospitals for treatment.
The program could be made more efficient by better
record keeping, and follow-up; by local area health
workers to ensure that the diseases/disabilities detected
during school health examinations, receive due medical
attention.
The first organized efforts to control blindness at national

level commenced with the launching of National
Program for Trachoma Control (NPTC) in 1963. A
meeting of Central Council of Health and Family Welfare
held in 1975 resolved that one of the basic human rights
was the right to see and therefore, it had to be ensured
that no citizen goes blind. Following this the NPTC was
renamed as the National Program for Prevention of
Visual Impairment and Control of Blindness in 1976.
7.2.19 NATIONAL CANCER CONTROL

PROGRAM
BNS Walia
This program was initiated in 1985, with the main
objectives of:
Prevention of tobacco related cancer.
Prevention of cancer of uterine cervix.
Strengthening of diagnostic and treatment equipment
for cancer at medical colleges and major hospitals.
Many regional cancer hospitals have been opened.
IEC activities emphasize on avoiding the chewing of
tobacco, pan masala and, self-palpation of breasts and
reporting to nearest dispensary for examination, in case
of symptoms referable to reproductive tract.
7.2.20 NATIONAL MENTAL HEALTH

PROGRAM (NMHP)
BNS Walia
It was launched during the 7th five-year plan, with a
small financial outlay. Not much was accomplished. The
objective of program included:
Provision of mental health services at district level.
Improvement of facilities in mental hospitals.
Training of trainers of PHC personnel in mental
health.
Program for substance use disorders.
Objectives of the Program

The strategy evolved for prevention of control of
blindness included:
Dissemination of information about eye care.
Augmentation of ophthalmic services so that eye care
is promptly availed off.
Establishment of a permanent infrastructure of
community oriented eye health care.
Management
National Blindness Control Program is cent percent
centrally sponsored program. Organizational structure
of the National Program consists of:
i. National Program Management Cell.
ii. State Program Cells.
iii. District Blindness Control Society looking after the
work in district exists in few districts at present
but is expected to be set up in all districts.
The National level cell is managed by the Directorate
General of Health Services, Ministry of Health and
Family Welfare. It was two divisions. The Technical
Division is headed by Deputy Director General (DDG)
and the Administrative division is headed by an
Additional Secretary level officer. At the State level, State
Program Officer is supervised by the State Director of
Health Services under the overall charge of the State
Health Secretary.
The State Central Mobile Units allocated to
Ophthalmology Departments of Medical Colleges, report
to the Director of Medical Education. The training of
paramedical ophthalmic assistants is carried out in
designated medical colleges.
212
The District Blindness Control Society is formed

as per society registration act. It is headed by the
Dy. Commissioner. It coordinates the work of blindness
control in the district.
Achievements
At the tertiary level, regional institutes of ophthalmology and the apex institute, i.e. Dr RP Center for
Ophthalmic Sciences, at New Delhi, have been established. Many medical colleges have been upgraded and
designated as training centers for paramedical
ophthalmic assistants. Eye banks have been set up in
government and nongovernmental sector.
At secondary level, district hospitals have been equipped for ophthalmic services by providing ophthalmic
equipment and manpower. District Blindness Control

Societies have successfully implemented projects in the
pilot districts, in which they had set up.
At the primary level, the services are provided by
the primary health centers equipped with ophthalmic
equipment and posting of paramedical ophthalmic
assistants.
There has been a sustained rise in the cataract
operations and IOL implantation.
Resources
The program has been receiving assistance from Danish
International Development Agency (DANIDA), the
World Bank and the Overseas Development Administration of UK.
7.3 Community Newborn Care

Shashi N Vani
IMPORTANCE OF NEWBORN CARE IN INDIA
The Infant Mortality Rate is a sensitive indicator of socio
economic development of a country. IMR has two distinct
components viz. the neonatal mortality (deaths during
first month of life) and postneonatal mortality (deaths
from 1 month up to 12 months of life). Most of the decline
in IMR has been due to reduction in the postneonatal
mortality. This has been possible because of success of
programs like Universal Immunization Program, control
of deaths due to diarrhoeal diseases and acute respiratory
infections (pneumonia). After impressive reductions in
1970 and 80s, the decline in IMR has not been very
noticeable. This is a cause for concern. For further
reduction in IMR measures to reduce neonatal mortality
must be undertaken in a big way.
India faces the biggest newborn health challenge
of any country in the world.
Of the total global burden, India has:
20% of total births
30% of total neonatal deaths
40% of still births
40% of low birth weight infants
25 of maternal deaths
This is the highest for any country in the world.
In India, 260 lakh babies are born every year of which
12 lakhs die within first four weeks of life. It is estimated

that one newborn dies every two minutes in India. Of
the total births in India about 30% are low birth weight
babies. Amongst the low birth weight babies in India,
2/ are full term but small for date babies, majority of
3
whom can be saved by simple measures. Remaining 1/3
are preterm babies and many of whom will need special
and intensive care.
ESSENTIAL NEWBORN CARE AND
NATIONAL HEALTH PROGRAMS OF INDIA
Newborn health was recognized as priority in the early
1990s. For the first time in India, it was introduced in the
National health program as a part of CSSM (Safe
Motherhood and Child Survival) program in 1992 at the
conclusion of UIP (Universal Immunization Program).
It was continued as a part of RCH (Reproductive and
Child Health) program. Since 1997, Government of India
has also incorporated Newborn care into Indias
adaptation of Integrated Management of Childhood
Illnesses (IMNCI training program) which devoted 50%
of overall training time to the care of newborn and young
infants. Its implementation strategy incorporates home
visits for preventive and promotive newborn care by
AWWs and ANMs. Neonatal health is recognized as the
key to child survival in the RCH program phase II (2005
to 2010).
Through RCH II and IMNCI a lot of efforts are being
made to improve newborn care at community level along
with the care at institution level.
SPECIAL ISSUES OF NEWBORN HEALTH IN INDIA
Majority of newborns are delivered at home and often
by untrained traditional birth attendants (> 60%).
There is wide state to state variation in neonatal
mortality rates and the related parameters. Kerala has
NMR as low as 10 whereas Orissa has NMR of around
70.
There are many other inequalities also in terms of
Urban Rural mortality rates, rich and poor mortality
rates, facilities available for the newborn care in terms
of quality and quantity, rate of institutional deliveries
and availability of skilled and properly equipped
attendants at the time of birth.
Incidence of Low Birth Weight babies is very high in
India. Low birth weight babies constitute 75% of
neonatal mortality and 50% of total infant mortality.
A lot of traditional and cultural practices of newborn
care are prevalent in our country influencing neonatal
survival in several aspects (beneficial, harmful as well
as harmless practices).
Within the neonatal period, 2/3 of deaths occur
during the first week of life, especially in first hour
and day of life.
Leading cause of neonatal mortality are sepsis
(bacterial infections causing septicemia, pneumonia
and meningitis), births asphyxia and prematurity.
First week deaths are mostly caused by asphyxia and
prematurity. Thereafter sepsis is the leading cause.
Other important adverse factors contributing to poor
neonatal outcome include poor nutrition and health
status of mothers and the future mothers (girl child
and adolescent girls) and lack of proper care during
pregnancy, childbirth and thereafter.
LEVEL OF NEWBORN CARE
Basic Care (Level I)
Almost 80 to 85% of neonates in our community require
only simple basic care which includes clean and safe
delivery by a skilled and properly equipped birth
attendant, basic resuscitation including drying,
213
positioning, suction of mouth and nose if secretions are

present and even use of bag and mask for positive
pressure ventilation, measures to provide adequate
warmth and maintain warm chain, early and exclusive
breast feeding for first six months of life, infection
prevention measures like strict hand washing before
handling the neonate, aspective cord care, eye care, etc.
and management of minor problems. All these are
included in essential newborn care. This level of care can
be offered in health care facility including PHC, CHC,
FRU and other hospitals and also at home. All the
functionaries with proper orientation and simple skills can
offer this level of care. Mothers can also offer this level of
care with the support from AWWs and ANMs of their area.
Special Care (Level II)
About 10 to 12% of newborns require special care in the
form of oxygen therapy, advanced neonatal resuscitation
including endotracheal intubation, intravenous fluids,
medications including antibiotics, phototherapy,
exchange transfusion, close supervision and monitoring
in a hospital. Such care is possible in district level
hospitals as well as medical college hospitals and private
centres of pediatricians. These level II are centers are
necessary to take care of majority of referrals from level I.
Intensive Care (Level III)
Only about 3 to 5% of newborns require highly sophisticated, technology dependant intensive care including
continuous electronic monitoring, mechanical ventilation, arterial blood gases and such investigative facilities.
Specially trained neonatologists and nurses offer such
care in selected centers.
SOME SPECIAL ASPECTS OF COMMUNITY
NEWBORN CARE IN INDIA
The Problem of Low Birth Weight Babies
Irrespective of primary causes of deaths, over 2/3 of
neonatal deaths occur among babies born with birth
weight < 2500 grams, i.e. LBW babies. As mentioned
earlier incidence of LBW babies in India is the highest in
the world. There are several sociocultural reasons apart
from medical reasons for such high incidence of LBW
babies. They include poor nutritional status of women
in general and pregnant and lactating mothers in
particular, hypertension, anemia, malaria, other chronic
214
infections like tuberculosis, tobacco abuse, poverty,

illiteracy, pregnancy at a very young age, short inter
pregnancy intervals poor antenatal care, lack of rest, etc.
All these need to be addressed in the programs related
to care of newborn in community.
A few simple interventions are very useful for the
care of LBW infants in resource constraint areas.
Kangaroo Mother Care (KMC) is one such important
method. Stabilized Low Birth Weight babies are
undressed fully except diapers, cap, socks and mittens
and put directly with their abdomen on mothers chest
so that direct skin to skin contact is achieved. The baby
gets adequate warmth from mother and also has better
weight gain because of augmented breast feeding. Baby
feels much secure and has steady heart rate and
respirations. Incidence of acquired infections, hypoglycemia and apneic attacks is much less. Thus KMC has
several advantages and is a comprehensive method of
care of LBW babies in community. With some training,
community health workers have found it very useful for
the care of weak, low birth weight babies. KMC has been
found useful in the care of very sick babies in intensive
care set up in developed countries also. Other family
members can also support the mother in giving KMC to
baby. Through RCH and IMNCI program KMC training
has been taken up in a big way and is being easily
accepted by mothers, family members as well as
community workers.
Feeding Low Birth Weight Babies with
Expressed Breast Milk from Mother
This is another simple and useful modality of rearing
these weak babies in our community. This training is
also given to the community workers. In summary, care
of the newborn in community is gradually gaining its
due importance in national health programs like RCH
phase II and IMNCI in our country. The main objective
is to achieve NMR of < 20 by the year 2010 as against
the current national average level of 38 and help achieve
IMR < 30 by year 2010, the Millennium Development
Goal.
It is proposed to improve the knowledge and skills
of all the levels of health care functionaries involved in
newborn care in our country and also to achieve change
in behavior and practices of the community members
for better standards of newborn care.
THRUST AREAS IN NATIONAL PROGRAMS

Care of the Girl Child
Improve nutrition
Vaccinations
Education
Respect in the family without any gender discrimination
Discourage selective female feticide and even neglect
of the girl child and infanticide.
Care of the Adolescent Girls
Improve nutrition
Prevention and control of anemia
Attention to personal hygiene
No early marriages, i.e. before the age of 18 years
No motherhood before the age of 21 years.
Care during Pregnancy

Good nutrition throughout pregnancy
Early registration of pregnancy
Regular ante natal check up, minimum of three (one
check up in each trimester) can be more also
Prophylaxis for anemia and tetanus
Detection of high risk and at risk pregnancies and
early start of management
Preparing for institutional deliveries/skilled birth
attendant well in advance
Birth preparedness with needed delivery kits, clean
linen, money, arrangement for vehicles for traveling
to hospitals in emergencies, prior information
regarding nearby referral hospitals.
Care during Delivery
Prefer institutional deliveries
One independent skilled attendant to take care of the
newborn immediately after birth
Adopt five cleans at the time of delivery (clean hands,
clean surface, clean tie, clean cut and clean cord)
Prompt resuscitation of the baby whenever required
Early skin to skin contact and warm chain maintenance. Avoid early bath to baby
Start breast feeding as early as possible preferably
within an hour of birth
To take all the measures to prevent infections
including thorough hand washing and handling the
baby
Examination of the baby and detection of congenital
defects requiring immediate attention
Detection of high risk cases and primary management
and safe transferal when required to a higher center
of newborn care.
215
cyanosis, pallor, umbilical infections, pustules

conjunctivitis, loose stools, etc.
Suitable primary care
Safe transferal when required to higher centers
Vaccinations: BCG, zero dose oral polio vaccine and
wherever available Hepatitis B.
Care during Postnatal Period
Warmth
Proper breast feeding with correct technique
Prevention of infections
Early detection of danger signals like refusal to take
feeds, not doing well, cold to touch, abnormal look
and behavior suggesting convulsions, jaundice,
Care during Follow up

Exclusive breast feeding for first six months
Routing vaccinations as per national immunization
schedule
Growth monitoring
Neuro developmental and neuro sensory assessment.
7.4 Under Five Clinics

Ajit Kumar
One of the most encouraging signs of out times is the
awakening of the public to the needs and rights of
children. The year 1959 ushered in a new era in child
welfare. To meet the special needs of the child, United
Nations adopted on 20th November 1959, the
Declaration of the Rights of Children, the Government
of India adopted a National Policy for children in August
1974. The policy declares that:
It shall be the aim of the state to provide adequate
services to children, both before and after birth and
through the period of growth, to ensure their full physical
mental and social development. These shall progressively
increase the scope of such services so that, within a
reasonable time all the children in the country enjoy
optimum conditions for their balanced growth.
Under five mortality is an important indicator of the
quality of health care. The under five mortality rate has
reduced from 109.3 to 94.9 per 1000 live births. Similarly,
the neonatal mortality rate for India has declined from
48.6 to 43.1 per 1000 live births and the infant mortality
rate has declined from 78.5 to 70 per 1000 lives
births.However, the national goal of decreasing the infant
mortality rate to 60 per 1000 live births still remains to
be achieved. Hence, the importance of schemes like
Under Five Clinics in both the rural and urban areasmore so, in the slums of the urban areas.
Children between 0-4 years constitute about 12.6

percent of the total population. Mortality in the age group
of 1 to 4 years is about 1 percent, the major causes being
preventable diseases like malnutrition, diarrhea,
dehydration, infectious diseases (like dephtheria,
measles, tuberculosis, pertussis, tetanus and polio) and
infestations.
For child growth care and development in the age
group of 0-5 years various strategies have been used,
singly or in combination for the betterment of their
health, nutritional status, psychological development and
also their education. A countrys future human resources
development is determined on the basis of the development indices like infant mortality, morbidity, prevalence
of disability, living conditions and education of children,
especially the under fives.
WHAT ARE UNDER FIVE CLINICS?
Ensuring child health is an investment for the future. It
embraces various aspects of comprehensive child care
with emphasis on preventive, social and cultural aspects
of child life. Total child care in its own environment is
the concept of under five clinics. These clinics offer
curative, preventive and promotive health services
within the resources available involving nonprofessional
auxilaries, paramedical personnel, undergraduates,
216
postgraduates. It is economical and reaches large number

of children in the community.
Under five clinics focus on the downward extension
of its services ot under five children and emphasizes early
identification of developmental delay in infants below
two years by Anganwaadi workers and organize
interventional programs by trained PHC medical staff.
The Under Five Clinic and ICDS programs are for the
people and by the people with the existing staff-both
medical and paramedical.
AIMS, OBJECTIVES AND SERVICES IN
UNDER FIVE CLINICS
Preventive Care
1.
2.
3.
4.
5.
6.
7.
Immunization to cover 7 major preventable diseases

Nutritional services
Health care and treatment of illness
Oral rehydration in diarrheal and dehydration
Family planningadvocating small family size
Growth monitoringroad to health cards
Health education and guidance.
Curative Services
Early diagnosis and treatment of acute and chronic
diseases and disorders of growth and development and
minor investigations.
Referral Services
Early detection and referral to a hospital.
The services in Under Five Clinics are rendered by
the PHC health team. The aim is that the clinics should
be self generating, utilizing local resources. Clinics should
be run at minimum expenses. The main brunt of the
clinics in on ANM and the multipurpose workers in the
PHC.
WEEKLY UNDER FIVE CLINICS
Every child between 0-5 years in the area is registered
and given a weight card. Children have to be registered,
weighted, examined by a doctor, immunized nutrition
advice given and supplementary nutrition given.
Children are referred to the hospital whenever required.
IMMUNIZATION
This is to prevent and protect vulnerable children from
common preventable diseases like tuberculosis,
diphtheria, pertussis, tetanus, polio, hepatitis and

measles. Immunization schedule as recommended by
Indian Academy of Pediatrics should be followed.
NUTRITIONAL SERVICES
Nutrition is one of the major problems in developing
countries. Most of the children in pre-school age group
suffer from Protein Calorie Malnutritionmore of caloric
deficiency than protein. It was founded by ICMR that
on an average, a preschooler lacks about 300 calories a
day. This is not only due to poverty but also due to
ignorance, local beliefs, customs and taboos. It is essential
to educate the community in using locally available cheap
vegetable protein in their diets. A protein packet formula
was devised by National Institute of Nutrition to meet
the needs of the children. These protein packets contain:
1. Bengal gram or any cereal
2. Wheat or jawar
3. Groundnut or any pulses
4. Sugar or any pulses
It weights 70 grams and gives about 300 calories. The
inclusion of these locally available vegetable proteins
brings down the cost. The most important aspect of these
packets is that they not only cure mild to moderate cases
of PCM but also serve as a practical method of nutrition
education to the mothers in the community. ANM plays
a major role in nutrition education. Anemia, PCM, rickets,
Vitamin A deficiency and nutritional blindness are
common in the age group, hence can be corrected in
Under Five Clinics. Vitamin A can be given as prophylaxis. Health Checkups help in identifying at risk
children.
ORAL REHYDRATION
In developing countries a preschooler has at least 2 to 6
episodes of diarrhea in a year. Every episode leads to
dehydration and lowering of nutritional levels. The ANM
can teach the benefit of oral rehydration which helps in
the reduction of deaths due to dehydration.
FAMILY PLANNING
About 60 percent of malnutrition can be wiped out if the
family number is restricted to 2 children with a gap of
three years in successive pregnancies. This can be
impressed to the mother in the Under Five Clinics. It is
important to gain the confidence of the mothers for infant
survial if we have to embark on successful family
planning at a larger scale.
HEALTH EDUCATION
It is the involvement of mothers in all programs of the
Under Five Clinics that can help in better upbringing of
children with regard to prevention, early diagnosis,
treatment of malnutrition, correction of dehydration by
ORS, vitamin A supplementation and immunization to
protect children under the ages of five from the seven
most common and preventable diseases.
GROWTH MONITORING
Use of growth charts road to health cards help in
identifying diseases in early stages, status of the child
regarding immunization, growth and nutritional levels.
Weight should be checked at monthly intervals during
first year, every two months during the second year and
every three months thereafter upto the age of 5 6 years.
The growth curve helps in early diagnosis of growth
failure and its etiology.
ENVIRONMENTAL SANITATION
Environmetal sanitation goes with the overall development of the community which is important in total child
care. Good roads, clean drinking water, closed drainage
helps in proper growth of the child. Poverty,
substandard housing, overcrowding, inadequate water
sanitation and sewage disposal facilities and related
environmental risks and insecurity characteristic of a
slum has a great impact on the survival and quality of
life of the urban poor children especially below the five
years group. The lack of safe water and sanitation
facilities increases the risk of intestinal infections and
parasitic diseases among children under five. Acute
respiratory infections, gastroenteritis measles, PCM and
malaria are the five major causes of 70 percent of under
five mortality.
217
ROLE OF UNDERGRADUATES IN
UNDER FIVE CLINICS
The doctor should be aware of the morbidity pattern and
local problems of children in a country. Medical students
should be exposed and made aware of the local disease
pattern to help in early diagnosis, referral and management. Undergraduates can play a major role in the proper
upbringing and health education programs, immunization programmes and also ones related to personal
hygiene, deworming, vitamin a prophylaxis and
maintaining road to health charts. Undergraduates
during their posting in social and preventive medicine
and pediatrics should be exposed to various preventive
pediatric programs. The undergraduates can help in the
early diagnosis of malnutrition, dehydration and in
educating the mothers in the use of locally available
vegetable proteins, use of oral rehydration, supplementary nutrition, and importance of immunization and
monitoring of growth of the child.
CONCLUSION
Under five clinics can run within the existing resources
and hence should be established in all the PHC centers
in the country to bring down the high mortality and
morbidity in children. This indirectly helps in the
successful implementation of family planning programs
in our country as a security of the surviving children is a
prerequisite for smaller sized families.
BIBLIOGRAPHY
1. Health Care of Children, Under Five Voluntary Health
Association of India: New Delhi.
2. Mathur YC, Reddy YR. Social Pediatrics in Hyderabad.
The Bombay Hospital Journal 1973;15:55-57.
3. Mathur YC. Experience with weight charts at primary
health centers. Indian Pediatrics 1975;12:101.
4. Mathur YC. Under Five Clinics-Institute of Child Health.
Indian Pediatrics 1975;12.
5. National Family Health Survey-3, 2005-2006.
6. The State of the World Children 2008, UNICEF.
218
7.5 The Girl Child

Shanti Ghosh
Sex ratio is a good indicator of the status of girls and
women in a society. According to the census of India
2001, the sex ratio stands at 933, which is an improvement over the figure of 927 in the 1991 census. The
country has witnessed an overall reduction in the sex
ratio from 972 in 1901 to 933 in 2001. There are considerable variations in the male to female ratio from one
state to another. Kerala has a sex ratio of 1058, the highest
in India. Changes in sex ratio in major states are
summarized in Table 7.5.1.
TABLE 7.5.1: Changes in sex ratio in states

year
Uttar Pradesh
Bihar
1991
2001
938
898
1061
921
Andhra Pradesh
985
978
Madhya Pradesh
972
920
Maharashtra
978
922
West Bengal
945
934
Tamil Nadu
1044
986
Rajasthan
905
922
Karnataka
983
964
Orissa
1037
972
Jharkhand
1032
941
Punjab
832
874
Gujarat
954
921
Kerala
1004
1058
Assam
919
932
Haryana
Uttaranchal
Chhattisgarh
867
936
985
861
964
990
Earlier data not available as the states were created only

recently.
Of the 18 states mentioned above, sex ratio has

deteriorated in 12 states. The maximum improvement is
in Kerala (1036 in 1991) and in Uttar Pradesh (876 in
1991).
In 1994, the Central Government passed the Prenatal

Diagnostic Technique Regulation and Prevention of
Misuse Act. This is referred to as the PNDT Act. The law
has many loopholes. Government laboratories and clinics
are monitored much more closely than private laboratories and clinics. Genetics tests are monitored much
more closely than ultrasound tests. In spite of the ban
imposed by the PNDT Act, many doctors continue to
communicate the sex of the fetus to parents. The Act has
not had any impact on the spread of sex selective abortions and this has become a socially accepted practice.
During the 1980s sex selective abortions spread to the
rural areas. It is estimated that more than 100,000 sex
selective abortions are performed annually in India and
this may be an underestimate. This problem seems to be
more in Punjab, Haryana, Delhi and Maharashtra but is
prevalent in every part of India. Punjab has one of the
highest sex ratio at birth in the world. This may be related
to lack of womens autonomy. Women tend to have more
autonomy in the South than in the North of India. The
percentage of mothers undergoing ultrasound
examination or amniocentesis was 22 percent in Punjab,
19 percent in Haryana, 42 percent in Delhi and 31 percent
in Maharashtra. This again may be an underestimate as
there are no reliable records.
Sex selective abortion is a two-step process involving
an initial determination of sex of the fetus followed by
abortion if the fetus is a female. Hoardings (Invest Rs
500 now and save Rs 50,000 later), posters, and billboards
openly canvass for sex determination and abortion.
The percentage of mothers undergoing ultrasound
examination or amniocentesis was 22 percent in Punjab,
19 percent in Haryana, 42 percent in Delhi and 31 percent
in Maharashtra.
Punjab (874), Haryana (861) have the worst sex ratio
while Tamil Nadu (986), Chhattisgarh (990) and Kerala
(1058) are at the other end of the spectrum. The sex ratio
in the 0 to 6 age group, which was 945 in 1991, has
declined to 927 in 2001.
According to the 2001 census, there were 49 districts
where for every 1000 male children aged 0 to 6 years
there were less than 850 female children (Table 7.5.2).
TABLE 7.5.2: Sex ratio of population for all age groups and
for 0-6 years age group 19812001
1981
All
0-6
ages years
Year
1991
All
0-6
ages
years
2001
All
0-6
ages
years
TABLE 7.5.3: Estimated death rates for

children 0-4 years old
Total
Male
Female
India
22.5
21.0
24.1
Andhra Pradesh
18.1
17.8
18.4
Bihar
22.9
21.2
24.8
Gujarat
19.6
18.5
20.9
Haryana
22.4
19.4
26.2
All India
935
971
927
945
933
927
Himachal
Pradesh
973
971
976
951
970
897
Haryana
870
902
865
879
861
820
Punjab
879
908
882
875
874
793
Rajasthan
923
954
910
916
922
909
Gujarat
942
947
934
928
921
878
Punjab
16.8
15.9
17.9
Maharashtra
937
956
934
945
922
917
Rajasthan
27.7
27.3
33.8
Uttar Pradesh
29.6
25.3
34.5
A majority of these districts were located in Punjab,

Haryana and Gujarat.
In a recently completed study in Mehsana district in
Gujarat and Kurukshetra district in Haryana, it was
observed that the last births had a stronger preponderance of boys than all other births. Among the
women who belonged to upper castes, whose families
were landed and who were literate there were more than
246 males for every 100 girls in the last births. This was
obviously due to sex-selective abortions.
Infanticide too has been reported from some districts
in the past but there is no authentic report recently. One
reason for the declining sex ratio also appears to be the
paradox of development characterized by smaller family
size and culturally determined notions of sex preference.
A study conducted in Madhya Pradesh and Rajasthan
(Bhind and Morena district) revealed that out of a sex
ratio of 837 at birth, the sex ratio of existing children 0 to
6 years was 500.
Estimated death rates for children 0 to 4 years by sex
and residence according to sample registration scheme,
1998 are given in Table 7.5.3. Female rates are higher in
every state.
Mortality rates for females are higher from postneonatal period onwards (Table 7.5.4).
At birth, there is a feeling of being let down and
disappointment if the child is a girl. There are no beaming
relatives or friends. There is discrimination in various
waysfood, attention, new clothes, outings, etc.
Schooling is considered unnecessary for the girl as she is
supposed to occupy herself with household chores and
looking after the younger sibling. There is subtle
219
Himachal Pradesh
16.7
14.1
19.7
Madhya Pradesh
32.6
31.6
33.7
Maharashtra
12.7
11.2
14.3
Orissa
29.0
28.7
29.4
TABLE 7.5.4: Mortality rates (1998-1999)

Male
Female
Neonatal
50.7
44.6
Postneonatal
24.2
26.6
Infant
74.8
71.1
Child
74.8
71.1
Under 5 mortality
97.9
105.2
discrimination even among the well off families mainly

about the quality of education, access to higher education
and taking up a profession, etc. The aim is to get the girl
married as soon as possible. A large number of girls get
married before the legal age at marriage.
The menace of dowry has increased tremendously
often leading to disharmony, cruelty and even death.
Demands go on for years after marriage.
Historically it would seem natural for the Vedic
Aryans to have a son preference because a pastoral
society of warriors needed men for protection of the race
and survival in a new country, yet Vedic literature does
not bemoan the birth of a girl child. In fact, special
mantras exist in the Rig Veda, the recitation of which is
supposed to lead to the birth of a girl child who will grow
up to be a learned lady. The position of the girl child
seems to have deteriorated after the first millennia,
especially in the North Indian states due to a change in
political equations. Early marriage, low status in
220
marriage due to widespread polygamy and practice of

seclusion among upper class women became rampant.
Access to education was also limited. Though the
Constitution and a vast body of legislation has promoted
gender equality, the status of the girl child continues to
be low. One indication is the low sex ratio of women.
Even though literacy rates have increased substantially, there is a vast difference between male (75.85) and
female (54.16) literacy. Kerala (90%) and Mizoram (88%)
have the highest literacy rates for women. Neither
education nor affluence have brought about any
significant change in the attitude towards the value of
women. In 1998-99, only 53.3 percent boys and 34.2
percent girls completed lower primary education, while
figures for upper primary were 35.6 percent and 19.7
percent respectively.
There are innumerable reports of trafficking in girls

for sexual activities, prostitution, etc. The unscrupulous
men (even women) and parents are partners in this crime
for sake of a little money.
It is a tragedy indeed that in a country where
innumerable goddesses are worshipped, the life of a girl
child today seems to be on discount.
BIBLIOGRAPHY
1. Census of India 2001.
2. Ghosh S. The girl child. Indian Pediatr 1986,23:120-22.
3. Jejeebhoy SG. Womens autonomy in rural India: Its
dimensions, determinants and the influence of context
in fertility termination in South Asia. In Sathar ZA,
Phillips JF (Eds). Oxford, Oxford University Press, 2001.
4. Visaria L. Sex selective abortions in the States of Gujarat
and Haryana: Some Empirical Evidence. Health Watch
Trust, New Delhi, 2001.
7.6 Customs and Beliefs in Child Rearing

Anil Mokashi
INTRODUCTION
Custom is something people do and belief is What they
think. We Know why a child falls sick and what to do if
he falls sick. The mother is not likely to know it. She will
believe the disease is caused by different reason. So she
wants to treat him in a way that her custom says. Unless
we teach her the right way of treating him, she is bound
to follow a neighbors advice. It is important to know
what people think and do for illnesses. The disease
have colloquial names. Unless you know them, you can
not talk with the mother. So find out local names for the
diseases. Changing customs is more important as it
directly reflects on children. Changing beliefs is not so
important. Some customs are useful, some are harmful,
while some are harmless. We should encourage useful
customs; discourage harmful customs and allow
harmless ones. Here we will just enlist the customs. Every
community has its own customs and you will have to
prepare your own list while trying to change what the
mothers do.
Five groups of customs are particularly important for
the health of children.
1. pregnancy and childbirth: delivery, newborn, cord
and placenta.
2.
3.
4.
5.
Infant feeding
Diseases: causes and treatment
Child rearing
Womens health
PRIME MESSAGES
A. Encourage useful customs.
B. Allow harmless customs.
C. Discourage harmful customs.
EXPLANATION
A. Encourage Useful Customs
1. For first pregnancy and delivery the pregnant lady
goes to her mothers place where she gets adequate
diet, rest and attention.
2. Rooming in of a mother and baby in an isolated
room avoids neonatal infections and helps
developing the bond.
3. Honey and warm water is a natural way of relieving
neonatal constipation.
4. Breast feeding till he is two years old bridges the
food gap.
5. Soaked biscuits are used as a weaning food. Biscuits
are available in every small village, are ready to feed
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
and very much socially acceptable they are hygienic

too.
When a child gets cold. Muscus is sucked out from
nose using a dropper or a cotton wick.
Warm milk with tamaring to cure sore throat.
Household medicines like tulas, honey, ginger,
lemon for common cold are much safer and useful
than antihistaminic, antibiotic and steroid drugs.
Honey, ghee, groundnuts are fed to bring out
measles.
An abscess is fomented with warm cloth.
Burnt bread is fed for poisoning.
Hand washing before eating is hygienic.
Feet washing by adults before entering the house is
good for infants crawling over the floor.
Naming ceremony on 12th day helps the child
identify with his name and develop personality.
Celebrations of the naming ceremony are done in
6th month. It avoids handling, kissing by guests in
newborn period.
First food ceremony at the age of 6 months.
Oil Massage improves weight gain length, peripheral blood flow, induces postmassage sleep,
prevents skin infection.,
Wrapping the baby to keep warm has reduced the
morbidity and mortality. Babys linen should be soft
cotton material with good absorptive properties.
B. Allow Harmless Customs

1. Burning or burying a placenta.
2. Fallen stump of umbilical cord is preserved for
religious purpose.
3. A religious garland of wooden sticks for jaundice.
4. A garlic garland for cough and cold.
5. Ear drops for otitis media.
6. Goats milk eye drops for conjunctivitis.
7. Human milk eye drops for conjunctivitis.
8. Ears are pricked with a religious ceremony; to cure
neck glands.
9. Religious ear pricking in Hindus.
10. Religious nose pricking in girls.
11. Religious circumcision in Muslims.
12. To prevent or cure teething troubles a copper
plate dental band is worn around neck; herb
dikamali is applied over gums, homeopathic
tablets are used in nearly every household.
13. Owa Water is fed or an adult blow air on childs
abdomen after chewing owa (cumin seeds) to cure
abdominal colic.
221
14. Some (pimpli) herbs are boiled with milk to make

the milk more digestible.
15. To help the child with delayed speech development,
a guava, half eaten by a parrot is fed in a belief that
he will start talking like a parrot.
16. Milk is boiledin silver vessel with a golden ring in it
and fedas a brain tonic.
17. An abdominal binder for newborns is supposed to
protect their soft abdomen from distending.
18. The fifth female child in a row of females was named
Nakusa , meaning unwanted.
C. Discourage Harmful Customs
1. After birth the baby is in wet liquor, blood soaked
cloth, loosing heat, getting cold. It is wrong practice
to neglect her once she cries.
2. Child bathing soon after is a common practice,
leading to a significant drop in babys temperature.
After birth keep the baby at 28 to 30 degree room
temperature.
3. Newborn is given vigorous massage before bath. It
is unnecessary and may be harmful. Fractures are
reported.
4. A practice of fuming herbs over burning coal may
be harmful and invite respiratory irritation.
5. Fomenting a newborn with burning coal below his
bed in summer months is harmful.
6. Swollen breasts of a newborn are squeezed and
massaged to express the milk resulting in more
swelling and infection.
7. Umbilical cord is cut by using razor blade, Knife or
crush with stones. Ash, cowdung, blacksoil, woolen
tape is used as an applicant on the cord stump. All
these practices may lead to sepsis or tetanus.
8. Mother and baby are isolated in an ill-ventilated
darkroom.
9. Home delivery with the help of experienced lady
is a standard practice and hospital delivery is
considered as an expensive fad.
10. Oil is instilled in nose, ears, eyes, and anus in an
attempt to lubricate the machinery.
11. Kajal is rubbed in the eyes.
12. Very hot water is used for bathing the baby.
13. Colostrum is thrown considering it harmful.
14. First feed is not given till milk flows It starves the
child and delays milk secretion. The prelacteal feeds
with honey, sugar water glucose water is given.
There is no need.
222
15. Breast-feeding is discontinued if lactating mother

suffers from tuberculosis, typhoid or fever.
16. Night breast-feed is not allowed to prevent colic.
17. Undiluted milk is not given in first year as it is
supposed to cause liver disease and glands in
childs abdomen.
18. Milk is given in very dilute form to cure the infantile
constipation and to make it digestibel;resulting in
marasmus.
19. A whisky bottle or gripewater bottle with a dirty
nipple is used as a feeding bottle. It is most unhygienic thing put in infants mouth.
20. Whenever the feeding bottle is offered. Its nipple is
wiped with pallu of the sari the lady wears.
21. A poor mother of a marasmic child purchases the
costly milk powder tin in good faith to make her
child strong and gives it in a very dilute form so
that tin lasts till next months salary day.
22. Three hourly feeding schedule adjusting the child
according to clock. He should be fed on demand.
23. Many mothers give one breast at one feeding on
advice of elderly experienced relative.
24. First food ceremony at 10 months of age. It is too
later for weaning.
25. Mother stop breast feeding after 5-10 minutes in an
attempt to avoid sore nipples.
26. Child is not given food till he eats with his hands.
27. Removing muddus: Back of a marasmic child is
rubbed. The hair gets rolled with the dirt. When this
rolled hair is put in water it gets unwind and moves
in water. This is explained as removing of Muddus
a colloquial name for Rickets.
28. An abscess is covered with oil, beetle-nut leaf or
tamarind.
29. Teething is considered to cause many illnesses.
People do self mediation and overdose of
vitamin D, Doctors advice. Vitamin D when mother
asks for a medicine.
30. Self medication with dangerous drugs, Balguti and
lead poisoning.
31. Improper medication spoon. It should be a 5 ml
spoon.
32. Blind faith in injections.
33. Immunization is avoided for the fear of fever gland
at the site or getting polio.
34. Household things like saffron, cowdung, lime, ink
is applied on BCG scar.
35. Presuming at various sites for various illnesses are

caused by not able to digest the food, food is
withheld till the child is cured.
36. Branding at various sites for various illnesses is a
very popular custom. For convulsions they brand
on temples, breathlessness they brand on abdomen.
37. Blaming daughter-in-laws diet for neonatal
problems and restricting her food intake is a very
popular practice.
38. Breast milk is withheld when infant gets diarrhea.
Many doctors overdiagnose breast-milk intolerance.
39. Vomiting and watery loose motions are managed
by with-holding water.
40. Anterior fontanel is covered with oil and beetle-nut
leaf, diverting attention from oral fluids in a child
with dehydration.
41. Purgatives are used to cure diarrhea, in an attempt
to cleanse the bowel.
42. A child on IV fluids is kept nil by mouth may be
because in older days, doctors practiced nil by
mouth for 1-2 days.
43. A child with high fever is wrapped in wollens to
prevent cold.
44. A child with measles is customarily not taken to a
doctor. The complications remain unattended and
take their toll.
45. Society demands injections for suppressing or
bringing out measles. May be because many doctors
provide placebo injections on demand.
46. Typhoid and jaundice are the disease that attract
strict food restrictions from the society. It might be
sometimes difficult to overcome the resistance to eat
well eat small and eat frequent advice. A discussion
may bring out a long list of allowed food items
that are nutritious. We should encourage the
allowed list than to discourage not allowed list.
47. Hot foamentation is given to a child with measles
to bring measles out. He may get overheated,
dehydrated, even get skin burns in the process.
48. It is presumed that it is good for the child to have
measles. Many parents point out failures of measles
vaccine as reason for not giving it.
49. Oily and fatty food items are prohibited as they are
supposed to cause cough and many illnesses.
50. Religious ceremony with sacrifice of animals,
money, food to cure a sick child diverts the attention
from real problem. The belief and custom continues
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
as many self limiting diseases get cured giving a

credit to the ceremony.
Wounds including operation wounds are desperately protected form water as it is supposed to
cause sepsis in the wound. The custom is universal
including educated and rich class. Important of
washing the wounds with soap and water prevent
sepsis needs to be informed to the society.
An abscess is allowed to burst by itself or punctured
by a sewing needle. People are afraid of incision and
drainage. They do not want to spend money. They
want home cure for abscess.
Boils are squeezed to express pus.
The wounds are covered with dirty cloth bandages.
Society is found of bandaging. In children, bandages
get soaked and become dirty and are a source of
infection.
A plethora of things are applied on wounds as a
home remedy. The harmful things include ink,
cowdung, saffron, tea powder, cows urine, human
urine, wet soil.
Warm belladona strip (adhesive) is applied over an
abscess in an attempt to ripen it. It is supposed to
be all the treatment that is required.
Children, with primary complex are not allowed to
mix-up with normal children. Their feeding
utensils are Keptseparate. It is too much of the unnecessary psychological strain for the child.
Frequent change of doctors for a child with
tuberculosis is harmful, as there is likelihood of
irregular medication and frequent change of drugs.
A fractured limb is massaged by a quack.
Vomiting is induced to bring out swallowed
kerosene.
Religious healers are popular for the cure of a snake
bite, scorpion bite or dog bite with occassional
disastrous results.
Unconcious or convulsing child is offered water as
an emergency treatment.
Opening of a lockjaw during convulsions receiveds
top priority unnecessarily, leaving other important
steps uncared for.
Eyes with foreign body, conjunctivitis are cleaned
by experts with tongue!
Household medicines used as eye drops are
harmful. Kajal is harmful.
Hot oil is used as ear drops for questionable earache,
may lead to deafness.
223
67. Hairpin is the most commonly used instrument to

remove wax from ears.
68. Leeches are allowed to suck faulty blood from
edematous parts and enlarged spleen.
69. Edematous parts are branded with hot coins.
70. Seasonal fruits are blamed for causing seasonal
illnesses.
71. For child who is late is walking or has a limb paralysis, heavy silver or copper rings are used as
therapeutic ornaments.
72. Child is buried upto waist in waste-refuge to cure
pollomyelitis or paralysis.
73. In a sophisticated rich family an infant is wrapped
in clean, ironed long drawsheets in a neat bundle.
He looses the freedom and gets delayed physical
milestones as he is physically restrained from
developing!
74. Opium is used as a tranquilizer routinely, addicting
or killing him in the process.
75. Alcohol containing gripe-water is used as child
sleeps well!
76. Abdomen is massaged to cure his Colic
77. An infant who cries too much is declared by an
experienced lady to have a Neck sprain. To remove
the sprain he is put in a cotton sling and revolved
around the operator. Or a sitting operator puts the
child prone on her extended legs. Fixes the head
between two great toes and stretches the cervical
vertebrae. It is an horrible sight to watch.
78. Primary teeth are never cleaned as a custom.
79. Tonics are used for weight gain as a deep rooted
custom.
80. Female children are neglected and discriminated at
all possible occassions.
81. Fallen stump of umbilical cord is preserved. It is
used as a medicine in the form of a paste when the
baby cries with abdominal colic or gets dental
problems or breathlessness.
82. A male child is reared with long hair and braids for
5 to 7 years till his first mundan is done at a sacred
place in front of family deity. It creates identity crisis
and child has to face humiliating situations amongst
peers.
83. Very strict discipline for a child is harmful for his
psychological development.
84. Overprotection and pampering are customs run for
generations.
85. Severe punishment for minor mistakes to teach him
lesson is harmful.
224
86. Allowing him to have his way to avoid his temper

tantrums is a faulty child raring practice
87. Destructive behavior of a child is neglected
presuming that he will calm down as he grows up.
88. Hydrocele of a new born is massaged presuming
that his leg must have been pulled by the elder sib.
BIBLIOGRAPHY
1. Adair SM. Pacifier use in children: A review of recent
literature, pediatr. Dent 2003;25(5):449-58.
2. Aggarwal KN, Gopta A, Pushakaran R, Bhargava SK,
Faridi MM, Prabhu MK. Effect of massage and use of oil
on growth, blood flow, sleep pattern in infants. Acta Ped
2002;91(5):546-54.
3. Ahamad FU, Rahaman ME, Alam MS. Prelacteal
feedings; Influencing factors and relationship to
establishment of Lactation. Bangladesh Med Res Counc
Bull 1996;22(2):60-64.
4. Ali AR, Smales OR, Aslam M. Surma and lead Poisoning.
Br Med J 1978;2(6142):915-16.
5. Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh
MD. Effect of home based neonatal care and management
of sepsis on neonatal mortality:Field trial in rural India.
Lancet 1999;354(9194):1955-61.
6. Bennett J, Azhar N, Rahim F, Kamil S, Traverso H, Killgore
G, Boring J. Further observations on ghee as a risk factor
for neonatal tetanus. Int J Epidimol 1995; 24(3);243-47.
7. Charles V, Charlex Sx. Strong influence of tradition on
child rearing practices in India. trrop. Geogr Med 1979;
31(3):459-63
8. Darmstadt GL, Mao-Qiang M, Chie Saha SK, Ziboh V A,
Blach RE, Santoshm M, Elias PM. Impact of tropical oils
on skin barrier: Possible implications for neonatal health
in developing countries. PMID: 12113324 (pubmed index
for medline).
9. Hidayat AA, Weatherhead RG, Al-Rajhi A, Johnson FB.
Conjunctival and Lachrymal sac pigmentation by Kohl
(eye liner). Br J Opthamol 1997;81(5):418.
10. Iyenger SD, Bhakoo ON. Prevention of neonatal
hypothermia in villages.Roles of domiciliary care taker.
Acta Pediatr 1992;81(11):859-63.
11. Jacob T John. Uday bodhankar. Birth attendants: One or
Two? Editorial Indian Pediatr 2001;38(4)327-31.
12. Johnson RB, Spencer SA, Rolfe P, Molla DS. Effect of post
delivery care on neonatal body temperature. Ind J Med
Res 2000;112:212-17.
13. Joseph Petrus, Johannes Van Gestel, Monique Pauline,
L Hoir, France Berend, Plotz. Risk of ancient practices in
modern tomes. Pediatrics 110(6):78.
14. Kamat M, Malkani R. Disposable diapers: a hygienic
alternative. Ind J Pediatr 2003;70(11):879-81.
15. Katiyar GP, Agarwal DK, Tripathi AM, Agarwal KN.
Feeding practices in Varanasi district. Indian Pediatrics
1981;18(1):65-70.
16. Kumari S, Saili A, Jain S, Bhargava U, Gandhi G, Seth P.

Maternal Attitude Practices in initiation of newborn
feeding. Ind J Pediatr 1988;55(6);905-11.
17. Larson EL, Cimiotti J, Haas J, Parides M, Nesin M, DellaLatta P, Saiman. Effects of antiseptic hand wash Vs
alcohol sanitize on health care associated infections. In
neonatal intensive care units. Arch Pediatr Adolsc Med
2005;159(4):377-83.
18. Medeves JM, O Brien B. The effect of bather and location
of first bath on maintaining thermal stability in
newborns. J Obstret Gynecol. Neonatal Nurs 2004;33(2):
175-82.
19. Medhi GK, Mahanta J. Breast-feeding, Weaning practices
and nutritional status of infants of tea garden workers
of Asam. Indian Pediatr 2004;41(12):1277-79.
20. Mullany LC, Darmstadt GL, Khatry SK, Tielsch JM.
Traditional massage of newborn in Nepal: Implications
for trial of improved practice. J Trop Pediatr 2005;
51(2):82-86.
21. Narayanana I, Puri RK, Dhanabalan M, Rao DC,
Fernandez A, Balakrishanan S. Some infant feeding and
rearing practices in a rural community in Pondicherry
Indian Pediatr 1974;11(10):667-71.
22. Nelson EA, Yu LM, Williams S. International child care
Practices study group members. International child care
practices study; Breast feeding and pacifier use. J Hum
Lact 2005;21(3):289-95.
23. Nelsons Textbook of Pediatrics. Part XI Care of newborn.
NB 458-60.
24. Ohagi S, Akiyama T, Arisawa K, Shigemori K.
Randomized controlled trial of swaddling versus
massage in the management of excessive crying in
infants with cerebral injury. Arch Dis Child 2004;89:21216.
25. Prabhakaran GN, Aswath PV, Shriram C, Vishwnath
AN. Infant feeding pattern in slums of Bangalore. Indian
Pediatrics 1987;24(10):895-98.
26. Read M, Catteneo A. The optimal duration of breastfeeding. IBFAN. Breast feeding Briefs 200;31-32;110
27. Sankarnarayanan JA, Mondkar MM, Chauhan BM,
Mascarenhas AR, Mainkar RV Salvi. Oil Massage in
neonates: An open randomized controlled study of
Coconut versus Mineral oil. Indian Pediatrics 2005;
42(9):877-84.
28. Sas D, Enrione MA, Schwartz RH. Pseudomonas
aerugenosa septic shock secondary to Gripe Water
Ingestion. Pediatr Infect Dis J 2004;23(2):176-77.
29. Sinha A, Pande H. Maternal and infant feeding practices
of HO tribe women in Bihar. College of homescience,
RAU Pusa 848125.
30. Stanton WR, Mc Gee R, Silva PA. Indices of perinatal
complications, family background, child rearing and
health as predictors of early cognitive and motor
development. Pediatrics 1991;88(5):954-59.
225
7.7 International Agencies and Child Health

Shashi N Vani
7.7.1 WORLD HEALTH ORGANIZATION (WHO)
It is a specialized, nonpolitical, health agency of the
United Nations, with headquarters in Geneva.
7th April is celebrated every year as World Health
Day.
A world health day theme is chosen every year to
focus attention on an aspect of public health.
Objectives
The objective of WHO is the attainment by all the
peoples of the highest level of health which is set out in
the preamble of the constitution. The current objective
of WHO is the attainment by all people of the world by
the year 2000 AD of a level of health that will permit
them to lead a socially and economically productive life
also known as Health for all by 2000 AD. The preamble
of the constitution states: Health is a state of complete
physical, mental and social wellbeing, and not merely
the absence of disease or infirmity. The enjoyment of the
highest attainable standard of health is one of the
fundamental rights of every human being without being
discriminated on the basis of race, religion, political belief,
economic and social condition.
The health of all people is fundamental to the attainment of peace and security and is dependent upon the
fullest cooperation of individuals and states.
The achievement of any state in the promotion and
protection of health is of a value to all. Unequal development in different countries in the promotion of health
and control of diseases, especially communicable
diseases, is a common danger. Healthy development of
a child is of basic importance. The ability to live
harmoniously in a changing total environment is
essential to such development.
The extension of the benefits of medical, psychological
and related knowledge to all people, is essential for the
fullest attainment of health. Informed opinion and active
cooperation on the part of the public are of the utmost
importance, in the improvement of the health of the
people. Government has the responsibility for the health
of its people, which can be fulfilled, only by the provision
of adequate health and social measures.
The WHO is unique among the unspecialized agencies in that it has its own constitution, own governing
bodies, own membership and own budget. It is part of,
but not a subordinate to the United Nations.
7.7.2 UNICEF (UNITED NATIONS INTERNATIONAL
CHILDRENS EMERGENCY FUND)
UNICEF is one of the specialized agencies of the United
Nations, established in 1946. In 1953, the general assembly
gave it a new name, UN Children's Fund but retained
the initials, UNICEF. In the early years, UNICEF and
WHO worked together on urgent problems such as
malaria, tuberculosis and venereal diseases. Later it
covered such fields as maternal and child health,
nutrition, environmental sanitation, health centers and
health education and programs which would directly, or
indirectly benefit child's health.
Greater attention is being given to the concept of the
Whole Child, meaning that assistance should
henceforth be geared not only to health and nutrition,
but also to their long-term personnel development and
to the development of the countries in which they live.
Content of Services
a.
b.
c.
d.
Child health
Child nutrition
Family and child welfare
Education formal and nonformal
In short, UNICEF activities cover programs assisting

in child survival, protection and development; interventions like immunization, improved infant feeding
practices, child growth monitoring, home- based diarrhea
management, drinking water, environmental sanitation,
birth spacing, education of girls and income generating
activities for women.
Promotion of ORS in diarrhea, family planning, safe
motherhood, awareness of the means to prevent AIDS
amongst youth and health workers, access to correct ARI
cases at all health care centers.
Nutrition
Reduction of severe and moderate malnutrition.
226
Vitamin A prophylaxis
Iodisation of salt in totality, for human consumption
Exclusive breastfeeding up to four months of age and
eighty percent of hospitals becoming Baby
Friendly.
Water and sanitation Provision of safe and clean drinking water and sanitary disposl of excreta. Eradication
of guinea worm disease.
Education Providing primary education to all children.
Child labor Reduction and elimination of child labor
and provision for their welfare and education.
Endorsement of the convention
child.
on the rights of the
Care of the girl child Eliminating female foeticide, and

infanticide, reducing early age of marriage, and ensuring
that girls go to school.
BIBLIOGRAPHY
1. Arneil GC: Pediatrics Education around the world.
International Child Health 1997;1:29.
2. Forfar's Textbook of Pediatrics (3rd ed), 1984.
3. Manual for orientation of ANM and supervisors
4. Modules of CSSM MCH division, Ministry of Health and
Family welfare, 1994.
5. Monograph on Integrated Training on National Programmes for Mother and Child Development CTC-ICDS,
Dept of Women and Child Development GOI, 1990.
6. National plan of Action, A commitment to the child.
Dept. of Women and child Development GOI, 1992.
7. Nelson Textbook of Pediatrics, (14th ed), 1991.
8. Park's Textbook of Preventive and Social Medicine (14th
ed) 1994.
9. Polany L: Manual of Community Pediatrics (2nd ed),
1996.
10. The Progress of Indian States, UNICEF, 1997.
11. The Progress of Nations, UNICEF, 1997.
12. The State of World's Children UNICEF, 1997.
7.8 Adoption and Care of Orphans

RD Potdar
DEFINITION
7. Special attention to disabled children.
Adoption is essentially a social process by which the

reciprocal need of childless parents and an orphan (or
parentdeprived) child is satisfied. Legally it may be
defined as Transfer of rights and responsibilities
concerning the child from biological or birth parents to
the adoptive parents irrevocably.
Adoption is also an instrument through which one
can ensure the following important childrens rights
accepted by the United Nations, Convention of Rights
of Children and the world community at large. These
are:
1. Inherent right to life survival and development,
2. Right to name and nationality
3. Childs interest being always a primary consideration
4. Special protection from physical harm and neglect,
5. No discrimination through universal brotherhood,
6. Social security through education, employment and
earning, and
Considering the above definition and objectives,

adoptions could be divided into various types like intrafamily adoptions, single parent adoptions, adoption of
older children, adoption of disabled or Special needs
children and intercountry adoptions.
Whatever the type it is always prudent not to do it
secretly (by feigning pregnancy) but do it properly within
the law of the country. Since the emotional, psychological, social and legal consequences of adoption are far
reaching in nature it must be conducted in a very open
and supportive environment. Parents should be strongly
advised not to arrange private or secret adoptions
through hospitals and medical practitioners directly.
Adoption must always be done through an institute
which has been recognised as a Fit Person Institute by
the Central Government. In all states of India there are
many orphanages and adoption agencies recognized in
this manner.
Laws
In India, two laws govern the process of adoption. First,
The Hindu Adoption and Maintenance Act 1956
governs all Hindus adopting children and the second,
The Guardians and Wards Act of 1890 governing
adoptions by parents who are not Hindus by religion. In
intercountry adoptions children are given for adoption
under the The Guardians and Wards Act of 1890 in
foster care till they are finally adopted according to the
law of the country of adoptive parents.
Every doctor should be conversant with the process
of adoption, be able to and should advise any prospective
adoptive parents on all aspects of adoption. The doctor
can help in all the following standard steps of adoption
process always using sympathy and empathy at all
stages.
Making up a Decision to Adopt
Childless couples who are involuntarily childless have
a desire for parenthood combined with complex set of
emotions ranging from guilt of infertility to apprehensions to fears related to the social status, family acceptance and reactions of decision to adopt, unforeseen
elements of taking home a child-borne by parents not
known and their own capabilities regarding coping up
with a new challenge in life.
Preparation for Adoption
Preparation for adoption, mentally, physically, procedure
and documentwise: The ideal age difference between at
least one parent and the baby to be adoptive should be
not more than forty years so that they have enough time
and physical strength on their side to look after the baby
till it becomes a young adult and legally a major. Parents
should be equipped with the following documents viz.
marriage certificate, proof of age, income certificate and
bank balance and property certificates (if any), Doctors
certificate regarding their health and also their infertility
status, references and photographs when they go to apply
for a baby for adoption.
Preadoption Counseling and
Home Study Preparation
This is done by the social worker of the agency and
consists of social and family background of both parents,
current marital and family relationships, attitudes and
227
motivation towards infertility, childlessness and adoption, anxieties regarding childs illegitimacy, social and
genetic background, sharing the fact of adoption with
family and the child, parenting experience, aspirations
and financial capabilities, recommendations of their
friends and referees.
Choosing a Child, Medical Screening and Certifying
the Fit for Adoption Report
While it is true that Choosing can imply a bias of an
arbitrary and discriminatory selection or rejection, in the
Indian context it should be left to the social worker to
place a child who is near compatible to adoptive parents
in looks, color of the eyes and complexion. This is likely
to ensure better adjustment and integration of the baby
in the new family and society.
While doing the medical screening for fitness the
doctor should remember that this baby should be
examined and certified fit, normal or otherwise in the
context of the situational background that the baby may
have suffered physical, nutritional and emotional
deprivation in the recent past.
Clinical examination consists of identification data,
anthropometry, systemic examination, detection of any
gross deficiency disorders and overt or covert anomalies
and their correctability potential, clinical clues to
metabolic disorders if observed and physical and mental
milestones evaluation. Standard investigations which are
expected to be done are, hemogram, urinalysis,
tuberculin test, X-ray chest, stool examination for
parasites, tests for VDRL, HIV, Hepatitis B,TORCH titers
and any other indicated tests with special reference to
hypothyroidism, hemolytic anemia, chromosomal
anomalies, and metabolic screening tests for mental
retardation like phenylketonuria, galactosemia,
aminoaciduria, etc.
The entire exercise should be a balanced one to ensure
welfare and maintain interest of both the baby and the
adoptive parents with a little more tilt towards childs
interest since the child is a totally dependent being.
Medical Care of the Orphans and
Adopted Babies
Vast majority of orphans who go for adoption after one
month of their age and those who were not abandoned
immediately after a hospital delivery are highly vulnerable to sepsis, malnutrition, frequent attacks of acute
228
respiratory and gastrointestinal and skin infections. They

may be frankly marasmic and lack immunity increasing
the incidence of morbidity and mortality amongst them.
In the management of sick orphans three actions are of
utmost importance. First is Immunization against
Hepatitis B in addition to standard schedule, second is
the Urgency of action when even slightly sick and the
third is Early use of higher antibiotics even if prima facie it
may appear an irrational and expensive proposition. By
introducing simple inputs such as IV fluids, oxygen
therapy and higher antibiotic therapy in the Orphanage
itself prior to transferring to a big hospital a large number
of such babies can be saved. Apart from this the care of
orphans and adopted babies should be like any other
normal baby.
In postadoption care, in addition to problems of
general health and standard immunization schedule, an
extra eye should be kept on feeding and sleep patterns,
motor development pattern, speech and language
development which may appear delayed for some time
initially. Advice of patience and perseverance is usually
very rewarding in most cases.
Follow-up and Postadoption Counseling
Follow-up after adoption is necessary for advice and care
in the following crisis situations which are likely to arise
in some of the babies:
1. Sudden change crises, where the baby may (and
parents) may take long time to cope up with the
suddenness of change in environment, climate, living
conditions, language, noise level, food styles and
surrounding strange faces resulting into different
types of reactions like anxiety, rejection or aggression
or any combinations of these.
2. Behavior crisis is likely manifest after first few years
and may be as a result of pampering and overprotection (or even a covert rejection) by one or both
parents and other family members. There may be a
considerable delay in detection and management of

likely behavior problems due to the unwillingness of
the parents to seek interventions by adopting an
attitude of keeping all in the family. Such problems
may become worse in adolescence if not tackled
earlier.
3. Communication and identity crisis may come up at any
age if the childs sense of security is not well ensured
by the parents and immediate family members. This
problem is more likely to come up in intercountry
adoptions because of the obvious difference in skin
color.
4. Crisis of assimilation is likely to occur in intercountry
adoptions in a small number of cases where the young
adults may face discrimination in getting jobs,
married, etc.
Every doctor must be aware of these problems and
be able to either counsel the family himself or convince
and refer them to the appropriate agencies.
Encouraging, Insisting and Helping the Parents
Encouraging, insisting and helping the parents to tell the
child about his or her adoption is most vital postadoptive
follow-up actions. Every child who is adopted must be
told that he or she is adopted by the parents themselves
howsoever it may appear difficult for them. When a child
comes to know the fact from sources other than his
parents, it can cause such a severe trauma (of betrayal or
breach of trust) that it might even ruin relations between
the parents and the child forever totally defeating the
very objective for which the adoption was undertaken
in the first place. Later the age of the child when the
trauma happens, worse are the consequences for the
parents. It is therefore necessary and appropriate to
encourage all adoptive parents to tell the child as early
in life as possible when the child can comprehend the
concept of biological and adoptive parenthood. If done
between the ages of six to ten years most children take
into their stride and future problems can be averted.
8.1. Child Abuse and Neglect: Meenakshi N Mehta ................................................................................................................................... 230

8.2. Child Labor: Meenakshi N Mehta, SR Banerjee .................................................................................................................................... 244
230
8.1 Child Abuse and Neglect

Meenakshi N Mehta
We are guilty of many errors and many faults
But our worst crime is abandoning the children
Neglecting the fountain of life,
Many of the things we need can wait
The child cannot.
Right now, is the time his bones are being formed
His blood is being made and
His senses are being developed
To him, we cannot answer
Tomorrow as his name is Today
Gabriala Mistral
[Noble Laureate poet, Chile]
India may be feeling proud with its booming economy,
decreasing IMR and birth rate and increasing life
expectancy. All these prevent death, but not necessarily
improve the quality of life, particularly those of infants
and children. Similarly the new medical interventions
and better diagnostic techniques although have brought
about reduction in mortality the morbidity rates are high
and continue to rise. As per 2006 years UNDP Human
Development Report, India has misplaced priorities, i.e.
Indian Government spends on defence almost same as
that on education and more than double on health. Even,
when government does allocate funds, there is no
guarantee that it reaches the intended beneficiaries, the
health and education benefits do not percolate down to
the most needy and the poor. As per the last NFHS
Survey [NFHS-3-2006], only 35% of men and 22% of
women complete 10 years of education; percentage of
malnourished children was 46%, 38% were stunted and
44% were routinely immunized. Out of 35 million Indian
children only 46% girls and 66% boys complete education
in rural areas, while in urban India 44% girls and 20%
boys drop out of schools. We have largest number of
malnourished children, kids affected by AIDS, Street
children and children out of school. About 60 million
children are engaged in labor, around 12-15 million are
bonded workers and one third of the 60 million children
are employed in households, hotels, dhabas, eateries,
food joints, hostels, clubs, tea stalls, and spas despite the
government ban for employment of children under
14 years from october 2006. Our underprivileged children

are denied food, security, education shelter, health, even
right to live and social status and most important love
the feeling of being wanted. Contrary to India being
signatory to the Rights of Children, a sizable number of
our children from disadvantaged background suffer
quietly from deprivation, exploitation, and abuse. Child
abuse physical, sexual, emotional or even economic is
an unconscionable crime. Regrettably, it is a bitter truth
that is rarely acknowledged in India.
Furthermore, children in all societies, in the process
of their normal upbringing are often neglected, maltreated, abused intentionally or otherwise by their
parents, guardians or caretakers. The norms of child
rearing differ culturally with wide differences between
conservative and advanced societies. Although child
abuse is not a new phenomenon it has been the subject
of serious concern during the recent years. Child abuse
and neglect is a significant community problem of
enormous gravity. However, the problem is more serious
in nations with economic restraints, chiefly because of
socioeconomic reasons and illiteracy. In addition children
living in especially difficult and endangered
circumstances such as street children, refugees, children
in armed conflicts and disabled children are particularly
vulnerable to abuse and exploitation. The sale, abduction
and trafficking of children across borders is increasing.
These children are at a very high risk of abuse and
need our attention yet there is no possible means of
prevention.
THE ISSUE
The forms and dynamics of child abuse have undergone
major changes in the new millennium, adding multifaceted dimensions, complexities and challenges. The
problem of child abuse and the web of its human rights
violation embrace some of the most critical aspects of
the worst forms of child exploitation and abuse on the
international human rights agenda. These complexities
include changing attitudes, social orientation, contexts
and regional dimensions of the problem.
Child Abuse, Neglect and Child Labor

CONCEPT, DEFINITION, NOMENCLATURE
Sir Henry Kempe suggested the term Battered Baby
Syndrome for injuries resulting from child abuse. In 1962
the American Academy of Pediatrics used this to focus
the attention of physicians on unexplained fractures and
other manifestations of severe physical abuse of children.
Since then the definition of child abuse and neglect [CAN]
has been broadened to include any problem resulting from
lack of reasonable care and protection of child and
adolescents by their parents, guardians or caretakers.
There are varying views on the definitions of child abuse.
There are those who make a distinctive between child
abuse and child neglect and there are others who do
make such a distinction. All too often one finds such terms
as child battering, child neglect, child abuse, child
maltreatment, and physical abuse being used by
different authors to refer to the same or very similar
occurrence.
According to Patricia Howland, the distinction
between child abuse and neglect lies primarily in the
element of deliberateness. Child abuse connotes parents
active and usually intentional behavior which causes
physical injury to the child, whereas child neglect refers
to passive indifference to the child and an inability to carry
out the expected roles of parenthood. A comprehensive
definition of child abuse and neglect was given by the
United States Congress when it declared that the term
child abuse and neglect includes, the physical and mental
injuries, sexual abuse and exploitation, negligent
treatment or maltreatment of child under the age of
eighteen or the age specified by the child protection law of
the state in question, by a person {including any employee
of a residential facility or any staff person providing out
of home care} who is responsible for the childs health or
welfare is harmed or threatened thereby, as determined in
accordance with regulations prescribed by the secretary.
In the broad sense most researchers and authorities agree
on the basic issue of child abuse resulting from parental
misuse or exploitation of the rights of parents and other
guardians to control and discipline children under their
care and which are detrimental to the childs health and
well-being.
Today child abuse does not only refer to physical
abuse, sexual abuse and trafficking; it adds many
dimensions of violation of basic human rights of a child.
It is an outcome of a set of interrelated, familial, social,
231
psychological and economic factors. These factors and

processes create a complex nexus between exploitation,
neglect and abuse as part of the larger perspective of
violation of child rights.
Other terms suggested for child abuse are Silvermans
syndrome, illegitimate child syndrome, Parental
dysfuntion, etc. A new term Nonaccidental injury, [NAI],
and child maltreatment, intentional or otherwise is now
well recognized.
EPIDEMIOLOGY AND INCIDENCE
In the developed countries of the west, the incidence of the
battered child ranged from 250 to 300 cases reported per
1 million populations. In its 2008 report, the state of
worlds children, United Nations Children Fund [UNICEF]
has estimated that about 100 million children around the
world are forced to live wholly or partially on the streets,
although reliable figures are particularly impossible to
calculate. Many such children are among the 300 million
who are subjected to exploitation, violence, and abuse
around the world. Most street children were found in poor
countries in Africa, Asia, Latin America and the Middle
East and also in parts of Eastern Europe and former Soviet
Union; although the actual number of street children in
each region is unknown. The problem can be judged from
social indicators such as primary education, school
enrollment and prevalence of child labour; compared to
SubSaharan Africa where 40% of girls and 36% of boys
are not enrolled in primary education, and 35% of children
between 5 to 14 years are drafted into labour force, partly
or wholly, in South Asia the corresponding figures are 9%
of girls, 16% of boys and 13% of children are obliged to
work.
In India the first case of battered baby syndrome was
described in 1967, and subsequently sporadic cases have
been reported in Indian literature. Moreover, till recently
there used to be lack of general awareness of CAN in its
wider perspective. For all practical purposes, it did not
exist except for scattered cases of physical abuse. The last
15 to 20 years have witnessed the changing trends of this
concept and scientific studies by Indian workers on the
various aspects.
In India, although the problem of child abuse is less
thought and recognized, in reality it continues to grow in
alarming proportions. Besides the health care providers
and professionals including the pediatricians are either
232
ignorant or have a general lack of sensitivity to the issues

of child abuse. Child abuse reporting is not mandatory in
India like many other countries. The majority of child
deaths in India, especially in nonurban areas are not
reported, investigated leave aside autopsied leading to
difficulties in knowing the precise number of deaths due
to child abuse. Besides the incidence of child abuse
amongst the child deaths represents only the tip of iceberg;
the much wider and albeit bigger incidence of child abuse
is widely prevalent within the families- in disciplining
the children, gender bias and discrimination for girls and
cultural practices of female foeticide and infanticide, girl
child marriage. Further, the vicious cycle of poor
pregnancy- maternal ill-health, high maternal mortality,
low birth weight babies, higher neonatal and infant
mortality, as well as out of family set up like institutions,
orphanages, street children, migrant children and
children of construction workers, child labourers from
organized and unorganized sectors, child prostitutes, war
refugees, trafficked children, kidnapped children and so
and so forthin short wherever there are children and
wherever there are adults to exploit them.
To generate awareness and to focus attention on the
issue of child abuse and exploitation in India, a
nationwide worlds largest ever, prospective study was
commissioned by the Government of India, Ministry of
Women and Child Development in association with
UNICEF and Save The Children Fund and carried out by
the NGO PRAYAS, Delhi. The report was released in
April 2007. The study was multicentric, involved 13 states
including Delhi, Maharashtra, Rajasthan, Uttar Pradesh,
Kerala, Goa and Madhya Pradesh, covered 17000 children,
teachers and NGOs. The findings are shocking, 2/3rds of
children were physically abused, 71% were beaten, 29%
of these needed medical attention and 56% had bled from
assault; 89% by parents, 65% kids at school underwent
corporal punishment. More than 53% of Indian kids were
sexually abused, almost 22% faced severe sexual abuse,
and 6% sexually assaulted.; in 50% of these cases the
abusers were known to the child or were in a position of
trust and responsibility, and most children did not report
the matter to any one. Younger children [5-12 years] faced
higher levels of abuse and in the backdrop of the Nithari
killings and sexual abuse of children in Delhi; the issue of
childrens safety is of great concern. Of the children
interviewed, 80% faced emotional abuse and
discrimination like denial of education to girls and 5%
had to resort to substance abuse to cope up with being
beaten regularly. The sexual abuse ranged from severe,

such as rape, violent sexual assault to milder forms as
molestation, fondling or forcible kissing, inappropriate
touch or exposure to pornography. As the constitution of
the sample surveyed consisted of children at home, school
children, those in institutional care, child labourers, street
dwellers, the incidence of abuse varied according to their
background, as we know the economic and the social
outcasts were twice condemned. Sexual abuse in children
was highest -31% in children at work, followed by 22% in
institutional care and 13% in family environment. In the
same study from Chennai, The Tulir Centre for Prevention
and Treatment of Sexual Abuse, revealed that one out of
every two boys school going, compared to 2 out of 5 girls
not necessarily going to school are sexually abused. Most
often senior boy or senior classmate is the abuser and
school toilet is the common place for abuse. The degree
and type of sexual abuse varied, milder in primary section
- touching and exposing private parts to most severe in
senior/secondary section- forced sex and even
homosexuality. The study also separately interviewed
2324 young adults between 18 to 24 years, half of whom
reported being physically or sexually abused as children.
There were similarities to physical abuse in that the
offending parents, have frequently been emotionally
deprived or abused in their own childhood. As regards
sexual abuse in the girls, mothers would know what is
going on and yet collude by avoidance, for either being
scared of the abuser being at the position of trust,
responsibility /boss at work, or from the same family or
being afraid of social stigma. This often led to repeat abuse
and escalation of abuse.
FACTORS LEADING TO CHILD ABUSE
Recent research on child abuse has tended to move away
from considering the influence of a single factor such as
personality disorder or mental illness and poverty towards
looking at the effect of a whole group of predisposing or
risk factors. Child abuse can happen in any family, at all
levels of society. Child abuse usually takes place in the
home, not in public settings. It occurs over a period of
time, and is usually not an isolated incident. Health and
community services identified that most abused other than
child sexual abuse occurs in families to which some or the
following apply.5 Though the exact etiology of child abuse
is not known, it is thought to be due to interaction of 3

primary factors - sociocultural beliefs, the childs and
parental factors.
233
6. Disappointment over the sex of the infant.

7. Ignorance of child rearing, unrealistic expectations.
8. Violence among adult family members.
Sociocultural Factors
There is a wide variation in sociocultural beliefs of the
developing and developed world. Some issues which are
prevalent only in certain regions of the world like Asia,
and high population density areas, leading to higher
incidence of child labour, and child sexual exploitation.
Similarly political instability and other internal
disturbances including conditions of insurgency and
weak implementation of legal provisions leading to break
down of families creating major problems, with
increasing number of child soldiers, refugee children,
trafficked children, and children on the streets. However
despite these situational differences, the basic factors
leading to child abuse are:
1. Values and norms of discipline and physical
punishment.
2. Family structure number of members in family, joint
or nuclear family system, socioeconomic status, etc.
3. Family and situational stresses poverty, illiteracy,
unemployment, alcohol abuse, isolation, poor
housing, caste system and landlessness.
4. Parent-child relationship, punitive child rearing style,
excess or unwanted children, role reversal
5. Lack of economic opportunities, rural urban
migration.
Child Producing Stresses
1. Mentally retarded, physically handicapped, disabled,
deformed or chronically ill
2. Hyperactive and behaviorally different, strong willed
children
3. Temperamental [Difficult]
4. Too many children, girl babies, premature infants,
foster child, boys twice more common than girls to
be victims of physical abuse.
Parent Producing Stresses
1. Low self esteem.
2. Depression.
3. Unhappy childhood experiences neglected or abused
as a child, emotionally deprived
4. Parental substance abuse
5. Character disorder or psychiatric illness.
PREDICTIONS
However, in addition to above factors there are situations
where child abuse is likely and can be predicted and thus
giving a warning. In assessing whether children are likely
to be abused it is useful to consider separately factors
relating to the parents, the child, and their social
conditions. If parents have certain personality
characteristics or have already demonstrated their capacity
to assault children and their child is difficult or
unrewarding, there is a strong possibility of injury being
triggered by any social crisis. The following have been
found to correlate with ill-treatment later in life.
The Parents
a. Young mother under the age of 18 years, is more likely
to maltreat her child.
b. Who were abused or have experienced family
disruption in their childhood
c. Lack family support and are unreasonably fearful of
caring for their child.
d. Have unreasonable expectations of their baby and treat
him as a much older child.
e. Have poor impulse control.
f. May be generally rigid or authoritarian; for example
the incidence of abuse is greater in some strict religious
groups and in the families of military personnel.
g. One, usually the father may be aggressively psychopathic and assault others within and without his
family. About 5% of abusing parents fall into this
category, and a similar proportion are psychiatrically
ill.
The Child
a. Was unwanted and there may have been denial of
pregnancy, requests for abortion or talk of adoption
b. Was separated from mother at birth, for example,
because of prematurity, and his/her initial attachment
to the mother was prevented or interrupted.
c. Is disappointing either because of a defect or because
the child of opposite sex was wanted.
234
d.
e.
f.
g.
Is hyperactive by day and troublesome/cries at night.

Is difficult because of illness
Is different from rest of the family
Girls are 3 times more likely than boys to be victims.
Social Factors
a. Crisis relating to housing, disconnection of services,
lack of safe water, hygiene, sanitation, unhealthy
environment.
b. Loss of work. chronic unemployment increases the
likelihood of abuse by fathers .
c. Poverty and economic crisis
d. Loneliness or isolation of mothers when partners have
left or are working away from home.
e. Marital crisis and new liaisons, step children are at
increased risk.
f. Unwanted pregnancy.
g. Harmful traditional practices like child marriages,
caste system, and child forced to work to support
family income, girl child discrimination/gender bias,
Devdasi tradition
Many families have some of the stresses listed, but
yet, one cannot identify in our social set up, all the social
stresses that precipitate or trigger child abuse or
maltreatment. It is worth remembering that child abuse
results from a series of stresses that impinge on parents
and children and new risk factors may operate for any
individual family which must be assessed at the clinical
level. Only by understanding the social, familial,
psychological concomitants of child abuse, the pediatrician can form a comprehensive opinion and management plan.
The presence of a single symptom or sign does not prove
that a child has been abused. Several symptoms together
or patterns of symptoms developing over a time indicate
that something is wrong, and the possibility of child
abuse and/ or neglect should be considered. One should
always be vigilant to the possibility of child abuse. In
extreme cases abuse can even kill the child. Regarding
sexual abuse boys and girls react differently. Boys who
have been abused get scared, do not share the traumatic
experience with anyone, for the fear of being considered
less of a man, and this can lead to revictimization. Boys
may turn extrovert, or at times violent. Vice versa girls
who are abused may feel self-destructive, may feel guilty.
Dealing with abuse is a lifelong struggle. Occasionally a

boy who has been abused grows to be anxious, lacks
confidence and self-esteem, is irritable, impulsive,
antisocial, prone to depression and has problem forming
trusting long term relationships. Worst he himself may
become abuser.
The forms of child abuse and neglect [CAN] may take
a variety of manifestations [Table 8.1.1]. The clinical
features of CAN vary from mild and insignificant to severe
the former may go unreported but suspicion is aroused
when they are recurrent. Rarely grave injuries are inflicted
and may prove fatal.
Munchausens Syndrome by Proxy
It is a manifestation of fabricated illness usually created
by an adulta parent/guardian, in a child which may
mimic a real illness, with an objective of drawing attention
of medical personnel and in turn getting self importance.
This condition has to be diagnosed by eliminating real
illnesses and having a strong suspicion of such an entity.
Although rare, timely vigilance is worthwhile, as it may
turn fatal before it is diagnosed and due care is given in
time. An example of one such case encountered by the
author is illustrated here (Fig. 8.1.13).
A 5 year old boy son of a rich farmer from Jalgaontown from Maharashtra, was brought by his father, to
LTMG Hospital, Sion, Mumbai, for history of
haemetemesis for about 7 days. On enquiry and on
physical examination nothing significant to account for
hemetemesis was found. He was not pale or sick. Liver
and/or spleen were not palpable, Pedal edema, and ascitis
or icterus were absent. All the investigations to find the
cause of hemetemesis, were normal. While under
observation for 15 days, he did not have hemetemesis even
once, although the father continued to complain about
the same. On insisting to save the vomitus, the father
showed a red colored liquid resembling blood, in a bottle.
None of the ward staff, or adjacent patients relatives had
witnessed the patient actually vomit. As the red liquid on
close examination did not seem to be blood, we sent the
same liquid for chemical analysis. On analysis by the
forensic laboratory, the red liquid was detected to be
sindoor powder {used by women to apply on forehead,
as a sign of marital status] dissolved in water The father
was interrogated and after much persuation, he accepted
to have fabricated the illness in the child. He was helped
by the psychiatrist before discharging the patient, to avoid
235
TABLE 8.1.1: Forms of child abuse and neglect

1. Physical: Cuts, bruises, haematomas, fracture, head injury, visceral injury, burns, ophthalmic injury, blunt trauma, injury due to slapping,
pushing, squeezing, kicking, shaking, -shaken baby syndrome [Figs 8.1.1 to 8.1.7.]
2. Nutritional: Failure to thrive, marasmus, stunting, deprivation of varying severity [Figs 8.1.8 and 8.1.12]
3. Sexual: (a) Rape, inscest, fondling, pornography, prostitution, involvement in sex related activities, exhibitionism, coercion (b) Female
foeticideand infanticide, Neglect of girl child and female discrimination deprivation from food, education, clothing, entertainment, love
and social status, early girl child marriage [Fig. 8.1.9]
4. Behavioral : Wariness of adult contact, aggressiveness/withdrawl, apprehension when other children or adults cry shout, prefers to
stay away from home as much as possible, excessive compliance, attaching readily to strangers, frequent absenteeism and unwillingness
to go to school, not reporting injury to parents or giving inappropriate explanation of an injury.
5. Emotional: Humiliation, depression, extremely low self esteem, passive, withdrawn, tearful, apathetic, aggressive or demanding
behavior, constant high anxiety, poor social and interpersonal skills, persistent habit disorders such as sucking, biting, or rocking,
self destructive behavior, and unexplained academic delays, comparision with siblings /other children, girl child neglect/discrimination
6. Nonaccidental poisoning: e.g. Opium.
7. Abandonment/ desertion
8. Substance abuse: Drugs which alleviate mood or create illusions, happiness, e.g. Cocaine, Marijuana, etc. and alcohol and allied
substances, [Fig. 8.1.10.]
9. Medical Neglect: By the professionals and health care personnel dealing with the medical management of the child and if neglected
could be potentially fatal.
10. Exploitation:
Sexual: Children used for prostitution/sex related trade, pornography and allied abuses -trafficked children, devdasis, etc.
Entertainment: Use of children as jockeys for camel race in the gulf countries, street dancing and street shows/games with
nondomesticated animals-monkeys, bears, elephants, camels, snakes etc., rope walking, pole climbing, making pyramids for
religious celebrations, fire jumping, or fire swallowing, in circus or marine activities.
Social Benefits: Use of children by schools, orphanages, NGOs, etc. for formal welcome programs, in rallies in parades, making
children wait in extreme hot or cold weather for long hours without provision of drinking water, toilet facilities.
Political: For wars, for party propaganda during elections, etc.
Labour: both in organized/unorganized sectors- for industries like carpet, lock, glass, fireworks, tin, cigarette watch, gunpowder,
chemical dye, bullet and explosives manufacturing and storage, as street children for unorganized sundry jobs on the teastalls, eateries,
food joints, liquor bars, small clubs /Matka dens, garages, roadside peddlers selling all sorts of articles, newspaper vendors, in railways,
on the vending machines, selling cinema /lottery tickets, cards.
Kidnapping: Use of kidnapped children for begging, as hooligans, for thefts stealing, house breaking, gambling and similar antisocial
activities [Fig. 8.1.11]
Trafficking of children: For various antisocial activities-namely slavery, prostitution, and sex related trades, domestic and industrial
labour, war, smuggling, entertainment, etc.
11. Neglect: For food, protection, housing, education, health, and medical problems, entertainment, family bonding most being loved, being
wanted, girl child neglect.
12. Miscellaneous: Manchaunsens Syndrome by Proxy [Fig. 8.1.13]
repetition of this incident or fabricating other serious

illness associated with high morbidity and mortality.
DIAGNOSIS
Abuse may not be an obvious diagnosis at an initial
consultation. The likelihood of CAN should be considered
in all cases of injuries in childhood, as well as in unusual
or bizarre circumstances. A careful history and detailed
examination of the child is essential. Parents who inflict
injuries on their children may seek medical attention at

different hospitals/health care facilities and give
misleading information so that a history of the previous
injury is not available, or deliberately hidden, so that abuse
is not suspected. Occasionally neighbours or friends may
provide useful information Children are often unable to
describe the events, especially when the parents are
present, but may give valuable details when questioned
separately. This is only possible when the abused child is
236
Figure 8.1.1: Found by police with multiple injuries of left

upper limb, neck and scalp
Figure 8.1.4: Raja, found abandoned on railway station,

was numb, lost within himself, after months started gradually
talking, would repeat what was talked to him. Later rehabilitated through remand homeMumbai
Figure 8.1.2: Rat litre marks on back as a result of baby

abandoned in garbage
Figure 8.1.3: Neonate deserted in cradle

in orphanage (abandoned)
Figure 8.1.5: 32 weeks (old) newbornabandoned in

railway compartment and brought by police to the hosptial
Figure 8.1.6: Kaliunknown girl deserted in the pediatric ward

in an unconscious state in 1981. Later rehabilitated through
remand homeMumbai
237
Figure 8.1.8: 16-day-old brought for loose-motions in

marasmic condition disserted in orphanage cradle
Figure 8.1.7: Multiple congenital anomalies

abandoned in garbage
of age and understanding or in a proper physical state to

narrate the incidence The problem is difficult and
complicated when the victim is an infant or a toddler,
dazed, drowsy or unconscious, or emotionally scared or
in a state of shock to reveal anything. Children rarely lie
about abuse. They may however retract an allegation of
abuse in the face of disbelief and denial. In CAN the
physical findings are often at variance with those expected
from the history. The features are often bizarre and do not
confirm or match with the manifestations of a known
Figure 8.1.9: Female achondroplasia

raped by fathers employer
disease or disorder. Besides evidence of physical abuse,

special attempts should be made to look out for evidence
of other forms of abuse, i.e. sexual, nutritional, behavioral
or emotional abuse as well as various forms of exploitation.
Appropriate radiological investigations are carried out,
238
Figure 8.1.12: Neglected childpsychiatric mother could not

and did not feed the baby who became marasmic
Figure 8.1.10: 9-10 year old girl brought
in alcoholic coma
Figure 8.1.11: Kidnapped, tortured and forcibly employed for

begging by Gundasantisocial workers
Figure 8.1.13: Patient of Munchausans

syndrome by proxy

whenever there is reasonable suspicion of CAN.
Considerable experience is required to handle these
problems, and the senior staff members should be promptly
consulted. Reporting to the law enforcement agencies is
essential, depending on the local situations.
EFFECTS OF CHILD ABUSE/NEGLECT
Child neglect can have severe deleterious short and long
term effects on childrens cognitive, socioemotional and
behavioral development. The immediate effects are often
noticeable, whereas some effects manifest late and unless
related to previous abuse, are difficult to be attributed to
the abuse in the past. These delayed effects include low
I.Q., motor problems, hyperactivity, physical defects,
increased intensity to reactions, less social responsibility,
poor impulse control, aggression, marked anxiety
feelings of rebellion and so on. Neglect occurring early
in life is particularly detrimental to subsequent
development. Relative to physically abused children,
neglected children have more cognitive and academic
deficits, may feel worthless, social withdrawal and
limited peer interactions and internalizing as opposed
to externalizing problems. Child abuse breaks down
childs trust in his/her family members. There is a strong
correlation between child abuse and later crime drug
abuse, poor social and marital adjustment and sexual
difficulties. Some of these problems may not have arisen
if these adults had not been abused as children. Abusive
behaviors are transmitted to next generation and child
abuse victims, may have permanent emotional and
mental scars of past abuse.
MANAGEMENT
The management obviously depends on diagnosis and
type of abuse. Physical injuries and abnormalities are
appropriately treated. More often than not the affected
child is never taken to a police or a physician or a
caretaker agency. Occasionally the police bring the child
found by them abandoned and hence there is no assess to
any history or family background. Illegitimate babies are
almost always disserted.
Not all abandoned babies or those found by police
survive. Even after the treatment of immediate cause,
rehabilitation on long term basis if not impossible, is
extremely difficult. It is time the existence of child sexual
abuse in India, is acknowledged and accorded the
seriousness it deserves. The nationwide GOI Ministry
239
study makes important recommendations including

legislative and policy changes, setting up outreach and
support services and advocacy. Though well-intentioned,
the suggestions will translate into little change in ground
reality unless there are specific interventions aimed at
diverse groups. The argument for the inclusion of sex
education in the school curriculum should be reinforced,
instead of the child getting half hazard and wrong
information and ideas about sex from his peers and
roadside cheap literature. Adults in India including the
politicians and policymakers need to grow up and
abandon their ingrained squeamishness about sexual
discourse for the sake of a healthy society. Child labor,
homelessness, and low education both low school
enrollment and high school dropout are unpardonable
mass crimes. It is the responsibility of government and
civil society to pull out all stops and deal with them on
priority basis. The management of CAN per se is
extremely complex and difficult. Whenever possible, the
child should be rehabilitated in his own family. The
parents and other family members need support and
counseling and no one else is best suited for this, than
their own family physician, if they have one.
Unfortunately amongst the poorer sections of society,
where the problem of CAN is high, due to socioeconomic
constraints, difficulty in assess to any health care facility,
because of their housing in the interior of rural or tribal
areas, as well as poor knowledge about child rearing,
illiteracy, and strong cultural beliefs, the question of
having their own family physician does not arise. In the
families, who have their own pediatrician, he can do this
job well. Voluntary agencies and social organizations may
be of help. In our country, foster care, adoption, and
placement in orphanages are of limited options. Improvements in general living conditions, social awareness, and
changes in the attitudes, economic status are important to
control the scourge of CAN. Responding to CAN is a
shared responsibility. The ramifications of CAN are so far
reaching, that it is beyond the scope of any one professional
to tackle it. The medical profession, including general
practioner, specialists, social services, the police, judiciary,
and the community, all have joint as well as specific roles
to play. Awareness towards CAN, its ill-effects on the
affected child, his/her family and the society, should be
generated amongst all above concerned disciplines.
Similarly, involvement of all the related Government
departments, police and legal functionaries is vital.
Pediatrician has the main role to play in terms of correct
240
diagnosis, management, rehabilitation, as well as

prevention not only in the same child, but also in the sibs.
He/She should be helped by the social services, the police
and the judiciaries for a comprehensive approach.
Ironically, till recently the pediatricians have been too busy
tackling infections and malnutrition and lack the needed
awareness to CAN. Even if rarely diagnosed, the
implementary judicial system, the Indian Penal Code does
not recognize child abuse. Child labor cannot be
abolished, as there are no alternative arrangements, for
the jobs for the parents of these working children, or
economic settlement of these families. To educate these
children, there are not enough schools, trained teachers
or the other necessary infra structure. With the drive and
propaganda for the abolition of child labour, without the
necessary provision for the rehabilitation of these working
children, the entire family starves along with the child.
This indirectly leads and encourages to recycling of child
labour in clandestine circumstances. It is depressing to
note that there is no legislation on child abuse and neglect
in India, whereas our neighbours, Sri Lanka and Pakistan,
with more or less similar socioeconomic background and
smaller than India in area as well as population are ahead
of us in legally dealing with child abuse.
PROVISION FOR SAFEGUARD/CHILD PROTECTION
IN INDIA
The Indian Constitution contains provisions for safeguarding the interests of children and protecting them
against cruelty and exploitation. Article15[3] empowers
the state to make any special provision in favor of children.
Article 39 [i] of the constitution enjoins the State that it
shall in particular direct its policy to ensure that childhood
is protected against exploitation and against moral and
material abandonment. Article 39[e and f] specify that the
state shall direct its policy in such a manner that the tender
age of the children is not abused and children are given
opportunities and facilities to develop in a healthy manner.
Article 24 prohibits from employment of children below
the age of 14 years in any mine, factory, or other hazardous
job. Article 45 provides for free and compulsory education
for all children upto the age of 14 years. Indian Penal
Code sections 363a, 365, 366, 366a, 366b, 370, 372, 373
and 376, too deplores child exploitation and considers
exposing a child below 12 years to physical risk or
disserting it with the intention of abandoning it, by the
parents or any other person entrusted with the care of the
child, kidnapping or maiming a child for begging and

selling a child for prostitution, etc. as offence. The National
Policy for Children 1974 confers the responsibility of
nature and solicitude of children on the nation and
expresses concern about all forms of neglect, exploitation
of and cruelty to children. The National Policy on
Education, 1986, too, adopts a child centered approach
and explicitly calls for firm exclusion of corporal
punishment from education system. The Child Labour
Policy adopted by the nation in1987, seeks to protect the
interest of children at work and to prevent their exploitation by the employers. Subsequently the National
Decadal Plan of Action for Girl Child [1991-2000] for
protection from exploitation, assault, and physical abuse
came in vogue . The National Initiative for Child Protection
[NICP] strives to ensure a childhood to every child in need
of care and protection. These are (a) street children, (b)
child labor (c) children who have been abused (d) child
victim of flesh trade (e) child addicts (f) mentally ill child
(g) children affected by HIV/AIDS (h) children affected by
conflicts and distress (i)child political refugees and (j)
children whose families are in great crisis. The Allied
system have a direct impact on childs life, they are (1) the
police, (2) the health care system (3) the judicial system (4)
the education system, 5)the transport system, (6) the labour
department, (7) the media, (8) telecommunication
department (9)the corporate sector (10) and all others
all of us. Every one can be an allied system.
National Charter for Children 2003 was announced
in 2003. This was done in accordance with the pledge in
the National Agenda of Governance, i.e. through National
Policy for Children 1974, wherein we are committed to
providing for adequate services to children, both before
and after birth and throughout the period of growth, to
ensure their full physical, mental and social development;
Underlying this charter is our intent to secure for every
child, its inherent right to be a child and enjoy a healthy
and happy childhood, to address the root causes that
negate the healthy growth and development for children,
and to awaken the conscience of the community in the
wider societal context to protect children from all forms of
abuse, while strengthening the family, society, and the
nation.29 While there is no single legislation to deal
exclusively with the problem of child abuse in India, there
are various acts such as Juvenile Justice Act 1986, Child
Marriage Restraint Act [Amendment], which deal with
one aspect or the other of child exploitation and cruelty. A

number of voluntary organizations are also engaged in
protection and rehabilitation of the abused children While
some of child abuse like child labour and to a lesser extent
female sexual abuse, have engaged the attention of
legislators, social welfare administrators and social
workers, not enough attention has been paid to other forms
of child abuse.
LEGAL ASPECTS
Raising children has been the concern of the parents and
not the government. The law has therefore given parents
the custody of children to give protection and care. The
law has however provided for intervention by society
when parental care is dangerously faulty or insufficient.
Two types of proceedings can result: (1) Criminal
proceeding against one or both parents in adult courts.
(2) Care proceedings for the child in the juvenile court.
Under the criminal proceedings, the case is brought in the
adult court under the children and young person act on
the grounds of cruelty. The prosecution must have
evidence which pine responsibility on one or more
individuals, If found guilty the adult can be imprisoned/
punished. Under the care proceedings the local authority
usually the police brings the case. A parent may be
acquitted in the adult court, but the juvenile court can take
its own action, for the court is primarily concerned with
the childs actual situation and welfare. Voluntary
arrangement may be made by the parent which can be
approved by the court. Almost a supervision order is
passed . Sometimes the child may be removed to another
place. As per the National Policy for Children of August
1974, which is in accordance with the constitutional
mandate of India, any child born in the territory of India
irrespective of the fact whether the parents or either of the
parents is an Indian Citizen would be an Indian citizen.
The various articles namely 5a, 24, 39f, 41, 45, 46, 47 of
Indian constitution offer a comprehensive care and
protection to any child born in India. Further as per the
International Convention of the Rights of Children, to
which India is a signatory, the child has the priviledge of
fulfillment of all the four sets of rights namely, the right to
survival, protection, development, and participation. The
Convention also said that the children are at a risk in
every country in the world and argued that children
invariably wind up at the bottom of almost all national
agenda for political and social actions.
241
A UNIFIED APPROACH TO PROTECTION/

PREVENTION
19 th November is the world day for Prevention Of Child
Abuse, launched in the year 2000, by the Womens World
Summit Foundation, at Geneva, Switzerland The
principal objective of the World Day is to help, create a
culture of prevention of child abuse emotional, physical,
and sexual and violence against children. It is organized
in synergy with the anniversary date of the Convention
of Rights of Children (20th November). A coherent policy
can be formulated to combat child abuse in the family
and society via primary prevention. This probably can
be achieved by increasing the awareness of the responsibilities of parents instead of blaming the community,
much less the Government. There is in this traditional
wisdom, but who will help the families who cannot help
themselves? More than making new policies concerning
child care and protection, implementation will be vital.
Facilities will have to be provided of supplying clothing,
food, housing and education, the basic rights of the child.
To what extent the National Policy for Children, The
National Decadal Plan for the Girl Child, The National
Initiative for Child Protection and The National Charter
for Children 2003, and the resolution on childrens funds
and special welfare programs will assist in the
comprehensive welfare of our Indian children, our future
national assets remains an unanswered query! The cause
of children has lacked concern and advocacy, whereas a
number of agencies and organizations have paid up lip
service some have made notable impact. In this scenario,
The Indian Academy of Pediatrics [IAP], has taken up
the cause of children, has opted Comprehensive Child
Care. The IAPs status is now recognized by the
government and important national/international
agencies like UNICEF, WHO, World Bank, etc. and its
advice is sought on important matters concerning
children. Hence IAP has constituted Child Abuse,
Neglect and Child Labour [CANCL] Committee to
spearhead its endeavour with the following goals: (1) To
reach out to the neglected, deprived and abused children
for their comprehensive needs including healthcare,
education and development, rehabilitation and protection. (2) To formulate recommendations to the government.
(3) To create social and community awareness to the
problems of child abuse and neglect in its various forms
and child labor and bring about attitudinal changes. To
242
implement these goals on a wider national scale, it has set

up branches in different states of India. Various strategies
have been formed for the implementation of its activities
and since the inception of this committee, considerable
work has been done, as well as planned for the future. As
one of the goals, the CANCL has submitted a proposal to
the Ministry-Government of India - Panchayati Raj, to
involve village panchayats for education, health and
immunization of rural children, to decentralize such
problems and to encourage village community
participation. Since the last three years, the GOI, has
launched, The National Rural Health Mission- NRHMto provide effective health care to rural population
throughout the country, with special focus on 18 states,
which have poor public health indicators and weak
infrastructure, with the emphasis on empowering the local
governments for its management at the village level. With
the success of NRHM, the GOI Ministry of Health is
planning to launch National Urban Health Mission
[NUHM] for providing basic health care facilities for the
urban population; 22 crore people will be covered,
including 5.5 crore urban slum dwellers under this scheme.
Last year in January 2007, IAP Child Rights Program was
launched under IAP Vision in collaboration with The
Royal College of Pediatrics and Child Health, UK, to focus
on Child Rights and Protection, for children of India.2 The
Tenth Five Year Plan[2002-07], viewed development of
children not only as the most desirable societal
involvement in countrys future, but as the right of every
child to achieve full developmental potential. However
the percentage share of sectoral allocation on children in
union budget 2006-07, was for child development 0.83%,
child health 0.556%, child education 3.487%, and child
protection 0.034% only.12 In the 11th five year plan, the
sum allocated for child protection is a mere 0.7%. We are
far behind our neighbour Bangladesh in spending for
health and education of our children. We need to put
money where it is most needed, and the citizens need to be
alert to prevent misappropriation of funds, the bane of
usual government program. After the report of the
Government of India Ministry of Women and Child
Development sponsored national study on child abuse
NSCA-revealing alarming facts on child abuse
Smt Renuka Chowdharyminister MWCD, gave
assurance for the remedial measures. MWCD, was
created in early 2006. This move along with increased
allocations for children in the budget for 2007-08, is a
reflection of the governments commitment towards
children. She said Indias children are Indias future as

the strength of the nation lies in healthy protected,
educated and well-developed child population that will
grow up, to be productive citizens of the country. She
dedicated this report to the nation with the hope that it
will help establish and strengthen policies, programs and
legislations on child protection. Further Smt. Deepa Jain
Singh, secretary -MWCD-GOI, has added that GOI is
focusing on issues of child abuse, has taken significant
steps to address child protection by setting up a national
commission for the protection of Child Rights, amending
the Juvenile Justice [CARE and Protection of Children]
Act 2000 and the Child Marriage Restraint Act 1929,
launching the offences against children prevention Bill.2
The Millenium Development Goals in 2000, adopted at
the Millenium summit are about children. Six of the 8
MDGs best met as rights of children to Health, Education,
Protection and Equality are protected. They will only be
sustained as the rights of every child are realized. These
same six match the goals set out in a A World Fit for
Children. If we are to meet these goals; we will only do so
with full participation of children and young people Carol
Bellamy, UNICEF-Executive Director. We must do more
than talk about our future, we must start to create it now.
said Kofi Annan, Secretary General of United Nations.
The Commissions for Protection of Child Rights Bill 2005,
has been passed on December 22, 2005, by both the houses
of the parliament, the Loksabha and the Rajyasabha. This
is a welcome news for the children of our country. We
have to wait and see how it benefits millions of children of
India. As one of the measures towards protection, a 24
hour toll free telephone helpline 1098, of The Ministry of
Social Justice and Empowerment is available for children
in distress and provide crises intervention like medical,
shelter, restoration to native place, protection from physical
or sexual abuse and also to rehabilitate them. This Ministry
of Social Justice and Empowerment, Government of India
is the nodal Ministry, with support from The National
Human Rights Commission, MTNL, UNICEF, Transport
Ministry, etc. as members of the board. This service was
operational in 56 cities and the government is planning to
expand it to cover the entire nation.6 In the recent past a
Home Ministry at the centre approved draft, was
circulated among states. This was in connection to protect
Indian children from child abuse physical, sexual,
economical. However the draft Offences against
children, Act 2006, is not comprehensive. No Ministry is
thinking of setting up Child Protection Units [CPUs] and

Child Protection Courts [CPCs], which would deliver these
new laws effectively and speedily. Thus the victimized
child for no fault of his/her will continue to go through
the adult courts. Some statistics which throw light on the
need of the dire requirements of these CPUs and CPCs;
40% of the girls and 25% of our boys are sexually abused,
half the abusers are adults who enjoy the trust of these
children. In 2001, 34.3% of our population was 0 to14
years of age, and 41.6% was 15 to 39 years. Thats sizable
chunk of our population left vulnerable, needing legal
facilitation by the state. It isnt complex to set up CPUs
and CPSs, several countries have them. Younger specially
trained police persons handle one CPU in each city; they
deal with all the cases where a child is a victim From the
filling of First Information Report [FIR], investigation of
the case, handling of the child where statements are
recorded on video by psychologists, so that the child is
not continuously retraumatized, medical examination on
premises, counseling, follow up visits, and the arrest of
the perpetrators. CPCs have sensitized judges, are child
friendly, case delays are not encountered, crossquestioning has limits, courts are in camera and victims
shielded from the accused. Indians have every right to
have CPUs and the CPCs. In absence of these our children
have to suffer. International pedophilics who have begun
enjoying India will prey with glee. Especially on boys
caught, they will prefer to be tried here, stay for years in
their cells and finally get away with a simple sentence.
The challenges facing children in the 21st century are
immense and will need to be faced if we are to achieve the
goal of child protection for all. Three specified constraints
are namely, poverty HIV/AIDS infection and war. In many
African and Asian countries the HIV/AIDS orphans and
pandemic has changed the social structure of society, with
AIDS orphans and children infected and affected with
AIDS becoming common. The consequences of posttraumatic stress resulting from war needs to be stressed
and the development of programmes that place children
in the center of relief programs to foster a culture of
protection in the background of poverty is essential.1,15
BIBLIOGRAPHY
1. Aggarwal K. Editorial; CANCL News, 2005;4[1]:2-3.
2. Aggarwal K. Current scenario of child abuse. Pediatrics
Today, 2008: Under publication.
3. Chadwick DL. Child Abuse. In: Rudolph AM, Hoffman
JLE (Eds). Text Book of Pediatrics, [19th ed] New York,
Connecticut: Appleton and Lange Norwalk 1991;760-89.
4. Child Abuse in India. A report on National Seminar on
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5. Child Abuse and Neglect. The doctors response, taken
from booklet on the protective services section, Victorian
Government, Dept. of Health and Community Services,
Australia, with guidance and assistance of a Doctors
reference group[3rd ed]. 1993, in CANCL News 2004;
3:21-5.
6. Child Help Line. CANCL News 2006;6[2]:53.
7. Ertem OI, Bingolar BE, Ertem M, Uy salz, Gozdasoglu S.
Medical neglect of a child, challenges for pediatricians in
developing countries. Child Abuse Negl 2002; 26[8]:75161.
8. Foreman DN. Detecting fabricated or induced illness in
children. BMJ 2005;331[2]:978-9.
9. Health and Education of women and children through
the Panchayat Raj Institution and National Rural Health
Mission. CANCL News, 2006;6[1]:8.
10. Hildyard KL, Wolf DA. Child neglect- development issues
and outcomes. Child Abuse and Negl 2002;26
[6-7]:620-9.
11. Indian Penal Code Sections: Immoral Traffic [Prevention]
The Juvenile Justice [Care and Protection of Children],
2000.
12. Kacker Loveleen. Child protection scenario in India.
Ministry of women and child development, Government
of India. CANCL News 2008;1:30-2.
13. Kanth AK. Legal and Judicial Implications of Child Abuse
in India-Global to National Perspective. Pediatrics Today
2008: Under publication
14. Kellog ND, Merard SN. Violence among family members
of children and adolescents evaluated for sexual abuse.
Child Abuse and Negl 2003;27[12]:1367-76.
15. Lachman P, Poblete X, Ebigb PO, Nyandiya-Bundy S,
Bundy RP, Killian B, Doek J. Challenges facing child
protection. Child Abuse Negl 2002;26[6-7]:587-617.
16. Mehta MN. Physical abuse of Abandoned children in
India. Child Abuse and Negl 1982;6:171-5.
17. Mehta MN. Abuse of Abandoned children in India, ICCW
News Bull 1990;37:3-7.
18. Mehta MN. Child abuse, neglect and child labour. In:
Parthasarthy A [Ed in chief]. IAP Textbook of Pediatrics
3rd ed. Jaypee Brothers Medical Publishers Pvt. Ltd, New
Delhi 2006;953-70.
19. Mehta MN. Child abuse and neglect. In: Udani PM (Ed).
Textbook of Pediatrics. NewDelhi and Jaypee Brothers
Medical Publishers Pvt Ltd, New Delhi 1991;1520-8.
20. Mehta MN. Sociomedical aspects of child abuse. J Appl
Med 1992;257-62.
21. Mehta MN. Child abuse and neglect. In: Gupte S (Ed).
Recent Advances in Pediatrics 4, Jaypee Brothers Medical
Publishers Pvt Ltd, New Delhi, 1994;58-87.
22. Mehta MN. Child abuse and neglect. In Banerjee SR (Ed).
Community and social pediatrics, Jaypee Brothers
Medical Publishers Pvt Ltd, New Delhi 1995;157-74 and
[2nd ed] 2008;326-57.
23. Mehta MN, Lokeshwar MR, Bhatt S, et al. Rape in
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Children. Child Abuse and Negl 1979;3:673-7.
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Mehta MN, Prabhu SV, Mistry HN. Types of physical
health problems in working children. In: Naidu US,
Kapadia K (Eds). Child labour and health. Tata Institute
of Social Sciences, Bombay 1982;138-49 based on National
Seminar on Child Labour and Health organized by Tata
Institute of Social Sciences and WHO, Bombay, 1981.
Mehta MN, Prabhu SV, Mistry HN. Child labour in
Bombay. Child abuse and Negl 1985;5:107-11.
Mehta MN, Munshi NN, Krishnan P. Adoptions: Follow
up from an Orphanage in Bombay. Child Abuse and Negl
1983;7:78-82.
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Illegitimate Babies, paper presented at the International
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in March 2007. Ministry of Women and Child DevelopmentRepots in Hindustan Times 2007 March 9, 10
April 10, 13- editorial and by Kanth A[ref.13], Aggarwal
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2007;21-2.
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33. Sangwan S, Menon V. Indian Penal Code does not
recognize child abuse, Hindustan Times 14th Dec, 2000
as quoted in CANCL News 2002;1:16.
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Pediatr 1993;91[1]1-3:642-8.
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Mumbai, April 16th, 2006.
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8.2 Child Labor

Meenakshi N Mehta, SR Banerjee
CHILD LABOR
Child labor is a pervasive problem throughout the world,
specially in developing countries. India has the largest
number of child labor in the world and constituted around
3.6 percent of the total labor force. Majority (75%) of them
work in rural settings and 1/3 are girls. But the alarming
feature of the problem in recent years was the enormous
increase of child workers in urban settings.
In India, a sizable number of children are still far away
from the hopes and expectations expressed in the UN
Convention on the `Rights of the Child. In the developing
countries like India, it is not uncommon to see a young
child behaving and becoming a premature adult, having
been pushed and burdened to `work, earn and support
the family. Children work in almost all the countries of
the world. Participation of children in work in different

forms is not unusual amongst various societies and this
is an acceptable phenomenon in the human history. In
the less privileged countries, culturally gradual
involvement in work occurs between the ages of 5 and 15
years.4-8 Although these children often help in their family
vocation, most of the times in the agricultural activities
and are not gainfully employed. An equal number who
have no family business, or income, or are in adverse
situation are forced to take up any activity which will
help to support the family. Whether they like it or not, they
land up working in inhuman stressful situations for petty
income. As economic work opportunities are limited in
the rural areas, children have to migrate to the urban areas
in search of jobs. Thus, the problem of child labor assumes

a grave issue in the cities and the townships of almost
every third world country.
HISTORICAL BACKGROUND
Child labor has a long history. From the ancinet times,
children worked in agriculture and as apprentices to
artisans. In colonial America, children who helped in their
own farms and households were commonly hired out to
perform similar tasks in neighboring farms and
households. Child labor underwent major expansion and
restructuring during 1700s as a consequence of the need,
created by the industrial revolution for large number of
workers. In that era most mill owners preferred to have
children rather than adults, children as young as eleven
years especially girls, were sent by their families to work
in the mills because the wages they could earn for exceeded
the volume of their parents at home on their rural farms.
Thus in the pre-industrial revolution period, the
phenomenon of child labor was prevalent all over the
world, though having an altogether different nature and
magnitude. In India, child labor was identified as a major
problem as early as 19th century. The first factory was
started about the middle of 19th century and children were
employed in cotton, jute mills and coal mines. As early as
1881, during the British period, legislative measures for
the protection of child worker employed in hazardous job
were adopted. In the 20th century industralized countries
have taken care of many child labor problems and evils.
However, these problems, and evils very much exist in
Africa and Asia.
DEFINITION
According to encyclopedia of Social Sciences (1959) child
labor was defined as: when the business of wage earning
or participation in self and family support conflicts
directly or indirectly with the business of growth and
education, the result is child labor. According to ILO (1986)
the definition of child labor is to include children below
the age of 15 years in work and employment with the aim
of earning a livlihood for themselves or for the families.26
UNICEF has given comprehensive formulation in its
attempt at defining the child labor:
1. Starting fulltime work at too early an age
2. Working too long within or outside the families so
that children are unable to attend school
3. Work resulting in excessive physical and psychological strain upon the child
245
4. Work and life on the street in unhealthy and dangerous

conditions
5. Too musch responsibility at too early an age with
inadequate remuneration for working out side the
family
6. Work that inhibits the childs self-esteem as in bonded
labor and prostitution.
The definitions therefore must be relevant to particular
situation in various countries. Various authors have also
tried to define it in various ways:
Kulshrestha defines it as the employment of children
in gainful occupations which are dangerous to their health
and denying them the opportunities of development.
Khan uses the term Child Labor in the sense of
gainful employment secured from the employed for
wages, whereas committee on child labor Govt. of India
defines it as that segment of populations which participates in work either pain or unpaid. Maheswari et al
it as any work done by the child in order to economically
benefit their families or themselves, directly or indirectly,
at the cost of their physical, mental, and or social development.
CHILD LABOR VERSUS CHILD AT WORK
The term child at work indicates unexploitative
employment of children, for example, in the developing
countries, children as they grow, learn to get involved in
the household work or vocation of the family as soon as
they are capable of helping. This helps the child in the
informal preparation and training for adulthood tasks.
Needless to say this is virtually free from any exploitation
or harmful effects and on the contrary may prove
interesting, educational and socially useful. However,
work outside the family environment involves a sharp
change of environment, discipline and lifestyle.
Thus child labor indicates employment of child for
economic wage earning work and the child is subjected
to various hazards related to his mental, physical, and
social health. The child looses his childhood abruptly
and is prematurely pushed to live an adult life and
shoulder responsibilities (Figs 8.2.1 to 8.2.23).
MAGNITUDE OF THE PROBLEM
The magnitude of such child labor is estimated around
100 to 200 million, which is 4 to 8 percent of the total
world employment (2.4 billion persons) in 1994 and after
a decade it would have increased considerably. Sixteen
nations of Asia9 contained 261.3 million child workers in
246
Figure 8.2.1: School dropout

Figure 8.2.4: Child working in road side restaurant
Figure 8.2.2: Children working on tea stall
Figure 8.2.5: Child working at the canteen

of industrial estate
Figure 8.2.3: Children working in college canteen
early 1990s. On an average in developing countries more

than 18 percent of children between 10 and 14 years are
estimated to be working which amounts to 18 million
children working as per official reports, whereas
247
Figure 8.2.9: Children working in plastic bottle factory
Figure 8.2.6: Child working in industrial hardware factory
Figure 8.2.10: Child working in

packing waste (dry) material
Figure 8.2.7: Girl working in packing industry
Figure 8.2.8: Children working in packing industry
Figure 8.2.11: Child working in plastic packing firm
248
Figure 8.2.15: Boy working in garage (on battery)

Figure 8.2.12: Girls working in hosiery factory
Figure 8.2.16: Brother and sister working

as cobblershoe repairer
Figure 8.2.13: Girls working in ready-made
garments factory
Figure 8.2.14: Children working in garage
Figure 8.2.17: Child working as cobbler
249
Figure 8.2.18: Child working as a fish seller
Figure 8.2.20: Child working to clean

road potholes and drains/gutter
Figure 8.2.19: Children working as vegetable vender
unofficial figures are around 100 million child workers,

i.e. 1 in every 16 children is a child labor.21 India has
probably the largest child labor force in the world
amounting to 17.4 million in 1990,2 and has increased to
20 million in 1994. (Indian Labor Ministry). From the
Government of India census 1991, out of total 203.3
million children between 5 and 14 years, 5.9 percent
children were in labor force. There is lack of information
on the vast majority of children engaged in the
unorganized sector and comprising about 92 percent of
Figure 8.2.21: Child keeping monkey as pet and worked

for entertaining people, doing road side shows
250
Figure 8.2.22: Child lifting heavy stones on neck and

doing shows for entertainment of people
the total labor force. In 1996, UNICEF estimated

178 million children in the age group of 6 and 16, of these,
the International Labor Organization estimated 14.4
percent children between 10 to 14 years as economically
active. The female children constituted 70 percent of child
workers in weaving industry and 90 percent in match
industry.
In India according to 2001 census there were 253.16
million children agent 5-14 years comprising 24.61
percent of the countrys total population. Nearly 75.38
percent of them lived in rural area. Out of 12.7 million
working children, approximately 5.78 million children
were classified as main worker and 6.89 million as
marginal workers. Main workers are those engaged in a
full-time economic activity and marginal workers are those
who are part-time workers as shown in Table 8.2.1.
TABLE 8.2.1: Distribution of work force in
million aged 5-14 years
Category
Main workers
Total
Rural
Urban
Marginal workers
Total
Rural
Urban
Both sexes
Male
Female
5.78
4.82
0.96
3.60
2.93
0.67
2.18
1.90
0.28
6.89
6.52
0.36
3.21
3.00
0.21
3.68
3.52
0.16
Source: Census of India 2001
Causes of Child Labor

The real causes of child labor are deep rooted in
inequality and poverty. This has become conventional
Figure 8.2.23: Child employed in hazardous street play

involving climbing and walking on poles/bamboo
wisdom, but what does it really mean? To begin with,

parents have little choice but to sent their children to work,
parents depends on their children. Child labor is a
socioeconomic problem. It is generally considered that the
socioeconomic conditions are the roots of child labor.
However, for ease of understanding they can be grouped
under three major heads, i.e. causes pertaining to:
Familial poverty, parental illiteracy/ignorance, parental
unemployment and death, large family especially with
more children, fathers addiction and debt, bonded labor,
etc.
Child poor academic scholastic performance and or
repeated failures at examinations, repeated birth of
female child in the same family, following the path of

elder sib who is gainfully employed, the sense of economic
independence, and false belief of social respect related to
earning.
Social poor access to educational facilities, poverty,
literary ignorance, lack of land reforms and appropriate
rural development, migration of children from rural to
urban areas in search of livelihood, economical
advantage of the employers by employing cheap labor
instead of employing adults; vulnerability to sexual
exploitation for prostitution. Further no threat of
formation of unions of the child workers (unlike adults)
and the most important the non-enforcement of child labor
laws and poor punitive law provisons.
WORKING CONDITIONS
Clear demarcations between hazardous and nonhazardous work are essentials to control and protect the
working child from the ill-effects related to the work. Any
occupation which allows the child while working to come
in contact with the harmful substances like chemicals,
dust, raw materials, unfinished products, wastes, effluents
or explosives/inflammable is termed hazardous.
Children working in the following industries are listed as
hazardous by the Child Labor Act (prohibition and
regulation) 1996, such as tobacco industry, carpet weaving,
cement manufacturing, stone quarry, wood carving, cloth
printing, silk weaving, zari work, dying and weaving,
match manufacturing, explosive and fireworks, mica
cutting and splitting, shellac manufacturing, tanning and
the construction work. The other industries like glass
manufacture, lock making, gem and diamond polishing,
and sex related activities like child prostitution should be
included. Table 8.2.2 lists the type of occupation and
related health hazards.
Among the non-hazardous industries are the ones,
where the children work in the unorganized sectors
mainly in the urban areas, like commerce and service
sectors, multigrade activities like roadside hotels,
restaurants, tea stalls, street vendors, working in garages,
as cleaners, on the petrol pumps, minor help in
construction work, as rag pickers, as news papers boys,
selling flowers, fruits and vegetables, and selling
miscellaneous items in the trains, stations, bus stops, etc.
At such work situations the risk of health hazards are
minimal. In the area of domestic work the risk of physical
and sexual exploitation is quite high (especially for
females) (Refer Table 8.2.2).
251
Consequences and Health Hazards of Child Labor20,21

Working children belong to critical period of important
physical and psychosocial development. It is the time of
pubertal and adolescent growth spurt and maturation
of personality development. Health hazards can be
divided basically into two groups:
1. Hazards inherent to the working children themselves
and
2. Hazards related to their occupation.
Working for long hours in unhealthy environment
has deleterious effect on childs health. Besides physical
health hazards children have to bear emotional,
psychological and at times sexual trauma. Children, who
work in industries where they have to carry heavy
weights, grow up shorter and weigh less than normal
children. (ILO 1996).
Children who are forced to work beyond their
physical capacity are prone to occupational injuries
because of fatigue, inattention and poor judgment. This
may be compounded with hunger and thirst for long
hours, inadequate and improper sanitary facilities, and
shortage of rest and sleep. Such children become irritable
or depressed and develop psychological symptoms like
headache, giddiness, inattention; lack of concentration
will further make them prone to otherwise avoidable
injuries. Children who develop serious injuries at work
and remain poorly treated are likely to land up with
permanent handicaps as well as social and emotional
maladjustments. Lack of adequate rest, sleep, food,
emotional deprivation, family support and no access to
entertainment or recreation as well as education may lead
them to take up and participate in antisocial activities
like, stealing, gambling, consumption of drugs and alcohol,
and at times sexual activities. Children entrapped in
brothels or gambling, etc. are at an additional risk of
developing venereal diseases like HIV/AIDS. In adult life
due to inadequate education, they are unable to compete
for better job opportunities and have to struggle for a
comfortable and socially gainful life. Children chronically
deprived of adequate food suffer from irreversible severe
malnutrition, poor immunity, hence are prone to infection
and may die prematurely.
Bonded Child Labor
Bonded labor is prevalent in some developing countries
like India, where the peasant family committed to
providing certain labor services by custom often in return
repayments of debt. One form of bonded labor is where
252

TABLE 8.2.2: Occupational health hazards
Occupation
Disease/disabilities/consequences
Baloon factories
Pneumonia, bronchopneumonia and breathlessness, heart failure.
Match and fireworks Industries
Breathing problems, severe burns, muscle fatigue, mutilation, deformities due to long
hours of work in one position, fire accidents, eye and kidney diseases.
Lock industry
Tuberculosis and respiratory tract diseases, asthma, pneumoconiosis, acute headache,

acid burns.
Glass and bangle industries
Heat stroke, conjunctivitis, tuberculosis, burns on face hands, eye sight defects, skin
diseases.
Slate industry
Silicosis, tuberculosis, asthma.
Stone quarries/Asbestos factories
Tuberculosis, respiratory disorders, physical injuries, asbestosis, pneumoconiosis
Brick kiln
Tuberculosis, urinary infections, eye problems, headache, shoulder pains, malaria,

injuries.
Gem polishing
.do.
Diamond polishing
..do..
Zari embroidery
Eye defects, spondylitis, lung ailments.
Handloom/powerloom
and silk products
Asthma, tuberculosis, bronchitis, posture related eye defects, byssinosis, spinal

problems.
Cotton hosiery
..do.
Printing and dyeing
Pigmentation and injuries to nails and fingers, posture related disorder.
Brassware
Eye injuries, respiratory disorders, tuberculosis, asthma and lung ailments, loss of limbs,
burns, vomiting, early death.
Carpet weaving
Eye defects, lung problems, distorted back, loss of fingers, poisoning from coloring
agents
Mines and pottery
Asthma, bronchitis, tuberculosis, eye defects, silicosis
Bidi making
Chronic bronchitis, tuberculosis, posture related disorders
Construction workers/
Domestic labor
Physical injuries, stunting, sexual abuse, drug addiction, isolation from society females
more vulnerable for sexual abuse as domestic workers
Watch and microcomputer

industry
Damage to eyesight, postural problems
Child prostitution
Physical injuries, risk of conception and threatened abortion, venereal diseases

including HIV/AIDS, emotional and psychological problems
Agriculture/farming
Due to constant wetness skin infections of feet, insect bites, allergic rashes due to
pesticides, risk of poisoning, cuts injuries to hands
Source:
1. Born to work- Neera Burra} In Child Abuse Neglect and Child Labor (CANCL) NEWS Vol. 1, 23-24, Jan 2002.
2. Children in darkness.
3. Press release- Oxford University Press, 1995.
children are pledged to landlords, often as domestic

servants as part of debt for all through out their lives.
In many of these situation, child workers are neglected
and poor nutrition and bad health. In India 8.7-21 percent
bonded laborers are below sixteen years of age. Another
type of bonded child labor which appears to be very recent
but increasing rapidly is constrictive military services.

Here children have been involved directly as solidiers or
paramilitary personnel. There may some benefits as in
regular food, clothing and shelter, medical attention to
these children but these can hardly compensate for the
danger of exposure to work.

LEGISLATION AND GOVERNMENT
POLICY ON CHILD LABOR
The laws governing child labor vary in different countries
and for different jobs undertaken by these children.
In India, the first Factory Act was passed in 1881 by the
British Government, defining the child labor as working
between the ages 7 and 12 years with working hours 9 and
with 1 hour rest. It took 10 years to raise this age limit to 14
years. Subsequent to that various laws were passed
periodically which were related to specific industries.
Regarding the Indian Government enforcement, the central
statutes mainly cover:
Employment in industries, mining, transport,
railways, ports, oil, and employment run by and
under the government;
whereas the state statutes cover
Shops and establishments, factories, plantations, etc.
As India is party to the ILO convention and considering its poor economic conditions, special provisions
are made and lower the standards for implementation.
The Indian law accepts the maximum hours of work
and deals with the following four matter:
1. Minimum age of employment of children
2. Medical examination of children
3. Maximum hours of works
4. Prohibition of night work for children
Unfortunately the Indian laws are not applicable to a
numerable unorganized industries including agriculture
and this is an important deficiency in our law.
To counteract the above shortcoming 1973 the ILO
passed a convention establishing 15 years as the
minimum age for working for most sectors, while
permitting light work from the age 13 years. This is to
safeguard childs health, morals, safety or prejudice his/
her school attendance. Although 28 countries have till
date actually ratified the convention, most have passed
legislation of their own along similar lines. Further
recommendations have been given by the Child Labor
Committee in 1979.
What Can be Done-Recommendations
The phenomenon of child labor is so complex and deeply
rooted in the society that it may not be wise to rely on
one single approach for its amelioration or elimination.
Although emotionally we might agree that child labor
should be abolished or banned; but whether we like it or
not, in reality and in practical terms we have no choice
253
but to agree with the ILO statement that suppressing

child labor is unlikely to improve the welfare of many of
the children unless substitute sources of income and
opportunities for personal development are created.
Protection and not abolition is the need of today. It sounds
good that children cannot and should not work and they
must be in schools, but do we have enough schools or do
the children have easy access to these schools and all
that goes with the primary and secondary education?
Besides, discrepancies exist between rural and urban
educational setups. Amongst the strategies suggested to
alleviate child labor are:
RECOMMENDATIONS
1. National campaign to create public awareness of its
pernicious effects
2. Enlisting trade unions to combat it
3. Create facilities for education formal and informal
4. Increase opportunities for adult employment and
fairer income distribution patterns
5. Measures to control population growth
6. Steps to improve overall socioeconomic development
7. Allowance to poor families whose children are in
schools.
These recommendations are idealistic, are extremely
difficult to be implemented. Till such time child labor
will thrive and continue, if not diminish. There is thus
urgent need for practicable and workable suggestions:
The NCLPS being the main initiative of the
Government of India constitute the backbone for
elimination of child labor activity in the country.
Specific measures which can be implemented are:
1. The employers with whom the children are
employed should be taken into confidence, and
could be motivated to have a more gentle and
humane attitude towards the children. Once
convinced, gradually they could be requested to
provide minimum facilities lacking in their work
place. 21,25 This should be done by the locally
influential political or religious leader or any
popular citizen, a social activist, a film star, etc, but
never a police or a lawyer as the latter may have
adverse effect. The employers who are already
motivated could then be looked upon as role models
and thus set examples to the other employers of that
area.
2. Work place and environment can be improved.
254
3. Adequate facilities for separate area for food/eating,

safe and clean drinking water, toilets- separate for
males/females, and washing area and sanitation.
4. Provision for health check up and treatment for
medical problems at the work place, arrangement for
investigations, referrals for specialized diagnosis and
appropriate care, all these free if possible.
5. Some arrangement for rest, recreation, games,
playgrounds/open areas for outdoor games, access
to gymnasiums at nominal cost, access to entertainment, television, radio, music, etc.
6. Motivation for taking formal/nonformal education
free of cost during free time or leisure hours,
attendance at night schools, street classes and
incentives to those who perform better academically17
7. Training in socially useful tasks like post, banking,
budgeting simple accounts and savings
8. Refrain from vices and addictions like smoking,
consumption of addictive drugs and substance abuse,
alcohol and sex education for prevention from
venereal diseases, AIDS and sexual abuse
9. To teach morals and how to lead a productive life
with tolerance to all the religions and social
adjustments
10. These measures are not only possible but have been
implemented successfully in various child labor
projects.21, 22
GOVERNMENT OF INDIA AND NATIONAL CHILD
LABOR POLICY AND PROJECTS (NCLP)
The concern for children and elimination of child labor
continues to be an area of great concern for the Government
of India. With a view to addressing the problem of child
labor, a National Child Labor Policy was announced in
1987 which is the genesis of the National Child Labor
Projects. A major activity undertaken by the NCLP is the
establishment of special schools of rehabilitation centers
to provide nonformal/formal education, etc. for children
withdrawn from employment in various hazardous
occupations and processes. In pursuance of this objective,
so far 100 NCLPS have been sanctioned which are being
implemented in various districts of 13 states across the
country for the rehabilitation of 2 to 11 lakh working
children. The NCLP is implemented by a district level
project society headed by the District Collector as its
chairman. He plays a key role in right from policy
formation, implementation and its eventful evaluation.

He has to play the pivotal function of holistic approach of
meaningful convergence of resources and staff at all levels
at center top officers to district and field middle level to
the lowest level functionaries, i.e. the people actually
performing the program. Thus, he has to interact and
coordinate with all the departments particularly
education, rural development, health, social welfare,
women and child development, nutrition, etc.
The NCLPS being the main initiative of the
Government of India constitute the backbone for
elimination of child labor activity in the country.
Children are the most precious resources, are the key
to the future of our planet. Every effort should be made
to protect their childhood, the time to grow, play and
learn. The first right of the child is the childhood, if that
is missed then the child misses all that goes with it. We
as the pediatricians, parents, guardians, teachers, social
workers, and caretakersthe advocates of children owe
a duty to our children and if determined we can do it.
BIBLIOGRAPHY
1. Acharya P. In: Ramesh Thapar (Ed): Seminar on child
labor. Malhotra Building, Janpath, New Delhi, (ED),
1982;18-21.
2. Banerjee SR. Child labor. Indian Pediatr 1990;27:3-4.
3. Banerjee SR. Female working. Children Indian Pediatr
1990;27:1153-55.
4. Banerjee SR. Child labor suburban area of Calcutta, West
Bengal. Indian Pediatr 1991;28:1038-42.
5. Banerjee SR. Child labor. In: Gupte S (Ed): Recent
Advances in Pediatrics, Jaypee Brothers Medical
Publishers, New Delhi 1992;2:134-49.
6. Banerjee SR. Agricultural child labor in West Bengal.
Indian Pediatr 1993;30:1425-8.
7. Banerjee SR. Child labor. In: SR Banerjee (Ed):
Community and Social Pediatrics. Jaypee Brothers
Medical Publishers, (1st ed.), New Delhi 1995;164-83.
8. Banerjee SR. Child labor. In: AK Patwari, Sachdev HPS
(Eds). Frontriers in Social Pediatrics. Jaypee Brothers
Medical Publishers (1st ed.), New Delhi,1998;78-89.
9. Batalvii IH. Childhood denied. The situation of children
in Pakistan. International Childrens right Monitor;
1990;1/2:14-6.
10. Banerjee SR. Child labor. In: Banerjee SR (Ed).
Community and social pediatrics, (2nd ed), JP Medical
Publishers, New Delhi 2008;375-6.
11. Burra N. Child labor in the urban industries of India.
World employment programme research, working
paper no. 25, ILO Publication, Geneva, International Labor
Office, 1988;30-3.

12. CANCL News. Child labor in major industries in India.
2002;1:23-4.
13. Falkner F. Editorial. International Child Health USA,
1994;2.
14. Ghosh S. Girl child in the SAARC countries. Indian Pediatr.
1990;57:16-9.
15. Gupte S. Child labor. Indian Pediatr 1987;24:177-80.
16. Khatu KK et al. Working children in India. Baroda. Baroda
Operation Research Group, 1983;69-70.
17. Kulshrestha JC. In: Kulshreshtha JC (Ed): Child labor in
India. New Delhi, Ashish Publishing House 1978 ;1-19.
18. Maheshwari RK, Karuanakaran M, Gupta BD, Bhandari
SR. Child labor. Indian Pediatr 1986;23:701-04.
19. Mehta Meenakshi N, Prabhu SV, Mistry HN. Child labor
in Bombay. International Jr Child Abuse and Neglect
1985;9:107-11.
20. Mehta Meenakshi N. Child abuse and neglect. In: Udani
PM (Ed): Textbook of Pediatrics, Jaypee Brothers Medical
Publishers (1st ed), New Delhi 1991;1520-28.
21. Mehta Meenakshi N. Child labor. In: Gupta BD,
Maheshwari RK (Eds): Recent trends in pediatrics,
Churchill Livingstone, New Delhi 1983;135-50.
22. Mehta Meenakshi N, Prabhu SV, Mistry HN. Types of
physical health problems in working children. In: Usha
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Naidu, Kamini Kapadia (Eds): Child labor and health.

Tata Institute of Social Sciences, Bombay, 1984;135-50.
Satyanarayanan K, Naidu AN, Narasing Rao BS.
Nutritional deprivation in childhood and the body size,
activity and physical work capacity of young boys. Am J
Clin Nutr 1979;32:1769-75.
Sawant ST. Legal aspects of child labor in India, CANCL
News, 2004;27-30.
Shah PM. Child labor. A threat to health and development [2nd revised edn]. Geneva, Switzerland, Defence
for Children International 1985;79-98.
Yajurvedi VP. Convergence and elimination of child
labor, Ministry of Labor, Government of India, CANCL
News 2003;2:16-7.
Mehta Meenakshi N, Banerjee SR. Child labour. In:
Parthasarthy A et al (Eds): IAP textbook of pediatrics.
Jaypee Brothers Medical Publishers Pvt Ltd, (3rd edn),
New Delhi 2006;959-71.
Pinto GJ. Child labor, New Delhi: UNICEF 1987;1-3.
ACKNOWLEDGEMENT
All photographs pertaining to this chapter are from
the collection of Prof Meenakshi N Mehta, with due
acknowledgement.
9.1 The Principles and Practice of Immunization: T Jacob John ............................................................................................................. 258
9.2 Vaccines and Vaccine Preventable Diseases: Today and Tomorrow: AB Desai ............................................................................. 262
9.3 Newer Vaccines: AK Dutta, Anju Aggarwal ............................................................................................................................................ 265
9.4 Vaccine Storage and Handling: RK Agarwal, Digant D Shastri ........................................................................................................... 271
9.5 Management of Adverse Effects Following Immunization (AEFI): M Indra Shekhar Rao, Tanmay Amladi .................................... 277
9.6 Approach to Management of Fever in Newborns, Children and Adolescents in Office Practice: Digant D Shastri .................... 285
9.7 Fever and Fever of Unknown Origin: PP Maiya ................................................................................................................................... 295
9.8 An Approach to a Child with Fever and Skin Rash: Jayakar Thomas ............................................................................................... 302
9.9 Tuberculosis in Children: Vimlesh Seth ............................................................................................................................................... 315
9.10 Abdominal Tuberculosis: Saroj Mehta, Vimlesh Seth .......................................................................................................................... 332
9.11 Neurotuberculosis: Vimlesh Seth .......................................................................................................................................................... 336
9.11.1 Revised National Tuberculosis Control Program (RNTCP) including Directly Observed Treatment: Vimlesh Seth ...................... 342
9.12 Poliomyelitis: Ashok Gupta .................................................................................................................................................................... 350
9.12.1 Differential Diagnosis of Acute Flaccid Paralysis: AD Tewari ............................................................................................... 354
9.12.2 National Immunization Days (NIDs) as a Vital Component of
Polio Eradication Strategy: Vipin M Vashishtha, Naveen Thacker .......................................................................................... 359
9.13 Diphtheria: AP Dubey, Jaydeep Choudhury ........................................................................................................................................... 362
9.14 Pertussis (Whooping Cough): YK Amdekar ......................................................................................................................................... 364
9.15 Tetanus: AP Dubey, Jaydeep Choudhury ............................................................................................................................................... 366
9.16 Measles: AP Dubey, Jaydeep Choudhury ............................................................................................................................................... 368
9.17 Mumps: Epidemic Parotitis: Ashok K Gupta ......................................................................................................................................... 370
9.18 Rubella: AP Dubey, Jaydeep Choudhury ............................................................................................................................................... 372
9.19 Staphylococcal Infections: AK Dutta, Anju Aggarwal ........................................................................................................................... 374
9.20 Pneumococcal Disease and its Prevention: Rohit C Agrawal ............................................................................................................ 376
9.21 Hemophilus Influenzae b Disease: RK Agarwal, Anju Aggarwal ......................................................................................................... 383
9.22 Typhoid Fever: YK Amdekar ................................................................................................................................................................... 383
9.23 Leprosy: Rajeshwar Dayal ...................................................................................................................................................................... 387
9.24 Leptospirosis in Children: S Ramesh ................................................................................................................................................... 392
9.25 Chickenpox (Varicella): AP Dubey, Jaydeep Choudhury ...................................................................................................................... 394
9.26 Dengue Illnesses: Ashok S Kapse ......................................................................................................................................................... 396
9.27 Infectious Mononucleosis: S Ramesh .................................................................................................................................................. 404
9.28 Respiratory Syncytial Virus Infection: A Balachandran, SO Shivbalan .............................................................................................. 405
9.29 Rotavirus Disease: Raju C Shah ............................................................................................................................................................ 408
9.30 Rabies: Tapan Kumar Ghosh, A Parthasarathy ...................................................................................................................................... 409
9.31 Pediatric HIV Disease: Meena Malkani .................................................................................................................................................. 414
9.32 Chikungunya Fever: Utpal Kant Singh, Rajniti Prasad .......................................................................................................................... 419
9.33 Malaria in Children: Ashok S Kapse ...................................................................................................................................................... 423
9.34 Kala-azar (Visceral Leishmaniasis): Yogesh Jain, Rakesh Lodha ....................................................................................................... 440
258
9.1 The Principles and

Practice of Immunization
T Jacob John
ACTIVE IMMUNIZATION
The induction of immune response by the deliberate
inoculation of appropriate immunogen(s) in the form of
a vaccine is termed as active immunization or simply
immunization or vaccination. In practice, this term applies to the inoculation of vaccine, regardless of the success
or failure of inducing the desired immune response.
PASSIVE IMMUNIZATION
The injection of pre-formed antibodies to a specific
antigen, in the form of antiserum or immune
globulin is termed passive immunization. The term
gammaglobulin is used to denote that the product is
not hyperimmune to any specific antigen, but contains
antibodies to all common antigens encountered by adults
from whom plasma had been collected for its extraction.
The physiological transfer of immunoglobulins across the
placenta to the fetus from the mother, provides natural
but passive immunity to the infant.
ANTISERA AND IMMUNE GLOBULINS
Antisera prepared in horses against tetanus toxin,
diphtheria toxin, rabies virus and snake venom are
widely used in India. Horse serum may cause hypersensitivity reactions including anaphylaxis and serum
sickness. The active principle is immunoglobulins; hence
unwanted components such as albumin may be removed
and more concentrated hyperimmune equine
immunoglobulins may be prepared. Even with such
preparations hypersensitivity remains a problem. The Fc
part of immunoglobulins are responsible for such
responses and removing Fc portion while preserving the
antigen-binding Fab portion has become the standard
prarctice in presenting equine hyperimmune immunoglobulins against rabies and hepatitis B antigens.
Homologous products prepared from pooled human
plasma are safer and more potent, but also more
expensive. Human immune globulins against tetanus,
rabies and HBV are available in India; elsewhere other
preparations are available, for example, Varicella-Zoster
immune globulin. Apart from these antigen-specific

products, human gammaglobulin preparations are
available for intramuscular and intravenous injection
either as replacement in hypogammaglobulinemia or for
therapeutic purposes in certain specific autoimmune
disorders.
IMMUNE SYSTEM AND RESPONSES
A network of cells with the functions of detection of any
specific immune response to introduced immunogens
constitute the immune system. The cells of the immune
system include antigen-presenting cells which detect and
ingest the microbes or their subunits in the vaccine, and
process and present the immunogenic epitopes to the T
and B lymphocytes which are thus stimulated to respond.
The CD4 positive T helper (Th) cells of Th-1 type respond
and regulate cell-mediated immunity (CMI) through
various subsets of cytotoxic lymphocytes, which are
mainly CD8 positive. Humoral immunity, mediated
through the different classes of antigen-specific
immunoglobulins, called antibodies, is induced by Bcells, but regulated by Th-2 cells. When stimulated, the
B-cells transform into plasma cells and secrete antibodies.
After adequate stimulation of the regulatory (T-cells) and
effector cells (T-and B-cells), memory cells (T- and B-cells)
survive for very long periods, ready to respond to the
same immunogens without delay, when introduced by
infection or immunization. Most protein antigens induce
complete immune responses, namely IgM and IgG
antibodies, CMI and memory. On the other hand,
polysaccharide antigens are T-cell-independent, meaning
thereby that they can only directly stimulate B-cells; the
consequent responses do not go through the class switch
from IgM to IgG and no memory cells are produced. Bcells become mature to respond to T-independent stimulation, only after the child is about two years old.
Mucosal immunization (with live attenuated viruses or
bacteria) induces mucosal (secretory) and serum IgA
responses also in addition to systemic immunity as described
above. However, mucosal protection from infection is
mediated through several factors and IgA is one of them.
Immunization and Infectious Diseases

The desired effect of immune responses to a vaccine
is protection from infection when exposed or at least from
disease even when infection occurs. However, most
immune responses to a variety of microbial antigens are
not protective. Live attenuated and killed viral and
bacterial vaccines elicit immune responses to a number
of antigens of the microbes. For subunit vaccines, the
protective antigens must be identified and included
for the vaccine to become successful.
TABLE 9.1.1: UIP schedule (1985)

Universal Immunization Program,
Childhood Immunization Schedule
Govt of India
BCG
: Birth or 6 weeks
OPV
: Birth, 6,10, 14 weeks
16-18 months
DPT
: 6,10,14 weeks
16-18 months
Measles : 9 months plus
DT
: 5 years
TT**
: 10 and 16 years
Vaccines in Current Use

The vaccines licensed in India include live attenuated
bacteria (BCG; S. typhi Ty 21a), live attenuated viruses
(OPV, trivalent and monovalent types 1 and 3; measles,
mumps, rubella, varicella, Japanese encephalitis,
rotavirus and hepatitis A), killed bacteria (B. pertussis),
polysaccharides (pneumococcal capsular antigens with
23 serotypes; S. typhi Vi; meningococcal capsular
antigens), protein-conjugated polysaccharides (H.
influenzae b antigens conjugated with different proteis;
pneumococcal conjugated antigens of 7 serotypes), killed
viruses (rabies, polioviruses, hepatitis A, Japanese
encephalitis, influenza and Kyasanur forest disease),
structural subunits (hepatitis B, B. pertussis, papilloma
virus).
Several combination vaccines are widely usedsuch
as DPT, MMR, DPT-HBV, DPT-Hib, DPT-HBV-Hib.
Schedules of Immunization
The Global Expanded Program of Immunization (EPI)
designed and popularized by the WHO recommends the
use of BCG, DPT, OPV, measles, HBV and Hib vaccines
for all infants. Booster doses of DPT, DT and TT and a
second opportunity for measles vaccine are recommended during later childhood and adolescence. The
National Immunization Program in India (Universal
Immunization Program, UIP) is sponsored and supported by the union government and implemented by state
governments. UIP gives BCG, DPT, OPV and measles
vaccines and has accepted in policy the inclusion of HBV
and Hib vaccines nationally.
The recommended age schedule of the primary and
booster doses of UIP vaccines is given in Table 9.1.1.
The Indian Academy of Pediatrics recommends the
supplementation of the UIP schedule with additional
doses of some of the vaccines and adding others not in
UIP. While the UIP vaccines will be given free of charge
259
**if
**
given for the first time at this age, give 2 doses at 4 weeks interval.
for pregnant mothers 2 doses of TT at 4 weeks interval
(if supplied by UIP) the families will have to purchase

non UIP vaccines. The IAP Immunization Time Tables
is given in Table 9.1.2.
The Logistics of Immunization
The Supply of Vaccines
Vaccines are allowed to be marketed in India, only after
licensing by the drugs controller. Every batch of vaccine
manufactured in India or imported, is checked for quality
assurance by the Central Research Institute (CRI) of the
Directorate General of Health Services at Kasauli. All UIP
vaccines are centrally purchased by the Department of
Family Welfare and distributed to the governments of
all states and union territories. Pediatricians are allowed
to collect all UIP vaccines from the local area health
authority without any charge, to be given to children
according to the national schedule. Vaccine utilization
must be accounted for by returning the list of beneficiaries.
Vaccines outside the UIP list, such as measlesmumps-rubella vaccine (MMR), hepatitis B vaccine
(HBV), H. influenzae b vaccine (Hib), typhoid fever
vaccines, Hepatitis A and Vericella vaccines which are
available for purchase from various vaccine distributors
have since been licensed in India.
The Cold Chain
All vaccines are susceptible to loss of potency, when
exposed to warm temperatures, but are very stable at 2
260
Age
Age recommended
Birth
BCG
OPV0
HepB 1
6 weeks
DTWP1/DTaP1
OPV1*/OPV1 + IPV1
Hib1
HepB2
10 weeks
DTWP2/DTaP2
OPV2/OPV2 + IPV2
Hib2
14 weeks
DTWP3/DTaP3
OPV3/OPV3 + IPV3
Hib 3
HepB3**
9 months
Measles
15-18 months
DTWP B1/DTaP B1
OPV4/OPV4 + IPVB1
Hib B1
MMR1
2 years
Typhoid#
5 years
DTWP B2/DTaP B2
OPV5
MMR2$
to 8C. Lyophilized vaccines (BCG, Measles, MMR) and

unadjuvanted liquid vaccines (OPV) are also stable when
frozen. Adjuvanted vaccines (DPT, HBV) lose potency
when frozen. If they accidentally freeze, they should be
rejected. When these norms are followed, vaccines should
be used within their date of expiry.
The system of transporting, distributing and storing
vaccines from the manufacturer right up to the point of
use under refrigeration using any convenient methods,
is referred to as the cold chain. In clinics, vaccines must
be stored in a refrigerator which maintains the inside
temperature between 4 and 8 degrees. If temperature falls
below 3, there is a chance for some vaccines to freeze
solid. Where vaccines are maintained in the cold chain
in clinics, multidose vials can be used to reduce cost.
Partially used vials must be maintained under cold
conditions for subsequent use. However, care should be
taken to disinfect the top, before puncturing the vial.
Reconstituted lyophilized vaccines (BCG, measles,
MMR, varicella and Hib) should be used immediately
after reconstitution. Multidose BCG or measles vaccine
may be used over some time, but they must be used up
within 6 hours; during the interim they should not be
frozen, but kept cold and not exposed to bright light.
Any left-over contents must be discarded after 6 hours.
10 years
Tdap
HPV^
Techniques of Vaccination
TABLE 9.1.2: Revised IAP immunization time-table (2008)
* OPV alone if IPV cannot be given

** The third dose of hepatitis B can be given at 6 months
# Revaccination every 3 years
$ The second dose of MMR vaccine can be given at any time 8
weeks after the first dose
^ Only females, three doses at 0, 1-2 and 6 months
Vaccines to be given after one to discussion with parents
Age
Vaccine
> 6 weeks
Rotavirus vaccine*
PCV 7#
Varicella$
Hepatitis A^
> 15 months
> 18 months
*Rotavirus vaccine [2/3 doses (depending on brand) at 4-8 weeks

interval]
# PCV 7 (three doses at 6, 10 and 14 weeks and 1 booster at
15-18 months)
$ Varicella (< 13 years single dose, > 13 years two doses at 4-8
weeks interval)
^ Hepatitis A (2 doses at 6 months interval)
Every pediatrician must familiarize oneself with the

descriptive leaflet supplied by the vaccine manufacturer
and also with the techniques of inoculation, side effects
and contraindications, if any.
When OPV is given, the nose of the infant should not
be pinched in order to make the infant to open the mouth.
Instead, a slight pressure may be applied on both cheeks,
between the upper and lower jaws, using the thumb and
a finger. There is no need to withhold breastfeeding for
long periods before or after giving OPV; in practice a
gap of 10 to 15 minutes is usually observed to breastfeed
after OPV.
BCG must be given intradermally; the preferred site
is the lateral aspect of the convex region of the left
shoulder. In infancy, intramuscular (IM) are given in the
anterolateral aspect of the high and subcutaneous
injections (SC) by pinching the posterior skin fold of
triceps muscle. HBV should not be given in the gluteus.

In older children, the deltoid muscle is often chosen for
IM injections and the triceps region for SC injections.
There is no need to warm the vaccine vial in the hands
before it is drawn in the syringe, or given in the mouth.
Frozen OPV needs to be just thawed before giving.
Adverse Reactions and Contraindications
All licenced vaccines except the brain tissue rabies
vaccine (not used now a days) and OPV are virtually/
completely safe products. However, all vaccines do cause
some adverse reactions, most of which are temporary,
self-limited and inconsequential. Specific contraindications are also very few. Minor illnesses are not a
contraindication to giving any vaccine. However, if the
nature of illness is not clear, caution must be exercised
in order to avoid the vaccine from being blamed for the
worsening of an illness. Immunization is better
postponed when there is any illness that requires
treatment, unless access to the infant is difficult later or
there is an outbreak of illness, e.g. measles. Every clinic
or hospital visit or admission must be used as an
opportunity to assess the immunization needs of the child
and to offer any pending doses.
No gastrointestinal or systemic reactions occur after
giving OPV and oral typhoid fever vaccines. On rare
occasions OPV-associated paralytic illness has been
documented in western countries, either in the vaccinee
or in adults in close contact with the vaccine. Its frequency
in India is unknown but it appears to be more common
than previously recognized; adults are not at risk in India,
since virtually all adults are immune due to prior
asymptomatic infections. Since hypogammaglobulinemia has been noted as a risk factor for vaccinevirus-induced paralysis, the recommendation is to give
the non-infectious killed polio vaccine to immunodeficient children. Indian experience is scanty and the
risk is not considered to be a factor in our policies. Infants
born to HIV-infected mothers, whether or not themselves
HIV-infected, are usually given OPV without problems.
DPT vaccine causes local inflammation and fever in
a proportion of vaccines. Paracetamol is advised to
prevent or reduce symptoms. If any neurological
reactions other than febrile convulsions are observed
within days after DPT, the infant must be carefully
assessed for any pre-existing disease process. There is
no evidence that DPT per se causes any neurological
illness; in specific instances of difficulty, expert opinion
must be obtained and discussed with the family before
continuing or discontinuing further doses of DPT.
261
The immunization clinic staff must be trained to

recognize vasovagal syncopal reactions and anaphylaxis
in vaccinated infants/children. While it is true that rural
health workers vaccinate at convenient places in the
villages where there are no facilities for resuscitation, and
in spite of no liability on the part of the doctor for a
genuine adverse reaction following vaccination, the clinic
must be equipped to handle such events. Any serious
event, not recognized as the usual side reaction of the
vaccine, must be reported to the local area health
authority.
Pulse Immunization
Herd Effect and Herd Immunity
Immunization against a specific disease mimics infection by the causative microbe in the inoculated
individual, inducing immunity without the risk of
disease. Only the immunized children are benefitted; the
unimmunized peers remain fully susceptible to infection
and disease, when exposed. However, as increasing
proportions of children in a community are immunized
against a specific disease, the transmission/circulation
of the infectious agent may be retarded; hence, the
incidence of disease may decline even in the unimmunized segment of the childhood population. This phenomenon is called the herd effect of the immunization
activity.
The term herd immunity refers to the proportion
of individuals in the population that are not susceptible
to the disease due either to natural infection or to
immunization or both. As immunization coverage
increases, herd immunity increases and herd effect may
become manifest. Herd effect can be recognized, only
if the incidence of disease is measured before and
during/after the immunization activities.
The Method and Purpose of Pulse Immunization
An epidemic of an infectious disease reaches a peak and
declines rapidly because of the very high herd immunity
consequent upon the epidemic spread of the agent. The
transmission may be interrupted soon after an epidemic.
Only when sufficient numbers of susceptible children
accumulate overtime, will the agent re-establish itself in
the community. This principle is applied in pulse
immunization. When a large proportion of susceptible
children are vaccinated in a short period of time, an
262
epidemic is simulated. The consequent herd effect

usually results in break of transmission of the agent. For
epidemic-prone diseases with more than one year of
inter-epidemic intervals, such as poliomyelitis and
measles, the pulsing of the vaccine may be conveniently
given at annual intervals. The term pulse immunization
is given to denote the repetitive campaigns at annual
intervals.
The herd effect of the total doses of vaccine given by
pulse would be much higher than when given routinely
throughout the year. In other words, better herd effect
for the same herd immunity is achieved with annual
pulse immunization. In developing countries where the
transmission of polio viruses is not interrupted in spite
of high coverage with the routine use of OPV, pulse
method can be applied to interrupt it. Since measles virus

is very contagious, it will be virtually impossible to
interrupt its transmission without resorting to pulsing
of vaccine at intervals, that are shorter than the regional
inter-epidemic intervals.
BIBLIOGRAPHY
1.
John TJ. Quovadis, Expanded Programme on Immunization? Indian J Med Res 2007;125: 13-6.
2. John TJ, Sammel R. Herd immunity and herd effect: New
insights and definitions. Euro J Epidemiol 2000;16:
601-6.
3. Writing Committee Singhal T, Amdekar YK, Thacker N.
Policy Update. IAP Committee on Immunization. Indian
Pediatr 2007; 44:390-2.
4. Writing Committee Singhal T, Amdekar YK, Agarwal
RK, Policy update. IAP committee on immunization.
9.2 Vaccines and Vaccine Preventable Diseases:

Today and Tomorrow
AB Desai
Experiences of the past lead us to a better future, hence,
it is important to know the events of the past. Infectious
diseases are as old as mankind. People knew how to deal
with some of the infections using herbs and many a times
they succumbed to infections. With increasing civilization and documentation, India, China, Egypt had their
own manuscripts. Increasing European influence made
the literature in various European languages especially
English more popular.
The practice of variolation was known since 1000 BC
in India and China, but the first documentation was by
Jenner in 1798 AD. He demonstrated use of variolization
in the prophylaxis of smallpox. Almost a century later,
Louis Pasteur the pioneer of immunology, from France
observed the process of attenuation and its use in
prophylaxis against infections. He suggested that terms
vaccine and vaccination should be used for all
substances and procedures useful for prevention of
infectious diseases.
Pasteur Institute established in Paris mainly for
research on rabies, soon became a seat for studies on
various vaccines. The antiserum therapy for prevention

and treatment of diphtheria and tetanus was soon found
out by Von Behring and later on led to the discovery of
toxoid, the detoxified toxin.
Twentieth century has been most memorable. The
important events of the century are:
i. Isolation of bacteria and viruses.
ii. Growing them in tissue cultures.
iii. Production of various vaccines both against
bacteria and viruses.
vi. Production of tissue culture vaccines against virus.
v. Advances in cell biology, genetic engineering and
in-depth understanding of immune mechanism
leading to development of recombinant DNA
vaccines.
vi. Eradication of smallpox by universal immunization.
vii. Pledge to eradicate poliomyelitis by 2000 AD.
viii. Pledge to eliminate neonatal tetanus and reduce
the mortality due to measles.

TABLE 9.2.3: Polysaccharide vaccines*
TABLE 9.2.1: Microbial vaccines*

Years Events
Years Events
1892 Cholera vaccine by Haffkine
1968
1971
1978
1980
1984
1896 Typhoid vaccine by Wright

1913 Diphtheria immunization, toxin-toxoid by Behring
1921 Tuberculosis vaccine by Calmette and Gurin (BCG)
1923 Diphtheria toxoid by Roman and Glenny
1923 Pertussis vaccine by Madsen
263
Meningococcus C vaccine (Gotschlich)

Meningococcus A vaccine (Gotschlich)
Vaccine against pneumococcal infection
Vaccine against Haemophilus influenzae type b
Vi Polysaccharide typhoid vaccine
*Adapted
from VaccinationNizar Ajjan (3rd edn)
1927 Tetanus toxoid by Roman and Zoller

1972 Acellular pertussis vaccine
*Adapted
TABLE 9.2.4: Vaccines under study
from VaccinationNizar Ajjan-(3rd edn)
ix. Many old vaccines like typhoid, rabies, yellow

fever, influenza, etc., are totally modified and new
safe, effective and economic vaccines are made
available.
x. Some old vaccines like cholera vaccine are discarded and attempts are on to prepare better and
safer vaccines.
There are about 200 infectious diseases caused by
bacteria, viruses, parasites and fungi. Some 21 vaccines
Cytomegalovirus vaccine
Gonococcal vaccine
Vaccines against parasitesmalaria, toxoplasmosis
Synthetic vaccines
Vaccines using genetic engineering
Idiotypic vaccines
Vaccine against dental caries
Leprosy vaccine
Vaccine against AIDS
*Adapted
from VaccinationNizar Ajjan (3rd edn)
TABLE 9.2.2: Viral vaccines

Years Events
Viral
1932
1937
1937
1949
1949
1954
1957
1960
1962
1966
1967
1973
1976
1984
Vaccines discovered before the development of tissue

culture techniques*
Yellow fever vaccine by Sellard and Laigret
Yellow fever 17D vaccine by Theilerthe first vaccine
prepared on embryonic chicken egg
First inactivated influenza vaccine by Salk
Mumps vaccine by Smorodintsev (live-attenuated
vaccine)
Viral vaccines discovered since the development of
tissue culture technique
Tissue culture of the poliomyelitis virus (Enders,
Robbin, Weller)
Inactivated poliomyelitis vaccine by Salk
Live attenuated oral poliomyelitis vaccine by Sabin
Measles vaccine first the Edmonston B (Enders) then
the Schwarz
Rubella vaccine (Weller, Neva and Parkmann)
Mumps vaccine (Weibel, Buynach, Hillemann, then
Takahashi)
Rabies vaccine cultivated on human diploid cells
(Wiktor)
Chickenpox vaccine (Takahashi)
First administration of the vaccine against hepatitis
B (Maupas, then Hillemann)
Hepatitis A vaccine
Rotavirus vaccine
Human papiloma virus (HPV) vaccine
*Adapted
from VaccinationNizar Ajjan-(3rd edn)
are available to fight against 25 diseases and many more

are on the way (Tables 9.2.1 to 9.2.4).
What will happen to various diseases in 21st
century and how many vaccines will be available are
the questions to be considered. The vaccination schedule
as proposed by Plotkin is shown in Table 9.2.5. It must
be re-emphasized that vaccination or immunization is a
lifelong need and does not end with the end of
childhood.
This is well-supported by the recent development of
a vaccine to prevent cervical cancer in women. It is
known that 99 percent of cervical cancer is caused by
human papilloma virus or HPV. HPV16 is the strain
linked to 50 percent of cervical cancers. The vaccine is
developed including HPV16 and has been tested in
sexually active women. None of them got infected with
HPV16 in a follow-up up to 18 months. Of course, more
trials and longer follow-ups will reveal the future and
we hope to prevent cervical cancer in large number of
women. A vaccine containing HPV16 and HPV18
together is expected to prevent 70 percent of cervical
cancer.
By 2008 the Human Papilloma Virus vaccine is
available for use in sexually active women (for details
read the section on newer vaccines).
264

TABLE 9.2.5: Predicted vaccine schedule for
2025 (Plotkin)
Age
Vaccine
0-1 year
BCG, HBV, DPT, OPV, Hib, measles, hepatitis A,

RSV (resp. syncytial virus) parainfluenza,
rotavirus, adenovirus, malaria, dengue, hepatitis
E, enterotoxigenic E.coli, cholera, Shigella,
Campylobacter, Pneumococcus and
Meningococcus V.
1-2 years
MMR, Booster, DPT, OPV, and Hib; Lyme

disease, dental caries, typhoid, schistosomiasis,
rabies, varicella.
4-6 years
Boosters DPT, typhoid, HBV
11-12 years Cytomegalovirus, Epstein-Barr, parvovirus, HIV,

herpes, human papilloma.
Adults
Pneumococcus, influenza
Regards the various vaccines under study listed in

Table 9.2.4. Rotavirus vaccine another revised vaccine is
now available. Vaccines against leprosy, aids, malaria
are not yet available for use. The trials have not been
successful at various stages.
Many new vaccines have been recently tried like the
vaccine against dengue fever. Earlier respiratory
syncytial virus vaccine had failed. Now fresh attempts
are taken up. Various types like live attenuated vaccine
and subunit vaccines are under trial. It is learnt that live
virus attenuated virus vaccine is not very efficacious.
Various old vaccines are modified like BCG can be
inhaled instead of being administered intradermally and
another advantage is that it does not require refrigeration.
Animal trials are successful.
Vaccine is defined as a substance which prevents
infectious diseases. There is a report that a vaccine is
developed for cure of hypertension. Whether it could be
called a vaccine? Or will there be a need to redefine
vaccine? This is a new field where substances are
developed to neutralize harmfully activated hormones,
to cure conditions like hypertension.
CHILD VACCINE INITIATIVE
WHO with the help of the research scientists is in the
search of an ideal universal vaccine. The process is
termed child vaccine initiative (CVI). The goal is to have
a vaccine which could be orally administered in one or
more doses after birth which can prevent many infectious
diseases.
During the World Summit in 1990 at Washington,

USA, the thought of good-high quality vaccine, accessible to all the worlds children, protecting them against
all major infectious diseases, administered in one or two
oral doses was conceived. CVI is a coalition of international agencies, national governments, nongovernmental organizations, public and private sector companies. It was established in 1991 to promote, coordinate,
and accelerate the development and introduction of
improved and new vaccines and thereby enhance the
protection of the worlds children against infectious
diseases.
Efforts of CVI and GPV (Global Program on
Vaccines and Immunization) of WHO (immunization)
TABLE 9.2.6: Vaccines for Asian children in

the 21st century (Lolekha S, 1997)
Vaccines usually used routinely
Oral polio vaccine (OPV), injectable polio vaccine (IPV)
occasionally
BCG
Diphtheria-pertussis-tetanus
Hepatitis B
MMRmeasles, mumps, rubella
Typhoid Vistrongly recommended
Travelers vaccine while traveling to endemic areas
Viral vaccines
Hepatitis A,C,D
Rotavirus
Respiratory syncytial virus (RSV)
Dengue
Herpes simplex
Japanese encephalitis
Varicella
Bacterial
Leprosy
Cholera
Meningococcus polysaccharide
Pneumococcus
Hib (Haemophilus influenzae B)
Shigella
Streptococcus
Parasitic
Malaria
Kala azar
Through pregnant mother immunization
Tetanus toxoid
Group B streptococcal vaccine

will help worlds children to fight against various
infectious diseases in the current century. The Global
Alliance on Vaccines and Immunization (GAVI) initiated
in 1999 is one step forward and aims at immunization of
all children against all diseases. There is already a shift
to the right in the age groups affected by some vaccine
preventable diseases, e.g. measles is affecting older
children, the whooping cough is more in adults. The
changes may make the vaccination program a lifelong
and even growing one. The world in 21st century will
not even see occasional faces with pox marks, will not
see any new cases of poliomyelitis, no neonatal tetanus
and no deaths due to measles. The rotavirus vaccine will
possibly prevent 4,79,000 deaths annually, 3,50,000 of
them from low income countries alone (Table 9.2.6 ).
GAVI has also launched a priority project on safety
of immunization practices in 1999. Discoveries in
molecular biology, immunology and genomics have
added to safety and efficacy in the development of potent
vaccines.
Safe vaccine administration is equally important. The
needle pricks besides being painful can also lead to various
265
other complications including infections, bacterial or viral.

Therefore, various methods of vaccine administration are
considered which can avoid pricks or make it less painful,
e.g. intranasal administration. During the mass immunization programs and also for individuals shot guns have
been used which avoids the needle prick. The syrings and
needles used have also been changed. To avoid introduction of viral infections by reusing the syring and
needles, autodisabled syringe are used which give the
precise dosage and cannot be reused. Use of devices are
also on the way wherein there is no needle prick.
Safe, effective, potent vaccines well-preserved by
various methods and safe, needle free administration will
make the immunization programmes effective and
widely acceptable and tear free as majority of recipients
are children.
A new antihypertension vaccine containing the action
of angiotensin in adults has been successfully tried with
3 doses in a 0, 4, 12 weeks schedule is promising in adults.
Large scale trials are however needed. Similarly a new
inhaled and anti TB spray dried vaccine has produced
promising recuts in abnormal model.
9.3 Newer Vaccines

The ultimate goal of any immunization program
is to eradicate the disease. However, the immediate goal
is to reduce mortality and morbidity of individuals and
groups. In the Universal Immunization Program (UIP),
only six vaccine preventable diseases are included taking
into consideration, the epidemiology, cost effectiveness
and availability of the vaccine in the country. In the last
decade, several new vaccines have been developed and
are available in the country. Physician should be able to
counsel the parents regarding the efficacy and importance of these vaccines in the present health situation.
This chapter includes a brief description of these
vaccines.
Typhoid Vaccine
Typhoid vaccine was included in the National Immunization Schedule till 1987 but then discontinued because
vaccine had lot of side effects and it was believed that
typhoid had low mortality. Now typhoid is occurring in
younger age groups and there is emergence of multiple
drug resistance typhoid. Hence, the need for typhoid

vaccines. There are three types of typhoid vaccines
available.
Parenteral Killed Whole Cell Typhoid Vaccine
The vaccine contains 1000 million heat killed phenol
preserved or acetone inactivated bacteria per ml. The
former is a liquid vaccine and the acetone killed is freeze
dried. This vaccine is now not available in India.
Efficacy The efficacy was 55-65 percent.
Dose and schedule: Dose for six months to ten years is
0.25 ml and more than 10 years is 0.5 ml subcutaneously
over the deltoid area and the second dose is repeated
after four weeks.
The booster dose of the same volume of vaccine is
recommended every three years.
Storage: The vaccine is stored in dark at 2 to 8C. The
liquid vaccine should not be frozen.
266
Adverse reactions: Local pain, swelling, redness, fever

and severe headache. Very rarely, severe reactions like
anaphylaxis, chest pain, liver damage, neurological
problems and reactive arthropathy could occur.
Precautions and contraindications: The vaccine is contraindicated in persons with a history of allergic or severe
reactions following previous dose and in pregnancy.
Live Oral Typhoid Vaccine
Ty21a live attenuated oral typhoid vaccine was available
as enteric coated capsule form. Ty21a is a mutant strain
developed by genetic manipulations and is devoid of O
antigen. This vaccine is not available in India.
Dose and schedule: The vaccine is administered as oral
capsule in three doses on alternate days (0,3 and 5th day)
and a booster dose every three years. This vaccine can
be given only after 5 to 6 years of age, as children below
this age group cannot swallow the capsule. Moreover,
the efficacy of the vaccine below five years of age group
has not been studied. The vaccine is stored at 4 to 8 C.
Efficacy: The efficacy of the vaccine in Egyptian study
was found to be as high as 96 percent. In subsequent
trials, the efficacy of the vaccine varied from 52 to 69
percent.
Adverse reactions: Fever, vomiting and abdominal pain
occurs rarely (< 1%). There are no contraindications.
Vi Polysaccharide Typhoid Vaccine
The Vi antigen of S. typhi is a capsular antigen with
known virulence property of the organism and is
available as injectable vaccine containing 25 microgram
purified Vi capsular polysaccharide per dose.
Dose and schedule: Since, this is a capsular polysaccharide vaccine, it is effective after the age of two
years. The dose is 0.5 ml single injection intramuscularly
in the deltoid region above the age of two years with
one booster dose every three years. The vaccine is stored
at 4 to 8 C.
Efficacy: The efficacy of the vaccine varies from 64 to 72
percent in various studies.
Adverse reactions: Pain, erythema and induration at the
local site and rarely fever. All the reactions are of mild
nature and self-limiting.
Inactivated Polio Vaccine (IPV)

This vaccine is prepared from the virus of the original
salk strain grown in monkey's kidney, human diploid or
vero cell line and is inactivated by formalin. Presently, it
is available as enhanced potency vaccine containing 40,
8 and 32 D antigen units against types I, II and III polio
viruses in 0.5 ml of the vaccine. The vaccine is also
available as quadruple vaccine along with DPT.
Dose and schedule: Three doses of 0.5 ml intramuscularly
along with DPT vaccine, can be given according to the
DPT schedule (6, 10, 14 weeks or 2, 3, 4 months or 2, 4, 6
months) of the country. The booster dose is recommended along with DPT at 18 months and five years of age.
After 6 months 2 doses are required.
Efficacy: The efficacy of the enhanced potency IPV is over
95 percent in various studies.
Adverse reactions: Local minor adverse reaction, e.g.
pain, swelling and erythema which is self-limiting.
Advantages over OPV: IPV is more thermostable than
OPV. It is recommended to be stored at 4 to
8 C.
It is more immunogenic and can be combined along
with DPT. It is the vaccine of choice for immunocompromised children.
Limitations of IPV: Apart from being costly, this vaccine
is not suitable for preventing circulation of wild polio
virus in the community which is the ultimate goal of polio
eradication.
Acellular Pertussis Vaccine
The whole cell pertussis vaccine in DTwP occasionally
causes major side effects. Hence, further modification of
the pertussis component has been made, by removing
the toxic fraction, i.e. lymphocyte promoting factor (LPF).
Acellular pertussis vaccine may be 2 component, 3
component or 5 component depending on presence of
toxin, pertactin, filamentom hemagglutinin, etc. This
vaccine has been in use in Japan since 1981.
Dose and schedule: The vaccine is a part of DTaP and
comes in liquid form. The dose is 0.5 ml administered
deep intramuscularly and is given at 6, 10 and 14 weeks
and the booster doses at 16 to 18 months and at five years
of age. The vaccine is stored at 4 to 8 C and should not
be frozen.
267
Adverse reaction: Local and systemic adverse reactions

like swelling, erythema, tenderness, fever and crying
episode are very mild and self-limiting.
thalassemics and hemophilics requiring repeated blood

transfusions.
Hepatitis B Vaccine
Most widely available hepatitis A vaccine contains

formaldehyde inactivated hepatitis A virus adsorbed
onto aluminium hydroxide.
Hepatitis B vaccine has been included as seventh EPI

vaccine by WHO since 1992. It is included in immunization schedule of Delhi and strategies are being
developed to include in the National Immunization
Schedule. Now only recombinant vaccines are used and
plasma derived vaccine is no more available.
Recombinant Vaccine
HbsAg DNA sequence from hepatitis B virus has been
isolated and integrated in the genome of common bakers
yeast, to produce recombinant vaccine. This vaccine is
highly immunogenic and is free from transmission of
blood-borne diseases.
Dose and Schedule
Vaccine is to be given in a dose of 10 g (0.5 ml) till 19
years and 20g (1ml) after that.
The recommended schedules are:
1. Birth, 6 and 14 weeks
2. 6, 10 and 14 weeks (combined DTPwc/hepatitis B can
be preferred).
3. For older children, adolescents and adults the
recommended schedule is first dose, after 1 month
and after 6 months.
Efficacy
Vaccine efficacy is more than 94 percent after recommended doses.
Adverse Reactions
Minimal local reactions at the injection site which are
self-limiting could occur.
At present booster dose of vaccine is not required.
Younger the age of infection more the chronicity of the
disease. To prevent mother to child transmission the
vaccine should be given soon afterbirth preferably within
12-48 hours. Till the vaccine is included in the National
Immunization schedule it is recommended in high-risk
groups, e.g. babies born to HBsAg positive mothers,
patients on hemodialysis, intravenous drug addicts,
homosexuals, medical and paramedical personnels,
Hepatitis A Vaccine
Dose and schedule 2 doses of 0.5 ml I.M. containing

720 ELU in children 1 to 18 years of age. After 18 years
vaccine containing 1440 ELU in 1.0 ml is used at 0 and 6
months, 0 being the elected date and a booster after 6
months.
Storage Vaccine should be stored at +2 to +8C and ot
to be frozen.
Adverse reaction Minimal, self-limiting local reactions
at injection site.
It is used in high-risk groups like food handlers,
travellers, persons working in nurseries and day care
centers. It can be given with other vaccines but at a
separate site. It can be given after 18 months in children.
It can be used as a routine vaccine because with
increasing sanitation and safe water supply incidence of
subclinical natural infection is low.
Other Hepatitis A Vaccines
Live attenuated hepatitis A vaccine has been manufactured from the H 2 strain in China. Dose is 1 ml
subcutaneous in children more than 2 years of age single
dose has been recommended by the manufacturers
longterm efficacy studies are awaited
Virosomal based hepatitis A vaccine has been
introduced. This vaccine is given in a dose of 0.5 ml
intramuscularly. It has faster induction of antibodies and
lesser side effects.
Hemophilus Influenzae b Vaccine
At present, only conjugated polyribosyl ribitol
phosphate (PRP) vaccine is used. There are four types of
conjugate PRP Hemophilus influenzae vaccines available.
They are PRP-D, PRP-CRM, PRP-OMP and PRP-T.
PRP-D
In this vaccine conjugation of PRP antigen with diphtheria toxoid is used. This vaccine has not been found to
be effective in infants, but is effective in children after
268
the age of one year. Hence, it is not recommended for

primary immunization in infants.
80 percent of the preumoccocal disease occur in children

less than 2 years of age.
PRP-CRM (PRP-HBOC)
7 Valent Conjugate Vaccine (PCV7)
In this combination, CRM197 protein from non-toxic

mutant diphtheria toxin is used. This vaccine is highly
immunogenic. The efficacy is more than 97 percent after
three primary doses, given at 2, 3, 4 months or 2, 4, 6
months or at 6, 10, 14 weeks along with DPT schedule.
The fourth dose is recommended at the age of 12 to 15
months. The vaccine is administered intramuscularly. If
the vaccine is missed before 6 months, then 2 doses at 1
to 2 months of interval is allocated up to 12 months
followed by one booster dose at 12 to 15 months of age.
After 12 months till 15 months primary immunization
consists of 1 dose followed by another dose after 15
months. After 15 months till 5 years of age only one dose
is recommended.
Vaccine contains 7 purified capsular polysaccharide of

S. pneumoniae coupled with a non logic variant of
diphtheria to CRM 197. It has serographs 4, 9v, 14, 19f,
23f, 18c, 16 b responsible for 85 percent of invasive disease
and 65 percent of otitis media in western countries. It
covers nearly 50 percent of the prevalant stains in India.
Dose is 0.5 ml IM. Schedule is same as DPT 6, 10, 14 weeks
with a booster at 15-18 months. After 6 months 2 doses
are required, single dose is required after 2 years.
Now 10 valent and 13 valent conjugate vaccines are
undergoing.
PRP-OMP
Conjugation of PRP with outer membrane protein of
meningococcus is done to produce this vaccine. The
advantage of this vaccine is that only two doses at two
months interval for primary vaccination with a booster
at 12 to 15 months of age, produces more than 97 percent
protective efficacy.
PRP-T
Tetanus toxoid is used in this vaccine for conjugation.
This vaccine is highly efficacious with almost 100 percent
seroconversion. The dosage schedule is same as in PRPCRM vaccine with very minimal self-limiting adverse
reactions.
Pneumococcal Vaccine
A 23 valent capsular polysaccharide vaccine is available.
The vaccine covers most of the prevalent strains of
Pneumococcus causing disease. It is given as a single dose
of 0.5 ml subcutaneously or intramuscularly in children,
more than two years of age. The vaccine being a capsular
polysaccharide, is not immunogenic in children of less
than two years of age. At present, the vaccine is
recommended in children with sickle cell disease,
functional and anatomic asplenia, nephrotic syndrome,
patients with cerebrospinal fluid leak and children with
malignancies.
Polysaccharide vaccine fails to elicit a protective
immune response in children less than 2 years, though
Meningococcal Vaccine
A capsular polysaccharide meningococcal vaccine is now
available. Available vaccines are monovalent group A
or C, bivalent A and C and a tetravalent vaccine
containing group A, C, Y and W-135. Each dose contains
0.5 ml containing 50 micrograms of each polysaccharide
available as lyophilized powder.
Dose and schedule: The vaccine is given as 0.5 ml single
dose after the age of two years subcutaneously. The
vaccine is not recommended for routine use and is to be
given in epidemic situation and in children with
functional asplenia and complement deficiencies.
Efficacy: Following single dose the vaccine efficacy in
children has been found to be 90 percent and in children
older than two years 75 percent. The vaccine is effective
for at least three years. The vaccine has no efficacy on
carrier state.
Mumps Vaccine
This is a live attenuated vaccine produced from either
Jeryl Lynn strain, Leningrad-3 or Urabe 3 strain. The
vaccine is available as combined vaccine with measles
and rubella (MMR) vaccine.
Dose and schedule: A single injection of 0.5 ml of vaccine
containing 5000 TCID either alone or in combination with
measles and rubella has been found to give an immunity
against mumps. The efficacy varies from 93 to 97 percent.
No booster dose is recommended. The vaccine is
recommended at 15 to 18 months of age.

Adverse reactions: It is a very safe vaccine. Minor allergic
reactions, febrile seizure, rash, pruritus and encephalopathy (very rare) have been reported.
Contraindications: In patients with immunodeficiency
diseases and lymphoreticular malignancies, mumps
vaccine should not be administered.
Rubella Vaccine
It is a live attenuated vaccine containing RA 27/3 strain
grown in human diploid cell line and is available for use,
either as monovalent rubella vaccine or in combination
with measles and mumps, as MMR vaccine.
Dose and schedule: The vaccine is usually given as single
IM or S/C injection along with mumps at the age of 15
to 18 months. However, the vaccine can be administered
at any age. It is contraindicated in pregnancy and in
immunocompromised and in malignant conditions.
Rabies Vaccine
For prophylaxis against rabies, several vaccines have
been made available.
Nerve Tissue Vaccine
The vaccine (Sample vaccine) contains, 5 percent weight
by volume rabies virus infected sheep brain. The dose
depends on the age and on the class of exposure and
varies from 2 ml to 5 ml and 7 to 14 doses are given
subcutaneously in the abdomen. The efficacy of the
vaccine is less than optimal. This vaccine is nowadays
not used because of severe adverse neuroparalytic
reactions, e.g. postvaccination myelitis and ascending
paralysis including death. The vaccine is occasionally
used in places where the other vaccines are not available.
This vaccine is used in postexposure prophylaxis.
Tissue Culture Vaccine
Following tissue culture vaccines are for both pre- and
post-exposure prophylaxis.
Human Diploid Cell Vaccine
It is produced from fixed rabies virus grown in W-1-38
or MRC-5 human kidney cell culture line. Side effects
are mild local reactions like pain, erythema, itching,
headache, nausea and abdominal pain. Efficacy is almost
100 percent. The vaccine is costly.
269
Purified Chick Embryo Vaccine

This vaccine is propagated in primary chick fibroblast
cell. This vaccine is also very highly immunogenic. The
adverse reactions are very mild local reactions and
lymphadenopathy, headache, lethargy and allergic skin
reactions.
Verocell Vaccine
The vaccine is produced by using continuous cell line,
e.g. baby hamster kidney fibroblasts. The efficacy is
excellent, i.e. 100 percent and very mild local and
systemic reactions.
Dose and schedule: Post-exposure prophylaxisAll
tissue culture vaccines are given in 5 doses on 0, 3, 7, 14
and 30 days. The vaccine is given intramuscularly in the
deltoid region or in anterolateral aspect of thigh in
infants. The vaccine is not given in gluteal region. The
dose is same irrespective of age viz 2.5 IU per dose in 1
ml or 0.5 ml as recommended by the manufacturer.
Preexposure prophylaxis: This is indicated in persons at
high-risk of exposure, e.g. laboratory staff working with
rabies virus, veterinarians, animal handlers and wildlife
officers. Three doses on 0, 7, 28 days are recommended
with reinforcing doses given 1 to 3 years, if the antirabies
antibody titer falls below 0.5 IU/ml.
If persons who have received full course of postexposure (re-exposure) prophylaxis get an animal bite
i.e, suspected rabies within 5 years of the last completed
dose, two doses on day 0 and 3 and after 5 years full
course of day 0,3,7,14 and 30 days of 5 doses are
recommended.
Varicella Vaccine
A live attenuated varicella (LAV) vaccine containing
OKA and DKA/Merck strain is now available. Since
1986, it has been given to all children in Japan as a routine
and is a part of routine immunization in USA.
Dose is 0.5 ml subcutaneously and as single dose in
children one year or older till 13 years. Two doses at an
interval of 1 month is recommended after 13 years of
age. It has an efficacy of 95 to 100 percent and common
side effect is varicella like rash and fever 1 week after
vaccination. It is indicated in immunocompromised
children and group of high-risk children like children
suffering from leukemia and malignant tumors, AIDS,
chronic kidney disease, nephrotic syndrome and children
270
on long-term steroids. Vaccine is also recommended for

all adults and adolescents above age of 15 years, who
have not been exposed to chickenpox.
Influenza Vaccine
Influenza vaccine is available as whole cell or split virus
vaccine. Strains of influenza virus used in the vacine have
to be changed every year according to the prevailing
strains in the geographical area. In children less than 13
years, two doses of split virus vaccine in dose of 0.5 ml
intramuscularly at one month interval is recommended
for first time. Thereafter single dose should be given
every year. It is recommended in high-risk groups, e.g.
immunocompromised children and children with
cardiopulmonary diseases as well as elderly people over
65 years of age. Now protein of influenza A virus which
is common to all strains of influenza A.
Japanese B Encephalitis Vaccine
Inactivated vaccine: An inactivated vaccine derived from
infected mouse brain is recommended for travellers to
endemic areas as well as in endemic areas. Vaccine is
given in a dose of 1 ml subcutaneously on day 0, 7 and
30 in travellers planning to spend more than 30 days in
endemic area at least 10 days before travel. It is also
recommended in persons residing in areas where
Japanese B encephalitis is endemic or epidemic. Dose in
children of 1-3 years of age is 0.5 ml. In India JE vaccine
manufactured at Kasauli is recommended in a dose of
0.5 ml, 2 doses at 1014 days interval with a booster at
1 year. This vaccine is 8088 percent efficacious.
Quadrivalent Vaccine
L1 protein of HPV serotypes 16, 18, 6, 11 are made into
moninfectious virus like particles using recombinant
DNA technology. Dose is 0.5 ml at 0, 2, 6 months.
Recommended age of starting the schedule is 10-12 years.
Bivalent Vaccine
This contains HPV serotype 16 and 18. Dose is 0.5 ml at
0, 1, 6 months. Recommened age of starting is 10-12 years.
Rotavirus Vaccines
Currently two live oral vaccines are available.
A monovalent attenuated human rotavirus vaccine
derived from human rotavirus strain 18-12 that contains
GIPIAC strain. It is available as a lyophilised vaccine to
be reconstituted with a diluent. First dose can be given
at 6 weeks (not later than 12 weeks). Second dose is given
4 weeks later. 2-dose schedule should be completed by
16 weeks and not later than 24 weeks.
A pentavalent human bovine reassortant vaccine and
consists five reassortants between the bovine WC 23
strain and human G1, G2, G3, G4 and P1A (8) rota virus
strain. Recommended schedule is 3 oral doses at 2, 4, 6
months starting at 6-12 weeks with a interval of 4-8
weeks. Vaccination should not be started after 12 weeks.
All 3 doses should be given before 32 weeks. It is available
as a liquid vaccine.
Vaccines are 85-98 percent efficacious against
rotavirus gastroenteritis and 42-59 percent efficacious
against hospitalization from diarrhea of any cause.
Cell Cultured Live SA 14-14-2 Vaccine
Tdap Vaccine
This vaccine contains neuro-attenuated strains of JE virus

(SA 14-14-2). Dose is 0.5 ml subcutaneously single dose
at 1 year of age with a booster after 1 year and a second
booster after 2 years. Vaccine is about 85 percent efficacious. It is recommended in endemic areas and in
travellers.
Immunity followting primary/booster DTP/DTaP

vaccination waves over 5-10 years. Standard strength
DTP and DTaP vaccines cannot be used in children above
7 years due to increased reactogenicity. Tdap vaccine
lower doses of diphtheria and acellular pertusis components, hance can be used in children above 7 years.
Systemic side effects are rarely seen. A dose of this
vaccine can be given at 10 years.
HPV Vaccine
Human papilloma virus serotypes 16 and 18 are
implicated in 70 percent of cervical cancers globally.
Types 6 and 11 are known to cause 90 percent of
anogenital warts.
Combination Vaccines
Combination vaccines are defined as multiple antigens
to prevent diseases or to protect against multiple strains
of infectious agents causing same disease. With the

increasing number of vaccines a child receives up to 13
pricks in the first year of life. Combination vaccines will
reduce the number of pricks, number of visits, increase
compliance and decrease the cost of vaccination as well.
Currently combinations available are hepatitis A +
hepatitis B, DPT + Hib, DPT + hepatitis B, DPT + killed
polio and DPT + killed polio + Haemophilus influenzae B
(Pentavalen). Efforts are on to combine as many vaccines
as possible, e.g. hepatitis A, hepatitis B, DPT, pneumococcal and Hib vaccines.
BIBLIOGRAPHY
1. Committee of Infectious Diseases Amterican Academy
of Pediatrics. Report of Committee of Infections diseases
Red Book, 27th Ed. 2006.
2. Dhah RC, Shah NK, Kukerja S. IAP Guide Book on
Immunization (4th edn). Committee on Immunization,
Indian Academy of Pediatrics. 2005-2006.
271
3. Immunogenicity and safety of a pediatric dose of a

virosome- adjuvanated to hepatitis. A vaccine : a
controlled trial in children 1-16 years. Ped Infect Dis J
2007;26:705-10.
4. Mittal DK, Dutta AK, Agarwal V; Immunization update
CBS Publishers and Distributors, New Delhi, 1994.
5. Murphy TV, Slade BA, Broder KR, et al. Prevention of
pertusis, tetanus and diphtheria among pregnant and
postpartum women and their infants recommendation
of advisory committee on Immunization practices (ACIP)
MMWR Recomm Rep 2008,57:1-51.
6. Parashar VD, Alescander JP, Glass Rl, et al. Prevention
of rotavirus gastroenteritis among infants and children
recommendation of ACIP, MMWR Recomm Rep.
2006,55:1-13.
7. Pneumococcal conjugate vaccine for childhood immunization - WHO position paper. Wkly Epidemiol Rec
2007;82:93-104.
9.4 Vaccine Storage and Handling

RK Agarwal, Digant D Shastri
The cold-chain is the system of transporting and
storing vaccines within the temperature range of 2C to
8C from the place of manufacture to the point of
administration. This temperature range is recommended
because outside this range vaccines may (very quickly)
lose their potency. Immunization service providers
should maintain their vaccine refrigerators as close as
possible to 5C, as this gives a safety margin of + 3C
The cold chain has three main components:
1. Transport and storage equipment,
2. Trained personnel, and
3. Efficient management procedures.
All three elements must combine to ensure safe
vaccine transport and storage. World Health Organizations Expanded Program on Immunization (EPI)
developed detailed guidelines on the maintenance of an
effective cold-chain. Maintenance of the cold-chain
system requires that processes are in place to ensure that
a potent vaccine reaches recipients. Apart from invention
of new heat stable vaccines, the improvisation in cold
chain and the understanding of the ideal methods of vaccine
storage and transport by officials, doctors and field staff are
the factors for the reduction of mortality and morbidity due to
vaccine preventable diseases.
The vaccines which are not stored in the recommended temperature range get degraded (Fig. 9.4.1).
Contrary to the common belief that exposure of vaccine
to the higher temperature only can be damaged, freezing
of vaccines also can causes degradation and consequently
total or partial loss of potency. Commonly the
degradation rate of a vaccine is determined by the storage
temperature: The higher the temperature, the more rapid
and extensive is the degradation. There are considerable
differences between degradation rates for different
vaccines. In spite of knowing all these facts, still at many
places vaccines are not stored and transported properly.
This leads stocks of vaccines exposed for varying periods
to elevated temperatures/ freezing.
Cold Chain Equipment Supplied under
the Immunization Program
Cold chain equipment is used for storing vaccines and/
or transporting them in an appropriate desired temperature to maintain its potency. There are equipment of
different capacity for storage of vaccines at different
levels as described below.
1. Walk-In-Freezers (WIF)
272

Primary
(National)
6 months
OPV
Intermediate
Regional
District
3 months
1 month
Primary health
center
Health post/Session
site
1 month
Daily Use
15C to 25C
BCG
Measles
MMR
MR
Yellow fever
Hib freeze
dried
WHO no longer recommends that

freeze-dried vaccines be stored at
20C. Storing them at 20C is
not harmful but is unnecessary.
Instead, these vaccines should be
kept in refrigeration and
transported at +2C to +8C.
+2C to +8C.
HepB
DPT
DPT + Hep B
DPT + Hieb
Hib liquid
DT
Td
TT
Diluent vials must NEVER be frozen. If the manufacturer supplies a freeze-dried vaccine packed with its diluent, ALWAYS store the
product at between +2C and +8C. If space permits, diluents supplied separately from vaccine may safely be stored in the cold chain
between +2C and +8C.
Figure 9.4.1: WHO recommended vaccine storage conditions

(Source: WHO-UNICEF Joint Statement on Effective Vaccine Store Management WHO/IVB/04.17)
2.
3.
4.
5.
6.
7.
8.
Walk-In-Coolers (WIC)
Deep Freezers
Ice Lined Refrigerator (ILR) (Fig. 9.4.2)
Automatic Voltage Stabilizer
Cold Boxes (Coolers)
Vaccine Carriers
Ice Packs
Figure 9.4.2: Ice lined refrigerator (ILR)
Domestic refrigerators that have a separate freezer

compartment are recommended for vaccine storage. Safe
vaccine storage is possible in most refrigerators if the
following procedures or modifications are carried out
and standards are maintained:
Vaccine should be stored in a dedicated refrigerator:
never store food or drink in vaccine refrigerators.
The refrigerator should maintain internal temperatures in the recommended range without fluctuating into the danger zones (<+2C, >+8C). The
refrigerator compartment should maintain temperatures between 2 and 8C. The freezer compartment
should maintain temperatures at or below 5 F
( 15C).
The refrigerator has not required repairing for last 2
years.
The refrigerator is free of any water or coolant leaks.
The door seals are in good condition and are sealing
tightly.
The door closes properly automatically on leaving it
free.
The refrigerator compressor does not make sound.
The size of refrigerator is adequate to meet individual
storage needs.

Tips for Better Vaccine Storage in
Domestic Refrigerators
A. Placement of Refrigerator
Refrigerator should be placed out of direct sunlight
and away from heat source.
B. Recognize Individual Vaccine Refrigerator
Before starting storing the vaccines in the refrigerator
identify which are the cold and warm areas in the
refrigerator. Also note the temperature variations from
top to bottom and from back to front.
C. Stabilize the Temperature of the Refrigerator
before Stocking
D. Monitoring Temperatures Inside the Refrigerators
Ensure that each domestic refrigerator storing vaccine
has a Celsius digital minimum - maximum thermometer.
The thermometer should be placed in a central location
within the storage compartment:
E. The Power Source
Avoid accidental disconnection
from the power source and to
ensure this mark the power
source clearly. This will prevent
the refrigerator from being
accidentally unplugged or
turned off. Arrange for alternative power-supply which will
very well back up load of at least
one refrigerator.
273
G. Store that Vaccines

in Enclosed Plastic
Containers/Labeled
Baskets
This will allow easy
identification
of
vaccines and minimize
the time spent with the Storing of vaccines in labeled
plastic containers
door opened searching
for vaccines. Do not
crowd the vaccines by overfilling the shelves. Allow
space between containers for air circulation. Vaccines or
its diluents must never be stored in the door of the
refrigerator. Freeze-tolerant vaccines (Measles, Mumps,
Rubella, OPV and BCG) should be placed in the shelves
identified as being the coldest and the freeze-sensitive
vaccines (DTP containing vaccines; Hib, Pneumococcal,
Influenza, Hepatitis, IPV and some varicella vaccines)
on shelves identified as having more stable temperatures
(e.g. no cold spots). Vaccine stock should be rotated with
1st to in 1st to outpolicy and vaccines with the
shortest expiry date are used first.
H. Keep the Door Closed as
Much as Possible
Safeguard the power

supply
F. In the Freezer, Place Water

Bottles or
Ice Packs/Gel Packs and Fill
Lower Drawers and Door with
Water Filled Plastic Containers
It will help to stabilize the
temperature by increasing the
Gel packs and ice
packs in freezer
cold mass. This will assist in
stabilizing the temperature in
refrigerator. This is particularly useful if there is a power
cut or other cause of refrigerator failure.
Minimizing the door opening

helps to keep internal
temperatures stable. The
vaccine refrigerators should
have a sticker to remind staff
of same.
Sticker on the refrigerator

door
I. Alarm Systems
Install a security/alarm system which will give a warning
if:
The temperatures rise or fall outside normal ranges.
There is power failure.
The door is left open.
J. Training and Assigning Staff
Good vaccine storage and handling depends on
knowledge and habits of the staff. Ensure that one person
is responsible for adjusting refrigerator controls.
274
K. To Develop Own Documented Protocols and

Procedures for Vaccine Storage
L. Immediate Identification of Breach in Cold Chain and
its Management
In order to ensure that effective vaccine is administered
it is important to promptly identify and manage cold
chain breaches. Establish and document protocols for
response to cold chain breaches.
M. Periodic Self-audit of vaccine storage
N. Ordering Vaccine
Keep vaccine stock to a minimum by regularly ordering
only the quantity of vaccine required for the period until
the next delivery.
Maintenance of the Vaccine Refrigerator and
Defrosting (Table 9.4.1)
The door seals should be in good condition so that the
door closes securely. Refrigerator seals should be checked
regularly to ensure that a good seal is maintained. If the
seals are damaged or there is leakage of cold air from
the refrigerator, it should be replaced soon. As ice-buildup can reduce the efficiency and performance of a
refrigerator the refrigerators that are not frost free
should be defrosted regularly to prevent ice build up.
During defrosting or cleaning of the refrigerator, move
the vaccines to a second refrigerator. This temporary
storage refrigerator must also be monitored to ensure the
correct temperature is maintained. Alternatively, the
vaccines can be stored in a precooled insulated container
with ice packs or ice until the normal vaccine refrigerator
is ready for use again. If the refrigerator coils are exposed

on the back, keep them clean and dust free. This will
improve operating efficiency.
PURPOSE-BUILT VACCINE REFRIGERATORS
Purpose-built vaccine refrigerators are the preferred
refrigerators for vaccine storage. It is recommended that
if possible purpose-built refrigerators are used by larger
vaccination services, including hospitals, pharmacies,
larger community health centres and larger general
practices. It is also recommended that they be used in
remote settings. They are considerably more expensive
than domestic refrigerators. The purpose built
refrigerators have following advantages over the
domestic refrigerator:
Do not require to be modified for vaccine storage.
They are programmed to maintain an internal
temperature between 2C to 8C.
Cabinet temperature is not affected by ambient
temperature and is stable and uniform.
TABLE 9.4.1: Checklist for Preventive Maintenance

External
Internal
1.
2.
3.
4.
1.
2.
3.
4.
The exterior is clean

It is firm on the floor
It is properly leveled
Its sides are at least 10 cm
away from walls
5. It is away from direct sunlight
6. Room is well ventilated
7. It is opened only when necessary
Doors seals properly without gap

The door seal is clean
Ice packs are in proper position
Vaccines are neatly placed with
space for air circulation
5. DPT, TT, HepB and DT are not
touching the cooling surface
6. Thermometer has been kept amongst
the vaccine
7. Temperature is recorded twice a day
Technical
1. Temperature is within prescribed limit
(if not, set the thermostat)
2. Voltage stabilizer is working properly
and equipment are connected through it
3. Plug of the voltage stabilizer is fitted
properly to the power line
4. There is no abnormal noise
5. Compressor mounting bolts are tight

Defrost cycle allowing defrosting without rise in
cabinet temperature
They automatically defrost
They have an external temperature reading display
and a maximum/minimum temperature continuous
display, and an alarm for deviations outside the
programmed temperature range.
Less demanding maintenance than domestic refrigerator.
Good temperature recovery, when the fridge is open
to access the vaccines.
Nearly all internal space can be used to store the
vaccines, so the size of the purpose built refrigerator
may be smaller than the previously used domestic
refrigerator.
Maintaining and Monitoring
Refrigerator Temperatures
To measure the temperature during storage of
vaccines, different types
of thermometers are used.
Minimum/maximum
thermometer is essential
requirement for temperature monitoring during
vaccine storage and transDigital thermometer
port. The minimum/
maximum thermometer should be placed on a middle
shelf and temperatures should be checked and recorded
daily. The most effective minimum/maximum
thermometer is a digital type
with a probe. If using a digital
thermometer with a probe,
place the probe directly in
contact with a vaccine vial or
package. The refrigerator
temperature should be read
around the same time each
day, preferably prior to each
working session. Minimum/
maximum thermometer must
Continuous temperature be reset regularly, the
recorder
thermometer battery must be
checked and replaced time to
time and one should choose a thermometer which
records temperature in Celsius.
275
Minimum/maximum: Tells the highest and lowest

temperatures reached, but will be difficult to read.
Digital: These are the most accurate constant monitors
and also offer continuous alarm capability to safeguard
against damage from refrigerator malfunction. But the
temperature probe must be placed in the proper location
inside the unit in order to get an accurate reading.
Continuous reading: Will record the temperature inside
the unit at all times, 24 hours a day, on a sheet of paper,
but the paper must be changed when it is running low.
Using this thermometer is the most effective method of
tracking the refrigerator/freezer temperature over time.
The minimum/maximum thermometer must be reset
regularly (i.e. at least daily, on work days) for meaningful
temperature recording. Ensure you choose a thermometer that reads Celsius. Different models of minimum/
maximum thermometers may vary in accuracy. They also
require annual checks to ensure accurate measurement,
as flat batteries or a damaged probe or cable can affect
readings.
Temperature Indicators
Vaccine Vial Monitor (VVM)
A vaccine vial monitor (VVM)
is a label placed on a vaccine
vial, which contains a heat
sensitive material. It registers
cumulative heat exposure over
time. A VVM enables user to
know whether vaccine has
been damaged by exposure to
heat or not. The inner square
of the VVM is made of heat
sensitive material that is light
at the starting point. The combined effect of time and
temperature causes the inner square of the VVM to
darken, graudally. The color change is irreversible. There
is a direct relationship between rate of color change and
temperature. Lower the temperature, slower the color
change and higher the temperature, faster the color
change.
Thus VVM gives information about the main factor
that affects vaccine potency (heat exposure over a period
of time). It does not give any information about the other
factors responsible for vaccine degradation, e.g. sunlight
and age. VVMs are not substitutes for expiry dates. Vaccines
must never be used after their expiry dates.
276

Power Failure
Vaccine vial monitor
Different types of VVM: Depending upon the heat stability

four different types are designed.
Apart from proper storage of the vaccines in the
refrigerator, it is equally important to safeguard the
vaccines during immunization sessions also to serve its
purpose of extending protection to recipients.
Reconstitution of Vaccine
Diluents for every vaccine are specifically designed
for the needs of individual vaccine, and therefore,
interchanging of it is not recommended.
As the diluents which are warmer than the vaccine
can affect the potency of live vaccines, it is recommended that diluents should be of the same temperature
as the vaccine at the time of reconstitution.
Use the entire volume of the cooled diluent supplied
when reconstituting the vaccine.
Reconstituted vaccines should be used within one
hour (30 minutes for varicella), provided they have
been kept between +2C to +8C and protected from
sunlight and fluorescent light.
Reconstituted MMR can be stored in the plastic
syringe in a dark place between +2C to +8C without
loss of potency for up to four hours.
MANAGEMENT OF COLD CHAIN PROBLEMS
Out of Range Temperature
If any temperature reading is outside the recommended
range, immediate action is required. Action may include
readjustment, repair or replacement of the unit and
removal of the vaccine to a functional unit till repair or
replacement is possible.
If the power failure is of 4 hours or less the vaccines

should be kept in the refrigerator and the door should
be kept closed.
If there is no back-up generator facility, another
storage unit in near by site should be identified and
assure that it is working properly.
Before moving vaccine, call the alternative storage
site to ensure that the back-up generator is working.
In situations where a location with a back-up
generator cannot be identified within a reasonable
distance, preparations should be made to have coolers
and gel packs ready to temporarily and safely store
vaccine.
If a refrigerator with a backup generator has not been
located or is not working, and for power failures more
than 4 hours store vaccines in a cooler with conditioned ice packs/gel packs.
Continue to monitor the temperature of the vaccines
by placing the thermometer probe inside a vaccine
box inside the cooler.
Dos
Mark power source to prevent accidental unplugging
or turn off.
Place water bottles or ice pack/gel packs in your
freezer.
Fill the lower drawers and the door with plastic water
containers.
Know your vaccine refrigerator by monitoring and
recording the temperatures throughout the refrigerator
Modify and stabilize refrigerator before stocking with
vaccine.
Store vaccines in original packaging in labeled plastic
containers.
Place freeze sensitive vaccines on temperature stable
shelves.
Place freeze-tolerant vaccines on coldest shelves.
A Celsius digital minimum/maximum thermometer
and a temperature recording chart is a must.
Check accuracy and change battery of thermometer
every 12 months.

Put thermometer probe in container of freezesensitive vaccines.
Check and record temperatures daily before the
vaccine is used.
Only 1 staff should be responsible for adjusting the
controls.
Establish written protocols for cold chain breaches.
Do vaccine storage audit at least every 12 months.
Rotate stocks to use near expiry vaccines first.
Keep an alternative means of vaccine storage
available.
Donts
Dont place refrigerator in direct sun light.

Dont store any vaccine in door of refrigerator.
Dont over stock your refrigerator with vaccines.
Dont open refrigerator door frequently.
Dont expose light sensitive vaccines to bright light
(most vaccines are sensitive to any form of UV light,
including fluorescent light).
Dont store diluents separately.
Dont use unconditioned the ice/gel packs. It can
easily cause vaccines to freeze.
277
Dont allow temperature to reach 0oC. Most vaccines

are to be considered to be damaged at 0oC.
Dont use un-chilled cooler.
Bibliography
1. Galazka A, Milstien J, Zaffran M. Thermostability of
Vaccines. WHO (Global Programme for Vaccines and
Immunziation), 1998.
2. Indian Academy of Pediatrics, Surat. Target-5, Guide to
vaccine storage and handling.
3. Department of Health and Human Services, CDC.
Atlanta. Vaccine Management, Recommendations for
handling and storage of selected biologicals.
4. Utah VFC program. Vaccine Management, Handling and
storage details for vaccines.
5. Weir E, Hatch K. Preventing cold chain failure: vaccine
storage and handling, 2004;JAMC 2004;171(9):1050.
6. Immunization in Practice: A practical guide for health
workers. WHO 2004.
7. Strive for 5, National Vaccine Storage Guidelines.
Australian Government Department of Health and
Aging.
8. Safety of vaccines affected by a power outage. Quick
Clinical Notes, Disaster management and response,
2004;2:62-3 CDC.
9. UK Guidance on Best Practice in Vaccine Administration.
The Vaccine Administration Task Force, Shire Hall
Communications, London.
9.5 Management of Adverse Effects

Following Immunization (AEFI)
M Indra Shekhar Rao, Tanmay Amladi
INTRODUCTION
Immunization is a major contributor to the success story
of child health in the last century, which has enhanced
and improved the child survival all over the world.
Vaccines used in National Immunization Programs are
extremely safe and effective. Several scientific ethical, and
statutory obligations are fulfilled by the manufacturers;
elaborate field trials regarding safety and protection
offered by individual vaccines are established before they
are recommended for routine use. However no vaccine is
perfectly safe and adverse events can occur following
immunization. In addition to the vaccines themselves,
being products of biological nature, the process of

immunization is also a potential source for adverse events.
An adverse event following immunization (AEFI) is
one that is believed to be caused by immunization.
Reported adverse event can be true adverse event or an
event coincidental to the immunization. For the purpose
of these guidelinesAEFIs are classified into five
categories.
Immunization can cause adverse events from the
inherent properties of vaccine (Vaccine reaction) or some
error in Immunization process (Program error). The event
may be unrelated to the immunization but have temporal
association (Coincidental event). Anxiety-related
278
TABLE 9.5.1: Classification of adverse events following

immunization (AEFIs)
Vaccine
reactions
Event caused or precipitated by the vaccine

when given correctly, caused by the inherent
properties of the vaccine.
Program error Event caused by an error in vaccine preparation,

handling, or administration.
Coincidental
Event that happens after immunization but not

caused by the vaccine a chance association.
Injection
reaction
Event from anxiety about, or pain from the injection

itself rather than the vaccine.
Unknown
Events cause cannot be determined.
Source: Immunization Safety Surveillance WHO 1999, p 9(2).
reactions can arise from fear or pain of the injection rather

than the vaccine itself. In some cases, the cause of AEFI
remains unknown (See Table 9.5.1).
The adverse event following the immunization may
be minor and anticipated, the one which is expected and
not severe enough to cause discomfort for a long duration
of time, e.g. pain or fever after STP vaccination; whereas
a severe or a rare event following the vaccine may be in
the form of unexpected anaphylactic shock or induction
of active disease following measles or OPV vaccine
respectively. Hypothetical type of reaction may be related
to vaccine scar, which has causal relationship relating to
the issues, which are themselves of controversial nature
occurring in vaccinated children.
The common vaccine reactions are due to the immune
response of the host and sometimes due to vaccine
components (e.g. aluminum adjuvant, and preserva-
TABLE 9.5.2: Adverse events following immunization

Anticipated reaction
Minor reaction
Pain, fever following DTP vaccination
Severe reaction
Disseminated BCG infection, anaphylaxis
Vaccine controversies MMR vaccination and autistic syndrome

and casual relationship
tives). A successful vaccine reduces these reactions to a

minimum while inducing the best possible immunity.
These anticipated reactions occur within a day or two of
immunization and they are listed in Table 9.5.3.
The vaccines scar-related adverse events have a very
casual link and are most often hypothetical as listed in
Table 9.5.4.
Another notable component of adverse events
following immunization is due to program errors that
would result from errors that would result from error
and accidents in vaccine preparation, handling or
administration (Table 9.5.5).
The identification and correction of these errors are
of great importance, which would otherwise lead to a
cluster of other events associated with immunization. The
most common program error is iatrogenic infection as a
result of non-sterile injection, e.g. sterile abscess, which
may have a systemic effect or blood-borne infection (e.g.
HIV, hepatitis B).
Each vaccine administered in the immunization
program has specific complications most of which are
anticipated and mild. Some of them are serious adverse
reactions, which always have to be expected, and
TABLE 9.5.3: Common, minor vaccine reactions and treatment

Vaccine
Local reaction
(pain, Swelling, redness)
Fever >38oC
Irritability, malaise and

systemic symptoms
BCG
Hib
Hepatitis B
90-95 percent
5-15 percent
Adults-15 percent
Children-5 percent
10 percent
10 percent
Up to 50 percent
Cold sponging at
injection site.
Oral paracetamol
2-10 percent
1-6 percent
5-15 percent
< 1 percent
10 percent
Up to 50 percent
Given extra fluids
Wear cool clothing
Tepid sponge or bath
Oral paracetamol
5 percent (Rash)
< 1 percent
25 percent
Up to 50 percent
Give extra fluids
Oral paracetamol
Measles/MMR/MR
Oral polio vaccine (OPV)
Tetanus/DT/dT
Pertussis (DTwP)
Treatment
Source: Immunization Safety Surveillance WHO 1999, p 10(2)
279
TABLE 9.5.4: Vaccination scars

Hepatitis B
Whole cell pertussis
Diphtheria, tetanus and pertussis
Inactivated polio vaccine
Influenza
Haemophilus influenzae type b
Measles, mumps and rubella
Multiple sclerosis, lupus, diabetes

Encephalopathy, epilepsy, learning disorders
Cot death/ sudden infant death syndrome (SIDS) HIV infection
Diabetes mellitus
Diabetes mellitus
Autistic spectrum disorder, inflammatory bowel disease, childhood arthropathy.
Rubella
Thiomerosal-containing vaccines
Aluminum-containing vaccines
Various vaccines
Ethical concerns because grown in cells from an aborted fetus, neurodevelopmental disorder, autism, muscular fibrosclerosis.
Diseases of unknown or only partially understood etiology, e.g. asthma, autism,
inflammatory bowel disease, cot death, chronic fatigue syndrome, immune deficiency,
leukemia, autoimmune diseases, learning disorders, increase in violent crime, etc.,
Source: Vaccines- Children and Practice Vol-5, No. 2, 2003 (3)
TABLE 9.5.5: Program errors leading to adverse events

Nonsterile injections
Reuse of disposable syringe or needles
Improperly sterilized syringe or needles
Contaminated vaccine or diluents
Reuse of reconstituted vaccine at subsequent session
Infection:
[e.g. Local suppuration at injection site, abscess, cellulitis,
systemic infection, sepsis, toxic shock syndrome, transmission
of blood-borne virus (HIV, hepatitis B or hepatitis C) ]
Vaccine prepared incorrectly

Vaccine reconstituted with incorrect diluent
Drugs substituted for vaccine or diluent
Local reaction or abscess from inadequate shaking effect of

drug (e.g. muscle relaxant, insulin)
Immunization injected in wrong site

Subcutaneous instead of intradermal for BCG
Too superficial for toxoid vaccine (DTP, DT, TT)
Buttocks
Local reaction or injection site abscess

Sciatic nerve damage (+ ineffective vaccine-hepatitis B and
rabies)
Vaccine transported/stored incorrectly
Increased local reaction from frozen vaccine (and ineffective
Contraindications ignored
Avoidable severe vaccine reaction.
vaccine)
Source: Immunization Safety Surveillance WHO 1999, p 30 (2)
immediate remedial measures have to be given as

described below.
VACCINATION COMPLICATIONS AND
THEIR MANAGEMENT
BCG
Anticipated reactions: Nodule formation at the site of
vaccination (3-6 weeks) which liquefies, ulcerates and
heals by tiny scar (10-12 weeks).
b. Regional axillary adenitis:

Below 2 cm no treatment
Fluctuant, more than 2 cm, treatment INH
(3-6 months)/excision.
c. BCG complex: Local lymphadenitis + Positive
Mantoux reaction + para-tracheal lymph node.
Treat with RHZ (2 months) + RH (4 months).
2. Systemic: Disseminated infection, TB osteomyelitis,
scrofuloderma treat like tuberculosis.
Adverse Reactions
DTP
1. Local:
a. Persistent discharging sinus at the site of vaccination.
Anticipated reaction: Pain, discomfort, fever, induration

(treatment analgesics + antipyretics) paracetamol 15 mg/
kg/dose.
280
Adverse Reactions
IPV
Local reaction: Erythema, induration. Patients sensitive

to streptomycin/neomycin might develop hypersensitive reactions as IPV contains these as preservatives.
Transient Arthralgia, rarely agitation, somnolence and
convulsions.
Incessant cry (more than 3 hours)

Febrile convulsions
Hyperpyrexia
Hypotonic hyporesponsive episode
(shock-like state)
Acute encephalopathy
Anaphylactic shock.
DTaP
Adverse events like pain or swelling are minimal with
above vaccine.
These reactions must be distinguished from syncope,
breath-holding spells, and anxiety, which are common
benign reactions, which only require symptomatic
treatment.
Clinical features of anaphylaxis: Involve multiple body
systems (skin, respiration, circulation).
a. Itchy urticarial rash, facial flushing.
b. Progressive edema involving face, mouth and body
parts.
c. Respiratory symptoms: Sneezing, coughing/
wheezing, airway obstruction.
d. Hypotension. Shock.
Treatment: Place the patient in recumbent position and
elevate the feet.
a. Clear the airway, establish breathing (O2 supplementation and bag mask application) and maintain
circulation.
b. Injection adrenaline (1:1000) 0.01 ml/kg SC/IM
(severe cases). Repeat dose at 20-min intervals till
response.
c. Volume expanders (20 ml/kg normal saline or RL
over 20 minutes) repeat till response.
d. Dopamine (5-10 microgram/kg/min and
dobutamine (5-40 microgram/kg/min)
e. Monitor vital signs.
f. Other measures: To reduce the absorption of vaccine
from injection site:
Placing a tourniquet above vaccination site.
Local adrenaline to reduce vaccine absorption
(only in vaccines given through SC route).
Measles
Anticipated reactions: Mild fever, rash, coryza (upto
4-7 days following vaccination).
Treatment: Paracetamol.
Adverse Reactions
a. Toxic shock syndrome (TSS) due to contamination of
measles vaccine by Staph aureus
b. Exaggeration of tuberculosis
c. Encephalitis.
Toxic shock syndrome: It occurs due to contamination
of measles vaccine with Staph aureus due to usage of
unsterile syringes, needles/and using a vaccine vial
beyond 4 hours after reconstitution.
C/F: Can occur after 30 minutes to few hours after
vaccination presenting with fever, vomiting, diarrhea,
shock.
Treatment : Should be treated as medical emergency.
a. ORS, paracetamol (home treatment )
b. IV fluids, (RL and normal saline), antibiotics
(cloxacillin 100-200 mg/kg/day in divided doses),
steroids, antipyretics, supportive therapy.
MMR
Anticipated reactions: Mild fever, rash, febrile seizures.
Mumps
Adverse reactions: Fever rarely, encephalopathy, seizures,
GBS, parotid swelling, hemolytic-uremic syndrome,
aseptic meningitis.
Rubella
OPV
Adverse Reaction
AEFI almost none

Very rarely vaccine associated paralytic poliomyelitis
(VAPP).
Arthralgia, lymphadenopathy, fever, sore throat.

Rarely thrombocytopenia and peripheral neuropathy.

Hepatitis B Vaccine
Local reactions: Soreness at the site of injection.
Systemic reactions: Mild fever, myalgia, arthralgia, rarely
anaphylaxis.
Typhoid Vaccine
281
c. Ascending paralysis
d. Encephalopathy.
Treatment of complications: Discontinue the vaccine,
bedrest, steroids, further vaccination if required by tissue
culture vaccine.
2. Tissue Culture Vaccine
1. AKD Vaccine (Acetone Killed)
Local reactions: Soreness
Local reactions: Pain, swelling, tenderness.
Systemic reactions: Headache, fever, anaphylaxis, rarely

transient neuroparalytic illness (Gullian-Barre type).
Systemic reactions Headache, nausea, fever and relapse

of chronic diseases like rheumatoid arthritis and
compensated cardiac conditions.
Meningococcal Vaccine
Local reactions: Inflammation
2. Vi Antigen Vaccine
Systemic reactions: Anaphylaxis rarely.
Local reaction: Mild pain, swelling for 1 day.
Pneumococcal Vaccine
3. Ty21 A (Oral Vaccine)

Local reactions: Diarrhea , vomiting.
Systemic reactions: Transitory exanthema.
Local reactions: Swelling , redness, pain.

Systemic reactions: GBS, anaphylaxis, relapse of ITP.
Wheezing, lymphadenopathy
Japanese Encephalitis Vaccine
Tetanus Toxoid (TT)
Local reactions: Redness, swelling, pain.
Repeated TT injections after trivial injuries can lead to

reduced immunogenicity, hypersensitivity, hemolytic
anemia, and amyloidosis. Also increased risk of
hemorrhagic disease of newborn.
Systemic reactions: Fever, headache.
Hib Vaccine
Local reactions: Mild redness, pain and swelling.
Varicella Vaccine
Local reactions: Papular vesicular eruption in less than 4
percent of vaccinees.
Systemic reactions: Mild fever, headache, pneumonitis,
arthropathy, breakthrough varicella.
Influenza Vaccine
Local reactions: Pain, swelling.
Systemic reactions: Rarely GBS (1 in 1,00,000). Transient
lymphadenopathy.
Rotavirus Vaccine
The mild undesirable side effect like fever, vomiting,
irritability and rash may occur. The risk of intussusceptions with rotavirus is not increased as with placebo
group.
VACCINES AND CONTRAINDICATIONS
Rabies Vaccine
1. Nervous Tissue Vaccine (Not used nowadays)
Local reactions: Pain, redness, itching, abscess formation.
Systemic reactions: Fever, headache, giddiness,
palpitation, chock, generalized urticaria.
Neuro-paralytic complications (1:5,500):
a. Cranial nerve paralysis
b. Paralysis of limbs
Vaccines might cause adverse reactions. It is often

difficult to prove definite cause-effect relationship
between the act of vaccination and subsequent complication. However, following guidelines will help in deciding
vaccine administration as shown in Table 9.5.6.
Guidelines for Safe Vaccination
Always ensure safe injection practices for safe health by
using disposable syringes.
282

TABLE 9.5.6: Vaccines and contraindications
1. Avoid: Live vaccine
Avoid: DTP (1st dose)
a.
b.
c.
a.
b.
Immunodeficient individuals
Immunosuppressant therapy
Chronic debilitating illness (till recovery)
Progressive neurological disease
Uncontrolled seizure disorder (postpone till control)
Avoid: Rubella vaccine during pregnancy

Avoid: Antibiotics effective against S. typhi: 1 week prior / after Ty21a vaccination
Avoid: If person is sensitive to egg protein measles vaccine should not be given
2. Delay: Live vaccine
a. Measles /MMR for 6 weeks following immunoglobulin therapy.

b. Severe febrile illness
3. Discontinue
DTP in case of severe postvaccinal reactions
4. Do not stop vaccination in:
a.
b.
c.
d.
e.
Malnutrition
Moderate fever
Respiratory infections
Mild diarrhea
Any benign ailment
Source: Bhatia Rajesh, Ichhpujani RL. Immunization against infectious diseases 1996; p 20-60
1. Select proper vaccine. Follow manufacturers

instructions (dose/route/administrations).
2. Maintain cold chain.
3. Inform the mother regarding vaccine benefits and
their anticipated reactions.
4. Obtain written or atleast oral consent before
vaccination.
5. Keep the child under observation for 30 minutes
after vaccination. Be equipped and geared up to treat
any untoward reactions.
6. Have always resuscitation kit ready.
7. Use desired injection procedure, i.e. load the vaccine
into appropriate syringe size. Discard the needle
used for drawing and use a fresh needle for injection
(1 syringe and 2 needles for each vaccination).
8. Do not mix vaccines in single syringe unless
approved for such use. Use different syringes for
different vaccines. Use different sites for injection.
9. Always use anterolateral aspect of thigh in young
children and deltoid area for older children for
injections. Never use gluteal region in children.
10. Avoid fomentation/vigorous rubbing after vaccination. Firm pressure for a few minutes is sufficient.
11. Document every vaccination procedure in the
immunization card and keep a copy of it.
12. Complete the vaccination schedule as per immunization calendar. Remind the mother regarding next
date.
13. There is no need to restart immunization within a

year of administering the first dose of multi-dose
vaccine, e.g. Hib, DTP, etc. if the child is not brought
for immunization on suggested date. Instead just
continue and complete the schedule.
The best way to minimize the adverse events
following the immunization is to anticipate the expected
type of reaction for a specific vaccine and to identify the
events vaccination.
PREVENTION AND TREATEMENT OF
VACCINE REACTION
It is mandatory for the person administering the vaccine
to have sufficient knowledge regarding vaccines and
expected side effects and to inform parents thoroughly
regarding such adverse effects, which may however
occur very rarely. It is also essential to be prepared and
to always have a kit with life saving drugs and
equipment at each place of vaccination.1
Advice on managing the common reactions should
be given to parents as well as the instructions to return
to the clinic if there are more serious symptoms. This
will help to reassure parents about immunization and
prepare them for common reactions. Program errors are
easily preventable. Identification and correction of these
errors are of great importance. WHO guidelines to avoid
program errors are as follows:

Vaccines must only be reconstituted with the diluent
supplied by the manufacturer.
Reconstituted vaccines must be discarded at the end
of each immunization session and never retained.
No other drugs or substances should be stored in the
refrigerator of the immunization center.
Immunization workers must be adequately trained
and closely supervised to ensure that proper
procedures are being followed.
Careful epidemiological investigation of an AFEI is
needed to pinpoint the cause and to correct immunization practices.
Reporting AEFIs
The reportable EAFI must include any death or serious
event believed by the public or health worker to be caused
by immunization (Table 9.5.7).
The minor common reactions such as local reactions,
fever, and self-limiting systemic symptoms need not be
reported. It is important for the persons administering
the vaccine to advise the parent/patient at the time of
immunization that these reactions are expected and
advise them how to manage these common reactions
(e.g. paracetamol to treat fever). For more serious
problems, the patient should be advised to return or to
seek medical attention and to allow detection of AEFI.
More importantly, they should be advised not to delay
283
treatment of a coincidental illness falsely attributed as

vaccine reaction. Severe local reactions, especially if
occurring in clusters, should be reported, as they can be
markers for program errors or for problems with specific
vaccine lots.
When to report ? Who should report ?
Reporting should be done as quickly as possible so than
an immediate decision on the need for action and
investigation can be made.
Private physicians and hospitals should also report
events that come to the notice. In the community,
peripheral health worker or supervisor should report to
the district office.
The report should contain at a minimum:
Description of the event
Timing of the event in relation to immunization
Vaccines given
Patients identifying details.
The routine vaccination program should continue
while awaiting the completion of the reporting and
investigation.
Responding to AEFIs
Private physicians and the health workers need to know
how to recognize, treat and report AEFI immediately as
TABLE 9.5.7: List of reportable AEFIs2

Occurring within 24 hours of immunization
Occurring within 15 days of immunization
Occurring within 3 months of immunization
Occurring within 5 days of immunization
Occurring within 1 and 12 months after

BCG immunization
No time limit
Anaphylactoid reaction (acute hypersensitivity reaction)

Anaphylaxis
Persistent (more than 3 hours) inconsolable screaming and crying.
Hypotonic hyporesponsive episode (HHE)
Toxic shock syndrome (TSS)
Severe local reaction
Sepsis
Injection site abscess (bacterial/sterile)
Seizures, including febrile seizures (6-12 days for measles.
MMR; 0-2 days for DTP)
Encephalopathy (6-12 days for measles/MMR; 0-2 days for DTP)
Acute flaccid paralysis (4-30 days for OPV recipient; 4-75 days for
contact)
Brachial neuritis (2-28 days after tetanus containing vaccine)
Thrombocytopenia (15-35 days after measles/MMR)
Lymphadenitis
Disseminated BCG infection
Osteitis/osteomyelitis
Any death, hospitalization, or other severe and unusual events that
are thought by health workers or the public to be related to immunization
Source: Immunization Safety Surveillance WHO 1999, p 23 (2)
284
per the guidelines discussed earlier. It is always wiser to

keep the community informed, investigate fully and
avoid making the premature statement about the cause
of the event. Always safeguard the public during
investigation.
Communicating with the Media
The media plays an important role in public perception.
The media are more interested in stories that will attract
attention, hence there is tendency to dramatize and
personalize the event. It is easy for the media to create
sense of panic and outrage about the events, which are
unrelated to immunization (coincidental). The guiding
principle dealing with media must be one should show
empathy and caring, honesty and openness, dedication
and commitment, whenever possible positive terms like
immunization safety or vaccine safety should be used.
Key messages have to be prepared before media contact
and they should include some of these facts:
That benefit of immunization in preventing disease
is well proven.
It is very risky not to immunize (risk of disease and
complications).
Vaccine-preventable diseases caused millions of
death and/or disability before the introduction of
vaccines, and that situation would return without
continued use of vaccines.
Vaccines do cause reactions, but these are rarely
serious and hardly ever cause long-term problems.
Immunization safety is of paramount importance,
and any suspicion of a problem is investigated
(advantage of well established immunization safety
surveillance).
The AEFI is currently being investigated but is likely
to be coincidental/due to a local problem (depending
on type of event), and the immunization program
must continue to keep the population safe from
disease.
Immunization Safety and Safe Injection Practices
The issues concerning the practices and policies dealing
with various aspects of correct administration of vaccines
focus on minimizing the risk of transmission of disease,
and maximizing the effectiveness of the vaccine. The term
encompasses the spectrum of events from proper
manufacture to correct administration, which includes
both injection safety and vaccine safety.
The immunization safety project includes the WHO,

UNICEF, UNAIDS, World Bank, PATH, Bill and
Melinda Gates Children Vaccine Program, Industry,
USAID, CDC who are the main partners and financial
supporters.
The project has main areas of focus:
1. Vaccine safety.
2. Research and development of safe thermostable
vaccines.
3. Access to safe vaccine delivery and safe disposal.
4. Identification and management of risks related to
immunization, develop resource material, train all
EPI managers in the surveillance and management
of adverse events following immunization.
5. Strengthening of monitoring system for vaccine
adverse event reporting system (VAERS).
The immunization focus, as established by the WHO,
has objective to eliminate sickness and death caused
by vaccine preventable diseases through the
development of strong, sustainable National
Immunization Programs, capable of delivering high
quality vaccines in a safe and effective way to all
children.
Safe and efficient immunization practices with
thorough knowledge of the vaccines, well-maintained
cold chain, proper parent education and efficient
resuscitation equipment are vital components essential
to make immunization most cost-effective public health
tool in child survival programs.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
6.
Adverse events following immunization. In:

Parthasarathy A, Lokeshwar Mr, Shah NK (Eds):
Immunization Digest. (1st edn). New Delhi: Jaypee
Brothers 2004;59-62.
Bhatia R, Ichhpujani RL. Immunization against infectious
disease 1996;20-60.
Immunization Safety Surveillance. Guidelines for
managers of immunization Programmes on reporting
and investigation adverse events following Immunization. Manila: WHO; 1999.
Rao M Indra Shekhar. Immunisation in clinical practice.
Jaypee Brothers 2005;37-46.
Rao I. Vaccination complications, their management and
contraindications. Paediatric Clinics of India 2001;36:
30-35.
Vaccines Children and Practice, 2003;vol.5(2).
285
9.6 Approach to Management of

Fever in Newborns, Children and
Adolescents in Office Practice
Digant D Shastri
Fever is one of the most common symptoms in children
in routine office practice. Feverish illness is also one of
the most common reasons for children to be seen in
hospital emergency departments and it is a leading cause
of admission to childrens wards. Many children
suffering from fever may be only mildly unwell and have
a focus of infection identified on clinical examination.
Fever in young children usually indicates an underlying
infection of some kind and, as such, the condition is a
cause of concern for parents and carers. The condition is
also a diagnostic challenge for healthcare professional
because it is often difficult to identify the cause. Infectious
diseases remain a major cause of childhood mortality and
morbidity. Often the illness is due to a self-limiting virus
infection and the child will recover quickly without
intervention. However, fever may also be the presenting
feature of serious bacterial illnesses such as meningitis,
septicemia, urinary tract infections and pneumonia. The
children with fever without apparent source (FWS) are
a particular concern to healthcare professionals because
it is especially difficult to distinguish between simple
viral illnesses and life-threatening bacterial infections in
this group. In general, FWS tends to be a problem in
young children. The younger the child, the more difficult
it is to establish a diagnosis and assess the severity of
illness. As a result, there is a perceived need to improve
the recognition, evaluation and immediate treatment of
fever in children.
Older Infants/Toddlers
Localise infection better than neonates, but may still
be pre-verbal.
Risk group for occult bacteremia (i.e. circulating
pathogens with no clear focus).
Frequently exposed to infectious diseases in group
childcare.
Get viral infections as well as the typical childhood
organisms of pneumococcus H. Influenza b and
meningococcus.
Older Children
Usually verbalize and localize symptoms well.
More tolerant to fluid loss-less likely to need IV
rehydration.
Can get typical childhood organisms plus others
such as Mycoplasma and infectious mononucleosis.
Causes of Elevated Temperature
Nenates and Young Infants
Fever is the bodys response to a variety of external and

endogenous stimuli such as infection, inflammation or
toxins and is generally medicated by the production of
pyrogens. It can also occur when body metabolic heat
production or environmental head load exceeds heat
losing capacity or when there is impaired heat loss.
Thus fever can be either due to:
1. Pyrogen production: Infection, inflammation,
toxin, cell destruction, immune mediated.
2. Metabolic: Infection, Malignancy, Hormonal.
3. Impaired thermal regulation: Central.
May not have the characteristic signs of serious

infection (temperature can be high or low).
Localising features may be absent.
Can deteriorate rapidly.
Young infants with fever, especially those under three
months of age, need rapid assessment and investigation,
and admission to hospital.
Infectious etiologies are the commonest cause of fever

particularly in children less then 5 years and serious
bacterial infection is the concern in the evaluation of
the child with fever. Following are some of the
common infectious cause of fever in children.
Meningitis, or encephalitis.
Upper respiratory tract infection (URI).
RATIONALE FOR CLINICAL APPROACHAGE
286
Bacterial or viral pneumonia.

Otitis media.
Malaria
Local skin infections, such as cellulites.
Oral infections, including pharyngitis due to
Streptococcus pyogenes (group A Streptococcus
species).
Urinary tract infection (UTI).
Generalized viral illness.
Amongst non-infectious causes, fever associated with
malignancy and that of rheumatoid origin are many
times overlooked. Rheumatic conditions leading to
fever are more common in grown up children
particularly adolescents. Fever of non-infectious
causes include following:
High external temperature (especially in the
warmer weather months)
Over bundling of children in colder weather
months
Recent exercise
Malignancy
Rheumatoid diseases
Complications of routine administration of childhood
vaccinations carry the risk of temperature elevation
as a common adverse effect.
Administration of the diphtheria, tetanus, and
pertussis (DTP) vaccine may cause fever within a
few hours after administration and may persist
up to 48 hours.
Administration of live virus vaccinations, such as
the measles, mumps, and rubella (MMR) vaccine,
may result in temperature elevations up to
7-10 days after its administration.
Clinical Assessment of Risk in a Child with Fever
The majority of children presenting with fever will have
either a self-limiting viral condition or an obvious cause
Traffic light system for identification of serious illness
Activity
Green-low risk
Amber-intermediate risk
Red-high risk
Normal colour of skin,

lips and tounge
Pallor reported by parent carer
Pale/mottele/ashen/blue
Responds to social cues

Stay awake
Strong normal cry/no cry
Content/smile
Not responding normally to

social cues
Wakes only on strong stimuli
Decreased activity
No smile
Not responding to social cues

Appears ill to health care professional
Does not waken, or if roused does not
stay awake
Weak high-pitched or continuous city
Grunting
RR > 60/min
Moderate to sever indrawing
Nasal flaring
RR >50/min in 6-12 months
> 40/min in > 12 years
SpO2 : < 95% in air
Crackles
Respiratory
Hydration
Normal skin and eye

Moist mucus membrane
Dry musus membrane

Poor feeding
CRT >3 sec
Reduced urine output
Reduced skin turgor
Others
None of amber or red sign

or symptom
Fever > 5 days
Children < than 3 months with a temp.

> 38C
Children aged 3-6 months with a temp.
> 39C
CRT = capillary refill time; RR = respiratory rate.
Swelling of limb/joint
Non weight bearing
Nonblanching rash
Bulgine fontanelle
Neck stiffness
Status epilepticus
Focal neurological signs
Focal seizures
A new lump > 2 cm
Billestained vomiting

for their fever for which specific treatment can be given.
Although most children with a fever will have a selflimiting illness, a minority will have a serious or even
life threatening illness. The priorities for healthcare
professionals should be to:
1. Identify any immediately life threatening features
2. Assess the childs likelihood of having a serious illness
of self-limiting illness, without necessarily diagnosing
any one particular condition
3. Determine a source of the illness to direct specific
treatment
4. Make appropriate management decisions based upon
the results of the assessment.
First, one should identify any immediately lifethreatening features, including compromise of the
airway, breathing or circulation, and decreased level of
consciousness. Children with fever should be assessed
for the presence or absence of symptoms and signs that
can be used to predict the risk of serious illness.
Traffic light system for identifying risk of serious
illness. Children with fever and any of the symptoms or
signs in the red column should be recognized as being
at high risk.
Children whose symptoms or combination of symptoms suggest an immediately life-threatening illness
should be referred immediately for emergency medical
care. Children with any red features but who are not
considered to have an immediately life-threatening
illness should be urgently assessed. Children with green
features and none of the amber or red features can be
managed at home with appropriate advice for parents
and carers including advice on when to seek further
attention form the healthcare services.
History
One should realize that there is no alternative to proper
history taking in routine office practice. Relevant history
and through physical examination form the base of
probable diagnosis. Obtaining an accurate history from
the parent or caregiver is important; the history obtained
should include the following information:
Age
Fever in infants less then 3 months of age is considered
evidence of serious bacterial infection until proved
287
otherwise and hence warrants immediate and close

attention.
Fever History
Ask what was childs temperature prior to presentation and how was temperature measured? Ask also
about the degree and duration of fever. The reason
for these questions is that it is often assumed that these
variables can be used to help differentiate serious
bacterial illnesses from less serious self-limiting viral
infections. Regarding the height of recorded fever, it
is often thought that there is a higher risk of serious
illness with increasing body temperature. High grade
fever (>41C) often indicates failure of distal
thermoregulation mechanism (heat stroke, malignant
hyperthermia, etc) occurring alone or in combination
with infection. Regarding duration of fever, many
times it is thought that an SBI is more likely with
increasing duration of fever. Fever lasting more then
4-7 day is very rarely likely due to viral illnesses as
usually viral fevers resolve spontaneously over a
shorter period of time. Always remember that normal
or low temperature does not preclude serious, even
life-threatening, infectious disease.
Ask about periodicity (pattern) of fever
Remitten Fever: Daily elevated temperature (>38C
or 100.4F), fever returns to baseline but not to normal
(98.6 C). The daily fluctuation of temperature is more
than 2C.
Intermitten Fever (Periodic Fever): Intermittently
elevated temperature (>35C, 100.4F), temperature
returns to baseline and to normal.
Hectic Fever: Daily elevated temperature (>38C or
100.4F), fever can have either a remittent or
intermittent pattern, the temperature excursion is
>1.4C (2.5F) e.g. intermittent bacteremia (dental
abscess, UTI), Familial Mediterranean Fever, Stills
disease, etc.
Sustained or Continuous Fever: Daily elevated
temperature (>38C or 100.4F) Fluctuation of
elevated temperature never >than 1C (1.5F), e.g.
Enteric fever, Drug fever.
Ask about progress of Fever: Fever due to viral infection
usually peaks over a day or two and gradually decline
over 3-4 days. Bacterial infection presents with fever,
288
which if untreated either persists or even gets worst over

the time. Sudden rise and decline of fever suggests the
likelihood of malaria infection
Chills and rigors: Rigors are common accompaniment with
infections like malaria, UTI bacterial endocarditic,
tonsillitis, pneumonia and deep seated abscess.
Inter febrile state: Evaluation of the clinical state of the
patient in between two fever parozysms is very useful
guide for predicting probable cause of fever. Carefully
assess the level of activity of lethargy, eating and drinking
pattern, sensorium, threshold of responsiveness, quality
of cry, etc. A child who continues to appear toxic,
lethargic, and apathetic even when the temperature
reaches normal is more likely to have a serious infection,
usually bacterial. Such a child should be observed
carefully. Against that the child whose inter febrile
clinical state depicts general well-being and who appears
non toxic in between fever spikes is more likely to have
viral fever.
Fever at presentation: If one finds that the infant has been
excessively bundled, and if a repeat temperature taken
15-30 minutes after unbundling is normal, the infant
should be considered afebrile.
Medical History
Urinary output: Inquire as to the number of wet
diapers.
Immunization history: What is the patients immunization status? Which vaccines have been given
recently?
Drug History: Ask about recent long term use of
antibiotic or recent high dose usages of drugs like
atropine, which cause poisoning, which many times
can cause drug fever.
Has there been recent antibiotic use?
Has there been exposure to illness through babysitters, day care contacts, or other caregivers? Are
other at home sick?
Ask about absence of perspiration: children with
Anhidrotic ectodermal dysplasia will have history of
absent/impaired sweating and history of high grade
fever particularly in summer months. Such children
have dry skin and spars hair with or without dental
abnormalities.
For the neonate, the history is explored for possible
evidence of poor feeding, vomiting, poor social
interaction, changes in the quality of crying, and
possible apneic episodes.
Any of these finding are reasons to suspect serious

bacterial infection and may warrant laboratory
evaluation.
The birth history is explored to ascertain risk
factors for underlying pathology, such as
prematurity, premature rupture of membrane,
maternal infections.
When assessing a child with feverish illness, one
should enquire about recent travel abroad and should
consider the possibility of imported infections
according to the region visited.
Physical Examination
The physical examination of the febrile child is directed
at locating a source of the temperature elevation, with
specific attention to potential serious bacterial illnesses.
Hypothermia is a common presenting vital-sign
abnormality in septic neonates. While performing a
complete physical examination, pay particular attention
to assessing hydration status and identifying the source
of infection. Physical examination of every febrile child
should include the following:
I. Record vital signs
Temperature: Rectal temperature is the standard.
Temperature obtained via tympanic, axillary, or oral
methods may not truly reflect the patients
temperature.
Core skin temperature mismatch: Measurement of
temperature difference between core and skin
temperature is particularly important in patient with
shock or sepsis. Such children show significant core
skin temperature mismatch beyond normal range.
Dissociation between temperature and pulse rate is
seen in older children in typhoid, brucellosis,
Legionnaires disease. Factious fever is also accompanied with inappropriately low pulse. Fever with
low pulse rate likely to be due to viral myocarditis,
fever with low pulse rate with high blood pressure
could be due to increased intracranial tension with
CNS infection
Respiratory rate: Presence of dyspnoea, tachypnea,
grunting, flaring, and retractions should be noted.
Blood pressure
One should record capillary refill time as part of the
routine assessment of a child with fever. A capillary
refill time of 3 seconds or longer should be recognized
as an intermediate-risk group marker for serious
illness.

Height of body temperature alone should not be used
to identify children with serious illness. However,
children in the following categories should be recognized
as being in a high-risk group for serious illness:
Children younger than 3 months with a temperature
of 38C or higher
Children aged 36 months with a temperature of 39
C or higher.
Children with temperatures form 39-39.5C (102.2103F) have an approximate 2-4% risk of having occult
bacteremia. Those with temperatures higher than
39.5C (103F) have an approximate 5-10% chance of
having occult bacteremia.
II. Observation of the infant or childs interactions with
the parent or caregiver is easily done while the history
is obtained.
What is the quality of the cry? Is it abnormal, high
pitched, or weak in effort?
Does the child appear afraid of the examiner?
Beyond infancy, healthy young children should
fear strangers. In this situation, the child who lies
on the examination table without much interaction or who is not disturbed by an ear
examination is more likely to have a more serious
illness.
What is the skin color? Are there areas of cyanosis
or jaundice? Are there any rashes present?
What is the response to social overtures? Does the
baby smile at the examiner? Does the baby smile
or appear interested in a small toy or other shiny
object? Social smile remains one of the best
predictors of well babies
III. Record an accurate weight as all pharmacologic and
procedural treatments are based on the weight in
kilograms.
IV. Concentrate on identifying source of fever: One
should also look for a source of fever and check for
the presence of symptoms and signs that are
associated with diseases.
Physical examination finding suggestive of serious
illness (e.g. serious bacterial infection) include the
following:
Presence of dysponea, techypnea, grunting, flaring,
and retractions should be noted. These finding are
abnormal and require further exploration (e.g. pulse
oximetry, chest radiography).
Hydration status should be documented. Specific
signs of dehydration might include dry mucous
membrane, sunken fontanelle, absence of tears
289
Symptoms and signs suggestive of specific diseases

Diagnosis to be
considered
Symptoms and signs in conjunction with

fever
Meningococcal
disease
Nonblanching rash, particularly with one

of more of the following:
an ill-looking child
lesions larger than 2 mm in diameter
(purpura)
capillary refill time of > 3 seconds
neck stiffness
Neck stiffness
Bulging fontanels
Decreased level of consciousness
Convulsive status epilepticus
Focal neurological signs
Focal seizures
Decreased level of consciousness
Tachypnoea (RR>60 breaths/minute,
age 0-5 months; RR > 50 breaths/minute,
age 612 months; RR>40 breaths/minute,
age >12 months)
Crackles in the chest
Nasal flaring
Chest indrawing
Cyanosis
Oxygen saturations < 95%
Vomiting
Poor feeding
Lethargy
Irritability
Abdominal pain or tenderness
Urinary Frequency or dysuria
Offensive urine or haematuria
Swelling of a limb or joint
Not using an extremity
Non-weight bearing
Fever for more than 5 days and at least
four of the following:
bilateral conjuctival injection
change in mucous membranes
change in the extremities
polymorphous rash
cervical lymphadenopathy
Meningits
Herpes simplex
encephalitis
Pneumonia
Urinary tract
infection
Septic arthritis
Kawasaki disease
when crying, and/or a lack of urine output (by

history).
Persistent irritability despite feeding or inability of
parents to console the child is concerning. True
irritability and lethargy are physical signs traditionally associated with an ill-child.
The presence or absence of meningeal signs should
be documented in older children.
Caution: In some infants and younger children
(perhaps less than 12-15 months), who develop
290
meningitis, specific meningeal signs, such as the

Kernig or Brudzinski sign, may not be present.
A hemorrhagic rash is classically described as
resulting from overwhelming systemic bacterial
infection due to meningococcemia but may be due to
other (usually serious) infections like malaria/
dangue. The presence of petechiae or purpura in
febrile children indicates the need for prompt
evaluation and therapy.
Management of Fever in Children
less than 3 months old
Although fever in the young infant is relatively
uncommon, when it occurs there ia higher risk of serious
bacterial infection than in later life. Approximately 10
percent of well-appearing young infants with a
temperature higher than 38C (100.4F) harbour a
serious bacterial infection or meningitis. The neonate
is at risk of rapidly developing infection because of a
relatively poorly developed immune system. Babies
born preterm or with low birth weight are particularly
vulnerable. The infections may be those acquired from
the mother at the time of delivery (e.g. group B
streptococcus), or hospital-or community-acquired
infections. SBI, particularly meningitis and UTI, are
more common in the first 3 months than later in
childhood. Because of the greater probability of serious
bacterial infection, a more aggressive approach to the
evaluation and management of fever is warranted in
young infants. Specific criteria, commonly termed the
Rochester Criteria, have been proposed to identify
febrile young infants at low risk for serious bacterial
infection.
ROCHESTER CRITERIA FOR IDENTIFYING
FEBRILE INFANTS AT LOW RISK FOR
SERIOUS BACTERIAL INFECTION
1. Infant appears generally well
2. Infant has been previously healthy:
Born at term (>=37 weeks of gestation)
No perinatal antimicrobial therapy
No treatment for unexplained hyperbilibrubinemia
No previous antimicrobial therapy
No previous hospitalization
No chronic or underlying illness

Not hospitalized longer than mother
3. Infant has no evidence of skin, soft tissue, bone, joint
or ear infection
4. Infant has these laboratory values:
White blood cell count of 5,000 to 15,000 per mm3
(5 to 15 109 per L)
Absolute band cell count of 1,500 per mm3 (1.5
109 per L)
Ten or fewer white blood cells per high-power
field on microscopic examination of urine
Five or fewer white blood cells per high-power
field on microscopic examination of stool in infant
with diarrhea
Infants younger than 3 months with fever should have the
following investigations performed:
Complete blood count
Blood culture
C-reactive protein
Urine testing for urinary tract infection
Chest X-ray only if respiratory signs are present
Stool culture, if diarrhea is present.
Lumbar puncture should be performed on the following children
(unless contraindicated):
Febrile neonate
Neonate with symptoms suggestive of sepsis
Neonate with suspected sepsis prior to starting
antibiotic
Infants aged 1-3 months with white blood cell count
(wbc) less than 5109/litre or greater than 15 109/
litre.
When indicated, a lumbar puncture should be
performed without delay and, whenever possible, before
the administration of antibiotics. Parenteral antibiotics
should be given to:
Infants younger than 1 month
All infants aged 13 months who appear unwell
Infants aged 13 months with a WBC count less than
5 109/litre or greater than 15 109/ litre.
Children with fever without apparent source
presenting with one or more red features should have
the following investigations performed:
Full blood count
Blood culture
C-reactive protein
Urine testing for urinary tract infection.

Following investigations should also be considered
in children with red features, as guided by the clinical
assessment:
Lumber puncture in children of all ages (if not
contraindicated)
Chest X-ray irrespective of body temperature and
white blood cell count.
Serum electrolytes and blood gas.
291
Flow chart 9.6.1: Child <3 months old with fever

(>38C Axillary)
Children with fever without apparent source who

have one or more amber features should have the
following investigations performed:
Urine should be collected and tested for urinary tract
infection
Blood tests: Full blood count, c-reactive protein and
blood cultures
Lumber puncture should be considered for children
younger than 1 year
Chest X-ray in a child with a fever greater 39C and
white blood cell count (wbc) greater than 20 109/
litre.
Children who have been referred with fever without
apparent source and who have no features of serious
illness (that is, the green group), should have urine
tested for urinary tract infection and be assessed for
symptoms and signs of pneumonia. Routine blood tests
and chest X-rays should not be performed on children
with fever who have no features of serious illness.
Management of Fever in Children
more than 3 months Old
For all patients aged 3-36 months, management decisions
are mostly based on the degree of toxicity and the height
of temperature. The Yale observation scale is a reliable
method for determining degree of illness. It consists of
6 variables: quality of cry, reaction to parent stimulation,
state variation, color, hydration, and response. A score
of 10 or less has a 2.7% risk of serious bacterial infection.
A score of 16 or greater has a 92% risk of serious bacterial
infection.
Most fevers in this age group are viral and the risk of
occult bacteriemia and SBI decreases with advancing age.
The risk of occult bacteriemia and SBI is higher in those
with temperature >39C. With widespread immuni
zation against Hemophilus influenzae infection, Streptococcus
pneumoniae has become the predominant cause of serious
bacterial infection in infants and young children.
Streptococcal bacteriemia affects fewer than 2% of wellappearing older infants and young children with a
temperature above 39C. Most children in this age group
clear streptococcal bacteriemia without antibiotic

therapy, Approximately 10% of infants and young
children with fever and S.pneumoniae bacteriemia
progress to a serious bacterial infection, and from 3 to
6% progress to meningitis (i.e., approximately one case
per 1,000 to 2,500 of these febrile children). The risk of
pneumococcal bacteriemia varies based on the patients
age, temperature and white blood cell count.
In children aged 3 months or older with fever without
apparent source, a period of observation in hospital (with
or without investigations) should be considered as part
of an assessment to help differentiate nonserious from
serious illness.
Medical Care
For children who appear ill, conduct a complete
evaluation to identify occult sources of infection. Follow
the evaluation with empiric antibiotic treatment and
admit the patient to a hospital for further monitoring
and treatment pending culture results. Children aged
3-36 months may not require admission if they meet the
following criteria:
Child was healthy prior to onset of fever.
292

Yale Observation Scale
Observation Items
1(Normal)
3 (Moderate Impairment)
5 (Severe Impairment)
Quality of cry
Strong with normal tone or

contentment without crying
Whimpering or sobbing
Weak cry, moaning, or

high-pitched cry
Reaction to parent
stimulation
Brief crying that stops or

contentment without crying
Intermittent crying
Continual crying or limited

response
Color
Pink
Acrocyanotic or pale extremities
Pale or cyanotic or
mottled or ashen
State variation
If awake, stays awake; if asleep,

wakes up quickly upon stimulation
Eyes closed briefly while awake

or awake with prolonged
stimulation
Falls asleep or will not

arouse
Hydration
Skin normal, eyes normal, and

mucous membranes moist
Skin and eyes normal and

mouth slightly dry
Skin doughy or tented, dry

mucous membranes, and/
or sunken eyes
Response (e.g., talk,

smile) to social overtures
Smiling or alert(< 2 mo)
Briefly smiling or alert briefly

(<2 mo)
Unsmiling anxious face or

dull, expressionless, or not
alert (<2 mo)
Child has no significant risk factors.

Child appears non toxic and otherwise healthy.
Childs laboratory results are within reference ranges
defined as low risk.
Childs parents (or caregivers) appear reliable and
have access to transportation if the childs symptoms
should worsen.
Treatment recommendations for children with fever
without a focus are based on the childs appearance, age
and temperature.
For children who do not appear toxic, temperature is
less then 39C treatment recommendations are as
follows: Observe for 48 hours and instruct parents to
return with the child sooner if the condition worsens.
If at 48 hours fever persist get investigations CBC,
MP, urine study and blood culture to rule out
infection.
For children who do not appear toxic and temperature is more than 39C treatment recommendations
are as follows:
Get investigations: CBC, MP, urine study to rule
out infection.
Consider no antibiotics; however, if absolute
neutrophil count is greater than 15,000/L,
consider ceftriaxone (50 mg/kg/dose).
Hospital admission is indicated for children
whose condition worsens or whose evaluation
findings suggest a serious infection.
For children who appear toxic, treatment recommendations are as follows:

Admit child, investigate for infection and administer parenteral antibiotics for further treatment;
pending culture results.
Observation in Hospital
Children with fever are often observed in hospital for a
period of time to help differentiate those with serious
illness from those with nonserious illness. This observation usually involves the repeated measurement of
vital signs as well as repeated assessments of the child
to look for the development of any clinical features that
would give cause for concern.
Antipyretic Interventions
Fever is a normal physiological response to infection and
a number of other conditions. Although it is a normal
response, majority of people, including many doctors,
nurses and parents, believe that fever should be treated
to reduce temperature. If it is thought necessary to reduce
fever, there are number of interventions that are or have
been used, either alone or in combination. Pharmacological treatments differ fundamentally from physical
treatments, as they aim to lower the hypothalamic setpoint rather than simply cool the body. Paracetamol and

nonsteroidal anti-inflammatory agents such as Ibuprofen
inhibit the action of the cyclooxygenase enzyme involved
in the production of the prostaglandin and other and this
is the basis of their antipyretic activity. There are a
number of physical interventions that can be used to
reduce body temperature, including undressing, fanning
and sponging with cool or cold water. These have
advantage of heat loss through convection and evaporation but do not treat the underlying causes of the fever.
Physical treatments do not reduce the levels of prostaglandins and so the temperature of the whole body is
not reduced. Furthermore, because the hypothalamus is
still set a higher temperature level, physical treatments
may cause shivering and other adverse effects as the body
aims to meet the hypothalamic set-point temperature,
which continues to be raised.
Paracetamol and Ibuprofen, the drugs most
commonly used to treat, fever, either in combination or
alternately. Paracetamol and Ibuprofen both are equally
effective and equally safe antipyretics. Combination
treatment offers no advantage over single drug therapy
and would not lead to clinically significant further
reduction of body temperature. Paracetamol is the most
widely used antipyretic medicine and has long term
record of excellent safety. It is antipyretic of choice in
the management of fever in any age group. The usual
dose and frequency of administration are 15 mg/kg every
4-6 hours with a maximum total dose of 90 mg/kg/day.
Oral paracetamol is usually well-tolerated, effective and
hence for management of fever parenteral antipyretics
not indicated. For children with intractable vomiting, or
post-operative state, a rectal suppository will be more
useful. Ibuprofen is an antipyretic of second choice and
it is also having good safety. The usual dose and
frequency of administration are 8-10 mg/kg/8 hourly.
In adults it is commonly associated with GI side effects,
but that is very uncommon in children. Since it can cause
upper GI side effects including GI ulcer it is contraindicated in dengue infections. Aspirin is not safe for
lowering fever because it can cause Reyes syndrome in
febrile children with viral infections.
Recommendations on Antibiotics
Antibiotics are used for suspected bacteriemia or
bacteriuria. Empiric antimicrobial therapy must be
comprehensive and should cover all likely pathogens in
293
the context of the clinical setting. Whenever feasible,

antibiotic selection should be guided by blood culture
and sensitivity studies. Children with fever presenting
to specialist pediatric care or an emergency department
should be given immediate parenteral antibiotics if they
are:
Shocked
Unrousable
Showing signs of meningococcal disease.
In children with fever and reduced levels of
consciousness, symptoms and signs of meningitis and
herpes simplex encephalitis should be sought. When
parenteral antibiotics are indicated, a third-generation
cephalosporin (for example, cefotaxime or ceftriaxone)
should be given, until culture result are available. For
children younger than 3 months, an antibiotic active
against listeria (for example ampicillin or amoxicillin)
should also be given.
Amplicillin inhibits the biosynthesis of cell wall
mucopeptides. It acts against gram-positive organisms
(excluding beta-lactamase-positive S aureus), enterococci,
gram-negative organisms (e.g. Escherichia coli, and
Proteus, Klebsiella, and Salmonella species), and betalactamasenegative H influenzae. The standard pediatric
dose is 50-100 mg/kg/d IV divided q6h for mild-tomoderate infections. For severe infections, the dose is
200-400 mg/kg/d IV divided q6h. Adverse effects
include glossitis, stomatitis, nausea, vomiting, black
hairy tongue, enterocolitis, pseudomembranous colitis,
diarrhea, hypersensitivity reactions, increasing serum
glutamic-oxaloacetic transaminase, anemia, thrombocytopenia, thrombocytopenic purpura, leukopenia, and
agranulocytosis.
Ceftriaxone is a third-generation cephalosporin that
inhibits cell wall synthesis. It acts against gram-positive
organisms, including beta-lactamase-producing organisms, but not enterococci, methicillin-resistant
S aureus, and Listeria species. It is active against gramnegative species (e.g., E coli, H influenzae, Moraxella
catarrhlis and Proteus, Klebsiella, Enterobacter, Citrobacter,
and Pseudomonas species) but not Acinetobacter species.
It is variable in its activity against Bacteroides fragilis
and Pseudomonas species. The pediatric dose is 50-100
mg/kg/d IV divided q12-24h. Adverse effects include
hypersensitivity, colitis, transient elevations of blood urea
nitrogen and serum creatinine, prolonged prothrombin
time (PT), and gallbladder disease.
Cefotaxime is also a third-generation cephalosporin
that shares similar activities with ceftriaxone. It also
294

Flow chart 9.6.2: Child < 3 years old with fever (>38C Axillary)
inhibits cell wall synthesis. Dosage is 100-150 mg/kg/d

IV divided q6-8h, and the meningitic dose is 200 mg/
kg/d IV divided q6-8h. Adverse effects include hypersensitivity, GI discomfort (e.g., nausea, vomiting,
diarrhea, colitis), neutropenia, increased liver enzymes,
and transient elevations of blood urea nitrogen and
creatinine.
Gentamicin is an aminoglycoside that inhibits
normal protein synthesis in suspeceptible organisms.
It is active against gram-positive organisms (except
methicillin-resistant S aureus and Streptococcus faecium),
gram-negative organisms (but not Xanthomonas
maltophilia, Pseudomonas cepacia, or Flavobacterium
species), and anaerobes. Dosing for the pediatric
population with normal renal function is 6-7.5 mg/kg/
d IV divided q8h for children, 7.5 mg/kg/d IV divided
q8h for infants and neonates, and 5 mg/kg/dIV divided
q12h for premature neonates and full-term neonates
aged 1 wk or younger.
BIBLIOGRAPHY
1. ACEP. Clinical policy for children younger than three
years presenting to the emergency department with
fever. ACEP Clinical Policies Committee; ACEP Clinical
Policies Subcommittee on Pediatric Fever. Ann Emerg
Med 2003;42(4):530-45.
2. Alpern ER, Alessandrini EA, Bell LM. Occult bacteremia
from a pediatric emergency department: current prevalence, time to detection, and outcome. Pediatrics 2000;106;
(3):505-11.
3. Baker MD, Bell LM, Avner JR. The efficacy of routine
outpatient management without antibiotics of fever in
selected infants. Pediatrics 1999;103(3):627-31.
4. Baraff LJ, Bass JW, Fleisher GR, et al. Practice guideline
for the management of infants and children 0 to 36
months of age with fever without source. Agency for
Health Care Policy and Research. Ann Emerg Med
1993;22(7):1198-210.
5. Baraff LJ. Management of fever without source in infants
and children. Ann Emerg Med 2000;36(6):602-14.
6. Bauchner H, Pelton SI. Management of the young febrile
child: A continuing controversy. Pediatrics 1997;
100(1):137-8.

7. Bonadio WA. The history and physical assessments of
the febrile infant. Pediatr Clin North Am 1998; 45(1):
65-77.
8. Brook I. Unexplained fever in young children: How to
manage severe bacterial infection. BMJ 2003;327(7423):
1094-7.
9. Crain EF, Gershel JC. Urinary tract infections in febrile
infants younger than 8 weeks of age. Pediatrics
1990;86(3):363-7.
10. Grover G, Berkowitz CD, Lewis RJ, et al. The effects of
bundling on infant temperature. Pediatrics 1994;94(5):
669-73.
11. Ishimine P. Fever without source in children 0 to 36
months of age. Pediatr Clin North Am 2006;53(2):16794.
12. Ishimine P. The evolving approach to the young child
who has fever and no obvious source. Emerg Med Clin
North Am 2007;25(4):1087-115, vii.
13. Lee GM, Harper MB. Risk of bacteremia for febrile young
children in the post- haemophilus influenzae type b era.
Arch Pediatr Adolesc Med 1998;152(7):624-8.
14. Luszczak M. Evaluation and management of infants and
young children with fever. Am Fam Physician 2001;64(7):
1219-26.
295
15. McCarthy CA, Powell KR. Screening for serious bacterial

infections in young febrile infants. Arch Pediatr Adolesc
Med 2000;154(3):315-6.
16. Nozicka CA. Evaluation of the febrile infant younger than
3 months of age with no source of infection. Am J Emerg
Med 1995;13(2):215-8.
17. Perrott DA, Piira T, Goodenough B, Champion GD.
Efficacy and safety of acetaminophen vs ibuprofen for
treating childrens pain or fever: A meta-analysis. Arch
Pediatr Adolesc Med 2004;158(6):521-6.
18. Schriger DL. Management of the young febrile child.
Clinical guidelines in the setting of incomplete evidence.
Pediatrics 1997;100(1):136.
19. Wahba H. The antipyretic effect of ibuprofen and
acetaminophen in children. Pharmacotherapy 2004;24(2):
280-4.
20. Wasserman GM, White CB. Evaluation of the necessity
for hospitalization of the febrile infant less than three
months of age. Pediatr Infect Dis J 1990;9(3):163-9.
21. Yamamoto LG. Revising the decision analysis for febrile
children at risk for occult bacteremia in a future era of
widespread pneumococcal immunization. Clin Pediatr
(Phila) 2001;40(11):583-94.
9.7 Fever and Fever of Unknown Origin

PP Maiya
Humanity has but three great enemies:
Fever, war and famine. Of these by far
the greatest, by far the most terrible is fever
Sir William Oscar
Fever in children is one of the most common manifestations of an illness, which makes the parents seek medical
attention early. Fever occurs when various infectious and
non-infectious processes interact with the hosts defense
mechanism. It is important that all children with fever
are carefully assessed to find the cause. Nevertheless cause
remains undetermined in a significant percentage of cases,
leading to the designation of FWF (Fever with out focus)
and FUO (Fever of unknown origin). But even with the
etiology being determined, fever remains the overriding
source of anxiety.
Definition
The narrow body temperature is maintained between a
range of 36.8 0.4 C (98.2 + 0.7 F) with a circadian
rhythm of lowest temp at 6:00 A.M (37.2 C or 98.9 F)

and highest temperature of 37.7 C or 99.9F at 4:00 P.M.
In general Fever is considered to be present if rectal
temperature is above 38.3 C, oral temp is above 37.8 C
or axillary temperature is above 37 C.
Mechanism of Fever
The fever reaction is a series of cellular events that begin
peripherally and ends centrally with a resetting of bodys
temperature set point. Unlike Hyperthermia fever
doesnt represent a failure of temperature control, but
rather an upward shift of the regulated temperature, as
a result of bodys exposure to infecting micro-organisms,
immune complexes, other sources of inflammation.
Various mediators like Cytokines, TNF, IL-1 and IL-6
stimulate PGE2 production in the anterior hypothalamus,
which then brings about rise in the temperature set point
by a variety of physiological mechanisms including
activation of cAMP. When this happens signals are sent
to various efferent nerves innervating peripheral blood
296

TABLE 9.7.1: Causes of fever without focus
Acute viral fever

Septicemia or Bacteremia
Vaccine associated fever
Urinary tract infection
Sinusitis
Hyperthermia
Occult Bacteremia
Prodrome of conditions like Infectious Mononucleosis,
Kawasakis disease, etc.
TABLE 9.7.2: Investigations in patients with FWF
Complete blood counts, CRP, ESR

Urine routine, Urine C/S
Blood C/S
Lumbar puncture( If indicated)
Occult Bacteremia
Figure 9.7.1: Pathogenesis of fever
vessels to conserve heat. The vasoconstriction causes the

feeling of chills which may lead to rigors with sudden
elevation of body temperature. Also the thermoregulatory center sends signal to cerebral cortex to initiate
behavioral changes like seeking warm environment,
extra clothing and flexed posture. All these mechanisms
act to elevate the core body temperature, so that the blood
bathing neurons in the anterior hypothalamus is warm
and matches with the new temperature set point.
Classification of Fever Syndromes
Fever with Focus
The majority of febrile episodes in children are associated
with infections. The diagnosis is made by identifying the
focus, e.g. Otitis media, respiratory infection, septic
arthritis, etc.
Fever without Focus (Table 9.7.1)
This term refers to fever of acute onset and short duration
(< 1 week) without any localizing symptoms or any
clinical signs on physical examination.
30% of the febrile children between 3-36 months have

no localizing signs of infections.
Occult bacteremia occurs due to H. Influenza, N.
meningitides, and salmonella in 4% of well appearing
children.
Risk factors: Total counts of > 15,000,Raised ESR, CRP
and ANC.
Increased incidence of occult bacteremia may be due
to maturational immune deficiency in the production
of opsonic IgG (Table 9.7.2).
Treatment Options
1. Obtain blood culture and start empirical antimicrobial therapy.OR
2. Obtain CBC, If counts are > 15,000 do a blood culture
and start antibiotics.OR
3. Observe selected cases as outpatients after blood for
C/S has been obtained and ask parents to bring back
the child if fever persists or condition deteriorates.
Fever with Nonspecific Signs
When the duration of fever is yet less than two weeks at
presentation and child manifests with hepatomegaly,
splenomegaly, rash, jaundice or lymphadenopathy
specific investigations for anicteric or icteric hepatitis,
enteric fever, malaria, infectious mononucleosis may
provide clues to diagnosis. Assess the epidemiological
details suggestive of Dengue fever, Leptospirosis, etc.

Recurrent Fever
This term refers to children presenting with episodes of
documented fever separated by days or weeks of normal
temperature.
For example, recurrent respiratory tract infections,
relapsing fever, dengue fever, lymphomas.
Fever Complicating Chronic Illness
A child who has fever persisting for over 2 weeks may
have a chronic disease to be investigated for lymphomas
or leukemia. Childhood tuberculosis may present in a
similar way.
TREATMENT OF FEVER
Whether or not to treat elevated temperature is a
common question. To determine an answer one must
first identify the cause of fever, degree of fever and
then establish goals of therapy.
In patients with fever of < 40 degree C there is no
benefit of antipyretic therapy.
The use of antipyretics will alter the pattern of fever,
which may mask the diagnosis.
Goal of the treatment is to correct fluid deficit and
ensure that the childs fluid intake is adequate.
The knowledge that fever is an important immunological defence mechanism has always been used to
support the arguments against treating fever. There is
enough evidence to support this view that uncomplicated
fever is relatively harmless.
Advantages of Fever
Increases immune response by increased production
of interferons, B cell proliferation Increased
bactericidal effect of PMNS.
Improves nutrition of cells with protective influence
on their activity.
Growth and virulence of several organisms like
Malaria, Syphilis is impaired.
Augments hepatic synthesis of acute phase reactants.
There are situations where fever can be harmful in
young children if not treated, e.g. debilitated or children
with systemic infections.
It is common experience that Fever often makes child
uncomfortable, Increases metabolic rate, increase O2
consumption and CO2 production, Increased demands
297
on Cardiopulmonary system, precipitates febrile

convulsions. Thence administration of antipyretics
becomes necessary.
Indications of Antipyretic Therapy
1.
2.
3.
4.
Fever > 101F

Febrile convulsions
Child is shivering
Child with heart disease.
SUPPORTIVE THERAPY
Physical therapy is often used to promote loss of heat in
high grades fever.
Remove excess clothing or blankets and keep the child
in well-ventilated room.
Encourage to take extra fluid to compensate for
increase insensible fluid loss and to maintain blood
flow necessary for heat dissipation.
Discourage vigorous activities.
Tepid sponging: It is cheap, easy and safe physical
measure to reduce body temperature. Studies have
found that tepid sponging is effective in the first 30
minutes.
Effect of sponging with water at different temperatures
Tap water
Luke warm
Cold water
20 min
15 min
20 min
0.2 degree C
0.8 degree C
0.1 degree C
Rapid cooling methods such as ice baths, alcohol rub

down and cool water enemas should be avoided.
WHO recommends fanning, tepid sponging and
cooling blankets for treatment of fever in children with
Malaria.
DRUG THERAPY
Most of the drugs used in antipyresis reduce levels of
PG synthesis in brain and thus sets the thermostate back
to normal. The pharmacological therapy includes
different classes of drugs with antipyretic-analgesic,
antipyretic or analgesic effects only. Aspirin once a
preferred drug is no longer used as it has potential to
cause Reyes syndrome. Acetaminophen, Ibuprofen and
Nimesulide are currently three preferred drugs in
treatment of fever (Table 9.7.3).
298
Paracetamol (Acetaminophen); (PCM)

Its the drug of choice in young children. Its analgesic
effect is equal to that of Aspirin but in clinical doses has
no anti-inflammatory effect. It is well absorbed orally and
is 50% protein bound. It is conjugated in liver to form
sulphate and glucuronide derivatives with a small
amount metabolized to toxic aryl intermediates which
is hepatotoxic when present in quantities greater than
the capacity of liver to conjugate with glutathione. It
exhibits linear dose relationship, higher doses has been
shown to be more effective than lower doses.
Neonates and infants handle PCM less efficiently and
are capable of forming reactive intermediates that causes
hepatocellular damage after multiple dosing.
It has been used alone or in combination with tepid
sponging with equal or better results. It has been used as
suppository in children with nausea or vomiting or
unconscious state with equal efficacy.
The dose is 10-15 mg/kg given at 4 hours interval
.The analgesic dose is 65 mg/kg/dose in divided doses.
Acute PCM toxicity occurs due to accidental exposure
with clinical features of anorexia, vomiting, abdominal
pain, jaundice, hematuria, and metabolic acidosis.
Diagnosis is based on history, clinical findings and raised
LFT. Treatment is with N acetyl cysteine.
Ibuprofen
It is a propionic acid derivative with a comparable
antipyretic efficacy with PCM or aspirin. (Ibuprofen in a
dose of 6 mg/kg has equal efficacy with 8-12 mg/kg of
PCM).
Dose 5-10 mg/kg /dose.
It can lead to gastric ulceration, hemorrhage,
Perforation.
Mefenamic Acid
It is a potent inhibitor of cyclo-oxygenase with both
central and peripheral action. It has been reported to have
longer duration of action and therefore more effective
than Ibuprofen.It has high rate of fecal excretion and
therefore causes diarrhea and other GI effects and
nephrotoxicity if used more than a week.
Nimesulide
It is relatively new drug with selective COX inhibitory
action. It achieves peak conc. in 1-4 hours after oral dose.
It can be used orally or rectally.
Dose is 1.5-2.5 mg/kg/dose. It has a faster and long

antipyretic effect as compared to PCM.
Mechanism of action: It inhibits Cyclo-oxygenase and
thus PGE2, free radical scavenger, anti-histaminic,
activity on myeloperoxidase.
Side effects: Excess perspiration, heartburn, and
flushing and skin rash.
Aspirin
It is an effective antipyretic-analgesic NSAID. It acts buy
inhibiting Cyclo-oxygenase and thus PGE2 in Hypothalamus. Biological half-life is only 15 minutes: t of
salicyclic acid is 2-3 hours.
Overdose leads to salicylism characterized by
hyperventilation, depressed level of consciousness and
severe metabolic acidosis.
Unequivocal evidence linked aspirin use in viral
infections like Influenza, chickenpox to Reyes syndrome.
Its use as antipyretic is gone into disrepture except in
specific conditions like rheumatic fever and other
collagen vascular disease.
Paracetamol is the drug of choice because it has
minimal side effects and doesnt affect the beneficial
effects of fever. Also it is safe to use in febrile children
with bronchial asthma, ITP or GI illness.
Most failures with antipyretic therapy are related to
underdosing .PCM can be increased to 15 mg/kg/dose
in resistant fever.
If no response then use Ibuprofen as second line. Its
the only antipyretic recommended by WHO as an
alternative. It can be used as a combination with PCM
under supervision.
Mefenamic acid or nimesulide are reserved only for
rare difficult cases. Avoid corticosteroids.
FEVER OF UNKNOWN ORIGIN
Fever of unknown origin (FUO) is defined as a single
illness that has lasted for 3 or more weeks, with
temperature greater than 38.3C on most days and with
uncertain diagnosis after 1 week of intense evaluation
which include hospitalization and CT of the abdomen.
FUO can be further categorised into four types depending on
the causes
1. Classic FUO: The child should have temperature
> 38.3C for a duration of > 3 weeks and should have
been evaluated on atleast 3 OPD visits or 3 days of
inpatient stay, e.g. Infection, malignancy, inflammatory diseases, etc.
299
TABLE 9.7.3: Comparing different Antipyretics

Drug
Pharmacokinetics
Dose
Drug interactions
Dose schedule
Currently not
favored
Peak
Metabolism
Aspirin
2 hrs
15 min
Hepatic
10-15 mg/kg/dose
Can displace protein

bound drug
Paracetamol
-1 hr
1-4 hrs
Hepatic
10-15 mg/kg/dose
Not significant
4-6 hourly
Ibuprofen
1-2 hrs
1.8-2 hrs
Hepatic
5-10 mg/kg/dose

bound drug
4-6 hourly
Mefenamic acid
2-4 hrs
2.5-3 hrs
Hepatic
4-12 mg/kg/dose

bound drug
6-8 hourly
Nimesulide
-1 hr
2 hrs
Hepatic
5-8 mg/kg/day
Not known
8-12 hourly
2. Nosocomial FUO: Temperature of > 38.3C developing on several occasions in a hospitalized patient who
is receiving acute care and in whom infection was
not manifest or incubating on admission. Three days
of investigations, including at least 2 days incubation
of cultures is the minimum requirement for this
diagnosis, e.g. sinusitis, clostridium difficile colitis,
drug fever, septic thrombophlebitis.
3. Neutropenic FUO defined as a temperature of 38.3C
on several occasions in a patient whose neutrophil
count is < 500/uL. The diagnosis of neuropenic FUO
is invoked if a specific cause is not identified after 3
days of investigation including at least 2 days
incubation of culture. For example candidiasis,
Aspergillosis, perianal infection
4. HIV Associated FUO defined as temp of > 38.3C on
several occasions over a period of > 4 weeks for out
patient or 3 days for hospitalized patient with HIV
infection.
The diagnosis is invoked if appropriate investigation over 3 days including 2 days incubation of
culture reveals no organism.
E.g. Mycobacterium avium intracellularae,

Tuberculosis, Non-Hodgkins Iymphoma, drug fever.
Etiology
There are a good number of causes for FUO. Incidence
of diseases causing FUO varies depending upon the age
of the child. In children less than 6 years of age most
common is infective cause accounting for 65% followed
by neoplastic 8% and autoimmune 8%. In the age group
between 7 to 12 years, infective causes accounts for 38%,
neoplastic 4%, autoimmune 23%.
Etiology of FUO can be classified into infective causes
and noninfective causes.
Table 9.7.4 lists the etiology for FUO.
DIAGNOSTIC APPROACH TO FUO
The diagnostic approach for each child has to be
individualized. It has to be kept in mind that in most
cases the cause of FUO is a familiar disease with an
uncommon presentation, rather than a rare disease. For
most patients diagnostic evaluation may be initiated on
Side effects of Antipyretics

Drug
Aspirin
GI
irritation
Peptic
ulcer
CNS
effects
Tinnitus
Hepatic
Renal
Bone
marrow
Bronchial
reactivity
Reyes
syndrome
+++
++
++
++
++
++
Paracetamol
Ibuprofen
++
Mefenamic acid
++
Nimesulide
++
300

Choosing the right drug
Cooling methods
Indications
Tepid sponging +
antipyretic drugs
H/O neurological disease

H/O cardiopulmonary disease
H/O fever > 40 degree
Septic shock
Tepid sponging alone
Very young infant

Severe liver disease
H/O hypersensitivity to antipyretics
Cold sponging
Heat illness
an outpatient basis. However young infants, children

who appear toxic or chronically ill and children who have
been febrile for a prolonged period should be
hospitalized for evaluation. Hospitalization helps in
documenting the fever, exploring the history further,
repeating the physical examination and maintaining
constant observation along with lab evaluation.
History
Carefully taken , detailed history is the most important
tool in the diagnosis of FUO.
Age: Neonates and young children are susceptible to
specific organisms like L monocytogenes, Group B
Streptococcus. Adolescents are susceptible for N
gonorrhea infection. Connective tissue disorders are
4 times more common in children who are more than
6 years old.
Sex: Chronic granulomatous disease and Brutons
agammaglobulinemia are restricted to boys. Pelvic
inflammatory disease occurs more often in females.
History of fever in the family members or neighbours
may point towards infectious cause of fever.
Contact with tuberculosis and past history of
exanthematous illness may suggest the possibility of
tuberculosis.
Pets in the house raise the possibility of toxoplasmosis,
visceral larva migrans, cat scratch disease.
History of pica, ingestion of dirt provides clue to the
diagnosis of toxoplasma infections.
Note should be made about the presence of epidemics
in the community like dengue, enteroviral and
leptospira infections for considering appropriate
diagnosis.
Take details regarding travel to areas with endemic
illnesses.
Recent history of surgery suggest possibility of occult
infection.
TABLE 9.7.4: Etiology for FUO

1. Infective cause
A. Specific infection
Bacterial:
Salmonella
Brucellosis
Meningococcemia
Mycoplasma pneumonia
Spirocheteal
Borrelia Burgdorferi
Leptospirosis
Parasitic diseases:
Amebiasis
Giardiasis
Toxoplasmosis
Fungal disease
Blastomycosis
Histoplasmosis
Clamydial
Lymphogranuloma venereum
Psittacosis
Rickettsial
Q Fever
Tick born typhus

Viruses
CMV
HIV
B. Local septic infections
Dental abscess
Sub phrenic abscess
Sinusitis
Tonsillitis
Tuberculosis
Yersiniosis
Actinomycosis
Relapsing fever
Syphilis
Babesiosis
Malaria
Coccidiomycosis
Rocky mountain
spotted fever
Hepatitis
Hepatic abscess
Bronchectasis
Mastoditis
C. Local infection without pus formation

UTI
Phlebitis
Ulcerative colitis
Regional enteritis
Diverticulitis
2. Noninfectious cause
Collagen vascular disorder
JRA
Juvenile dermatomyositis
Neoplastic
Leukemia
Neuroblastoma
Metabolic
Gout
Endocrine
Thyrotoxicosis
Hypersensitive reaction
Serum sickness
Drug fever
Miscellaneous
Cirrhosis of liver
Familial mediterrean fever
Poisoning
Fictitious fever malingering
Behcets disease
SLE
Lymphoma
Wilms tumor
Porphyria
Addisons disease
Sarcoidosis
Whipples diseases

A history of abdominal pain or diarrhea even weeks
before the onset of fever may be a clue for enteric
infection or intra-abdominal abscess.
Medication history should be looked into and should
include over the counter preparation, topical agents
including atropine (Atropine induced fever).
Genetic background of the patient is important for
conditions like Riley-Day syndrome.
Physical Examination and Clues to
the Diagnosis Of FUO
Careful and meticulous physical examination is
mandatory in all children with FUO. Repetitive
examinations, preferably daily examination is important
to pick-up subtle or new signs which appear during the
course of illness and help in identifying the etiology.
Following are the clinical parameters which give clues
to the diagnosis.
Temperature
Temperature pattern during hospitalization may give
clues to the diagnosis e.g. (1) Intermittent: Malaria, acute
pyelonephritis (2) Continuous: Typhoid, Miliary TB,
Subacute bacterial endocarditis (SABE), Pneumonia, (3)
Periodic/undulating: Hodgkins, brucellosis.
Pulse rate: Relative bradycardia (Typhoid, meningitis,
dengue, Weils disease).
Anemia: Malaria, Kala-azar SABE, ALL, chronic diseases.
Lymph node: All lymph nodes should be described and
recorded.
Generalized lymphadenopathy: Hodgkins disease, TB,
ALL, Secondary syphilis.
Localized lymphadenopathy: Glandular fever.
Jaundice: Infectitious hepatitis, Weils diseases, malaria,
liver abscess, infectious mononucleosis.
Skin rash: Viral exanthematous illnesses like measles and
varicella, meningococcemia, dengue, septicemia, SABE,
rickettsial illness.
Clubbing: Lung abscess, bronchiectasis, SABE, liver
abscess.
Arthritis: Rheumatic fever, SABE, meningococcemia,
leukemia.
Bony tenderness: Arthritis, leukemia.
Fundus: Choriod tubercules in tuberculosis.
301
CVS
CVS should be examined for murmurs daily.
The presence of sick and toxic look may suggest
bacterial etiology. A child who otherwise looks well in
spite of fever may have a non-infective cause of fever.
Investigations (Table 9.7.5)
Investigations should be appropriate and based on
clinical history and physical findings.
Following table lists the investigations which are
routinely done for patients with FUO. Further investigation depends upon the childs presentation which is
listed as advanced investigation.
Routine investigations should include total and
differential counts, peripheral smear, ESR urine analysis,
blood culture. Total count greater than 11,000/ mm3 have
a high likelihood of bacterial infection. Conversely,
absolute neutrophil count of less than 5,000/mm3 is
against indolent bacterial infection except typhoid fever.
Periperal eosinophilia provides clue to parasitic
infestation, immunodeficiency disorder or occult
malignancies. Direct smear examination with Giemsa or
Wright stain reveals organisms of malaria, toxoplasma,
relapsing fever, etc.ESR exceeding 30 mm per hour
indicates inflammation and need for further evaluation.
TABLE 9.7.5: Routine and Advanced investigations
Routine Investigations
Complete blood counts
ESR, CRP
Liver biopsy
Chest X-ray
Peripheral smear (night smears for filaria)
Mantoux test
Urine analysis
Blood and urine cultures
Stool examination (occult test also)
Liver function test
CSF analysis
Ultrasonography
Bone marrow aspiration and biopsy
Lymph node biopsy
Advanced Investigations
Serum for virological studies
Autoimmune work up (RA factor, ANA factors)
ECG/ECHOCT/MRI
Barium studies
Isotope scans
Lymphangiography to localize retroperitoneal, aortic and iliac
lymphnodes.
Exploratory laparotomy.
302
ESR greater than 100 mm/hour may suggest tuberculosis, Kawasakis disease, autoimmune or malignant
diseases. Blood culture should include aerobic and
anerobic cultures. Chest X-ray should be an initial
investigation. X-ray of the sinuses, mastoids or GI tract
may be indicated by specific history or physical findings.
Other investigations like ultrasonography, CT scan, bone
marrow examination must proceed stepwise. Lumbar
puncture is necessary in young infant or child with
meningeal signs, altered mental status, etc.
Isotope scans with technetium-99m, gallium citrate,
indium-111 labeled leukocytes help in localizing
inflammatory processes.Bronchoscopy, laparoscopy,
gastrointestinal endoscopy and mediastinoscopy may be
warranted on individual merits of the case. Lymphangiography is resorted to localize aortic, iliac and retroperitoneal lymph nodes. Exploratory laparotomy is
performed when all the other diagnostic procedures fail.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
6.
7.
8.
9.
Treatment
As far as possible any treatment for FUO should be
started only when sufficient grounds for diagnosis are
available. Mild antipyretics are given for the patient
comfort. Empirical trial with antibiotics may mask the
diagnosis of infective endocarditis, osteomyelitis or
meningitis. Exception may be the use of ATT in a critically
ill child with possible disseminated TB. In general
observation of the temperature pattern, repeated clinical
examination, careful laboratory evaluation and interpretation of the results might throw a light on the diagnosis.
Specific treatment depends on the diagnosis.
10.
11.
12.
13.
14.
15.
Campbell AGM. The child with fever. In Campbell AGM,

Neil Macintosh (Eds). Forfar and Arneils text book of
Pediatrics, 5th Edn, 1998;1282-4.
Chandra J. Antipyretics in children. Indian Journal of
Pediatrics 2002;69:69-74.
Chandrashekhar PH. Pyrexia of Unknown origin. Arch
Int Med 1994;154:841-9.
Cunha BA. fever of unknown origin. Infect Dis Clin
North Am 1996;111-27.
Gelfand JA, Dinarell CA. Fever and Hyperthermia. In
Fauci AA, Braunwald E, et al (Eds). Harrisons principles
of internal medicine, 14th edn: 1998;84-90.
Krishnan S. FUO, IAP J Pract Ped 1994;2:289-91.
Martin I Lorin. Fever of unknown origin, In McMillan,
Deangelis, Feigen et al (Eds). Oskis Principles and
Practice of Pediatrics 1999;3:844-8.
Martin I Lorin. Pathogenesis of fever and its treatment.
In McMillan, Deangelis, Feigen, et al (Eds). Oskis
Principles and Practice of Pediatrics 1999;3:848-50.
Mieler ML, et al. Fever of unknown origin. Pediatr Clin
N Am 1995;42.
Powell KR. Fever of unknown origin Part 16, section 2,
Nelson Textbook of Pediatrics, 16th edn 2000;142-7.
Robinson MJ, Roberton DM. FUO.Practical Pediatrics
1995;3:301-4.
Sarah S, et al. Distinguishing among prolonged,
Recurrent and periodic fever syndromes. Pediatr Clin N
Am 2005;52:811-35.
Singh M. Fever of acute onset: A practical approach. IAP
J Prac Ped 2002;4:85-90.
Singh M. Fever with out focus. IAP J Prac Ped 1997;5:
139-42.
Singh M. Symptomatic management of fever in children:
A rational approach. IAP J Prac Ped 1999;1:75-80.
9.8 An Approach to a Child with

Fever and Skin Rash
Jayakar Thomas
Skin rashes in a child with fever is always a cause for
great concern. They can be caused by a drug reaction, an
infection, or an allergic reaction. The skin can only react
to injury in a few ways, and many different agents can
cause rashes that look the same. Often, the symptoms in
addition to the rash help make the diagnosis, such as a
history of insect bites, exposure to other ill children or
adults, recent use of medication, environmental
exposures, or prior immunizations. Most rashes caused

by viruses do not harm the child and go away over time
without any treatment. However, some childhood rashes
have serious or even life-threatening causes. A physician
should be familiar with these rashes. Many rashes can
look the same, making it difficult to know the exact
diagnosis. About 10% of all febrile children have a
dermatological problem.

Some examples of skin rash in a febrile child
Drug rash
Kawasakis disease
Systemic lupus erythematosus
Erythema infectiosum
Dermatomyositis
Measles
Urticaria
Rubella
Allergic vasculitis
Varicella
EMF
Herpeszoster (disseminated)
Toxic epidermal necrolysis
Typhoid
Staphylococcal scalded skin syndrome
Erythema marginatum
Scarlet fever
Meningococcemia
Erysipelas
Bacterial endocarditis
The approach to such a situation is a challenge and

in clinical practice, physicians lean on their eyes in no
other situation more than they do when confronted by
an acutely ill child with fever and a skin eruption.
An algorithmic or stereotyped approach to a child
with fever and skin rash would not sound meaningful.
Prudence, however, demands a systematic approach. It
will comprise of:
1. Careful history taking
2. Astute clinical examination
3. Relevant laboratory work-up
History taking with regard to the fever, the points to
be considered include:
Duration of fever
Variation with time of day
Drug intake
Itching/burning/pain
Other symptoms
With regard to the skin rash, the points to be
considered include:
Distribution of rash
Morphology or pattern of skin rash
Evolution
Prodrome, if any.
Clinical Examination
This will include:
Grade of fever
303
Pattern of fever
Type of skin lesions
Configuration
Arrangement
Distribution
Site of first appearance
Evolution
Tenderness
Mucosal involvement
Palms/soles/hair/nails
Other systems.
The morphology of the skin lesions may contribute
reasonably to its cause in relation to the fever. It is
common to see more than one type of morphology at a
given point of time. Drug reactions are classical examples
of such presentation. At times the lesions go through
stages, and in such cases the presenting lesion along with
relevant evidence from the history on evolution will help
clinch the diagnosis. Yet others may start in a particular
form and continue the same morphology, as in measles
and rubella. Therefore it is mandatory that the physician
familiarizes himself with a sound knowledge of the
morphology of skin lesions in the different disorders.
Definitions of these patterns are given in the Chapter on
Skin Diseases in Children.
Some examples are shown below. These are only
guidelines and should not be considered as complete and
comprehensive.
Macules, papules,
and blisters
Drug rash
SLE
Erysipelas
Meningococcemia
Bacterial endocarditis
Macules and
blisters
EMF
TEN
SSSS
Varicella
Macules only
Dermatomyositis
Urticaria
Allergic vasculitis
Scarlet fever
Kawasakis Disease
Erythema infectiosum
Measles
Rubella
Erythema marginatum
Typhoid
Laboratory Work-up
Essential investigations include:
Complete hemogram
Urine microbiology
Blood biochemistry
Smear examination from skin lesion
Gram/Leishman/AFB
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Dark field microscopy

LE cell test
Blood serology
Skin biopsy.
Many childhood diseases have bacterial or viral
causes and include a rash of some type. As study
continues and more and more vaccines become available,
these diseases become less of a threat to the childs longterm health. A rash of any kind should be taken seriously,
however, and may require a laboratory work-up for
evaluation.
Viral and Bacterial Disorders
Chickenpox
The characteristic rash appears in crops. An otherwise
healthy child usually has 250-500 lesions but may have
as few as 10 or as many as 1500. Each lesion starts as a
red macule and passes through stages of papule, vesicle,
pustule, and crust. Redness or swelling around a lesion
should lead to suspicion of secondary bacterial infection.
The vesicle on a lesions erythematous base leads to its
description as a pearl or dewdrop on a rose petal.
Varicellas hallmark is the simultaneous presence of
different stages of the rash. Some lesions may appear in
the oropharynx. Eye lesions are rare. New lesions
continue to erupt for 3-5 days. Lesions usually crust by 6
days (2 to 12-d range), and heal completely by 16 days
(7 to 34-d range). Prolonged eruption of new lesions or
delayed crusting and healing can occur with impaired
cellular immunity. Fever usually is low-grade (100-102F)
but occasionally may be as high as 106F. In otherwise
healthy children, fever typically subsides within 4 days.
Prolonged fever should prompt suspicion of complication or immunodeficiency. Outcomes of in utero
varicella infections vary, based upon the timing of the
infection. Neonatal varicella can be a serious illness,
depending upon the timing of maternal varicella and
delivery. If the mother develops varicella within 5 days
before or 2 days after delivery, the baby is exposed to
the secondary viremia of the mother. The baby acquires
the virus transplacentally but acquires no protective
antibodies because of insufficient time for antibodies to
develop in the mother. In these circumstances, neonatal
varicella is likely to be severe and disseminated.
Prophylaxis or treatment is required with varicella-zoster
immune globulin (VZIG) and acyclovir. Without these
drugs, mortality rates may be as high as 30%. The
primary causes of death are severe pneumonia and

fulminant hepatitis. Onset of maternal varicella more
than 5 days antepartum provides the mother sufficient
time to generate and pass on antibodies along with the
virus. Full-term neonates of these women usually have
mild varicella because of the attenuating effect of the
transplacentally acquired antibodies. Treatment with
VZIG is not recommended in such cases, but acyclovir
may be used, depending on individual circumstances.
Laboratory studies are unnecessary for diagnosis because
varicella is obvious clinically. Most children with
varicella have leukopenia in the first 3 days, followed by
leukocytosis. Marked leukocytosis may indicate a
secondary bacterial infection, but this is not a dependable
sign. Most children with significant secondary bacterial
infections do not have leucocytosis. A Tzanck smear
involves scraping the base of the lesions, then staining
the scrapings to demonstrate multinucleated giant cells.
This finding, however, is not sufficiently sensitive or
specific for varicella and should be replaced by the more
specific immunohistochemical staining of such scrapings,
if available. Serology mainly is used to confirm past
infection to assess a patients susceptibility status. This
helps determine preventive treatment requirements for
an adolescent or adult who has been exposed to varicella.
Among the many serologic studies, the most sensitive
are the indirect fluorescent antibody (IFA), fluorescent
antibody to membrane antigen (FAMA), neutralization
test (NT), and radioimmunoassay (RIA). These timeconsuming tests require specialized equipment that
renders them unsuitable for routine use. Commercially
available latex agglutination (LA) and enzyme-linked
immunosorbent assay (ELISA) tests are sensitive and
rapid. Although the complement fixation test often is
used, its sensitivity is low. Children with high temperatures and respiratory signs should have a chest x-ray
to confirm or exclude pneumonia. Chest X-ray findings
may be normal or may show diffuse bilateral nodular
infiltrates in primary varicella pneumonia. X-rays also
may detect focal infiltrates suggestive of secondary
bacterial pneumonia. Children with neurological signs
should have their cerebrospinal fluid (CSF) examined.
The CSF of patients with varicella encephalitis may have
few or as many as a hundred cells that are polymorphonuclear or mononuclear, depending on the timing
of the lumbar puncture. Glucose levels are normal.
Protein levels are normal or slightly raised. Treatment is
mainly directed to manage pruritus with cool compresses

and regular bathing. Scratching is discouraged to avoid
scarring. Trimming the childs fingernails and having the
child wear mittens while sleeping may reduce scratching.
Some children with varicella have reduced appetite and
should be encouraged to take sufficient fluids to maintain
hydration. Adequate hydration is especially important
if the child is receiving acyclovir, as the drug can
crystallize in the renal tubules if administered to
dehydrated individuals. Chickenpox is not always
benign. In certain well-defined groups, varicella can be
severe and even fatal. Antiviral drugs are recommended
for adolescents, adults, and children on steroid or
salicylate therapy and for children who are otherwise
immunocompromised. Acyclovir is the only adequately
studied drug of this class.
Measles
The incubation period from exposure to onset of
symptoms ranges from 8-12 days. The prodromal phase
is marked by malaise, fever, anorexia, conjunctivitis,
cough, and coryza. The entire course of uncomplicated
measles, from late prodrome to resolution of fever and
rash, is 7-10 days. Cough may be the final symptom to
appear. Fever: A temperature exceeding 101F begins
with the prodrome and persists 7-10 days. Koplik spots
(i.e., bluish-gray specks or grains of sand on a red base)
appear on the buccal mucosa opposite the second molars
near the end of the prodrome, just prior to appearance
of rash. This enanthem begins to slough as the rash
appears. An erythematous and maculopapular rash that
becomes confluent begins on the face, then proceeds to
the trunk, extremities, palms, and soles and lasts for about
5 days. Patients appear most ill during the first or second
day of the rash. Desquamation, which spares the palms
and soles, may occur after 1 week. The rash may be absent
in patients with underlying deficiencies in cellular
immunity. Generalized lymphadenopathy, mild hepatomegaly, and appendicitis may occur because of generalized involvement of lymphoid tissue. Laboratories can
confirm measles by demonstrating more than a 4-fold
rise in immunoglobulin G (IgG) antibodies between acute
and convalescent sera. IgG antibodies may be detectable
4 days after the onset of the rash, although most cases
have detectable IgG antibodies by about a week after rash
onset. Thus, take specimens on the seventh day after rash
onset and repeat 10-14 days later to confirm the case as
soon as possible. Patients with SSPE have unusually high
titers of measles antibody in their serum and
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cerebrospinal fluid. The earliest confirmation of measles

using IgG antibodies takes about 3 weeks from the onset
of illness, a delay too long to permit implementation of
effective control measures. Myxovirus (MV) can be
isolated from nasopharyngeal swabs. Viral genotyping
in a reference laboratory may determine whether an
isolate is endemic or imported. In immunocompromised
patients, who may have poor antibody responses that
preclude serologic confirmation of measles, virus
isolation from infected tissue or identification of measles
antigen by immunofluorescence may be the only method
to confirm the diagnosis. Leukopenia occurs in the late
stages of viremia. Elevated hepatic transaminase levels
may be detected in patients with MV hepatitis.
Administration of antibiotics (if evidence exists of otitis
media or bacterial pneumonia), vitamin A supplements
(particularly for children aged 6-24 mo), or ribavirin
(experimental) is considered treatment modalities. To
prevent or modify measles in exposed susceptible
individuals, administering MV vaccine or human
immunoglobulin is tried. Vitamin A treatment for
children with measles in developing countries has been
associated with a marked reduction in morbidity and
mortality. The World Health Organization recommends
vitamin A administration to all children with measles in
communities where vitamin A deficiency is a recognized
problem and where the MV-related mortality rate
exceeds 1%. Of note, low serum concentrations of vitamin
A are found in children with severe measles. Thus,
supplemental vitamin A in patients aged 6 months to 2
years who are hospitalized with measles and its
complications (e.g. croup, pneumonia, diarrhea) is found
useful. Also vitamin A supplementation is given for any
patient who meets the following criteria:
1. Is older than 6 months and has measles
2. Is not already receiving vitamin A supplementation
3. Is immunodeficient
4. Has clinical evidence of vitamin A deficiency
5. Has moderate-to-severe malnutrition
6. Has recently emigrated from an area with high
mortality rates due to measles.
Rubella (German measles)
Rubella virus is transmitted from person to person via
the aerosolized particles from the respiratory tract. A
history of exposure may not be present. Individuals may
acquire the infection from a completely asymptomatic
patient or from an individual shedding the virus during
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the incubation period. The incubation is usually 14-21

days after exposure to a person with rubella. Prodromal
symptoms are unusual in young children but are
common in adolescents and adults. The following signs
and symptoms usually appear 1-5 days before the onset
of rash:
Eye pain on lateral and upward eye movement (a
particularly troublesome complaint)
Conjunctivitis
Sore throat
Headache
General body aches
Low-grade fever
Chills
Anorexia
Nausea
Tender lymphadenopathy (particularly posterior
auricular and suboccipital lymph nodes)
Forchheimer sign (an enanthem observed in 20% of
patients with rubella during the prodromal period;
can be present in some patients during the initial
phase of the exanthem; consists of pinpoint or larger
petechiae that usually occur on the soft palate).
The laboratory diagnosis of rubella can be made either
though serologic testing or by viral culture. The serologic
diagnosis consists of demonstrating the presence of
rubella-specific immunoglobulin M (IgM) antibody in a
single serum sample or observation of a significant rise
in rubella-specific immunoglobulin G (IgG) antibody titer
between the acute and convalescent serum specimens
drawn 2-3 weeks apart. False-positive rubella IgM test
results have been reported in persons with other viral
infections (e.g. acute Epstein-Barr virus [EBV], infectious
mononucleosis, cytomegalovirus [CMV] infection,
parvovirus B19 infection) and in the presence of
rheumatoid factor (RF). To demonstrate a 4-fold rise in
rubella-specific IgG antibody, a serum sample should be
obtained as soon as possible during the acute phase of
infection and tested for rubella-specific IgG antibody. An
aliquot of this serum should be frozen and stored for
repeat testing later. Then, a second serum specimen is
collected at 2-3 weeks and tested in the same laboratory
at the same time with the first serum sample. The levels
of rubella-specific IgG are compared between the first
and the second sample to show a significant rise in
antibody titers. Rubella viral cultures are time consuming, expensive, not readily available, and used mainly
for tracking the epidemiology of rubella virus during an
outbreak. Complete blood count: CBC may reveal

leukopenia and thrombocytopenia. It is used to monitor
the course of thrombocytopenia. Histologically cutaneous
lesions are nonspecific and demonstrate only a mild,
superficial, perivascular, lymphocytic infiltrate.
Treatment is supportive. No specific antiviral agent for
rubella is currently available. Starch baths and antihistamines may be useful for uncomplicated rubella and
troublesome itching. For complicated cases, treatment is
as follows:
For severe arthritis affecting weight-bearing joints,
encourage rest. Nonsteroidal anti-inflammatory
drugs (NSAIDs) may be helpful, but corticosteroids
are not indicated.
For patients with encephalitis, provide supportive
care with adequate fluid and electrolyte maintenance.
Thrombocytopenia usually is self-limited but, if
severe, consider intravenous immunoglobulin (IVIG).
Corticosteroids have not demonstrated any specific
benefit. Splenectomy is not indicated.
Drug therapy is currently not a component of the
standard of care for rubella.
Scarlet Fever (Scarlatina)
Thought not to be common in India scarlet fever is an
infection caused by toxin-producing group A beta
hemolytic streptococci (GABHS) found in secretions and
discharge from the nose, ears, throat, and skin. It may
follow streptococcal wound infections or burns, as well
as upper respiratory infections. The mucous membranes
usually are bright red, and scattered petechiae and small
red papular lesions on the soft palate are often present.
During the first days of infection, the tongue is heavily
coated with a white membrane through which edematous red papillae protrude (classic appearance of white
strawberry tongue). By day 4 or 5, the white membrane
sloughs off, revealing a shiny red tongue with prominent
papillae (red strawberry tongue). Red, edematous,
exudative tonsils are typically observed if the infection
originates there. The characteristic exanthem consists of
a fine erythematous punctate eruption that appears
within 1-4 days following the onset of the illness. It first
appears on the upper trunk and axillae and then becomes
generalized, although it is usually more prominent in
flexural areas, such as the axillae, popliteal fossae, and
inguinal folds. It may also appear more intense at
dependent sites and sites of pressure, such as the

buttocks. Capillary fragility is increased, and often,
transverse areas of hyperpigmentation with petechiae
in the axillary, antecubital, and inguinal areas (Pastia
lines) can be observed. The face is usually flushed, and
circumoral pallor is observed. The eruption imparts a
dry rough texture to the skin that is reported to resemble
the feel of sandpaper. The cutaneous rash lasts for 4-5
days, followed by fine desquamation, the extent and
duration of which is directly related to the severity of
the eruption. Cultures of the infected oropharynx or other
infected areas should be obtained. CBC commonly
reveals a leukocytosis. An increase in antistreptolysin
O (ASO) titers can be observed but is a late finding and
usually of value only in retrospect. Patients whose
bacterial source may suggest another process (e.g. a
patient with a suppurative leg wound who may have
osteomyelitis) should be evaluated accordingly. The
microscopic findings of the eruption of scarlet fever are
nonspecific and have an appearance similar to that of
other exanthematous eruptions. A sparse perivascular
infiltrate usually consisting of lymphocytes primarily
with a slight amount of spongiosis in the epidermis is
present. Slight parakeratosis may be present, which
probably correlates with the sandpaper like texture of
the skin.
Antibiotic therapy is the treatment of choice for scarlet
fever. Cultures should be obtained where organisms
other than streptococcal bacteria are suspected. The
desquamating rash that follows is self-limited, with only
emollients necessary for care.
The drug of choice is benzathine penicillin G
administered IM or penicillin VK administered orally for
10 days. First-generation cephalosporins may also be
used. Erythromycin should be considered in patients
allergic to penicillin.
Fifth Disease
Fifth disease, also known as erythema infectiosum or
slapped cheeks disease, is caused by a virus
(parvovirus B19). This disease tends to occur in the winter
and spring but can happen year-round. Erythema
infectiosum typically has an incubation period of 4-14
days and is spread primarily via aerosolized respiratory
droplets. Transmission also occurs through blood
products and from mother to fetus. The prodromal phase
often is mild enough to be noticed only rarely but may
include headache, coryza, low-grade fever, pharyngitis,
and malaise. Infrequently, nausea, diarrhea, arthralgias,
307
and abdominal pain may occur. In hosts who are

immunocompetent, the patient is viremic and capable
of spreading the infection only during the incubation
period. Classic cutaneous findings follow within 3-7 days
for some patients, while other patients may manifest no
findings. Pertinent physical findings predominantly are
limited to the skin and joints. The exanthem begins with
the classic slapped-cheek appearance. The bright red
erythema appears abruptly over the cheeks and is
marked by nasal, perioral, and periorbital sparing. The
exanthem may appear like sunburn, occasionally is
edematous, and typically fades over 2-4 days. Within 14 days of the malar rash, an erythematous macular-tomorbilliform eruption occurs primarily on the extremities. While the eruption tends to favor the extensor
surfaces, it can involve the palms and soles. Pruritus is
rare. After several days, most of the second stage eruption
fades into a lacy pattern, with particular emphasis on
the proximal extremities. Despite its synonym, slappedcheek disease, the reticulate pattern is distinctly
characteristic for erythema infectiosum and may be the
only manifestation of the illness. The third stage lasts
from 3 days to 3 weeks. After starting to fade, the
exanthem may recur over several weeks following
physical stimuli, such as exercise, sun exposure, friction,
bathing in hot water, or stress. In adults, an acute
polyarthropathy is more likely to result than classic
erythema infectiosum. Polyarthropathy may start with
a typical prodromal illness and some cutaneous aspect
of erythema infectiosum but more often manifests simply
by a new onset of symmetric joint pain. Arthropathy is
more common in women and can last for days to months.
Sites most commonly affected include joints of the hands,
wrists, knees, and ankles. Unlike rheumatoid arthritis,
joint pain worsens over the day, and no joint destruction
occurs. The synovial fluid is acellular and devoid of viral
particles. The diagnosis of erythema infectiosum usually
is based on clinical presentation alone, and a workup for
patients with the classic presentation is not necessary.
For patients with other PV-B19associated signs or
symptoms, or for exposure in a woman who is pregnant,
confirmation of infection may be helpful and can be
accomplished with the following specialized tests:
IgM assays (enzyme-linked immunoassay, radioimmunoassay)
Dot blot hybridization
Polymerase chain reaction
308
Skin biopsy is not necessary or does not aid in

diagnosis but may reveal nonspecific changes, including
mild basilar vacuolarization, dyskeratotic cells, and a
sparse perivascular infiltrate.
Since erythema infectiosum most often is a benign
self-limited disease, reassuring the parents often is the
only intervention necessary. For patients with arthralgias
or pruritus, symptomatic relief can be obtained using oral
analgesics and antihistamines or topical antipruritic
lotions (e.g. alum lotion or calamine lotion). Symptomatic
relief of erythema infectiosum may be provided using
nonsteroidal anti-inflammatory drugs (NSAIDs),
antihistamines, and topical antipruritics. For an acute
aplastic crisis, supplemental oxygen and blood transfusions may be necessary. Intravenous immunoglobulin
(IVIG) is helpful for chronic anemia in patients who are
immunocompromised.
Roseola Infantum
Roseola is also called exanthem subitum and is a common
childhood virus caused by the human herpes virus 6.
The disease usually occurs in children younger than 4
years. The classic patient with roseola is a 9- to 12-monthold infant in previously good health and who has an
abrupt onset of high fever (40C), which lasts for 3 days
with nonspecific complaints. A febrile seizure occurs in
15% of patients. Rapid defervescence is striking with the
onset of a mild, pink, morbilliform exanthem. In patients
who are immunocompromised, the onset of symptoms
is usually abrupt, with fever, malaise, and CNS and other
organ system involvement. Despite the high fever, few
clinical findings are observed early in the course. The
lack of upper respiratory infection is notable, and
meningeal signs and encephalopathy are not present.
Gastrointestinal symptoms, signs of electrolyte
imbalance, or evidence of dehydration are rarely present.
A febrile seizure, with no residual findings, may have
occurred. After cessation of fever, the characteristic rash
appears. The eruption is generalized and subtle. It is
composed of either discrete, small, pale pink papules or
a blanchable, maculopapular exanthem that is 1-5 mm
in diameter. This rash may last 2 days. The characteristic
enanthem (Nagayama spots) consists of erythematous
papules on the mucosa of the soft palate and the base of
the uvula. The enanthem may be present on the fourth
day in two thirds of patients with roseola. In response to
the early acute febrile presentation, laboratory studies
may include CBC, urinalysis (UA), blood culture, and
cerebrospinal fluid examination. If the patient presents

with a febrile seizure, a seizure workup may be indicated.
Diagnosis may be confirmed by virus isolation,
seroconversion (immunoglobulin M [IgM]), or detection
of viral DNA sequences in peripheral blood mononuclear
cells. Typical ballooning cells may be seen histologically
in any organ system affected with HHV-6 infection. At
present, no medical antiviral therapy is available for
HHV-6 infection that causes roseola. Thus, treatment is
supportive. Acute or chronic antiseizure medications are
not recommended for infants who have had a febrile
seizure secondary to roseola.
Coxsackieviruses and Other Enteroviruses
The enteroviruses, including the coxsackieviruses, are a
very common cause of fever and rash in children. Two
diseases are caused by coxsackieviruses, called handfoot-and-mouth disease and herpangina. Coxsackievirus
infections are more common in the summer and autumn.
In hand-foot-and-mouth disease, the children develop
fever and rash. The rash includes blisters to the mouth
and tongue and to the hands and the feet. Herpangina
causes a fever, sore throat, and painful blisters or ulcers
to the back of the mouth. No specific treatment is
available except acetaminophen or ibuprofen for fever.
The diseases are not harmful but can be prevented with
good hand washing and not eating off someone elses
plate or sharing straws.
Impetigo
Impetigo is a superficial skin infection with streptococcal
or staphylococcal bacteria. It is often found around the
nose and mouth but can occur anywhere. The rash is
more common in the warmer months. It can also be an
additional infection to skin that has been damaged, such
as in scabies, poison ivy, eczema, or drug reactions. It
begins as small superficial blisters that rupture leaving
red, open patches of skin. Often a honey-colored crust
forms over this rash. The rash is very itchy. Impetigo is
also highly contagious. A child can spread the infection
to other parts of the body or to other people. This infection
of the skin is easily treated with topical or oral antibiotics.
The child usually is no longer contagious after 2-3 days
of therapy, and the rash begins to heal in 3-5 days. When
the impetigo occurs in addition to poison ivy or scabies,
the child may benefit from an anti-itch medication while
the antibiotics are taking effect.

Life-threatening Rashes
Life-threatening rashes are uncommon, and your child
usually appears quite ill if he or she has a life-threatening
rash. Fever and petechiae are the common symptoms.
These two symptoms are present with many rashes and
are often signs of a more serious condition. Children can
develop petechiae from a number of causes. It is not
unusual for forceful coughing or vomiting to cause
petechiae on the face and chest. Petechia with fever is
more concerning, although most of these children have
a viral illness that does not require any therapy. A small
percentage (2-7%) may have diseases that need immediate evaluation. Petechiae are red dots on the skin that
do not fade when pressure is applied. The dots represent
bleeding from the capillaries leaving a small, temporary
blood blister in the skin.
Meningococcemia
Meningococcal disease is a communicable infection
caused by Neisseria meningitidis. It is transmitted from
person to person via respiratory secretions. N meningitidis
infection can be clinically polymorphic. The most
common disease presentation is meningitis. Rarely, N
meningitidis infection may manifest as chronic meningococcemia that resembles the arthritis-dermatitis
syndrome of gonococcemia; however, acute meningococcal septicemia (also called meningococcemia) is the
most devastating form of the disease. Meningococcemia
can kill more rapidly than any other infectious disease.
Early recognition is critical to implement prompt
antibiotic therapy and supportive care. Treatment must
be instituted rapidly because irreversible shock and death
may occur within hours of the onset of symptoms.
Cutaneous manifestations in meningococcemia may be
important clues to the diagnosis. Skin involvement can
be the most dramatic aspect of the disease and is often
the first sign that leads to the clinical consideration of
meningococcemia. It follows an upper respiratory
infection and is associated with headache, nausea,
vomiting, myalgias, and arthralgias. Not all children
appear toxic. The initial presentation may be difficult to
distinguish from a viral syndrome. While a slower clinical
presentation can occur in persons with a milder form of
disease, fever may increase dramatically with rapid
clinical deterioration. In fulminant meningococcemia, a
hemorrhagic eruption, hypotension, and cardiac
depression may be apparent within hours of the initial
309
presentation. Cutaneous manifestations of meningococcemia are common and can be the presenting sign of
disease. Petechiae are the most common sign, occurring
in 50-60% of patients with meningococcemia; however,
urticarial and maculopapular lesions also may occur
initially. Petechiae are most often located on the
extremities and trunk but may progress to involve any
part of the body. Petechiae may appear in groups under
areas of pressure. With progression of meningococcemia,
pustules, bullae, and hemorrhagic lesions with central
necrosis can develop. Stellate purpura with a central
gunmetal-gray hue is characteristic and should be
considered highly suggestive of meningococcemia. Large
maplike purpuric and necrotic areas related to the
development of DIC are characteristic of fulminant
meningococcemia. Noncutaneous physical findings are
altered mental status, neck stiffness, irritability, seizures,
nerve palsies, gait disturbance, nausea, vomiting, and
unstable vital signs. Meningococcemia can be confirmed
with blood culture, lumbar puncture, and a Gram stain
of lesional skin biopsy or aspirate specimens. In
meningococcemia, organisms have been isolated by
blood culture in almost 100% of patients, yet the results
are not available for 12-24 hours. A throat culture should
be obtained; however, the diagnosis of meningococcemia
cannot be made solely based on a positive result from
throat culture because asymptomatic colonization is not
uncommon. Complement deficiencies should be sought
for complicated infections and recurrent or familial
disease. Meningococcal meningitis causes a polymorphonuclear leukocytosis in the cerebrospinal fluid, which
can be evaluated using lumbar puncture. In meningococcemia, Gram stain results of the cerebrospinal fluid are
often negative. Detection of N. meningitidis capsular
polysaccharide antigen in cerebrospinal fluid and urine
with rapid serologic tests based on latex particle
agglutination is commercially available. In an effort to
obtain a more rapid diagnosis, several studies have
concentrated on the identification of meningococci from
skin specimens. Up to 50-80% of rigorous skin scrapings,
lesional aspirates, or punch biopsy samples from bullous
or pustular lesions reveal gram-negative N. meningitidis
with Gram staining or Brown-Hoppmodified Gram
stain; however, these results must be interpreted with
caution because many gram-negative commensals are
possible on the skin. Hitologically cutaneous petechiae
and purpura correspond to thrombi in the dermal vessels
composed of neutrophils, platelets, and fibrin. Acute
310
vasculitis with neutrophils and nuclear dust present

within and around vessels leads to hemorrhage into the
surrounding tissue. Meningococci can often be seen in
the luminal thrombi and vessel walls. Intraepidermal and
subepidermal neutrophilic pustules also may be present.
The most important measure in treating meningococcemia is early detection and rapid administration of
antibiotics. Penicillin G is the antibiotic of choice for
susceptible isolates. A third-generation cephalosporin
(e.g. cefotaxime, ceftriaxone) can be used initially in septic
patients while the diagnosis is being confirmed or in
countries such as the United Kingdom or Spain, where
penicillin-resistant strains of N. meningitidis have been
isolated. Intensive supportive care is required for patients
with fulminant meningococcemia. Components of
treatment include antibiotic therapy, ventilatory support,
inotropic support, and intravenous fluids. Central venous
access facilitates the administration of massive amounts
of volume expanders and inotropic medications needed
for adequate tissue perfusion. If DIC is present, fresh
frozen plasma may be indicated. Treatment is individualized depending on the severity of hemodynamic
compromise of the patient. Many experimental and
alternate therapies have been tried with varying success.
Currently under study are treatments to inhibit
inflammatory mediators (e.g. monoclonal antibodies to
endotoxin, tumor necrosis factor, interleukin-1,
interleukin-6, and interferon-gamma). Anecdotal reports
show removal of inflammatory mediators by dialysis
may offer some benefit. Fibrinolytic treatment using
recombinant tissue plasminogen activator or the
administration of highly purified protein C concentrate
may prove to be helpful adjuncts to conventional therapy
to improve tissue perfusion in the presence of DIC. The
goals of therapy are to eradicate the microorganism, to
reduce morbidity, and to prevent complications.
Lyme Disease
Lyme disease is caused by the spirochete Borrelia
burgdorferi, which is transmitted by Ixodes species of tick,
mostly Ixodes scapularis (the common deer tick). The
presenting signs and symptoms depend on the stage at
which the disease is recognized, as follows:
Early diseaseUsually 7-14 days after a tick bite. Two
thirds of patients with Lyme disease present with the
typical rash, erythema migrans (EM). The rash may
be a confluent patch of erythema or may have central
clearing. The rash typically expands over days and is
not evanescent. During early disease, with or without

the rash, patients may complain of fever, chills,
myalgias, arthralgias, headache, and malaise. In the
area of the tick bite, tender adenopathy may be noted.
Early disseminated diseaseUsually develops 3-10
weeks after inoculation. Approximately 25% of
individuals infected with B. burgdorferi have signs and
symptoms of disseminated disease at presentation.
Multiple EMs are relatively small erythematous
macules (1-5 cm) and often are oval. Unlike primary
single EMs, these lesions can be evanescent and do
not show the typical expansion over days. Patients
with early disseminated disease may complain of
fever, myalgias, arthralgias, malaise, and headache.
Aseptic meningitis may develop at this stage.
Cranioneuropathies, especially peripheral seventh
nerve (Bell palsy), are common (3% of Lyme disease).
Encephalitis is rare. Carditis may present as complete
heart block.
Late diseaseWeeks to months after inoculation.
Arthritis is the hallmark of late disease. It tends to
involve large joints (knee involved in 90% of cases).
Arthritis needs to be differentiated from arthralgia,
which is common in early disease. Most patients
presenting with late disease do not have a history of
EM because the rash would have led to earlier
treatment and, therefore, prevention of late disease.
Laboratory investigations play a vital role in
diagnosis. WBC count can be normal or elevated.
Erythrocyte sedimentation rate usually is elevated.
Serum glutamic-oxaloacetic transaminase (SGOT) may
be elevated. C3 and C4 generally are normal or slightly
elevated. Antinuclear antibody (ANA) and rheumatoid
factor test results are negative. Microscopic hematuria
and mild proteinuria also have been described. Joint fluid
in patients with arthritis may have 25,000-125,000 WBCs
per mm3, often with a polymorphonuclear predominance. Cerebral spinal fluid (CSF) in patients with
meningitis has mild pleocytosis (<1000 cells per mm3)
with lymphocyte predominance. Diagnosis can be made
clinically in the early stages of disease by the presence of
EM rash. Culturing B. burgdorferi is impractical; the
organism is difficult to culture and requires an invasive
procedure, such as biopsy or lumbar puncture, to obtain
adequate samples. Serology is the standard of diagnosis
in later stages of the disease. Reported specificity of Lyme
serology is only 90-95%. Therefore, the positive predictive
value of the test is highly dependent on the prevalence

of disease. Lyme serology should not be performed in
children with nonspecific symptoms and no history of
exposure or in children in nonendemic areas. Antibodies
are known to persist for many years despite eradication
of the infection. Hence, diagnosis of repeat infection or
evidence of cure can be difficult. Treatment for all stages
of Lyme disease requires antibiotics. Facial nerve palsies
improve without treatment; however, antibiotic
(doxycycline) therapy should prevent late disease.
Similarly, arthritis improves without treatment but tends
to recur in the same joint or other new joints. Administer
antibiotic therapy to patients who develop a flulike illness
within 3 weeks postexposure to a deer tick (in an area
endemic for Lyme disease).
Kawasaki Disease
Kawasaki disease (also called mucocutaneous lymph
node syndrome) is of unknown cause, although it is
suspected to be caused by a bacteria or virus. It usually
affects children younger than 9 years. It can have serious
effects on your childs heart if not diagnosed and treated
correctly. Patients with classic Kawasaki disease must
have 5 of the following symptoms, with fever an absolute
criterion:
Fever, lasting more than 5 days and refractory to
appropriate antibiotic therapy
Polymorphous erythematous rash
Nonpurulent bilateral conjunctival injection
Oropharyngeal changes, including diffuse
hyperemia, strawberry tongue, and lip changes (e.g.
swelling, fissuring, erythema, bleeding)
Peripheral extremity changes, including erythema,
edema, induration, and desquamation
Nonpurulent cervical lymphadenopathy.
Other findings may include irritability, coronary
artery aneurysms (CAA), pericardial effusion, myocarditis, congestive cardiac failure, stiff neck secondary to
aseptic meningitis, facial palsy, cerebral infarction, sterile
pyuria, proteinuria, nephritis, acute renal failure,
arthralgias or arthritis, pleural effusion, diarrhea,
hepatitis, obstructive jaundice, hydrops, pancreatitis, gall
bladder distention, meatitis, vulvitis, urethritis,
conjunctivitis, and uveitis. Dermatological manifestations include peripheral extremity gangrene, pustules,
erythema multiforme-like lesions, perianal desquamation, macules, papules, measles like rash, scarlet feverlike erythema, and induration at the site of Bacille
Calmette-Gurin (BCG) inoculation (commonly observed
311
in Japan). Up to 10-45% of published cases have

incomplete or atypical clinical presentations. The 2 most
commonly missing findings are cervical lymphadenopathy and polymorphous rash. Mucous membrane
changes, on the other hand, are the most common
manifestations of Kawasaki disease, occurring in more
than 90% of patients with either typical or atypical forms
of the disease. No specific laboratory test exists; however,
certain abnormalities coincide with various stages. Mildto-moderate normochromic anemia is observed in the
acute stage along with a moderate-to-high WBC count
with a left shift, which is a predominant sign of immature
and mature granulocytes. Many of the acute phase
reactant markers, such as the erythrocyte sedimentation
rate (ESR), C-reactive protein, and serum -1-antitrypsin
are elevated. Culture results are all negative. Antineutrophil cytoplasmic antibodies, antiendothelial cell
antibodies, antinuclear antibody, and rheumatoid factors:
These are within the reference range. Thrombocytosis
typically develops during the second or third week of
illness, with an average of 700,000 per microliter.
Thrombocytopenia is associated with severe coronary
artery disease and MI. Chest radiography should be
performed to assess baseline findings and to confirm
clinical suspicion of CHF. Echocardiography is the study
of choice to evaluate for CAAs. Ultrasonography: Gall
bladder ultrasonography may be necessary if any
suggestion of liver or gall bladder dysfunction is present.
Obtain a scrotal ultrasound in males to evaluate for
epididymitis. Although epididymitis is generally an
inflammatory process that affects boys aged 9-14 years,
it can be observed in younger males with HenochSchnlein purpura and Kawasaki disease.
The main goal of treatment is to prevent coronary
artery disease and relieve symptoms. Full doses of
salicylates (aspirin) and intravenous gammaglobulin are
the mainstays of treatment. All patients are hospitalized
for intravenous gammaglobulin and observation until
fever is controlled. Patients with small aneurysms must
take aspirin. Dipyridamole is indicated in patients with
larger aneurysms. Patients taking long-term aspirin
therapy should receive an influenza vaccination to
protect against Reye syndrome.
The pathophysiology in Kawasaki disease involves
inflammation. The patients own immune system
probably causes the vasculitis that leads to morbidity and
mortality in Kawasaki disease. Early and aggressive
intervention improves outcome. Standard treatment
312
includes aspirin and intravenous immunoglobulin to

treat inflammation and prevent consequences of
coronary artery disease. Other anticoagulants or antiplatelet agents (e.g. warfarin, dipyridamole) are
occasionally used.
Vascular Reactions and Drug Reactions
Toxic Epidermal Necrolysis
Toxic epidermal necrolysis (TEN) is a severe mucocutaneous exfoliative disease with an uncertain pathogenesis
and a high mortality rate. It can usually be distinguished
from the morphologically similar, but more benign,
staphylococcal scalded skin syndrome (SSSS) according
to historical and epidemiological factors. While
controversy exists regarding the classification of TEN as
a separate entity or a severe form of erythema multiforme
(e.g., Stevens-Johnson syndrome), the clinical distinction
is of little significance in an emergency clinical setting,
because the etiology and immediate treatment of these
potentially life-threatening diseases are similar. The
primary manifestation of TEN is the appearance of an
erythematous confluent morbilliform eruption that
rapidly evolves into exfoliation of the skin at the dermalepidermal junction, resulting in large sheets of necrotic
epidermis and the underlying shiny, denuded dermal
surface. This process seems to be immune-complex
mediated. Although the exact pathogenesis of TEN is not
understood, most experts agree that it represents an
idiosyncratic reaction to a drug or chemical agent. Graftversus-host reaction, viral infections, measles immunization, lymphoma, leukemia, radiotherapy, and contact
with toxic fumigant have been associated with TEN.
Idiopathic causes, as in erythema multiforme, account
for a significant percentage of TEN. Drugs related to TEN
may include the following:
Sulfonamides and sulfones
Pyrazolone derivatives (e.g. phenylbutazone,
oxyphenbutazone, phenazone)
Antibiotics (e.g. aminopenicillins, trimethoprim,
cephalosporins, ciprofloxacin, doxycycline, erythromycin, tetracycline)
Anticonvulsants (e.g. phenytoin, phenobarbital, and
carbamazepine)
Nonsteroidal anti-inflammatory drugs
Allopurinol
Antituberculosis drugs (e.g. thiacetazone, isoniazid)
TEN is estimated to occur in 0.22-1.23 cases per
100,000 population. Septicemia, GI hemorrhage,
leukopenia, pneumonia, fluid and/or electrolyte

imbalance, and renal insufficiency are the major
complications that contribute to a mortality rate of
approximately 15-40%. Old age, extensive skin lesions,
neutropenia, and impaired renal function are poor
prognostic factors. The recovery period usually is
prolonged. While SSSS occurs predominantly in children,
TEN affects more adults more than children. The
prognosis in geriatric patients is unfavorable. In addition
to characterizing the physical, constitutional, and
mucocutaneous symptoms, a detailed history should
focus on known etiologies of TEN, such as medication
or chemical agent use, maternal-fetal transfusion, blood
product administration, recent infections, measles
immunization, or recent radiotherapy. Prodromal
symptoms may precede skin lesions by 1-2 weeks. Fever
is the most common symptom. Upper respiratory
infection-like symptoms, such as malaise, anorexia,
headache, sore throat, cough, nausea, vomiting, and
diarrhea, are present. The skin is diffuse, erythematous,
and painful, and tender skin lesions are present. The scalp
usually is spared. Mucous membranes have painful
inflammation and blisters on the mucosal surfaces,
especially the oropharynx. These symptoms may limit
oral intake. Pain and photophobia are common ocular
findings and result from purulent conjunctivitis. These
usually begin 1-2 days prior to the onset of the rash.
Physical examination may show the following:
Pyrexia may be present.
Skin lesions may begin as hot, tender, erythematous
morbilliform or discrete macules that rapidly coalesce
and become patches of loose skin. These patches may
wrinkle, slide laterally, and separate with slight
pressure (Nikolsky sign).
The oral mucosa especially is susceptible to inflammation, blistering, and erosion. The vaginal tract
epithelium also may be involved.
Eye involvement may result in bilateral purulent
conjunctivitis, which manifests as edema, crusting,
and ulceration with pain and photophobia.
Pulmonary involvement leads to bronchopneumonia
in approximately 30% of all cases. Many patients
require ventilatory support because of respiratory
failure.
Differential diagnosis should include StevensJohnson syndrome and staphylococcal scalded skin
syndrome. No definitive or specific emergent laboratory

tests are indicated. Basic laboratory tests may be helpful
in planning symptomatic or supportive therapy. The CBC
may reveal leukopenia of uncertain cause. Significant
fluid loss may occur. Fluid and electrolyte status must
be monitored. Regarding BUN and creatinine levels,
elevated serum creatinine levels occur in a significant
portion of patients, because of dehydration. Urinalysis
may reveal hematuria and proteinuria, which indicate
renal involvement. Positive culture findings for
Staphylococcus aureus from the conjunctiva, nose, throat,
perineum, and skin suggest an infectious cause. In the
correct clinical setting, this finding may be used to
differentiate SSSS from TEN. Chest radiography may be
performed to detect possible pneumonia, as clinically
indicated. While excisional or punch biopsy can be
performed to determine the level of dermal and/or
epidermal separation to differentiate SSSS from TEN, this
may not be a procedure to be undertaken in most
emergency situations. It is, however, the diagnostic
procedure of choice to be performed as soon as feasible.
Prehospital care is similar to that of burns. In severe TEN
in which the barrier function of the skin is compromised,
contamination and evaporation must be minimized. The
patient should be treated as one with extensive burns is
treated, that is, with the application of dry, sterile
coverings. Fluid and pulmonary status must be carefully
monitored. No specific definitive therapies for TEN exist;
therefore, intensive care is supportive. Care is given to
minimize fluid and electrolyte loss and prevent
secondary infection. Volume and electrolyte replacement,
along with respiratory stabilization, are the primary
concerns. Adequate analgesia should be provided. Silver
sulfadiazine should be avoided because it may precipitate TEN. Antibiotics are of no proven benefit if biopsy
findings prove the presence of TEN and not SSSS. Use of
systemic steroids is controversial; most experts do not
recommend their use. Silver nitrate 0.5% wet dressing
may be used. Discontinuation of the offending agent (if
identified) should be immediate. Internal medicine or
critical care specialists should be consulted, depending
on severity of disease. Ophthalmologists may manage
ocular manifestations and help prevent sequelae.
Further inpatient care includes continuance of supportive
care and meticulous wound care to prevent secondary
infection. Transfer to intensive care unit or burn unit may
be necessary for those patients with involvement of a
large body surface area or with hemodynamic instability.
313
Numerous complications appear to be unfavorable

prognostic signs. These include the following:
Neutropenia
Renal insufficiency
Septicemia (Pseudomonas aeruginosa, S aureus, gramnegative species, and Candida albicans)
GI hemorrhage
Pneumonia
The overall prognosis of TEN is poor, with a mortality
rate as high as 40%. Major sequelae include Sjgrenlike
syndrome, symblepharon (adhesion between the
palpebral and conjunctiva), entropion (inward curling
of eyelid), ectropion, trichiasis (inversion of the
eyelashes), corneal opacity, blindness, esophageal and
vaginal stenosis, anonychia (loss of the nails), and
hypopigmentation or hyperpigmentation. Patient
education is directed to emphasize avoidance of any
identified causative factors
Erythema Multiforme
It is a reaction of the skin to different causes as viral
infections (commonly herpes simplex), bacterial, mycotic
or parasitic infections, drugs, or systemic diseases
(rheumatic fever, systemic lupus erythematosus, etc.).
This reaction pattern of blood vessels in the dermis with
secondary epidermal changes is exhibited clinically as
characteristic erythematous iris-shaped papules and
vesicobullous lesions typically involving the extremities
(especially the palms and soles) and the mucous
membranes. The characteristic lesions are also known
as target lesions. The eruption begins rapidly with
varying degrees of constitutional symptoms. It is
distributed bilaterally and symmetrically in a centrifugal
pattern. Stevens-Johnson syndrome is a severe bullous
form of erythema multiforme; the mucous membranes
are severely involved and there are severe general
constitutional symptoms. The duration of lesions is
several days; lesions develop over 10 days or more.
Patients may have a history of prior episode of erythema
multiforme. Skin lesions may be pruritic or painful.
Mouth lesions are painful and tender. Constitutional
symptoms may be present in the form of fever, weakness,
and malaise. Skin lesions consist of macules (48 hours)
evolving to papules, 1 to 2 cm; lesions may appear for 2
weeks. Vesicles and bullae (in the center of papule
forming the so-called iris or target lesions) are typical.
314
Lesions are dull red. Iris or target lesions are typical (see
above). Lesions may be localized to the hands or
generalized. They are usually bilateral and often
symmetrical. The sites of predilection include the dorsa
of hands, palms, soles, forearms, feet, elbows and knees;
the penis (50%) and vulva may be also involved. Over
the mucous membranes, lesions may occur in the mouth
and on the lips (99%). Pulmonary manifestations may
be present; the eyes may be affected with corneal ulcers
and anterior uveitis. Histological changes are observed
in the epidermis and dermis. An inflammatory process
is seen characterized by perivascular mononuclear
infiltrate, and edema of the upper dermis; in lesions with
bulla formation, there is eosinophilic necrosis of
keratinocytes with subepidermal bulla formation. All
attempts must be made to rule out occult viral, fungal,
and bacterial infections. In severely ill patients, systemic
corticosteroids are usually given (prednisolone 50 to 80
mg daily in divided doses, quickly tapered), but their
effectiveness has not been established by controlled
studies. Control of herpes simplex using oral acyclovir
may prevent development of recurrent erythema
multiforme.
Staphylococcal Scalded Skin Syndrome
Staphylococcal scalded-skin syndrome (SSSS) is a toxinmediated epidermolytic disease characterized by
erythema and widespread detachment of the superficial
layers of the epidermis, resembling the effects of scalding.
It occurs mainly in newborns and infants under 2 years
of age. Severity ranges from a localized form, bullous
impetigo, to a generalized form with extensive epidermolysis and desquamation. Clinical spectrum of SSSS
includes:
1. Bullous impetigo,
2. Bullous impetigo with generalization,
3. Scarlatiniform syndrome,
4. Generalized scalded-skin syndrome.
Synonyms: Pemphigus neonatorum, Ritters disease.
A low-grade fever may be present. The child is
irritable.
Skin findings: Bullous impetigo: Lesions are often
clustered in an intertriginous area and consist of intact
flaccid, purulent bullae. Rupture of the bullae results in
moist red and/or crusted erosive lesions.
Generalized SSSS: A very tender, ill-defined erythema

occurs initially. With epidermolysis, the epidermis
appears wrinkled. The unroofed epidermis forms
erosions with red, moist base. Initially, lesions are present
on the face (periorificially), neck, axillae, and groins,
becoming more widespread in 24 to 48 hours. The initial
erythema and later sloughing of the epidermis are most
pronounced periorificially on the face, and in the flexural
areas and pressure points: on the neck, axillae, groins,
antecubital area, and back.
Scarlatiniform syndrome: Presentation is like scarlet fever
but without pharyngitis, tonsillitis, and strawberry
tongue.
Nikolskys sign (gentle lateral pressure causes shearing off of
superficial epidermis): Positive.
Mucous membranes: are usually uninvolved.
Investigations include:
Gramss stain:
Bullous impetigo: findings include pus in bullae and
clumps of gram-positive cocci within PMNL.
Generalized SSSS: Gram-positive cocci are only observed
at colonized site, not in areas of epidermolysis.
Bacterial culture:
Bullous impetigo: Staph. aureus is isolated.
Generalized SSSS: Staph. aureus is only present in colonized
site of infection, i.e. umbilical stump, conjunctiva, or
external ear canal; culture of sloughing skin or bullae
usually yields no pathogens.
For a newborn, hospitalization and treatment with
IV cloxacillin, 200 mg per kg body weight per day in
divided every 4 hours, are preferable.
Hospitalize infants with extensive sloughing of skin
or if parental compliance to treatment is questioned.
With reliable home care and mild involvement,
cloxacillin, 30 to 50 mg per kg body weight per day, can
be given orally. Topical care includes baths or compresses, and mupirocin ointment, bacitracin, or silver
sulfadiazine.
The reader is reminded that the above description is
narrated only as guidelines and is advised to refer to other
standard books of dermatology for more comprehensive
information.
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9.9 Tuberculosis in Children

Vimlesh Seth
Childhood tuberculosis is neglected in endemic areas
with resource constrainsts in high-burden countries as
in India, because the children
i. Are considered to develop mild forms of disease
ii. Mostly the lesions are sputum-negative and
contribute little in the transmission of disease.
In endemic areas, children contribute a significant
proportion of the disease-burden and suffer severe
tuberculosis related morbidity and mortality particularly
when associated with HIV infection, severe malnutrition
and are above the age of 10 years.
The common perception that children rarely develop
severe forms of tuberculosis is true in nonendemic areas
but not so in endemic areas. Because of the difficulty of
establishing an accurate diagnosis of childhood
tuberculosis, the true extent of morbidity and mortality
related to tuberculosis in endemic areas is not available.
Despite the huge burden, the access to antituberculosis
treatment in children remains poor, as tuberculosis control
program focuses predominantly on the treatment of
sputum smear-positive adults. However, now in Revised
National Tuberculosis Control Program (RNTCP) i.e.
Directly Observed Therapy Short-course (DOTS), separate
algorithms have been prepared for the diagnosis of
childhood tuberculosis. In these algorithms, besides X-ray
chest and tuberculin test, lot of emphasis has been given
to signs and some symptoms in relation to pulmonary
and extrapulmonary tuberculosis. In the latter, the
commonest is lymphadenitis followed by neuro-,
abdominal-, and skeletal tuberculosis, to name a few.
Tuberculosis (TB) is caused by Mycobacterium
tuberculosis. It mainly infects the lungs, though it can
affect other organs as well.
When a patient with sputum positive untreated TB
disease coughs or sneezes, the air is filled with droplets
containing bacteria. Inhaling these infected droplets is
the usual way a person gets TB.
Children are not considered infectious, and usually
get the infection from an infectious adult. The incubation
period varies from weeks to years, depending upon the
health status of the individual and whether the infection
is primary, progressive or reactivation TB. It is a chronic
disease that can persist for years if not treated.
The most common type is human type. The genus

Mycobacterium includes the species responsible for
causing tuberculosis. M.tuberculosis, M.bovis, M.african is
also called Mycobacterium tuberculosis complex.
There are several other types of mycobacteria that are
collectively called Non-tuberculosis mycobacteria (NTM),
and were called atypical mycobacteria in the past. They
have been increasingly recognized to cause pulmonary
and non-pulmonary infections which is partly explained
by the increase in the number of susceptible/immunocompromised individuals such as those suffering with
AIDS. They are also called mycobacterium other than
tubercule bacilli (MOTT).
Epidemiology
Tuberculosis has become one of Indias worst enemies.
Women and children are worst effected. Studies
conducted on the socio-economic impact of TB have
projected that over three lakh children are orphaned by
the disease every year and over a lakh women are rejected
by their families once they contract the disease, inspite
of the illness being treated free of cost from Government
funds.
Fear of becoming homeless and social isolation, leads
over 75% of women diagnosed with TB, to dismiss their
constant coughing as seasonal. Thousands of children
drop out of school, while over 20% of them take up jobs
in order to supplement income especially if the father
has TB, thereby adding already to the unwieldy problem
of child labor. Several studies conducted by Tuberculosis
Research Centre (TRC) Chennai, between 1997-2006,
confirmed that TB had tremendous impact on patients
households in-terms of decrease in income and affecting
therapy, health, education, nutrition particulary if the
patient was a wage earner.
As per TRC study over 35% of patients admitted were
not able to afford to buy adequate food, clothing and
books for children due to lack of income. TBs greatest
impact is on productive adults, in the age group of 15-59
years. They are also the parents on whom the survival
and development of children depends. Thus as very
316
rightly said TB has the potential to have impact on the

development of both individual and society.
It is further emphasized that TB results in more stigma
in women than in men. The man abandons his wife,
remarries. On the other had no body marries a single
girl who develops TB.
Impact of TB-killer disease in India
India has 3.8 million TB patients at any time

India estimates 3% of new cases of MDR
Till date, 6.7 million patients in India have received DOTS
treatment thus averting more than 1.22 million deaths
Over the last 10 years, 26 million patients have been placed
on effective TB treatment globally
But the disease still kills 4,400 people every day.
The clinical profile of childhood tuberculosis in

developing countries is different in comparison to Europe
and North America or so called low-burden disease
countries. The extent of tuberculosis in children is a
reflection of Tuberculosis Control Program in a particular
area. Epidemiological data regarding the extent of
tuberculosis in children is lacking globally, India being
no exception. It is due to difficulty in diagnosis.
Udani1 has described tuberculosis in children as a
pyramid in three categories:
Group I
These patients are admitted in the hospital and constitute
6 to 10 percent of total pediatric admissions, majority of
them have serious disease like meningitis, miliary disease
or severe pulmonary involvement. They constitute the
apex of the pyramid.
Group II
Majority of patients in this group have non-specific
symptoms, some may have characteristic symptoms.
They are either undiagnosed, untreated or inadequately
treated.
Group III
This group constitutes the base of the pyramid. These
children are either asymptomatic or have nonspecific
symptoms, hence are usually undiagnosed and remain
untreated. They constitute the reservoir of primary
infection from which various post-primary complications
(group I and group II) develop. These are forerunners of
a large percentage of chronic pulmonary tuberculosis in

adults.
Children are usually infected with tuberculosis by an
adult or an older child with sputum smear-positive
pulmonary tuberculosis, often a family member. They
are less likely to be infected with a smear-negative
contact. In younger children less than two years who are
not ambulatory outside the household, the source of
infection is in the house unlike an older child whose
contact is from the community. The best way to prevent
tuberculosis in children is the proper identification and
treatment of tuberculosis in adults with sputum smearpositive disease. The case notification in children due to
tuberculosis has been 6-20 percent of all TB cases
registered with National Tuberculosis Control Program.
In India the prevalence of primary tuberculosis infection
in children is alarming. The annual risk of TB infection
is 1.5, and 40 percent of children by 16 years acquire
infection, and nearly 10 percent infected eventually
develop disease. Five percent of these develop disease
in the 1st two years of infection. This large pool of infected
children means that TB will continue to be a major
problem in the foreseable future.
Data on all forms of TB amongst children is not
available in India. Most surveys conducted have focused
on pulmonary tuberculosis and no significant population
based studies on extrapulmonary tuberculosis are
available.
Chakraborty has summarized the incidence and
prevalence of tuberculosis in NTP data as given below:
TABLE 9.9.1: Annual incidence and prevalence of
tuberculosis infection (NTP data)
Age (Years)
<5
5-9
10-14
All ages
Incidence of infection
(%)
Prevalence of
infection (%)
0.8
1.1
1.3
1.6
2.8
13.4
38.0
The risk of infection in children depends on the extent

of exposure to infectious droplet nuclei. If a mother has
sputum smear-positive pulmonary tuberculosis, her
infant is more at risk of developing the disease because
of the chance of inhalation of large number of infectious
droplets.
The majority of infected children do not develop TB
disease in childhood. The only evidence of infection may

be a positive tuberculin skin test. The likelihood of
developing disease is greatest shortly after infection. This
declines steadily with time. Infants and young children
under five are more likely to develop the disease. The
majority of children will present with symptoms within
one year of infection. For infants particularly the timespan between infection and disease may be as little as
6-8 weeks. Various immunosuppressive illnesses
facilitate the progress of infection to disease, such as HIVinfection, measles, whooping cough, protein energy
malnutrition.
Types of Strain
An untreatable TB strain causes alarm. A survey
conducted by WHO and the US Centre for Disease
Control (CDC, Atlanta) analysed the data from 2000-2004
and found that XDR-TB is most frequent in the countries
of former Soviet Union and Asia. A virtually untreatable
form of tuberculosisextreme drug resistant TB (XDRTB) is spreading all over the world, including India,
causing nearly 100% mortality. WHOs coordinator for
TB/HIV and drug resistance programme Paul Nunn
called it an explosive combination.
Nunn told that 52 of 53 patients with XDR-TB in South
Africa died with in 210 days between January 2005 and
March 2006. Even in US which has the best medicines
available, 33% diagnosed to be suffering from this strain
died.
At present the problem of XDR-TB in India is small
but there is severe burden of HIV patients. The
combination of two is almost lethal. He recommends
India must undertake a survey to gauge the extent of
XDR-TB particularly in Mumbai because there is very
large burden of HIV over there. Nunn has the following
other suggestions for India:
i. Increase the number of laboratories to diagnose TB
cases.
ii. Improve management of clinical cases.
iii. Strengthen basic TB care to prevent emergence of
resistance by ensuring good compliance.
iv. Increase collaboration between HIV-TB control
program to provide necessary prevention and care
of coinfected patients.
According to Health Ministry records, over 30% of
the fresh cases are suffering from XDR-TB while over
12% of old cases undergoing treatment have acquired
this strain. This new strain is not only resistant to the
317
two first-line drugs isoniazid and rifampicin, but also

are resistant to the six other drugs used for second-tier
in therapy. TB has become the 2nd largest killer of AIDS
patients in India. Over 60% of all AIDS patients contract
and ultimately die of TB. National AIDS Control
Organization (NACO) has now decided to scale up and
integrate the National AIDS and TB Control Programs
from 2006. Director of the TB control program (Ministry
of Health and Family Welfare) has stated that every year
1.8 million new cases of TB occur in India, of which 0.8
million are infectious. Unless these are treated properly,
each TB infectious case can infect 10 to 15 persons a year.
Not properly treated TB patients can become incurable.
Since no new drug has been discovered since 1968, the
germs have started developing drug resistance.
As per data available nearly 40 million children are
likely to be exposed to the risk and nearly 3-4 million
under five years are estimated to be infected and may
progress to disease. In a study conducted in Chengalput
in South India, it was found that prevalence rate was
very high. There were 420 active cases of tuberculosis
per 1,00,000 population. This survey did not include
children under five years. In India the annual rate of
infection is 20 to 25 times higher than in developed
countries.
Trends in Tubercular Disease
At a referral hospital in India, an increase in the
proportion of cases of extrapulmonary tuberculosis has
been observed over the last three years. The increase was
reported to be due to increase in tubercular lymphadenitis. The severe form of tubercular disease such as
meningoencephalitis has shown a decline. However, the
kind of picture is not so in other medical schools where
still a significant proportion of indoor admissions due to
tuberculosis is because of meningooencephalitis. A point
which needs to be emphasized is that when suspected
tuberculosis does not respond to the usual drugs,
infection with a resistant strain has to be kept in mind
and investigated from the very beginning. However, it
is a difficult situation because tuberculosis in children
still is paucibacillary. Here lies the importance of
screening the children of a sputum smear-positive adult.
Family survey of an index case in a given child gives,
only 20-30% contact positivity available in the best hands.
318
Pathogenesis
Ghons lesion results at the site of initial organisms
depositon. Initially (for the first 4-6 weeks) unrestrained
multiplication occurs with in the Ghon-focus and bacilli
drain via local lymphatics to the regional lymph nodes
and beyond. The upper lobe lymph nodes drain to
ipsilateral-paratracheal nodes, whereas the rest of the
lung drains to perihilar and subcarinal nodes with
dominant lymph flow from left to right. The Ghon
complex is represented by both the Ghon focus, with or
without some pleural reaction and the affected regional
lymph nodes.
Occult dissemination frequently occurs during this
early proliferative phase before cell-mediated immunity
is fully activated. Therefore, with active contact tracing
and aggressive screening (collection of specimens in
asymptomatic patients) is expected to find some positive
cultures before the onset of the disease.
Uncomplicated hilar adenopathy remains the most
common disease manifestation in children and is
considered the hallmark of primary tuberculosis. The
progression to disease is indicated by the onset of
persistent, nonremitting symptoms.
In terms of pathophysiology, microbiology and
natural history, asymptomatic hilar adenopathy is more
indicative of recent primary infection than active disease
(Figs 9.9.1 to 9.9.4).
Within the Ghons focus, containment is usually
successful. Poor containment and unrestrained organism
proliferation may cause progressive parenchymal

damage with ultimate breakdown of Ghons focus.
Infants and HIV-positive children who have poor cellmediated immune response are most vulnerable to this
type of cavitation. In contrast immune-competent
adolescents seem to mount an excessive (damaging)
immune response in an attempt to contain the organism.
Children with adult-type of disease are frequently
sputum smear-positive and they contribute to disease
transmission particularly in congregate settings such as
schools.
Exuberant lymph node enlargement, associated with
edema and small airway size in children less than 5 years
cause most of the complications of extraluminal
compression.
Polyps or granulomatous tissues secondary to
inflammatory changes in the bronchial wall cause
intraluminal obstruction. This type of obstruction can
also result when caseous material is deposited into an
airway after lymph node eruption. Hence, radiological
signs should be interpreted with caution in the absence
of clinical data. Hilar adenopathy can be very sensitively
deducted by high resolution computerized tomography
(CT). It is important to point out that CT has got no role
in the evaluation of asymptomatic, immune competent
children exposed to tuberculosis.
In everyday practice, distinguishing between the
signs and symptoms of recent primary infection and
active disease is less relevant in high-risk children (less
Figure 9.9.1: Types of pulmonary tuberculosis
Figure 9.9.2: Progression (local) in lymphatic nodes (complicated lymph node TB)
Figure 9.9.3: Hematogenous spread
319
320
Figure 9.9.4: Chronic pulmonary tuberculosis (CPT) (CPT seen mainly in adolescents and adults)
than 3 years of age and or immune compromised). In

this group infection frequently progresses to disease,
sometimes with rapid progression.
Radiological signs vary from segmental to lobar
hyperinflation, with partial obstruction and segmental
to lobar collapse can result due to total obstruction and
resorption of distal airway. Dose and virulance of the
bacilli determine the extent of pathology due to aspiration
of caseous material. Pure hypersensitivity response to
dead bacilli and or toxic products can result in transient
parenchmal consolidation. Continued pneuomonic
process can result in progressive caseating pneumonia.
This type of caseating pneumonia frequently results in
parenchymal destruction and cavity formation.
The following factors are responsible for cavitary
disease in children:
1. Poor containment at the site of organism deposition
(very young and or immunecompromised children).
2. Aspiration of live bacilli when a diseased lymph node
ruptures into an airway with destructive caseating
pneumonia in the distal segment or lobe. (Children
less than 5 years of age).
3. Mainly children older than 10 years of age, develop
adult-type disease.
Children between 5 and 10 years of age are
immune competent and at lowest risk to progression
of disease.
4. Disseminated miliary disease occurs predominantly
in very young (immune-immature) and immunecompromised such as HIV-infected or severely
malnourished. These children have poor containment
of organisms both with in the regional lymph nodes
or at multiple sites of occult dissemination. 20 to 30%

of cases develop tuberculous meningitis (TBM) which
is the most dangerous complication of disseminated
disease (it is usually meningoencephalitis, which
affects the mental development of child).
Natural History of Disease
The prechemotherapy literature is not so well documented hence the natural history of tuberculosis in children
is also not known. Clinician and researchers have limited
access to the important studies which were conducted
before 1950 and not available in the electronic database.
After the availability of safe and effective antituberculosis
agents, the studies on the natural course of disease could
not be conducted.
Case Definition
The most important variable that determines the risk to
progress to disease after M.tuberculosis infection in
immune competent children is the age. The infants are
at the highest risk. The risk drops but remains significantly high in the second year. It reaches its lowest level
in children infected between 5 and 10 years of age. The
other factors which determines the progression is HIV
infection and degree of malnutrition. 95% of children
who progress from infection to disease do so with in 12
months. Hence, it is prudent to categorise children less
than 3 years as high risk category. Active disease is
accompanied by persistent, non-remitting symptoms and
disease progression is slow which provides opportunity
for symptoms based diagnosis.

DISEASE DIVERSITY
Profile of Tuberculosis in Children
Based on clinicoimmunological study by Seth, the
following profile of tuberculosis in children has emerged:
i. Tuberculin positive, asymptomatic with no manifest
radiological tuberculous lesion. The asymptomatic,
Mantoux positive (ASMP) group.
ii. Tuberculin positive, with symptoms of tuberculosis
but without any manifest tuberculosis lesion. The
symptomatic positive (SMP) group.
iii. Pulmonary primary complex (PPC) which is of three
types (a) nodal, (b) parenchymal) and (c) parenchymal plus nodal.
iv. Tuberculous lymphadenitis (TBL) with or without
pulmonary lesion (nodal, parenchymal or nodal
plus parenchymal).
v. Progressive primary disease (PPD)
vi. Miliary tuberculosis (MTB)
vii. Meningeal tuberculosis (TBM) more precisely
meningo-encephalitic type tuberculosis.
viii. Tuberculosis of other organs (abdominal, bones and
joints). Accurate disease classification is important
because of its prognostic significance and decision
to be taken about the regimen whether RNTCP,
intermittent or continuous.
In tuberculosis in children, it is always not possible
to put every child on RNTCP recommended regimens
due to logistics difficulties. At times parents can afford
the therapy with the help of some NGOs and it is more
cost effective and practical to use continuous therapy.
Immunology of Tuberculosis
It is well-known that outcome of infection with
Mycobacterium tuberculosis in man varies enormously
from person to person. In one group of subjects, it evokes
no response at all. The infection is contained and there is
no disease but the subject may have a positive tuberculin
test. In an another group, the infection produces slow
development of host response with development of
primary complex, tuberculin positivity, cell-mediated
immunity and containment of infection but no progression. However, with lowering of immunity there may
be progressive disease from primary comlex. In other
group of subjects, there is aggressive response against
the bacilli and there is no containment or control of the
first infection which results in progressive disease,
321
whether in the lungs, mediastinal lymph nodes, their

local complications or hematogenous spread and
involvement of various organs. Another group of
patients, who had primary infection usually in childhood
may develop granulomatous but necrotizing or destructive cavitary form of tuberculosis at a later date as
happens in adolescents, adults and in old age. There is a
fourth type of subjects in which there is no cavity but
rapidly progressing pneumonic form with widespread
dissemination as seen in malnourished children or HIV
infection in whom immunity is compromised. It may be
noted that bacilli do not produce endo- or exotoxins. The
result depends upon their ability to withstand and
survive the onslaught by the host defence mechanisms.
It is important to understand the fact that various clinical
and pathological manifestations of tuberculosis are
directly due to tissue damaging host responses.
This host response leads to infection in two directions,
one cell-mediated protective response leading to
immunity and other causing inflammatory illness and
tissue destruction mediated by products elaborated by
host cells while trying to contain the bacilli. Though these
responses are mainly dependent on genetic makeup, with
severe infection and with large number of bacilli, the
child is likely to get progressive disease.
Mechanism of Lysis of Mycobacteria by
CD4 T-cells, Lymphokine-activated (LAK)
Cells and TNF Alpha
T-cells and natural killer (NK) cells: NK-cells are stimulated
by cytokine, interleukin 2 (IL-2). Moreover, sensitized
mycobacteria show increased susceptibility to lysis by
TNF alpha. These cells control the infection by releasing
various enzymes in the host tissues like proteinases,
nucleases and lipases. These enzymes produce local
inflammation which reduces the caseation or cavitation.
As mentioned earlier CD4 + T-cell functions are dependent on replication to secretion of cytokine interleukin 2.
When there is dysfunction of the CD4 + T-cells as happens
in severe malnutrition in children and progressive HIV
disease, tuberculous disease progresses further with
further depletion of CD4 + T-cells. There is reduced
cytotoxic function, decreased IL-2 production which leads
to reduced LAK cells and as well as TNF alpha function.
Thus, in malnourished children there is adverse effect on
CMI and DTH. There are various probable practical
implications in immune deficient children and in these
322
infants and young children with severe PEM because of

poor CD4 + T-cell function the infection is progressive.
There is high incidence of life-threatening disease like
miliary tuberculosis, hematogenous tuberculosis and its
various local complications, more often tuberculosis
meningoencephalitis, tuberculous meningitis, etc. The
delayed hypersensitivity in the skin is impaired and leads
to negative tuberculin test. The other implication of
immune deficiency in malnourished children is in liver
histology, with the presence of few tubercles and many
histiocytic nodules. Moreover, the incidence of hepatic
tuberculosis is high in malnourished adults at autopsy.
Diagnosis
intrathoracic manifestations. Hence, sensitive bacteriological based diagnostic approaches are particularly of
use only in endemic areas where children frequently
present with advanced disease.
Bronchoalveolar lavage It requires the use of a flexible fiberoptic bronchoscopy and has additive value when used
in combination with gastric lavage. However, this
technique is highly specialized and is not easily available
in most of the endemic areas.
Gastric aspirate provides a slightly better yeild than
nasopharyngeal aspiration. The latter does not require
hospitalization and fasting and is minimally invasive.
Sputum-smear microscopy: Often it is the only diagnostic

test available in endemic area, positive in less than
10-15% of children with probable tuberculosis. In adulttype of disease the yield is high and sputum smear
microscopy has definite value in older children (>10
years).
Poor bacteriological yields are also due to the problem
of collection of bacteriologic specimens. Two or three
fasting gastric aspirates collected on consecutive days
(usually requiring hospital admission) are routinely
performed in young children who cannot cough up
sputum. The gastric aspirate can be collected early
morning on out patients basis after over night fast.
Induced-sputum collection By using hypertonic saline the

yield of bacilli is similar to three gastric aspirates.
There is difficulty in achieving bacteriological
confirmation of the diagnosis of childhood tuberculosis
in non-endemic areas and younger age group in endemic
area where the disease is paucibacillary. Presentation is
due to dissemination of disease and location of primary
lesion is difficult. The following criteria are used:
Known contact with an adult index case frequently
with in the household
A positive tuberculin skin test (TST)
Suggestive signs on the chest radiograph
This triad provides a fairly accurate diagnosis in
settings where exposure to M.tuberculosis is rare and often
documented. However, its accuracy is reduced in
endemic areas where exposure to M.tuberculosis is
common and often undocumented as the exposure is
mostly outside the household except in children less than
two years. A positive TST reaction remains a fairly
accurate measure of infection with M.tuberculosis inspite
of National Program of BCG vaccination and exposure
to mycobacteria other than tuberculosis (MOTT).
In endemic areas a positive TST is induration > 10
mm. Clinical features and the chest radiography are
given due importance in diagnosis. Even the latter is not
easily available in endemic areas like India, particularly
in remote or not so remote areas (urban health clinics).
Despite this limitation, chest radiogram in symptomatic
children is the most widely used diagnostic criterion in
clinical practice.
2. Culture Yields
Scoring System
Culture yields are also low (<30 to 40%) in probable

tuberculosis. Culture positivity depends on the specific
Various scoring systems have been developed as a

scapegoat for suggested diagnosis in endemic areas. A
A high degree of suspicion is essential because of high

prevalence of tuberculous infection and disease in
children in India. The prechemotherapy literature that
describes the natural history of disease in children
identifies three factors:
The need for accurate case definition.
The importance of risk stratification
The diverse spectrum of disease pathology.
Due to the absence of a gold standard, the diagnosis
of childhood tuberculosis presents a major challenge.
1. Bacteriological Confirmation
The accepted gold standard is of limited use in children
because of the paucibacillary nature of the disease and
poor yield of bacteria.

critical review of these indicates that they are of limited
value and lack standard symptom definitions and
adequate validation. Developing standard symptom
definitions through consensus of expert opinions are
difficult. Better guidance can be achieved by objective
measurement of the potential diagnostic value of
different value of these fairly-defined symptoms. This
requires validation in prospective, community based
studies that include children from all relevant risk
groups. Children showing neurological symptoms like
irritability, refusal to feed, headache, vomiting or altered
sensorium can be highly suspected to have TBM.
These symptoms based diagnostic approaches have
less value in high-risk children (less than 3-yr of age and
or immune compromised). In the latter, there is a definite
role of early diagnosis, and preventive therapy and even
treatment of latent tuberculosis.
Clinical Features
Clinical features are variable depending upon the age of
the child, immune competence, dose of infection,
nutrition of the child and genetic factors. However, the
child may develop progressive primary disease usually
in the lungs and lymph nodes and may develop
extrathoracic complications with mild, moderate or
serious clinical manifestations. Following are some of the
presenting clinical features:
Typhoid like fever in infancy and early childhood,
which may often be missed as pyrexia of unknown
origin.
Pneumonia which fails to resolve, even though the
symptoms may be controlled with or without even
non-tuberculosis drugs.
A prolonged pyrexia not due to other detectable
causes like typhoid or urinary tract infection, or heat
pyrexia in summer.
Persistent cough particularly pertussoid type or
stridulous cough with whistling sound, indicating
endobronchial tuberculosis and bronchial obstruction.
Persistent wheezing in the chest more commonly due
to allergic bronchitis is also seen with endobronchial
or endotracheal disease. Recent studies have revealed
that the hyperreactivity of a bronchial mucosa can be
caused by tuberculoprotein, from pulmonary or
mediastinal nodes, and the symptoms of persistent
or recurrent bronchitis, pertussoid cough and/or
323
asthma, which do not respond well or recurs in spite

of conventional treatment. Studies have proved the
relation between pulmonary TB and asthma.
Precipitation of asthma with provocative dose of PPD,
given by insufflation will not only produce an attack
of asthma, but also raise the basal specific serum lgE
value to significant high lgE levels after PPD
provocative dose.
Pain in the chest in an older child with pleurisy.
General symptoms like weakness, fatigue, poor
appetitie and/or unexplained loss of weight.
Fever of vague illnesses following measles, or
whooping cough.
Respiratory distress of different severity with minimal
or no signs in the lungs, can be caused be enlarged
subcarinal nodes due to compression of the carina
(tracheal bifurcation), while chronic cough can be
caused by various mediastinal nodes, hilar, more so
by paratracheals and subcarinal nodes (SCLN), which
are in contact with or which indent the trachea. The
lymph node enlargement is much more common in
BCG vaccinated children than nonvaccinated and
would be the main diagnostic problem in infants
covered by BCG vaccination.
Child with abdominal pain, distention of abdomen,
steatorrhea, chronic diarrhea, malabsorption and
doughy abdomen with hepatosplenomegaly with or
without abdominal mass due to mesenteric adentitis,
matted intestine or rolled up omentum. At times they
present with subacute intestinal obstruction (see in
Chapter 9.10 on Abdominal Tuberculosis).
Tuberculosis of the nervous system is the most
important cause of death in a tuberculous child. The
presenting features in early stages are persistent fever,
headache, vomiting, anorexia, constipation and
apathy alternating with irritability (see Chapter 9.11
on Neurotuberculosis).
Immunology (Diagnostic Evaluation)

Serological Tests
These are currently unable to diagnose childhood
tuberculosis with accuracy. Sputum-based polymerase
chain reaction (PCR) tests have shown variable results
and hence are of limited utility. Heminested PCR
technique using uninfected children as control group
limits its utility for the diagnosis of latent infection from
the active disease.
324
Immunological Tests
Novel T-cell based assays (T-SPOT-TB Oxford Immunotec Antigen UK) and Quanti FERON TB Gold (Cellestis,
velencia, CA) may improve the ability to diagnose
M.tuberculosis infection. This has particular relevance in
immune compromised malnourished children (particularly less than 3 years) in whom TST programs poorly.
T-SPOT-TB assay is more sensitive than traditional TST,
has better performance in associated HIV-infection which
has to be treated for probable tuberculosis. It is
independent of CD4 + T-cell count. The use of M.
tuberulosis specific antigents such as ESAT-6 and CFP-10
provides superior specificity as these tests are not
influenced by BCG vaccination and rarely by environmental mycobacteria. It is important to emphasize that in
the absence of symptoms, or radiological signs indicative
of disease, qualitative T-cell assays like TST fail to make
the distinction between infection and disease.
Problem of Associated HIV in Diagnosis
The specificity of symptoms based diagnostic approaches
is reduced by the presence of chronic HIV-related
symptoms and is further limited due to rapid progression
of the disease.
Chest radiography interpretation is complicated by
HIV-related morbidity and atypical presentation. Hence,
in this group there is more value of microbiological
diagnosis. HIV will not only lead to rapid progression of
disease but may precipitate i.e. reactivate the latent
infection. The traditional TST has poor diagnostic ability,
as only 50% or less children with HIV infection and
bacteriological confirmed tuberculosis have TST positive
despite using an induration of 5 mm as only a cut off
point for positivity. This is a major limitation and a more
reliable measure of infection will be to identify children
with infection who will benefit from preventive
chemotherapy.
These new diagnostic tools are of value in nonendemic areas for contact and immigrant screening and
in endemic areas with limited resources to assess their
ability to detect M.tuberculosis infection in HIV-infected
individuals.
Pattern of Disease in BCG Vaccinated Children as
Compared to the Nonvaccinated Children
The type of tuberculosis seen in BCG vaccinated children
is commonly intrathoracic tuberculosis, particularly
mediastinal lymph node tuberculosis and its local

complications. The higher incidence of intrathoracic
disease in vaccinated children is because intradermal
BCG vaccination cannot prevent lodgment of natural
virulent tubercule bacilli in the lungs and development
of primary infection and its progressive local complications. However, BCG vaccination reduces the
hematogenous dissemination of infection in vaccinated
children. In nonvaccinated children, relative incidence
of intrathoracic lesion is less compared to vaccinated
because there is hematogenous spread of the bacilli to
various organs and systems with development of
metastatic foci. Hence, miliary tuberculosis, tuberculous
meningitis and hematogenous TB are much more
common in nonvaccinated than in vaccinated children.
Mediastinal lymph node tuberculosis is one of the
important manifestations in BCG vaccinated children.
The enlarged nodes may be missed on X-ray film of chest
but can be identified by newer imaging techniques such
as CT and MRI scans.
Changing Clinical Presentation of Neurotuberculosis
(Refer to Chapter 9.11 on Neurotuberculosis)
The incidence of clinical manifestations of various types
of neurotuberculosis are different in vaccinated than in
nonvaccinated children. For example, serous tuberculous
meningitis is two to three times more common in
vaccinated children than in nonvaccinated children.
Because of better T-cell function in vaccinated children,
generalized or characteristic tuberculous meningoencephalitis is less common in these children unless they are
severely malnourished. Localized tuberculous disease of
the brain or meninges is more common in vaccinated
children. In children with serous tuberculous meningitis
there is no diffuse brain involvement and hence child
may present with fever, headache, vomiting and
meningeal signs and he is usually conscious and alert.
He may have evidence of raised ICT demonstration by
Macewens sign being positive and papilledema. He may
develop neurological deficit by involvement of blood
vessels and nerves and/or develop hydrocephalus by
exudate at the base of the brain blocking the basal
cisterns. Hence, there is never clinical picture of serious
tuberculous meningitis but there is higher incidence of
tuberculoma in vaccinated children. These diagnostic
possibilities should be kept in mind as this is going to be
a common presentation.

Treatment
Basic Principles
Antituberculosis treatment aims to cure the individual
patient and to prevent the emergence of drug-resistant
strain with in the community by following principles:
Rapid reduction of organism load
Effective eradication of dormant and intermittently
metabolizing (persistent) bacilli.
Achieving this with minimal side effects in the child.
Bactericidal Drugs
Ensure rapid reduction of the organism load which
(i) improves clinical symptoms, (ii) limits disease progression, (iii) terminates transmission and (iv) prevents
the emergence of drug resistance.
325
offer protection against the development of resistance.

It may also assist in the eradication of organisms
especially in fibrocaseous tissues with poor drug
penetration. Host immunity plays an important role
throughout. It is of particular importance in (i) eradication of organism and thus (ii) preventing relapse. Due
to poor host immunity relapse rates are very high in
children with associated HIV-infection.
When the mycobacterial load is very high, any
antituberculosis drug used in isolation is vulnerable to
resistance from naturally occurring mutants. Random
resistance is extremely rare to multiple drugs. Therefore,
is recommendation of the use of multiple drugs in
combination, during the intensive phase of treatment. It
drastically reduces the risk of treatment failure inspite
of heavy bacillary load.
Intensive Phase
Sterilizing Drugs
Ensure the effective eradication of dormant and
intermittently metabolizing (persisters) bacilli, thus
preventing disease relapse. These principles provide the
rationale behind the intensive and continuation phases
of current antituberculosis treatment regimens.
Assuming that there is complete drug susceptibility
and there is no immune compromised state, each of the
first-line drugs makes a specific contribution during
different periods of drug action.
Bulk of the organism load is eliminated with the virtual

elimination of risk of drug resistance. To prevent the
emergence of drug resistance, good adherence is very
necessary as several cycles of mycobacterial killing (when
drugs are taken) and regrowth (when drugs are not
taken) favors selection of drugs-resistant mutants. These
mutants may accumultate additional random mutations
resulting in the emergence of multiple drug resistance.
It lasts 4 to 8 weeks. Slower growing extracellular bacilli

are killed. The rate of killing is determined more by the
physiological state of the bacilli and less by the
bactericidal activity of the drug. During this period
bactericidal activity of rifampin (RMP) is important and
pyrazinamide (PZA) contributes by killing extracellular
bacilli that persist in acidic areas of inflammation.
Operational issues in treatment include:

Access to early and accurate diagnosis.
Uninterrupted provision of quality-assured drugs
and appropriate regimen.
System to ensure good treatment adherence.
Fixed-dose combination should be used whenever
possible to reduce the risk of drug resistance.
Adherence must be ensured.
Quality assurance is essential to ensure optimum
bioavailability of all constituent drugs.
With proper implementation of the World Health
Organisations directly observed therapy, short-course
(DOTS) strategy, all the above mentioned operational
issues are addressed. However, the main emphasis on
sputum smear-positive disease excludes the vast majority
of children. There is desperate need to improve service
delivery to children with tuberculosis, particularly in
endemic areas with limited resources.
Period 3
Use of BCG for Prevention Strategy
It lasts 4 to 6 months. Persistant intracellular bacilli are

eradicated mainly by RMP, although INH continues to
Variable results are obtained for the efficacy of BCG

vaccination due to variation in strain-specific immuno-
Period 1
Lasts 2 to 3 days during which time fast growing
extracellular bacilli which comprise the vast majority of
the organisms load are killed. This is achieved mainly
by the excellent bactericidal activity of isoniazid.
Period 2
326
genicity, timing and technique presence or absence of

environmental mycobacteria (MOTT) and the effect of
multiple reinfection events as occurs in endemic areas.
BCG vaccination offers little or no protection against
adult-type of disease but helps in the protection against
disseminated (miliary) disease in young infants less than
two years. However, when the environmental mycobacterial exposure is low and the adolescent is TST -ve, BCG,
is protective.
BCG is contraindicated in HIV-infected children.
However, in asymptomatic HIV exposed infants, WHO
recommends the use of BCG vaccination.
The treatment in children needs description as
follows:
1. Preventive therapy
2. Treatment of latent tuberculosis
3. Curative treatment.
1. Preventive Therapy
As recommended by Indian Academy of Pediatrics the
following groups of children are considered for
preventive therapy.
Asymptomatic Mantoux positive < 3 years
Asymptomatic Mantoux positive < 5 years with grade
IIII or IV malnutrition
Mantoux positive recent converter/no signs
Healed lesion normal chest X-ray or calcification/
fibrosis
Children < 3 years with history of sputum smear
positive contact with in the household
Children < 5 years grades III or IV malnutrition
with sputum smear positive contact with in the
family
The recommended regimen is 6HR.
In an effort to most accurately describe this intervention, the American Thoracic Society (ARS) supports
the replacement of both these terms with treatment of
latent tuberculosis infection (LTBI). Case detection and
cure of active disease are critical to reducing transmission.
Treatment of LTBI intervenes at an earlier point in the
cycle, by preventing the development of disease in those
who were previously infected.
In India it is time that recommendation of single drug
5 mg/kg of isoniazid for 6 months in children under five
exposed to sputum positive in the household be changed
to the use of two drugs (6HR) when the exposure is to a
contact with MDR organism. Doctor looking after the
adult sputum positive should be able to decide which
regimen the concerned child need to be put on.
3. Curative Treatment
Bacterial load and anatomic distribution of bacilli apart
from primary drug resistance are the major determinants
of success of chemotherapy.
In sputum-smear positive disease, it is often
cavitatory with high bacillary load and an increased risk
of random drug resistance against individual drugs.
Miliary disease can be often associated with penetration
of the bacilli into central nervous system. In this, the
adequate drug penetration against blood-brain barrier
is essential for treatment.
The main variables that influence the success of chemotherapy
is to identify following groups of children with tuberculosis:
1. Those with sputum smear-negative disease.
2. Those with sputum smear-positive disease (cavitary)
3. Those with disseminated (milliary and meningoencephalitis)
disease.
4. Special organs/systems: Gastrointestinal, bone and joint
2. Treatment of Latent Tuberculosis
DOTS Strategy
Young children with tuberculosis infection are more

likely than adults to develop serious forms of disease.
Exposure at any early age to infectious tuberculosis is
common in less developing countries like India. There
are many children with subclinical infection.
Among the interventions which can control the
spread of tuberculosis is preventive chemotherapy or
chemoprophylaxis. These terms are often a source of
confusion for patients and providers and the majority of
candidates are infected with TB and the role of therapy
is secondary rather than primary prevention.
DOTS is the recommended strategy for treatment of TB

and all pediatric TB patients should be registered under
RNTCP.6 Intermittent short-course chemotherapy given
under direct observation as advocated in the RNTCP
should be used for children.
Table 9.9.2 shows the RNTCP treatment regimens.
In patients with TBM on category I treatment, the four
drugs used during the intensive phase should be HRZS
or HRZE. Continuation phase of treatment of TBM and
spinal TB with neurological complications should be
given for 6-7 months extending the total duration to 8 to
327
TABLE 9.9.2: Treatment regimens for children under RNTCP

Treatment
category
Type of patients
TB treatment regimens
IP
CP
CAT I
New sputum smear-positive PTB,

Seriously ill* sputum smear-negative
PTB, seriously ill EPTB
2H3R3Z3E3***
4H3R3
CAT II
Sputum smear-positive relapse,

Sputum smear-positive treatment
Failure, sputum smear-positive treatment
after default.
2S3H3R3Z3E3/
1H3R3Z3E3
5H3R3E3
CAT III
Sputum smear-negative and EPTB

not seriously ill**
2H3R3Z3
4H3R3
IP Intenstive phase, CP continuation phase

* Seriously ill sputum smear-negative PTB includes all forms of PTB, other than primary complex. Seriously ill EPTB include TB
meningitis (TBM), disseminated/milliary TB, TB pericarditis, and TB peritonitis and intestinal tuberculosis, bilateral or extensive pleurisy,
spinal tuberculosis, with or without neurological complications, genitourinary tract tuberculosis, bone and joint tuberculosis.
** Not seriously ill EPTB include lymph node tuberculosis and unilateral pleural effusion.
***Prefix indicates months and subscript indicates thrice weekly.
PTB Pulmonary tuberculosis
EPTB Extrapulmonary tuberculosis
* For details see the chapter on RNTCP
9 months. There should be well controlled studies in a

larger number of children with neuro-tuberculosis. Seth
has shown the efficacy of intermittent therapy in
tubercular meningoencephalitis in a well controlled
study but in a small number of cases and needs a larger
controlled study to confirm the same.
Steroids
Should be used initially in hospitalized cases of TBM and
TB pericarditis and reduced gradually over 6 to 8 weeks.
In all instances before starting a child on category II
treatment, she/he should be examined by a pediatrician
or a TB expert, and in view of the growing evidence that
the use of ethambutol in young children is safe, ethambutol
is to be used as per RNTCP regimens for all age group.
To assist in calculating required dosages and
administration of anti-TB drugs for children, medication
is available in the form of combipacks in patientwise
boxes limited to childs weight in four categories.
Pediatric-focused monitoring is an integral part of the
program. Wherever possible, follow-up sputum examination is to be performed with the same frequency as in
adults.
Clinical or symptomatic improvement is to be

assessed at the end of the intensive phase of treatment.
Improvement should be judged by absence of fever or
cough, a decrease in the size of lymph nodes and weight
gain. Radiological improvement is assessed by chest
X-ray examination in all smear-negative pulmonary TB
cases at the end of treatment.
Continuous Therapy in Pediatrics
Although it is recommended that all children should be
treated under RNTCP but in some circumstances
treatment can be continuous when it can be afforded
easily but it is difficult to follow adherence as in the
program. This will ensure better adherence.
For poor parents, the wage loss and travel time
involved are limitations because in real-life situation, one
cannot assure 100% coverage of all cases. This is true of
all National Programs in India. At least the drug regimen
can be decided by a doctor at the Primary Health Centre
in case of non-neurological tuberculosis, i.e. the types
described above. Pediatric-focused monitoring is an
integral part of the program. Wherever possible, followup sputum examination is to be performed with the same
frequency as in adults.
328
Clinical or symptomatic improvement is to be

assessed at the end of the intensive phase of treatment.
Improvement should be judged by absence of fever or
cough, a decrease in the size of lymph nodes, weight gain.
Radiological improvement is assessed by chest X-ray
examination in all smear-negative pulmonary TB cases
at the end of treatment.
DRUG RESISTANT TUBERCULOSIS

DEFINITION
Drug resistance in mycobacteria is defined as insensitivity of mycobacteria to a sufficient degree to be
reasonably certain that the strain concerned is different
from a sample of wild strains of human type that have
never come in contact with the drugs.
Types of Drug Resistance
Drug resistance in TB may be broadly classified as
primary or acquired. When drug resistance is demonstrated in a patient who has never received antituberculosis treatment previously, it is termed primary
resistance. Acquired resistance occurs as result of
specified previous treatment.
The level of primary resistance in the community is
considered to reflect the efficacy of control measures in
the past while the level of acquired resistance is a measure
of ongoing TB control measures. However, the World
Health Organization (WHO) and the International Union
Against Tuberculosis and Lung Disease (IUATLD), in the
light of discussion in several International fora, have
replaced the term primary resistance by the term drug
resistance among new cases and acquired resistance
by the term drug resistance among previously treated
cases.
iv. Ignorance of health care workers in epidemiology,

treatment and control of the disease.
v. Improper prescription of drug regimens.
vi. Interruption of chemotherapy due to adverse effects
of drugs.
vii. Non-adherence of the patient to the prescribed drug
therapy.
viii. Availability of anti TB-drugs over-the-counter
without prescription.
ix. Massive bacillary load.
x. Illiteracy and low socio-economic status of the
patients.
xi. Epidemic of HIV infection.
xii. Laboratory delays in identification.
xiii. Use of non-standardized laboratory techniques,
poor quality active pharmaceutical ingredient, lack
of quality control measures, and
xiv. Use of anti-TB drugs for causes other than tuberculosis.
Multidrug resistant tuberculosis (MDR-TB) requires
treatment with second-line drugs. These drugs have
limited sterilizing capacity and not useful for short-course
chemotherapy. Thus the problem of transmission is
crucial to the disease in children. It is of grave concern
when there is contact of a child with MDR tuberculosis
in the family resulting in primary resistant infection.
MDR-TB has important implication both for individual
patient and tuberculosis control program.
The modern era of tuberculosis is characterized by a
rise in the number of cases of infection with MDR-TB.
This has also lead to outbreaks of MDR-TB and individual
cases that are only marginally treatable and often fatal.
World Health Organization (WHO) in 1993 on World
Tuberculosis Day declared tuberculosis as a global
emergency. MDR-TB has been described as the third
epidemic, complicating the epidemic of HIV.
Diagnosis
Causes of Drug Resistance

A variety of factors namely management, health provider
and patient related, are responsible for the emergence of
drug resistance in M.tuberculosis. These include:
i. Deficient or deteriorating TB control programs
resulting in inadequate administration of effective
treatment.
ii. Poor case holding.
iii. Administration of sub-standard drugs, inadequate
or irregular drug supply and lack of supervision.
Since the clinical presentation of both the sensitive and

drug resistant tuberculosis is the same, the only certain
way of diagnosing tuberculosis is by isolating the
infective strain and assessing its susceptibility pattern.
AFB isolation in tuberculosis, in children except in
cavitary disease is low (25-44%) even in the most
advanced centers. Adult contacts of children should be
assessed for history of prior antituberculosis therapy with
persistent sputum-positivity. Since, this is a pointer
towards drug-resistance, children with such adults

should be watched for any (i) lack of response or
(ii) deterioration on treatment.
Diagnosis of drug resistance is further confounded
by certain peculiarities of the disease. The resolution of
radiographic abnormalities of chest can take months or
years even after successful treatment. Also posttuberculosis hyperreactivity, bronchiectasis and other
residual lesions can cause symptoms with persistence of
radiological shadows.
In 15-20 percent infection with susceptible organisms,
lymph nodes of considerable size persist even after
complete therapy. These may fluctuate intermittently.
Histopathology in such cases may show sterile granuloma. AFB can be isolated in cases of drug-failure or
relapse.
Tuberculomas of brain may increase in number, as
well as size, even on successful treatment. Anatomically
they heal over a period of months or years. A patient can
have recurrence of convulsions during the healing phase.
Such symptoms do not necessarily imply a relapse or
resistance to antituberculosis chemotherapy.
Various reasons may be responsible for delay in
diagnosis of MDR-TB. In a recent report of tuberculosis
in children when the emphasis was on the isolation of
Mycobacterium tuberculosis by rapid methods using
induced sputum, the delay in starting the therapy was a
median of two days when the MDR-TB source case was
taken into account. It was a delay of 246 days if the drug
susceptibility pattern of the source case was not
considered. Correlation between the isolate of the child
and source case was 68 percent. This suggests that there
is a need to define the resistant tuberculosis in children.
If a child has had a contact with an adult patient
particularly in the household with documented MDRTB, he can be considered to be suffering from MDR-TB.
He should be started on an appropriate therapy after
taking the requisite samples for culture and sensitivity
for M.tuberculosis.
If a patient fails to improve after appropriate
antituberculosis drugs with good compliance, he may
be suffering from resistant tuberculosis and should be
referred to an appropriate center dealing with drug
resistant tuberculosis. The primary care physician should
not start the child on a regimen for drug resistant
tuberculosis.
Predictors of Drug Resistance in Children
Pattern of drug-resistance among children with tuberculosis tend to reflect those found among adults.
329
Predictors of drug-resistance in children are given in

Table 9.9.3:
TABLE 9.9.3: Predictors of drug resistance
Previous antituberculosis therapy

HIV infection in the child or source case of adult
Known contact with an adult patient with MDR-TB
In children with HIV infection or cavitary lesion, treatment
is extended upto 24 months in children with HIV infection
or cavitory lesions
Intermittent regimens are not recommended.
If patients M.tuberculosis culture remains positive

after 4 to 5 months of treatment, it should be retested for
susceptibility to both first and second-line drugs. If this
is not available, as is often the situation in India, at least
two new drugs should be added while continuing
original medication if available. Addition of new drugs
should be based on susceptibility testing.
If patient develops an adverse drug reaction, the
offending drug can be removed and rest of the regimen
continued. Alternatively, a new medication can be
substituted. In general first-line drugs are well tolerated
by children and the adverse effects are more often by
second-line drugs. Children on second-line drugs must
be monitored for liver, renal and hearing tests periodically.
Management
The management of MDR-TB in adults has been
extensively documented including India. However, little
is known about its diagnosis and management in
children. After the streptomycin was introduced in the
treatment of TB, very early it was found that there were
frequent relapse and emergence of a population of
streptomycin resistant M.tuberculosis.
The current threat is due to emergence of strains
resistant to the two most potent anti-TB drugs viz.,
isoniazid(H) and rifampicin (R) (MDR-TB). The response
of patients with MDR-TB to treatment is poor and
mortality rate is usually high.
The number of MDR-TB patients has increased in
India and the concern of the government of India is to
prevent the increase in the incidence of XDR or extremely
drug resistant cases which have no cure.
The Health Ministry is dolling out the DOTS Plus
program to manage MDR-TB in several states by early
June 2008 and in 17 other states by May 2009.
330
TB infects 8 lakh people in India every year and when

treated inappropriately (the administration of drugs is
stopped prematurely or is not done properly), the patient
not only remains sick, but the bacteria that causes the
illness may develop resistance to drugs ordinarily used
to treat tuberculosis.
MDR-TB is difficult to treat and drugs used cause side
effects. The people infected spread it readily to others.
In Indias TB control program, laboratories to diagnose
MDR-TB are being accredited in states like Delhi, West
Bengal, Kerala, Rajasthan, Tamil Nadu, Andhra Pradesh
and Haryana.
The Stop TB Partnership opined that plans to combat
drug-resistant TB need to be prioritized by the
Government, which should increase the number of
laboratories to diagnose MDR-TB and introduce rapid
methods to quickly identify drug-resistant patients.
Principles of Treatment of MDR-TB
Drug Therapy of MDR-TB
Even under ideal conditions, M.tuberculosis is isolated

from induced sputum or gastric aspirate in 50% of
children with pulmonary tuberculosis. Culture yields
from other anatomic sites are lower. For this reason the
clinician should be aware of the resistance pattern in the
community since, in vast majority of cases of resistant
tuberculosis in children, it is primary. Susceptibility
information can be obtained from the M.tuberculosis
isolated from the adult who transmitted the infection.
The treatment can be as follows depending upon the
disease in the child from known contact or unknown
source.
The treatment of MDR-TB is a challenge since it

involves the use of second-line reserve drugs which
are not only more expensive but are also more toxic
and less effective than the standard drugs. These drugs
include aminoglycosides (capreomycin), thionamides,
fluoroquinolones, cycloserine and para-aminosalicylic
acid (PAS).
When to Suspect Drug Resistance
Drug resistance should be suspected whenever:
Therapeutic progress is not maintained
Bacterial relapse occurs during treatment
Recurrence occurs in a patient previously treated for
tuberculosis and their contact including children.
Associated HIV infection.
Once there is strong possibility of drug resistance
complicating therapy:
i. All treatment should be reconsidered.
ii. Culture and sensitivity studies should be undertaken using rapid methods of identification of AFB
on smear and culture.
Repeated examination of gastric lavage and induced
sputum specimen, examination of fine needle aspiration
(FNA) material in non-resolving lymphadenitis must be
undertaken. Further, drugs should not be added
piecemeal to the existing regimen as this will lead to
decrease of drugs for use in an effective alternative
therapeutic regimen.
MDR-TB should always be treated in consultation

with a clinician who is experienced in treating the
disease.
Patients should be treated with at least 2 or preferably
3-4 drugs to which the strain isolated from the patient
or adult source-case is known to be sensitive.
Aminoglycosides or capreomycin should be one of
the medications as studies have shown that its use is
a good predictor of culture conversion and survival.
Bactericidal drugs should be used as far as possible
Treatment should be given for at least 12 months after
culture of bacilli has converted to negative.
Some important features of anti-TB drugs used in
chemotherapy of MDR-TB are given in Table 9.9.4.
Treatment of Drug Resistant Tuberculosis Disease
1. Children with Resistant Disease with Known Adult

Patients with MDR Tuberculosis
All children with MDR-tuberculosis need individualized
treatment regimen (ITR). The children in this category
should first receive any oral first-line drugs to which the
isolate from the adult source case is sensitive. Second,
all regimens must include an injectable agent for a
minimum of six months after culture conversion, and
an oral quinolone for the duration of therapy. Children
who yet do not have five drugs in their regimen should
receive additional second-line drugs (ethionamide,
cycloserine or PAS). If a strain is highly resistant and the
childs regimen still contains less than five drugs,
additional agents with known antituberculosis acitivity
(e.g. amoxicillin/clavulanic acid or clofazimine) can be
added.
331
TABLE 9.9.4: Antituberculosis drugs for the treatment of MDR tuberculosis

Drugs
Aminoglycosides
Streptomycin
Average
daily dose
(mg/kg)
Routes
Tolerance
Toxicity
Type of antimicobacterial activity
15
Injection
Moderate
Medium
Bactericidal against actively

multiplying bacteria
Kanamycin
Injection
Poor
Medium
Amikacin
Injection
Medium
Medium
Capreomycin
Injection
Moderate
Medium
10-20
Oral
Good to moderate
Medium
Bactericidal
20-30
7.5-15
15-20
10-20
10-12 g
Oral
Oral
Oral
Oral
Oral
Good
Good
Good
Moderate
Tabs
Granules
Low
Low
Low
High
Low
Bactericidal at acid pH
Weak bactericidal
Bacteriostatic
Bacteriostatic
Bacteriostatic
Thionamides
Ethionamides
Prothionamides
Pyrazinamide
Ofloxacin
Ethambutol
Cycloserine
PAS
2. Children with Tuberculosis Disease

without Known Contact
These are children who fail to respond to appropriate
antituberculosis treatment. The treatment failure may be
due to several reasons, including inappropriate regimen,
poor adherence, or wrong diagnosis. It is recommended
that attempt should be made to ascertain the diagnosis
of TB again by subjecting appropriate specimens for
isolation of M.tuberculosis and category 2 treatment
should be started (2SHRZE, 1HRZE, 5HRE).
The family should be counselled to achieve 100%
compliance. Children who are already on this regimen
for 3 months but show no improvement, should be
considered for treatment for MDR-TB in a specialised
centre of WHO.
The recommendations of Indian Academy of
Pediatrics for management of drug resistant tuberculosis
in children are given in Table 9.9.5.
Treatment of Drug Resistant Infection
Isoniazid alone has been recommended for children who
have a contact with a drug-susceptible adult. In areas
with high rates of isoniazid resistance, rifampicin
(10 mg/kg) for 6-12 months is recommended.
TABLE 9.9.5: Suggested drug regimen for proven drug

resistance in relation to HIV status
HIV status
Isoniazid
Rifampicin
Multi-drug
HIV-ve
12RZE
18-24 HRZ
3 sensitive
drugs for 2
years after
culture-ve
HIV+ve
18 RZE or
18-24 HZE
12 months after or 12 months
culture-ve
after culture-ve
3 sensitive
drugs for 2
years after
culture-ve
Preventive therapy for children likely to be infected

with resistant strain, a combination of PZA and EMB or
PZA and a fluoroquinolone for 12 months is recommended. Children should be followed up carefully
during and after treatment for the development of signs
and symptoms of tuberculosis disease. All children
infected with MDR-TB should be treated for disease.
In children less than 2 years of age who have high
risk of developing a life threatening disease all possible
attempts should be made to isolate the organism. Any
child who has AIDS has to be treated as associated
tuberculosis disease.
332
Concept of DOTS Plus
Prevention
Two basic approaches to DOTS Plus have been proposed:

i. Individualized treatment regimen and
ii. Standardized regimen including second and thirdline drugs. In pediatric practice, it is still recommended to individualize the regimen as described
above.
The prevention of MDR-TB depends upon an effective

use of the principles of tuberculosis control. The timely
identification and adequate treatment in a special TB
center is of formost importance in preventing further
spread. Due emphasis has to be given for contact tracing
of children of an adult with suspected or proven MDRTB.
BIBLIOGRAPHY
Newer Drugs
This is amoxicillin-clavulanic combination showing
promise for treatment of MDR-TB. Imipenem, amoxycillin-clavulanic acid, interferon gamma via aerosol,
newer rifamycins (rifabutin, rifatazil) and recombinant
interleukin are some of the drugs under investigation. A
recently investigated compound which appears encouraging is oxazolidinone.
Immunotherapy
M.vaccae vaccine used in small trials in adult patients,
has shown some benefit. Mode of action is possibly by
regulation of cell-mediated immunity with enhancement
of Th1 and down regulation of Th2 cells. It is shown by
faster bacteriologic conversion, reduction in ESR, increase
in body weight, resolution of radiological opacities,
leading to betterment in clinical status.
1. Chakraborty AK. Prevalence and incidence of tuberculosis infection and disease in India: a comprehensive
review. World Health Organisation, Geneva, Switzerland
1997, WHO/TB/97/33.
2. Kabra SK, Lodha R, Seth V. Tuberculosis in children
what has changed in 20 years? Indian J Pediatric 2002;
69 (suppl)1:55-10.
3. Mariais BJ, Rober P, Gie H, Donald P, et al. Childhood
pulmonary tuberculosis, old wisdom and new
challenges. Am J Rep Crt Care Med 2006;173:1048-90.
4. Seth V. Revised National Tuberculosis Control-Programmanagement of tuberculosis in children. In IAP Text Book
of Pediatrics. Jaypee Brothers medical Publishers (P) Ltd,
New Delhi, 2009;351-58.
5. Seth V, Lodha R, Kabra SK. Pulmonary tuberculosis. In:
Seth V, Kabra SK (Eds): Essentials of Tuberculosis in
Children, (3rd edition). Jaypee Brothers Medical
Publishers (P) Ltd: New Delhi 2006;109-33.
6. Treatment of Childhood Tuberculosis: Consensus
Statement Recommendations of Indian Academy of
Pediatrics, India Pediatr 1997;37:1093-6.
7. Udani PM. Tuberculosis in children in India. Pediatric
Clin India 1903;25:125-31.
9.10 Abdominal Tuberculosis

Saroj Mehta, Vimlesh Seth
Tuberculosis is still common in the tropics and continues
to figure in the differential diagnosis of medical and
surgical emergencies of acute abdomen.
DEFINITION
It is defined as tuberculosis infection of the abdomen
including gastrointestinal tract (GIT), peritoneum,
omentum, mesentry, lymph nodes and other solid organs
of the abdomen like liver, spleen and pancreas. It has
been well described in adults. There has been paucity of
literature on abdominal tuberculosis in children due to
its protean manifestations and difficulty in diagnosis.
Etiopathology
Mycobacterium tuberculosis, M.bovis and mycobacteria
other than tuberculosis (MOTT) can cause abdominal
tuberculosis. Due to pasteurisation of milk and the
custom of boiling it before consumption, tuberculosis due
to M.bovis is rarely seen in India. The likely mechanism
for the infection of the bowel include direct infection of
tubercule bacilli from either infected sputum or dairy
products. The other mechanism is hematogenous spread
through the bile from focus elsewhere in the body or
direct extension from the other organs. Tuberculous
peritonitis can occur due to ulceration of an abdominal

TABLE 9.10.1: Sites of involvement in
abdominal tuberculosis
Intestine
Ulcerative; hypertrophic;
Ulcerohypertrophic; miliary
Peritoneum
Exudative (generalized or localized)
Dry plastic, fibroblastic, miliary
Omental adhesive
Lymph node
Mesenteric, other local nodes;
Retroperitoneal
lymph node, or a tubercular ulcer, or as a result of

transmural infection of the bowel without perforation.
Primary infection of the intestines can occur due to
involvement of peritoneal lymph nodes.
Clinical Features
Abdominal tuberculosis can be of the following types:
Classic plastic form
Ascitic form
Involvement of mesenteric lymph nodes.
In children nearly two-third cases have predominantly involvement of GIT. Peritoneal involvement
occurs only in one-third cases. Isolated nodal involvement (Tabes mesenterica) is uncommon (about 4%). The
sites of involvement in gastrointestinal tract, in order of
frequency are, ileum, colon, ileocecal region, jejunum and
duodenum. The types of lesions in various organs are
given in Table 9.10.1.
Table 9.10.2 the shows the possible clinical symptoms
and signs of abdominal tuberculosis in children.
Peripheral lymphadenopathy (33%) and some
pulmonary signs may provide significant pointers to
etiology of abdominal findings. Abdominal disease is
more often disseminated in children, unlike adults in
whom it tends to localize, often resulting in subacute
obstruction.
Clinical presentation of abdominal tuberculosis is
very variable and may mimic common childhood
illnesses like diarrhea, fever, pain abdomen, etc. The most
common symptoms are abdominal pain followed closely
by anorexia and weight loss and chronic or recurrent
diarrhea. Association of low grade pyrexia and cough
may arouse suspicion. Duration of symptoms may vary
from, as short as two weeks, to as long as a few years.
The clinical signs include distention of abdomen, visible
peristalsis, doughy feel on palpation of abdomen, ascites
333
TABLE 9.10.2: Abdominal tuberculosis

clinical features at presentation
Clinical features
% of patients
Symptoms
Pain abdomen
Anorexia
Fever
Chronic diarrhea
Loss of weight
Diarrhea
Vomiting
Constipation
Cough
88
77
68
64
84
18
31
5
57
Signs
Distension of abdomen
Ascites
Peritonitis
Doughy abdomen
Enterocutaneous fistula
Hepatomegaly
Splenomegaly
69
19
39
4
52
21
and vague lump in abdomen accompanied by hepatomegaly and splenomegaly. Evidence of tuberculosis
elsewhere in body should always be looked for.
Diagnosis
The investigations which are needed to establish the
diagnosis can be divided into two categories:
Definitive Diagnosis
Definitive diagnosis is accepted only when acid-fast
bacilli (AFB) are demonstrated in the tissue, or typical
tuberculosis granuloma with caseating necrosis has been
established. However, this is not always possible in
abdominal tuberculosis. Many techniques are now
available which have improved diagnosis. Previous
methods of culture were painstaking and took 6 to 10
weeks to yield results. Rapid methods of culture on
modified culture media are now available which have
vastly improved the yield of AFB. Methods of identification of AFB have also improved a lot. Further, methods
to obtain material from lesions in gastrointestinal tract,
peritoneum and masses in abdomen have also improved.
Some of these techniques are given below (Table 9.10.3).
Investigations
Fine needle aspiration cytology (FNAC) from
palpable mass in abdomen or ultrasound guided
334

TABLE 9.10.3: Definitive diagnosis of
abdominal tuberculosis
Criteria
Demonstration of AFB in lesion/ culture
Tuberculous granuloma with caseating necrosis
Material
Surgical specimen
Fine needle aspiration
Endoscopic biopsy
Peritoneoscopic biopsy
Liver biopsy
Ascitic fluid
Supportive diagnosis
Identification of contact (adult patient)

Mantoux test/Tuberculin test
Radiology (contrast and double contrast meal and enema
techniques), chest and abdomen skiagram
Ultrasound abdomen
CT scan for nodal involvement
Adenosine deaminase (ADA) in ascitic fluid
Serological tests
aspirated material can be used to identify AFB, typical

cell reaction and caseation material and for culture.
It is a safe and quick method of definitive diagnosis.
Upper and lower GI endoscopy has provided an
access to direct visualization of mucosal lesions. At
the same time, biopsy can be obtained from the lesion
under direct vision. With the help of fine needle
threaded through endoscope, aspiration of material
can be obtained from deeper part of the lesion.
Peritoneal biopsy with the Vim-Silverman needle or
under direct vision through peritoneoscope can
provide requisite material for AFB, cytology and
culture.
Ascitic fluid obtained from free or localized collection
is useful for culture and cytology by concentration
methods.
Liver biopsy gives varied changes such as granulomatous hepatitis, miliary tubercules, conglomerate
tubercles, and nonspecific hepatitis, fatty inflammatory cell infiltrate, portal inflammation, portal fibrosis,
Kuppfer cell hyperplasia, tuberculomas, abscesses
and cholangitis in abdominal tuberculosis.
Laparotomy may now be rarely needed and only
when other methods fail. It is indicated when
diagnosis of tuberculosis is strongly being considered,
particularly if subacute obstruction or fistula exist.
Surgical specimen with characteristic gross appear-
ance of hypertrophy, peritoneal and regional lymph

node involvement with caseation are highly
suggestive. Histopathology, demonstration of AFB
and culture of bacilli provide the most accepted
definitive diagnosis.
Supportive Diagnosis
More often than not, diagnosis of abdominal tuberculosis
rests on supportive or circumstantial evidence. These
include:
Mantoux test is likely to be positive (more than 10
10 mm) in 50 to 60 percent cases. Negative test does
not exclude tuberculosis.
Radiology
Skiagram of chest as an evidence of co-existing
pulmonary disease is variable (as low as 6% to a
high of 90%)
Plain skiagram of abdomen may reveal multiple fluid
levels suggestive of subacute intestinal obstruction
(nearly 20%) or calcification in lymph nodes (intraabdominal) or mass shadow of omentum, lymph
nodes single or matted together, etc.
Barium meal with follow-through is very useful to
determine the nature, the site, extent of involvement of GI tract, peritoneum and nodal masses.
Lesions like ulceration, stricture, hypertrophic
segments, malabsorption pattern, matted intestinal coils (indicating peritoneal involvement),
compression or separation of coils due to enlarged
lymph nodes and fistulous tract can be delineated.
This technique of barium contrast study has been
vastly improved by double contrast (provided by
air pushed along-with thin barium). The precision
to pin-point lesions in small intestine has been
greatly enhanced.
Barium enema is indicated when colonic lesions are
suspected. Ulcerations, hypertrophic segments
and strictures can be diagnosed. Double contrast
with air has improved this technique of diagnosis.
In our experience radiological investigations in
clinically suspected cases, have served as best
supportive evidence of diseases.
Ultrasound and CT scan. CT scan has been useful in
locating pockets of ascites, and outlining typical
appearance of enlarged lymph nodes with radiolucent center indicative of caseation necrosis. MRI is
not of much value.

Adenosine deaminase (ADA) in the peritoneal fluid
in tuberculous peritonitis is raised many folds.
Sensitivity and specificity of this test is 95 to 100
percent and 96 to 98 percent respectively. ADA in
the ascitic fluid is very helpful to differentiate
tuberculous peritonitis from other causes of
peritonitis. Thus, with high clinical index and
judicious employment of relevant tests, in most cases
diagnosis can be made.
To summarise, abdominal tuberculosis is a paucibacillary disease and hence microbial evidence is not
easily available. For a definitive diagnosis, tissue
specimens can be obtained by one of the following
techniques:
i. Fine needle aspiration cytology (FNAC) from
intraabdominal masses which can be done only in
a palpable mass and biopsy can be guided by an
ultrasound or CT. Endoscopic biopsy can be done
of the submucosa.
ii. Ascitic fluid collection for cytology, chemistry and
AFB culture.
iii. AFB culture in the tissue biopsy specimen. Ascites,
and outlining typical appearance of enlarged lymph
nodes with radiolucent center indicative of caseation
necrosis. MRI is of not much value.
iv. Adenosine deaminase (ADA) in the peritoneal fluid.
Complications
The relatively common complications of tuberculous
enteritis include obstruction, fistula formation, perforation with abscess, hemorrhage, enterolithiasis and
traction diverticula. Rarely perforation may occur, with
resultant peritonitis. Early institution of antituberculosis
therapy prevents complications.
Treatment
WHO has prepared guidelines for National Programs
with the objective of effective treatment. Effectiveness
of treatment is determined by two major factors: (i) the
cure rate, and (ii) lower drug resistance. In order to
achieve these objectives, treatment is divided into (a) an
intensive phase to effect prompt bactericidal effect
(b) and a continuation phase to sterilize the lesion of
bacteria to prevent relapse.
Abdominal tuberculosis including peritoneal,
gastrointestinal and nodal involvement has been
included under category 1 by WHO. Category I is
335
2R3H3Z3/4R3H3 (For details refer to the Chapter on

RNTCP).
At times one can use a continuous regimen using the
same drugs. Some pediatricians and pediatric surgeons
still are comfortable using a regimen containing
ethambutol, 2HRZE 4HR. Current information suggests
that 90 percent of patients with enteric tuberculosis, and
even a higher percentage of peritoneal tuberculosis cases
respond to this regimen. Less frequently the continuation
phase may have to be extended for 7-10 months. In
populations with low probability of drug resistance,
initial phase may be managed with three drugs only.
Hepatotoxicity due to drugs should be monitored
with transaminases periodically in first 6 to 8 weeks of
therapy. If hepatotoxicity occurs, both the drugs isoniazid
and rifampicin should be stopped and ethambutol
(15 mg/kg) is given till the time there is complete recovery
of hepatic injury. At this point, INH and rifamipicin can
be restarted. In most cases hepatotoxicity does not recur.
If hepatotoxicity recurs, isoniazid and ethambutol
combination may be used for continuation phase.
Role of Surgery in Abdominal Tuberculosis
The role of surgery is limited to tissue diagnosis and is
needed for management of complications such as
obstruction, perforation, fistula formation or rarely
significant bleeding.
Summary
Abdominal tuberculosis remains significant problem in
the developing world. The clinical manifestation can be
protean and nonspecific and hence diagnosis requires a
high index of suspicion. Only 15 to 20 percent of patients
with abdominal tuberculosis have concominant lung
disease. Treatment of this type of tuberculosis is
essentially by chemotherapy, and only rarely surgical
intervention is required.
BIBLIOGRAPHY
1. Bajpai M, Gupta DK. Abdominal tuberculosis. In Seth V,
Kabra SK (Eds): Essentials of Tuberculosis in Children.
3rd edition. Jaypee Brothers Medical Books Publishers
(P) Ltd. New Delhi 2006;143-56.
2. http://www.pediatriciancall.com 10.2.06
3. Seth V. Revised National Tuberculosis Control Program
(RNTCP) Directly Observed Treatment, in IAP Textbook
of Pediatrics, Ed: Jaypee Brothers Medical Publishers (P)
Ltd. New Delhi 2009;351-58.
336
9.11 Neurotuberculosis
Vimlesh Seth
Neurotuberculosis (tuberculosis of the central nervous
system) is represented by different and possibly
concomitant forms of which the most important are
tuberculous meningitis (TBM) and tuberculoma. It is the
result of complex mechanisms that operate to produce
multifarious changes in all structural and cellular
components of the cerebrum, cerebellum, brainstem and
spinal cord. Considering all ages, TBM is a more frequent
manifestation of neurotuberculosis than brain
tuberculoma.
TUBERCULAR MENINGITIS (TBM)
Introduction
Tuberculous meningitis (TBM) is a potentially curable
disease of the central nervous system. A complete
neurological recovery will depend upon early confirmative laboratory diagnosis along with institution of
appropriate chemotherapy. M.tuberculosis demonstration
by conventional methods is not only less sensitive but
also yields false negative results. TBM was first described
by Robert Whytt in 1769 as dropsy of the brain. Charles
Moorhead, described its pathology in 1847.
Human tuberculosis still remains one of the major
public health problems in most of the developing
countries despite world wide tuberculosis control and
eradication program along with availability of newer
shorter duration diagnostic techniques and therapeutic
modalities. Childhood tuberculosis, a reflection of adult
tuberculosis is a problem with limitation of application
of newer diagnostic techniques due to non-availability
and maintenance of adherence to treatment (short-course
chemotherapy of RNTCP) in India.
Increasing evidence of HIV-infection has added to
the increase in the problem of tuberculosis, equally
applicable to children as in adults. Every year, estimated
eight million new cases are added with 2 million deaths.
TBM is the most important cause of death in children
amongst all types of neurotuberculosis. Inspite of BCG
vaccination and antituberculosis drugs, malnourished
children die of TBM. If they recover they are left with
severe residual sequelae. Though BCG vaccination
reduces the life-threatening complications of childhood
TB, there are newer manifestations of tuberculosis in BCG

vaccinated children.
Neurotuberculosis is a more important problem in
developing countries due to:
I. Ineffective TB control program for adults.
Poor contact tracing in children < 5 years of adult
sputum +ve pulmonary tuberculosis (PTB) and
failure of preventive therapy in this high risk age
group.
Failure of timely treatment of latent tuberculosis
in the age group of < 5 years.
II. Emergence of drug resistant strains.
III. Increasing prevalence of HIV/AIDS.
IV. Overcrowding, poor nutritional status and poverty.
Before HIV, the most important determinants for the
development of tuberculosis meningitis (TBM) were age
and poor nutritional status. HIV predisposes to the
development of TBM among the extrapulmonary
tuberculosis. The risk increase as the CD4 count declines.
Epidemiology
Tuberculous meningitis (TBM) is the most important
cause of death in children amongst all types of
neurotuberculosis. In an autopsy study of 3646 children1
from Mumbai, of the 356 deaths due to all types of
tuberculosis, 190 had TBM without tuberculoma, 32 had
TBM with tuberculoma and 11 had tuberculosis who had
miliary TB with brain edema. In a recent study between
1990 and 1992, deaths due to TBM had come down to
40 percent.
In spite of BCG vaccination and antituberculosis
drugs, malnourished children die of TBM and if they
recover, they have severe residual sequelae. There is no
doubt that BCG vaccination has been effective in
reducing the life-threatening complications of childhood
TB, yet one has to recognize newer manifestations of
tuberculosis in BCG vaccinated children.
Pathology
Mycobacterium tuberculosis is responsible for most
tuberculous infections of the CNS. M.bovis and
M. africanum are the less frequent causative organism.

It is believed that the bacilli reach the CNS by the
hematogenous route secondary to disease elsewhere in
the body. Mycobacteria filter from the blood by lungs,
liver, spleen and bone marrow, while they get trapped
in organs like brain where there is no reticuloendothelial
system.
The classic work of Rich and McCorduck forms the
basis for its current understanding. CNS tuberculosis is
accepted to occur as a three step process.
1. Initially, hematogenous seeding of the meninges
occurs either during the stage of bacteriemia of
primary tuberculous infection or shortly afterwards.
These initial lesions (Richs foci) may be in the
meninges, subpial or subependymal surface of the
brain or the spinal cord.
2. This is followed by a quiescent phase which may last
from few weeks to many decades.
3. In the third step, the mycobacteria in these Richs foci
multiply and then a immune or traumatic stimulus
causes them to rupture resulting in the clinical
manifestations of neurotuberculosis.
Tuberculous meningitis develops when the Richs
focus which has been established in the brain, meninges
or spinal cord during hematogenous dissemination from
primary infection, bursts in the subarachnoid space and
produces generalized meningitis. The pathology is
characterized by exudates specially at the base of the
brain, edema of the brain, infarction due to large or small
vessel obstruction or presence of small or large
tuberculoma in the cerebral hemispheres, cerebellum or
brainstem. The exudate in TBM is predominantly at the
base of the brain as infection spreads in the subarachnoid
space and particularly in basal cisterns. The exudates in
the middle cranial fossa produces obstruction of the basal
cisterns which are glued by the exudate, leading to
hydrocephalus. Apart from the exudate, there is edema
of the brain, affecting white matter more than the gray.
Basal exudates by obstructing the large arteries like
middle cerebral and its branches cause infarction of the
areas of brain supplied by these arteries. Engulfment of
the cranial nerves at the base of the brain by exudates
produces various types of cranial nerve palsies. The
exudates at the base of the brain may track upwards to
subthalamic nucleus with contralateral hemiballismus
or along the Sylvian fissure, involving the middle cerebral
arteries.
337
Classification of Neurotuberculosis (Udani)

Tuberculous meningitis with characteristic CSF
findings
Serous tuberculous meningitis with,
normal CSF
mild increase of proteins and cells but normal
sugar and chloride
Tuberculous encephalopathy without clinical
evidence of meningitis, usually normal CSF
Acute infantile hemiplegia due to ischemic focal
lesion in the brain and perifocal edema or due to
lesion in the internal capsule
Localized meningitis
Localized basal meningitis
Posterior fossa meningitis
Cerebellar syndrome with clinical features of
midline cerebellar syndrome with hemispheric
cerebellar signs
Cerebellar syndrome with hemispheric
cerebellar signs
Mixed type
Isolated spinal tuberculous meningitis (without
cranial meningitis or cerebral involvement)
Tuberculous polyneuritis (Guillain-Barre syndrome),
before, during, or when the child is recovering from
serous TBM (rare)
Tuberculous radiculomyelopathy (not uncommon
and usually associated with TBM)
Tuberculous neuritis (rare)
Tuberculoma
Intracranial, cerebral, cerebeller; single or
multiple; small or large usually with edema
Associated with TBM.
Clinical Features
It will be desirable to describe the clinical features of
classical tuberculous meningitis before various modified
clinical pictures of neurotuberculosis in BCG vaccinated
children are described, as more than 90 percent of infants
have been vaccinated by the year 2000.
Age and Sex Incidence
TBM is commonly seen in the first 5 years of life with
more than 65 percent of the cases belonging to this age
group. TBM is usually more common in males than
females.
338
Clinical Stages of TBM

The three traditional stages of TBM are not sharply
defined, and clinical features often overlap.
First Stage
The first stage symptoms are of nonspecific illnesses.
When symptoms persist or if there is a contact with an
adult whose sputum is positive for AFB, diagnosis should
be suspected. The first stage is known as the stage of
meningeal irritation. The child has fever often with a
typhoid-like temperature, associated with headache,
vomiting, constipation and apathy alternating with
irritability. Often a shrill cry is present when child is
disturbed. Deep tendon reflexes are usually brisk. The
apathy may progress to drowsiness but still the child can
be awakened to take feeds. In infants and young children,
onset may be acute and may simulate pyogenic
meningitis. In older children when onset is subacute,
there may be behavior disturbances, and the child may
mistakenly be referred for psychiatric evaluation.
Second Stage
In stage II, symptoms of cerebral involvement are present
characterized by convulsions, neurological deficits and
cranial nerve palsies, such as squint, disturbances of
vision, facial asymmetry, ptosis and dilated irregular
pupils. Convulsions occur in almost 65 percent of the
cases at some stage of the disease. Paralytic forms include
hemiplegia, monoplegia and at times, spastic quadriplegia. Hemiplegia on one side and hemiballismic
movements on the other side are common. Features of
increased intracranial tension including severe headache,
vomiting and visual disturbances and meningeal signs
may be present. In infants and young children, there is
bulging fontanellae and separation of sutures with
Macewen sign or cracked pot sound on tapping the head.
The child becomes semicomatose and can be aroused
only with difficulty with painful stimuli. Cutaneous
manifestations of autonomic nervous system disturbance
may be present.
Third Stage
Third stage is heralded by deep coma, well-marked
meningeal signs, progressive neurological deficits,
dilated and almost fixed pupils to light. Signs of
brainstem compression may be present with marked
neck retraction, opisthotonous, decorticate and decerebrate spasms. Decerebrate rigidity may appear followed
by spasticity. Child may develop irregular or Biots
breathing. In the terminal stage, pupils are dilated and
fixed. Patient may develop hyperpyrexia of central origin
and may die.
Modified Clinical Pictures of TBM-Usually Seen in
BCG Vaccinated Children
Atypical clinical pictures in vaccinated children are being
observed because of the localization of lesions in
meninges, brain, spinal cord and peripheral nervous
system. This is presumed to be due to presence of
activated T lymphocytes which are lodged in the organ
or the tissue after intradermal BCG vaccination. The
localized lesions in various parts of the brain in a
vaccinated child may be isolated or present with different
combinations of pathological lesions with varied clinical
features. However, as the number of T cells or their
function is not adequate enough to prevent the
complications, they only modify the picture by localization of lesions in various parts of the nervous system
(Table 9.11.1).
It can be appreciated that depending upon the
localized lesion in the meninges or any part of the brain,
spinal cord or peripheral nervous system, the patients
may present with protean clinical manifestations.
Diagnosis
The onset of the disease is generally insidious with a
vague symptomatology that makes the diagnosis
difficult.
Clinical diagnosis of TBM is easy if:
i. There is characteristic clinical presentation
(symptoms and sign of meningial irritation)
ii. Characteristic CSF (cytology and biochemical
changes)
iii. Imaging abnormalities (CT, MRI, and PET).
Confirmation of diagnosis of TBM rests on the
isolation of Mycobacterium tuberculosis. The bacilli are
seldom seen by staining and culture which takes several
weeks and is associated with a low yield. This leads to a
delay in starting treatment for this potentially treatable
disease. Early treatment can reduce the morbidity and
mortality.
The following criteria could prove to be helpful in
early diagnosis of TBM in children.

TABLE 9.11.1: Modified neurotuberculosis in
BCG vaccinated children
A. Localized lesions in the meninges
i. Meningeal tuberculoma
ii. Serous tuberculous meningitis at the base of the brain
which results in severe hydrocephalus, hemiparesis with
or without cranial nerve palsies
iii. Localized meningitis on the superolateral surface of the
brain.
iv. Localized meningitis in the posterior fossa with unilateral
or bilateral cerebellar hemispheric signs or lesions in the
vermis of the cerebellum with signs of disturbance of
equilibrium
v. Isolated or localized spinal tuberculous meningitis with or
without compression of the spinal cord or involvement of
the spinal cord
B. Localized lesions in the brain and spinal cord
i. Internal capsule due to lacunar infarct resulting in
hemiplegia in conscious and alert patients
ii. Thalamic nuclei with or without involvement of adjacent
structures
iii. Basal ganglia, caudate nucleus, putamen and globus
pallidus
iv. Subthalamic nucleus-development of hemiballismic
movements and hemiplegia on the opposite side
v. Optic nerve by the exudate or tuberculoma-primary or
secondary optic atrophy
vi. Aqueduct with dilatation of third and lateral ventricles
vii. Geniculate bodies and/or superior colliculi with impairment
of vision particularly involvement of eye movement like
upward gaze
viii. Brainstem with development of locked in syndrome
ix. Midbrain with cranial nerve palsy particularly 3, 4 and 6
cranial nerves and nucleus and other areas in midbrain
x. Lower part of the brain and medulla with involvement of 7,
8, 9, 10, 11, and 12 cranial nerves.
xi. Lateral columns, spinothalamic tract, posterior columns in
the spinal cord with signs of lateral column involvement
below the site of the lesion, signs of anterior horn cell
damage at the site of lesion and attacks of severe pains
with involvement of sensory tracts, and there may also be
loss of sense of position.
Essential Features
1. Fever for two weeks.
2. Abnormal CSF findings (pleocytosis with more than
20 cells, predominantly lymphocytes (greater than
60%), protein greater than 100 mg percent, sugar less
than 60 percent of the corresponding blood sugar.
Plus any two of the following:
1. Evidence of extraneural tuberculosis
2. Positive (family) history of exposure to a case of
tuberculosis.
339
3. Positive Tuberculin Skin Test (TST) (ITU, PPD)

(>10 mm induration)
Due to nonavailability of ITU of PPD, TST is done by
5TU of PPD.
4. Abnormal CT findings (two or more of the following):
i. Exudates in the basal cysterns or in the Sylvian
fissures.
ii. Hydrocephalus
iii. Infarcts
iv. Gyral enhancement.
Neuroimaging
Skiagram of Skull: Sutural diastasis may be apparent
on radiograph of skull in infants with hydrocephalus.
Computed tomography (CT), magnetic resonance
imaging of head, (MRI) or positron emission
tomography (PET) if available particularly when the
differential diagnosis is between neurocysticercosis
and tuberculosis.
CT scan and MRI are useful both for diagnosis and
monitoring of management of increased intracranial
pressure. CT and MRI have enhanced the diagnostic
accuracy of neurotuberculosis, but they are still not
pathognomonic for the diagnosis of the disease. They
may reveal thickening and intense contrast enhancement
of meninges especially in basilar region.
CT Findings
Thick basilar exudates appear as intensely enhancing
area in the basal cisterns. (spider leg appearance) and in
the sylvian fissures. Ventricular enlargement is present
in a majority of patients. Hydrocephalus is usually of
the communicating type due to blockade at the level of
cisterns. Periventicular ooze suggests high pressure.
Sensitivity of MRI and CECT
Unenhanced MRI scans are relatively less sensitive
than contrast enhanced CT (CECT) in distinction of
diffuse meningitis.
Contrast enhanced MRI is superior to CECT in
detecting diffuse and/or focal meningial granulomatous lesions.
MRI is better than CT in detecting infarcts.
Angiography
The carotid or magnetic resonance angiogram (MRA)
shows changes in the circle of Willis including uniform
340
narrowing of large segments, irregular beaded appearance and complete occlusions. They are secondary either
to vasculitis or mechanical compression by basilar
exudates.
TABLE 9.11.2: Drug regimens used by AIIMS, TRC

(Chennai) and recommended by IAP and RNTCP (DOTS)
Center
Drug regimen
Intensive
phase
Continuation phase
AIIMS, New Delhi
SHRZE
1 HRZE
4-6 HRE
9
12
TRC Chennai
2 SHRZ
10 HE
12
IAP
2 HRZE
10 HRE
12
DOTS (RNTCP)**
2H3R3 Z3E3
4 H3 R3E3 CAT I DOTS

6 months
Molecular Diagnosic Methods

These fall into three categories:
1. Biochemical tests detecting products released as a
result of the host response.
2. Immunological test that detect mycobacterial antigen
or antimycobacterial antibody in the CSF.
3. Molecular biological tests that detect DNA fragments
of the organism.
Electrophysiological Studies
Electroencephalographic abnormalities have been
reported in upto three-fourth of patients with TBM. EEG
abnormalities include diffuse theta to delta waves
slowing (68.7%), intermittent rhythmic delta activity in
frontal region (46.8%), right to left asymmetry (15.6%)
and epileptic form discharges (12.5%). The EEG findings
correlate with the severity of meningitis, the degree of
coma and outcome at three months.
Abnormal brainstem auditory evoked response
(BAER) have been reported in children having impaired
hearing.
TREATMENT
Total
duration
(months)
* IAP Indian Academy of Pediatrics (consensus)

**RNTCP Revised National Tuberculosis Control Program of
Government of India.
TABLE 9.11.3: Recommended doses of drugs as per

Indian Academy of Pediatrics
Drug
Dose (mg/kg)
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
Streptomycin
Prednisone
Daily
Intermittent
5
10
25
20
20
1
15
15
30*
30**
30
* Never < 5 mg/kg, to be rounded to the closest higher dose

** No studies have been reported in children.
Chemotherapy
Drug regimens used for TBM at the All India Institute of
Medical Sciences (New Delhi), TRC Chennai, recommended by Indian Academy of Pediatrics (IAP); and
RNTCP (DOTS), are given in Table 9.11.2:
Tables 9.11.3 and 9.11.4 give the recommended doses
of various antituberculosis drugs.
Supportive Measures
i. Mannitol 20% (Intravenous) 5 ml/kg body weight
followed by 2ml/kg every 6 hourly for two days
Oral glycerol given by nasogastric tube (50% in
2.5% dextrose)
ii. Intravenous fluids/nasogastric feed, vitamin and
mineral supplements.
iii. Antiepileptic drugs, if needed.
TABLE 9.11.4: Suggested pediatric doses of antituberculosis

drugs for intermittent therapy under RNTCP as combipacks
for different weight categories*
Drug
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
Streptomycin
Dosage
(mg/kg)
10-15
10
30-35
30
15
Weight of the child (kg)

6-10
11-17
18-25
26-30
For details see the chapter on

RNTCP
*Currently there are four age categories which are likely to be

increased to five due to operational difficulties encountered in
the program.
Doses used by AIIMS and TRC Chennai are almost similar to
IAP.

Hepatotoxicity
In case of overt toxicity there is pain in abdomen,
vomiting and hepatic enlargement. All hepatotoxic drugs
should be stopped. Patient to be started on ethambutol
and streptomycin. The following flow diagram shows
the management of hepatotoxicity.
Hepatotoxicity
Stop all hepatotoxic drugs
Institute for 7 days streptomycin and ethambutol
341
v. Increased detection rate with the easy availability

of CT and MRI.
Diagnosis
1. Clinical features of raised intracranial tension
2. Focal neurological signs.
3. Intractable epilepsy.
Investigations
CT scan, MRI, PET
PET helps the differential diagnosis better between
cysticercosis and tuberculomas.
Treatment
Repeat AST, ALT
if they are normal or are

showing a declining trend.
Rifampicin 10 mg/kg/day
+ INH 2.5 mg/kg/day for 7 days
Repeat AST, ALT, if normal
Add PZA (30 mg/kg/day)

Increase INH (5 mg/kg/day)
Chemotherapy
Antituberculosis regimen
2 HRZE 10 HR with oral dexamethasone 0.15 mg/
kg/day
6 hourly for 6 to 8 weeks tapered over 2 weeks.
Surgery rarely required
Cerebral Tuberculosis Abscess
It is diagnosed by:
i. Microscopic evidence of pus
ii. Inflammatory reaction in the abscess wall
iii. Demonstration of AFB in the purulent material or
in the abscess wall or positive culture of
M. tuberculosis.
Surgery
Treatment
It has been shown that addition of ventriculo peritoneal

(VP) shunt in children who are in advanced, i.e. IIIrd
stage of TBM only adds to more morbidity as survival
leaves the child with lot of neurological deficits. Hence,
early diagnosis and prevention are more important than
heroic intervention by VP shunt.
Cerebral TB abscess requires surgical excision/ stereotactic aspiration along with chemotherapy in comparison
to tuberculoma which responds to antituberculosis
therapy alone.
Tuberculoma
Intracranial tuberculoma is an important cause of space
occupying lesion in both the developed and developing
countries. The rising incidence of tuberculoma is
attributed to:
i. Emergence of drug resistant strains.
ii. Ineffective TB control program.
iii. Increasing prevalence of HIV infection.
iv. Overcrowding and poor nutritional status.
TUBERCULAR ARACHNOIDITIS
2HRZE10HR is given for one year, surgical intervention
may be required where medical management fails.
TUBERCULAR ENCEPHALOPATHY
Spinal
POTTS spine and POTTS paraplegia.
Non-osseous spinal cord tuberculosis management
is surgical.
Spinal tuberculous meningitis.
342
Diagnosis By MRI
For details of uncommon form of neurotuberculosis, the
reader is referred to Seth and Kabra.
Prevention
BCG does not prevent the development of primary
complex and its local complications, but it helps to reduce
hematogenous spread of infection. Incidence of tuberculous meningitis is 5 to 7 times higher in non-vaccinated
children than in vaccinated ones. As TBM is a complication of primary tuberculosis, prevention of tuberculosis
in children is very important.
BIBLIOGRAPHY
1. Rich MR, McCordock HA. The pathogenesis of tuberculous meningitis. Bull John Hopkins Hosp 1933;52:5-37.
2. Udani PM, Gulati S, Kabra V, Seth R, Seth V. Case studies
in Neurotuberculosis. In: Seth V, Kabra SK (Eds):
Essentials of Tuberculosis in Children, 3rd edn. Jaypee
Brothers Medical Publishers, New Delhi, 2006;228-47.
3. Udani PM, Parthasarathy A. Neurotuberculosis. In
Parthasarathy A (Editor in Chief): Indian Academy of
Pediatrics Text Book, 3rd edn. Jaypee Brothers Medical
Publisher 2006;225-30.
9.11.1 REVISED NATIONAL

TUBERCULOSIS CONTROL
PROGRAM (RNTCP) INCLUDING
DIRECTLY OBSERVED TREATMENT
Vimlesh Seth
Tuberculosis continues to be a major public health
problem. The number of persons infected with tubercle
bacillus worldwide is estimated to be 1.7 billion, of which
1.3 billion live in developing countries. The annual
incidence of new cases of all forms of tuberculosis
(pulmonary and extrapulmonary) worldwide is estimated to be about 8 million, of which about 95 percent live
in developing countries. The total number of tuberculosis
cases at a given time worldwide is 16 to 20 million, of

whom about 8 to 10 million are sputum smear-positive
and highly infectious. In India, more than 40 percent of
adults are infected with tuberculosis. Approximately 1.5
million cases are put on treatment every year and more
than 1000 persons die of tuberculosis everyday in India.
It has been realized that tuberculosis control measures,
if rightly applied with political and administrative
commitment, have the potential to become one of the
most cost-effective health control intervention.
In India the fight against tuberculosis can be
successfully carried out within the framework of
National Tuberculosis Program (NTP). This program is
part of general health plan of the country.
In a comprehensive review of the outcome measures
of the NTP by the World Bank, the World Health
Organization (WHO), and the Government of India
(GOI) in 1992, it was concluded that the desired results
of tuberculosis control were not being achieved and this
culminated in a revision of NTP strategy.
The revised strategy to control tuberculosis was pilottested in 1993 in a population of 2.35 million, and then
extended to 13.85 million populations in 15 states/ Union
Territories (UTs) in the country. With this strategy in
these areas, and quality sputum microscopy, cure rates
doubled as compared to conventional treatment. Thus,
the Revised National Tuberculosis Control Program
(RNTCP) was born with the following salient features:
i. A goal of achieving a cure rate of 85 percent along
with efforts to enhance case finding in order to detect
at least 70 percent of the estimated cases of smearpositive pulmonary tuberculosis.
ii. Involvement of non-governmental organisations
(NGOs), information, education, communication
and improved operational research.
Epidemiological Basis of TB Control Activities
A simple model of pathogenesis of tuberculosis given
below helps in better understanding, the epidemiological
basis of TB.

The major factors that determine the risk of becoming
exposed to the tubercle bacilli include number of
infectious cases in the community, duration of their
infectiousness and the number and nature of interactions
between a case and a susceptible contact per unit time of
infectiousness.
The Revised National TB Control Program
After 1992, despite the National Tuberculosis Control
Program (NTCP) which was in existence since 1962, there
was no appreciable change in the epidemiological
situation in the country.
HIV/AIDS epidemic and the spread of multidrug
resistant TB (MDR-TB) were threatening to further
worsen the situation in India too, due to infection with a
new resistant strain (XDR).
In the light of recommendations and concern
expressed by the Central Health Council, steps were
taken since 1993 to improve the Revised National
Tuberculosis Control Program (RNTCP). In selected
areas with World Bank assistance, RNTCP adopted the
internationally recommended directly observed therapy
short-course (DOTS strategy), an acronym for direct
observed therapy, short-course. On March 24, 1997, the
Director General of the World Health Organization
declared that The DOTS strategy represents the most
important public health breakthough of the decade, in
terms of lives which will be saved. In the revised
strategy, although passive case finding has replaced
active case finding, the responsibility of cure for the
patient has shifted from the patient to the health system.
DOTS is essentially a community-based systematic
strategy which ensures free of cost tuberculosis
treatment and cure, and has been acknowledged as a
breakthrough in our quest to stop tuberculosis.
RNTCP was started on a pilot basis for coverage of 18
million population. High treatment success rate was
observed. A rapid expansion of program began in 1998.
About 775 million population of country has been
covered till 2003. Remaining coverage was planned by
2005. Cure and completion rates of tuberculosis in
children have been above 90 percent under RNTCP, in
contrast to 80 and 70 percent for those outside the
program and 70 percent where the default rates lie
between 21 to 33 percent.
The five fundamental principles of the WHO
recommended DOTS strategies are:
343
i. Effective Political and Administrative Commitment:

Since tuberculosis is the leading infectious cause of
death among adults, which can be cured and the
epidemic reversed to topmost priority, which has
been accorded by the Government of India, must
be continued and expanded at state, district, and
local levels.
ii. Good Quality Diagnosis: Here the case finding is done
primarily by microscopic examination of sputum of
patients attending the health facilities with cough
of 3 weeks duration or more with sputum microscopy using binocular microscopy and quality
reagents. All the microscopists of the designated
microscopy center are extensively trained. The
system also ensures multitier cross-checking and
quality assurance of sputum smear examination.
iii. Good Quality Drugs: This includes regular and
uninterrupted supply of drugs, the drugs being
supplied by the manufacturers to the project sites,
in boxes earmarked for each category of patient,
along with sufficient buffer stocks ensured.
iv. Short-course Chemotherapy given in a Program of DOTS:
This program uses the best anti-TB medications
available. However, unless treatment is taken by
patients, it will fail. This is why, the heart of the
DOTS program is directly observed treatment, in
which a health worker or other trained person, who
is not a family member watches as patient swallows
the anti-TB medicine in their presence. With shortcourse it is easier to prevent drug resistance by using
directly observed treatment, and achieve high cure
rates.
v. Systemic Monitoring and Accountability: The cure rate
and other key indicators are monitored at every level
of the health system to identify areas requiring
intensified supervision. The outcome of the
treatment is systematically recorded at every level
of health system. If any area is not achieving
90 percent sputum conversion rate at the end of
3 months, and 85 percent cure rate, supervision is
intensified.
Another objective of the RNTCP is 70 percent
detection of new sputum smear-positive cases. However,
the target for case detection should only be attempted if
cure rate of already detected patients is more than
85 percent. One should remember to increase the cure rate
before attempting to achieve case detections target.
344
Structure of the Revised National Tuberculosis

Control Program
The RNTCP has a central division, state, district and subdistrict levels, and health units. An additional structure
of the RNTCP is the district tuberculosis control society
(DTCS). DTCS is responsible for monitoring the program
implementation, arranging necessary logistics such as
transport and procuring materials such as laboratory
consumables.
In order to implement the RNTCP, the state tuberculosis headquarters and the state tuberculosis training
and demonstration center are being strengthened. In
addition, tuberculosis units are being established at the
sub-district level, covering a population of approximately
5 lakh. Each tuberculosis unit includes newly created
posts of one senior tuberculosis laboratory supervisor
(STLS). A designated medical officer-tuberculosis control
(MO-TC) is made responsible for all the program
activities at the tuberculosis units level.
Consensus Guidelines of Diagnosis and
Management of Tuberculosis in Children
Before the RNTCP, the national program lacked specific
guidelines for the management of children below 5 years
of age and the emphasis steered towards children in the
age group between 5 to 15 years.
In spite of the inherent difficulties in studying the
epidemiology of tuberculosis in children, because of
nonavailability of sputum, it must be emphasized that
pulmonary primary complex must be diagnosed at the
earliest, irrespective of the BCG status so as to prevent
hematogenous dissemination and its serious lifethreatening manifestation like miliary tuberculosis and
tuberculous meningitis in infants and young children and
cavitatory disease in the adolescent groups.
Preventive Therapy
Asymptomatic children under 6 years of age exposed to
an adult with infectious (smear-positive) tuberculosis
should be given isoniazid (5 mg/kg) for 6 months.
Management of Pediatric TB under RNTCP
Childhood TB is a reflection of the prevalence of sputum
smear-positive pulmonary tuberculosis (PTB) and the
extent of TB infection in the community. Children suffer
from more serious forms of TB and are more likely to die
if not treated properly and in time. It is estimated2 that

globally about 1.5 million new cases of TB occur and
130,000 children die annually due to TB. Due to
difficulties in diagnosis of pediatric TB under field
conditions, reliable data on disease incidence and
prevalence is not available.
Even young children are often found to be AFB smearpositive. Although most pediatric tuberculosis cases are
smear-negative, it is always recommended to obtain three
sputum samples. A positive-smear establishes a firm
diagnosis and is an objective finding to be monitored
during treatment.
In the revised strategy, specific guidelines have been
laid down for the management of tuberculosis in children
and for the childhood contacts of sputum positive
patients.
Diagnosis
Suspected cases of pulmonary tuberculosis shall include
children having fever and or cough for more than
3 weeks, with or without weight loss or no weight gain,
and history of contact with a suspected or a diagnosed
case of active tuberculosis within last 2 years. Children
showing neurological symptoms like irritability, refusal
to feed, headache, vomiting or altered sensorium may
be suspected to have tuberculous meningitis.
The diagnosis of tuberculosis in a child should be
based on continuation of clinical presentation, sputum
examination (whenever possible) chest X-ray (PA view),
Mantoux test with 1TU PPD (RT23, with Tween 80,
positive if induration > 10 mm after 48-72 hours) and
history of contact. PPD would be supplied by CTD to
district headquarters. However, still 5TU (0.1 ml) of PPD
is being used. Existing RNTCP case definitions will be
used for all cases diagnosed. Use of currently available
scoring systems is not recommended for diagnosis of
tuberculosis in children.
Where diagnostic difficulties are faced, the child
should be referred to a pediatrician for further management.
The diagnosis of tuberculosis in children rests largely
on the clinical history, contact history, X-ray chest
evaluation, and the tuberculin test. While the tuberculin
test is helpful in evaluating for tuberculosis in children,
a positive test does not confirm disease and a negative
test does not rule it out. Children (especially below
5 years of age) usually can not expectorate sputum to
345
Figure 9.11.1.1: Diagnostic algorithm for pediatric pulmonary TB
allow a definite diagnosis until they are old enough.

Therefore, the RNTCP recommends that evaluation
of child contacts of sputum positive cases should be
done in consultation of a pediatrician to rule out active
disease and to decide chemoprophyaxis (Fig. 9.11.1.1).
Treatment of Tuberculosis in Children

DOTS is a recommended strategy for treatment of
tuberculosis and all pediatric tuberculosis patients should
be registered under RNTCP. Intermittent short-course
chemotherapy given under direct observation as
346
advocated in the RNTCP, should be used in children. To

assist in calculating required dosage and administration
of antituberculosis drugs in children medication should
be made available in the form of combipacks in patientswise boxes linked to childs weight (Tables 9.11.1.1 and
9.11.1.2).
TABLE 9.11.1.3: Suggested pediatric dosages for

intermittent therapy
Drugs
TABLE 9.11.1.1: The new formulations

to be used in RNTCP
Rifampicin
Isoniazid
Ethambutol
Pyrazinamide
75/150 mg
75/150 mg
200/400 mg
250/500 mg
TABLE 9.11.1.2: The pediatric population is divided into

four weight bands for purpose of treatment
6-10 kgs
11-17 kgs
18-25 kgs
26-30 kgs
To assist in calculating dosages and administration

of anti-TB drugs for children, the medication would be
made available in the form of patient wise-boxes, linked
to the childs weight. The recommended dosages for
children, in mg/kg, are given in Table 9.11.1.3.
Treatment is given according to categories. These
categories must be strictly adhered to (Table 9.11.1.4).
Therapy per dose

(Thrice a week)
(mg/kg)
Isoniazid
10-15
Rifampicin
10
Pyrazinamide
30-35
Streptomycin
15
Ethambutol
30
In patients with TBM on category I treatment, the four

drugs used during the intensive phase should be HRZS
(instead of HRZE). Continuation phase of treatment in
TBM and spinal TB with neurological complications
should be given for 6-7 months, thus extending the total
duration of treatment to 8-9 months. Steroids should be
used initially in hospitalized cases of TBM and TB
pericarditis and reduced gradually over 6-8 weeks. In
all instances, before starting a child on Category II
treatment, she/he should be examined by a Pediatrician
or TB expert, wherever available.
As recommended by WHO, and in view of the
growing evidence that the use of ethambutol in young
children is safe, ethmbutol is to be used as per RNTCP
regimen for all age groups.
TABLE 9.11.1.4: RNTCP treatment categories and regimens for children

Treatment category
Type of patients
Treatment regimen**
IP
CP
Category I
New sputum smear-positive PTB

New Sputum smear-negative PTB,
seriously ill*
New extra-PTB, seriously ill*
2H3R3Z3E3***
4H3R3
Category II
Sputum smear-positive relapse

Sputum smear-positive treatment failure
Sputum smear-positive treatment after default
2H3R3Z3E3S3 +
1H3R3Z3E3
5H3R3E3
Category III
New sputum smear-negative, not seriously ill**

New extra-PTB, not seriously ill**
2H3R3Z3
4H3R3
*In children, seriously ill sputum smear negative PTB includes all forms of sputum smear-negative PTB other than primary complex.
Seriously ill EPTB includes TB meningitis (TBM), disseminated TB, TB pericarditis, TB peritonitis and intestinal TB, bilateral
extensive pleurisly, spinal TB with or without neurological complications, genito-urinary TB, and bone and joint TB.
**Not seriously ill sputum smear negative PTB includes primary complex. Not seriously ill EPTB includes lymph node TB and
unilateral pleural effusion.
***Prefix indicates month and subscript indicates thrice weekly.

DETAILED DESCRIPTION OF TREATMENT
IN EACH CATEGORY
Category I
New cases who are sputum smear-positive, or seriously
ill-patients with smear-negative or extra-pulmonary
disease.
Treatment
In category I the treatment is given in two phases. The
first phase is intensive phase and consists of isoniazid,
rifampicin, pyrazinamide and ethambutol given under
direct observation thrice a week on alternate days and
lasts for 2 months. This is immediately followed by the
second phase, i.e. continuation phase, which consists of 4
months of isoniazid and rifampicin given thrice a week
on alternate days, the first dose every week being directly
observed. If the sputum smear is positive after 2 months
of treatment, the 4 intensive phase drugs are continued
for another 1 month before starting the 4-months
continuation phase. If the sputum smear is positive after
5 or more months of treatment, the patient is declared as
a failure and is placed on CAT II treatment afresh.
In patients with TBM on category I treatment, 4 drugs
used during intensive phase should be HRZS (instead
of HRZE). Continuation phase of treatment in TBM and
spinal tuberculosis with or without neurological
complications should be given for 6 to 7 months,
extending the total duration of treatment to 8 to 9 months.
Steroids should be used initially in hospitalized cases of
TBM and tuberculous pericarditis and reduced gradually
over 6 to 8 weeks. In all instances before starting a child
on category II treatment, the child should be examined
by a pediatrician or tuberculosis expert.
Category II
Category II have retreatment cases including patients
with relapse, failure, treatment after default and
others. Such patients are generally sputum smearpositive.
Treatment
Category II also, the treatment is given in two phases.
The intensive phase consists of two months of isoniazid,
rifampicin, pyrazinamide, ethambutol and streptomycin
all given under direct observation thrice a week on
347
alternate days, followed by one month of isoniazid,

rifampicin, pyrazinamide and ethambutol, all given
under direct observation thrice a week on alternate days.
This is immediately followed by the continuation phase,
which consists of 5 months of isoniazid, rifampicin, and
ethambutol given thrice a week on alternate days. The
first dose of every week being directly observed part of
therapy. If the sputum smear is positive after 3 months
of treatment, the 4 oral intensive phase drugs are
continued for another one month before starting the
5 months continuation phase.
Category III
Caterogy III includes patients who are smear negative
or who have extrapulmonary TB and are not
seriously ill.
Treatment
In category III also, the treatment is given in two phases.
The intensive phase consists of isoniazid, rifampicin, and
pyrazinamide given under direct observation thrice a
week on alternate days and lasts for 2 months. This is
immediately followed by the continuation phase, which
consists of 4 months of isoniazid and rifampicin given
thrice a week on alternate days, the first dose of every
week being directly observed. If the sputum smear is
positive after 2 months of starting the treatment, the
patient is considered a treatment failure and begun afresh
on category II treatment.
Children are rarely sputum smear-positive and thus
generally receive category III treatment. Ethambutol
should not be given to children who are too young to
report reduced vision or have their visual acuity assessed.
Pediatric focused monitoring should be an integral part
of program. As much as possible, follow-up sputum
examination is to be performed at same frequency as in
adults. Clinical/asymptomatic improvement should be
at the end of intensive phase and also at the end of
continuation phase of treatment. Improvement should
be judged by absence of fever or cough, a decrease in
size of lymph nodes and weight gain. Radiological
improvement needs to be assessed by chest X-ray
examination in all smear-negative pulmonary tuberculosis cases at the end treatment (Fig. 9.11.1.2).
348
Figure 9.11.1.2: Clinical monitoring
DOTS is the recommended strategy for

treatment in adults as well as children
All pediatric TB patients should be registered
under RNTCP.
Chemoprophylaxis
Recent infection with tubercle bacilli is one of the risk
factors for disease development. The younger the child,
the higher is the risk of breakdown of infection into
disease. Therefore, child contacts of smear-positive TB
cases, especially those below 6 years of age, must be
screened for symptoms of tuberculosis. In case of
symptoms being present, the diagnostic algorithm of
pediatric TB should be followed and the child should be
given a full course of anti TB treatment if she is diagnosed
as a TB case. For asymptomatic children and those who
are not found to be suffering from TB, chemoprophylaxis
with isoniazid (5 mg per kg body wt) should be administered daily for a period of six months. This is regardless
of the BCG vaccination status.
To ensure that proper preventive chemotherapy is
given to children, enquire (or have the health workers
enquire) from all smear positive tuberculosis patients
under treatment, if they have children under 6 years of
age. Explain to them how children can acquire the
infection which may later develop into tuberculosis.
Make sure that the children are brought to a health unit
for screening.
The DOTS strategy has been rightly accorded the
highest priority in the current WHO promoted Stop TB
campaign since in the present era of multi-drug resistant
tuberculosis (MDR-TB) and the HIV/AIDS, DOTS has
been shown to prevent the emergence of MDR-TB as well
as cure tuberculosis in a HIV reactive patient.

Children have also been identified as a high-risk
group. The administration of BCG as an essential
component of the universal program of immunization
to all newborns and infants up to 9 months of age is
important. Compulsory childhood contact survey
(especially below 5 years of age) of an adult infectious
case must also be made a reality in addition to the use of
standard treatment and preventive therapy protocol.
Finally, tuberculin surveys of children below 5 years of
age must be undertaken, to observe the changing
epidemiology from time to time.
LACUNAE IN THE MANAGEMENT OF PEDIATRIC
TUBERCULOSIS IN RNTCP
Diagnosis
The emphasis being made in diagnosis as follows:
Primary health center (PHC) by a health worker, atleast
an Anganwadi worker of ICDS or auxillary nurse
midwife based on presentation of symptoms in a child
and ideally by doing the clinical evaluation of all children
at least below 6 years in a family having a sputumpositive adult in the household.
It is very important particularly when the malnutrition is still rampant in India and there is added exposure
of children to HIV and AIDS infection, which significantly compromise the immune system of the child
leading to the danger of occurrence of severe degree of
disease with rapid progression due to limitations in the
use of available drugs.
2ND TIER
District Hospital
In the district hospital facilities should be available for
mantoux testing and chest X-ray. However, these
facilities are not freely available. It is unlikely even now
349
to readily procure tuberculin for readily testing of

mantoux test because Guindy Laboratory Chennai does
not have Copenhagen strain of bacillus for making
tuberculin.
In medical colleges, pediatricians in practice and other
doctors taking care of children are using 5TU of PPD
available privately. In the presence of threat of HIV-AIDS,
MDR-TB and already existing malnutrition of various
grades (particularly severe), it is quite pragmatic to use
this PPD. Seemingly there is no harm to use it in the
program, till the Ministry of Health, Government of India
is able to procure PPD for the program.
ACKNOWLEDGEMENTS
The guidelines for management of pediatric tuberculosis
under Revised National Tuberculosis Control Program,
(RNTCP) in India were developed during the national
workshop arranged at LRS Institute of Tuberculosis and
Respiratory Diseases, New Delhi on 6th and 7th Aug,
2003, which was attended by renowned pediatricians
from Indian Academy of Pediatrics (IAP), TB experts,
TB control program managers from central TB Division,
Directorate General of Health Services, Ministry of
Health and Family Welfare and representative from
WHO. The tables and figures in this chapter are
reproduced from the recommendations from the
guidelines for the management of tuberculosis in
pediatrics under RNTCP.
BIBLIOGRAPHY
1.
Chauhan IS, Arora VK. Management of pediatric

tuberculosis under the revised national tuberculosis
control program (Meeting held on 6th and 7th August,
2003) Consensus Statement. Indian J Pediatr 2004;71:
341-3.
2. Seth Vimlesh, Khosla PK, Semwal OP, et al. Visual
evoked response in tuberculosis children on ethambutol
treatment. Indian Pediatric 1991;28:713-7.
350
9.12 Poliomyelitis
Ashok K Gupta
Etiology
The poliovirus is an enterovirus. There are three serotypes: 1, 2 and 3. All three can cause paralysis, although
type 1 causes paralysis most often, type 3 less frequently,
and type 2 rarely. Most epidemics are due to type 1. Cases
of paralysis associated with the vaccine are usually
caused by types 3 and 2. As immunization coverage levels
increase and the incidence of poliomyelitis drops, type 2
is the first serotype to disappear.
Epidemiology
The most common route of transmission is fecal-oral.
Close contacts can also be potentially infected through
pharyngeal secreations. One week after the onset, little
virus remains in the throat but continues to be excreted
in stools for up to 6 to 8 weeks. Cases are most infectious
during the first few days, before and after the onset of
symptoms.
Man is the only reservoir of infection. A long-term
carrier state is not knwon to occur. The half-life of
excreted virus in the sewage in warm climate is only 48
hours and spread of infection through sewage can occur
only during this period. However, given the large
number of inapparent infections, the wild virus can
potentially spread far and wide very quickly, if there is
high population mobility in the districs and states.
The incubation period from exposure to the virus, till
the onset of symptoms is usually 7 to 10 days (range of
4-30 days). The initial illness is followed by a few days
which are relatively free of symptoms before the onset
of paralysis. Fever is present at the time of onset.
Poliomyelitis has a marked seasonal increase from
May to September, with a peak in July-August. The
intensity of the peak has fallen and in areas of low
incidence, polio cases are seen as sporadic cases which
occur at anytime during the year. In the states which have
successfully implemented the pulse polio immunization
such a pattern of sporadic incidence could be expected.
vomiting, and diarrhea. If the later stages of the disease

do not develop, this minor illness is known as abortive
poliomyelitis, which cannot be diagnosed by clinical
criteria alone. With or without a few days of wellbeing,
there follows abrupt onset of major neurological illness.
The patient is anxious, irritable, often sweating, with
fever around 38 to 39C headache, stiffness, and pain in
the neck, trunk, and limbs. Nuchal rigidity and a positive
Kernig sign are present. In about one-third of patients
that reach this stage, the condition resolves in about a
week and is then known as nonparalytic poliomyelitis
that is, aseptic meningitis due to poliovirus. The
remainder progress rapidly to paralysis, which may be
preceded by pain and fasciculations in the muscles to be
affected. Paralysis usually appears during the fever,
rarely afterward, and may be the first sign of poliomyelitis in infants or very young children. It may evolve
rapidly or progress gradually over a week or so. The
pattern of paralysis is variable, typically asymmetrical,
and usually affects the lower limbs more seriously than
other muscles. Bulbar and encephalitic signs may appear.
The paralysis is of lower motorneurone type, flaccid with
absent tendon reflexes. It tends to be more severe,
extensive and possibly progressive, if there was
strenuous physical exercise in the incubation period.
Paralysis may be more severe or localized in a traumatized area, for example, following irritating vaccine
injection, provocation poliomyelitis or recent tonsillectomy, which may provoke severe bulbar paralysis.
Paralysis classically presents as follows.
Spinal Form
Clinical Manifestations
Muscles innervated by spinal nerves are affected by

paralysis, often preceded by diminution or loss of deep
reflexes a few hours before weakness is detectable.
Paralysis is more widespread in early stages because
many temporarily injured anterior horn cells may recover
function. Some muscle groups usually escape serious
damage and slow functional recovery can progress over
many weeks or months. Most commonly affected, in
order of frequency are:
Typically, a minor prodromal illness lasts several days,

with fever, sore throat, anorexia, and occasionally nausea,
In the lower limb

Quadriceps

Tibialis anterior
Peroneal muscle
In the upper limb
Deltoid
Biceps
Triceps
In the trunk
Abdominal muscles
Back
Intercostals
Diaphragm
Respiratory paralysis can cause life-threatening
impairment of ventilation, commonly associated with
involvement of shoulder muscles.
Bulbar Form
This most severe and dangerous form of poliomyelitis
results from damage in the brainstem, particularly the
medulla. Any case of poliomyelitis with usually rapid
and stormy onset and development, drowsiness or
marked apprehension, should be watched for signs of
medullary involvement, which require intensive medical
care; rarely it may progress rapidly to death despite
therapy. The main patterns are as follows:
1. Cranial nerve nuclei involved:
a. III to VII nerve nuclei, with good prognosis and
recovery usual.
b. IX to XII nerve nuclei, with difficulties in
swallowing and clearing the pharynx, where
pooled saliva and mucus can obstruct airways or
be inhaled. Airway clearance and maintenance of
ventilation are essential to preserve life.
2. Respiratory center impaired: Irregularities of rate and
rhythm of breathing may lead to respiratory failure
and sudden collapse.
3. Circulatory center impaired: Hypertension or peripheral
circulatory failure can occur, sometimes with
hyperpyrexia.
Multiple neurological signs may coincide with
hypoxia and hypercapnia from ventilatory dysfunction
and death with acute myocarditis. Encephalitic forms of
poliomyelitis are often combined with bulbar or
bulbospinal features.
In preparalytic and paralytic stages the cerebrospinal
fluid is usually clear, rarely hazy, with increased cells
(10-500/mm3), predominantly lymphocytic. The cell
count is maximal in the preparalytic stage, when
351
polymorphs transiently predominate. A raised protein

level persists for some time after the cell count has
reverted to normal, an example of albumino-cytological
dissociation to be distinguished from the Guillain-Barre
syndrome.
Clinical Management
For the abortive form, simple analgesics, sedatives, an
attractive diet, and bedrest until the childs temperature
is normal for several days, suffice. Avoidance of exertion
for the ensuing 2 weeks is desirable, and there should be
a careful neuromusculoskeletal examination 2 months
later, to detect any minor involvement.
Treatment for the nonparalytic form is similar to that
for the abortive form, relief being indicated in particular
for the discomfort of muscle tightness and spasm of the
neck, trunk, and extremities. Analgesics are more
effective when combined with the application of hot
packs for 15-30 minutes every 2-4 hours. Hot tub baths
are sometimes useful. A firm bed is desirable and can be
improvized at home by placing table leaves or a sheet of
plywood beneath the mattress. A footboard should be
used to keep the feet at right angle with the legs. Muscular
discomfort and spasm may continue for some weeks,
even in the nonparalytic form, necessitating hot packs
and gentle physical therapy. Such patients should also
be carefully examined 2 months after apparent recovery
to detect minor residuals that might cause postural
problems in later years.
Management of paralytic poliomyelitis and other
cases of acute flaccid paralysis in the acute phase is
symptomatic. The child needs rest and care to ensure
that there is no stress on the affected muscles. Care is
also required to see that the child does not get secondary
infections. Massage and injections during this period are
contraindicated.
Uncomplicated cases of single lower limb or both
lower limbs and trunk involvement can be treated at
home. However, if poliomyelitis is suspected, such
children should be examined by a physician as early as
possible, to confirm diagnosis, rule out high-risk
factors, such as early respiratory involvement and for
proper advice to parents on the care of the child at home.
Treatment of the Acute Phase of Paralytic
Poliomyelitis (Table 9.12.1)
Complete bedrest
Correct positioning of affected limb(s)
352

TABLE 9.12.1: Differential diagnosis of paralytic poliomyelitis
Signs and symptoms
Polio
GBS
Transverse myelitis
Traumatic neuritis
Progression of paralysis
< 4 days, maximum 7
From hours to 20 days
Fever onset
Present
Absent
Absent
Variable
Flaccidity
Acute, asymmetrical,
proximal
Acute, symmetrical,
distal
Acute, lower limbs,

symmetrical
one limb
Muscle tone
Diminished
Diminished
Diminished in
lower limbs
Diminished in limb
DTRs
Decreased or absent
Absent
Absent in lower limbs
Decreased or absent
Sensation
Severe myalgia and

backache
Cramps, tingling,
hyperesthesia
Anesthesia of lower
limbs
Pain in gluteal region
Cranial nerve
Only when bulbar and

bulbospinal
Often present
Absent
Absent
Decreased respirations
Only when bulbar and

bulbospinal
In severe cases
Absent
Absent
CSF: WBCs
Protein
High WBCs
Normal of slightly
increased
< 10 WBCs
Normal
Normal or slightly
elevated
Normal
Normal
Bladder dysfunction
Transient retention
Sometimes
Present
Absent
Conduction velocity
3 weeks
Normal, then slightly

decreased
Abnormal, demyelination
Normal
Abnormal in sciatic
nerve
EMG-3 weeks
Abnormal
Normal
Normal
Normal
Sequelae
Severe, asymmetrical
atrophy
Absent or minimal
Moderate atrophy
Peroneal atrophy
Passive movements of the joints

Warm water fomentation
Symptomatic treatment for fever and pain
No massage or intramuscular injections
Report immediately, if there is progression of
paralysis.
Complete bedrest is essential during the acute phase.
There should not be any stress on the muscles involved.
The mother or other persons caring for the child should
frequently change the posture of the child in bed, every
two to three hours. The child should be placed on the
stomach for short periods each day, to avoid the risk of
pneumonia.
The limb should be placed in the optimum position
for relaxation of the paralyzed muslces. The affected
limbs can be positioned with pillows or rolled towels.
The recommended positions are: hip-slight flexion; knee5 degress flexion; foot-90 degress support against the sole
of the foot. Place rolled towels to prevent external
rotation. Rolled towels should also be placed under the
knee for positioning of hips and knees. Joints and
paralyzed muslces should be moved passively gently

through full range of motion of prevent contractures.
Such movements should be done for 10 minutes, two to
three times a day. The movements should involve all
joints of the affected limb. The movement should be
within the range of pain. Fomentation using hot packs
with soaked towels wrapped around the affected parts
for 10 minutes, two to three times, daily, should be started
as soon as possible, and continued up to six weeks after
onset of paralysis.
There should be no restriction on diet and normal
food may be given to the child, if she/he accepts.
Children may experience constipation during this period.
Transient urine retention may be noted which may be
relieved by alternate hot and cold compresses over the
suprapubic region. However, if constipation lasts for 3
days or if there is no urine for 24 hours, such children
should be immediately brought to a hospital.
In 2 to 20 percent of the cases, the outcome may be
fatal due to involvement of muscles affecting vital
functions, especially respiration. If the child shows any

respiratory distress; if the paralysis is progressing and
cases of upper limb involvement in the first week of
illness should preferably be hospitalized. Indications for
referral to the hospital are listed below.
Indications for Hospitalization
Progression of paralysis
Respiratory distress
Bulbar involvement
Paralysis of upper limbs of < 3 days
Marked drowsiness
Other complications.
As the acute phase of illness subsides and recovery
of strength begins, the emphasis shifts to active rather
than passive movements and a vigorous program of
physical therapy is initiated to regain muscle power.
Management of the recovery phase begins with a careful
assessment and recording of muscle power of the sick
muscle groups to serve as a baseline. The degree of
recovery ranges from minimal to complete. Maximum
recovery of the affected muscles takes place in the first
six months, but slow recovery continues up to two years.
Physical therapy is necessary to prevent deformities and
contractures due to muscle imbalance or improper
posture. Physical therapy under a qualified physiotherapist is important for regaining muscle power and
rehabilitation of the child.
Complications
Paralytic Poliomyelitis
It may result from single or multiple superficial intestinal
erosions; perforation is rare. Acute gastric dilatation may
occur abruptly during the acute or convalescent stage,
causing further embarrassment of respiration; immediate
gastric aspiration and external applications of ice bags
are indicated. Mild hypertension of a few days or weeks
duration is common in the acute stage, probably related
to lesions of the vasoregulatory centers in the medulla
and especially to underventilation. In the later stages,
because of immobilization, hypertension may occur
along with hypercalcemia, nephrocalcinosis, and
vascular lesions. Dimness of vision, headache, and a
light-headed feeling in association with hypertension,
should be regarded as premonitory of a frank convulsion.
Cardiac irregularities are uncommon, but electrocardiographic abnormalities suggesting myocarditis are
353
not rare. Acute pulmonary edema occurs accasionally,

particularly in patients with arterial hyper hypertension.
Pulmonary embolism is uncommon despite the immobilization and results in hypercalciuria, which in turn
predisposes to calculi, especially when urinary stasis and
infection are present. A high fluid intake is the only
effective prophylactic measure. The patient shoud be
mobilized as much and as early as possible.
Virus Isolation
Stool specimen culture for purposes of isolation of wild
poliovirus is by far the best diagnostic test. Virus usually
can be found in the faeces from 72 hours prior to onset of
paralysis and up to 6 weeks or more after infection, with
the highest probability of virus isolation during the first
2 weeks, after onset of paralysis.
Strategies for Polio Eradication
Simultaneous administration of OPV to all suspectable
infants and children interferes with the circulation of wild
polio virus in the community. It is therefore important
to ensure complete coverage with OPV during National
Immunization days so that no wild polio virus remains
in the circulation in the environment.
Polio eradication is defined as nil cases of paralytic
polio by wild polio virus in last 3 calendar years along
with absence of wild polio virus in the community, when
excellent clinical and virological surveillance exists and
the coverage of routine OPV is more than 80 percent.
Polio elimination is defined as nil cases of paralytic
poliomyelitis by wild polio virus in one calendar years
with other criteria being the same as in eradication.
Conduct Pulse Polio Immunization days every year
for 3 to 4 years or until poliomyelitis is eradicated.
Sustain high levels immunization coverage through
the routine delivery systems.
Monitoring of OPV coverage at the district level.
Improved surveillance capable of detecting all cases
of acute flaccid paralysis due to polio and nonpolio
etiology.
Rapid case investigation, including the collection of
stool samples for virus isolation.
Follow-up of all cases of acute flaccid paralysis, at 60
days to check for residual paralysis.
Outbreak control for cases confirmed or suspected to
be poliomyelitis to stop transmission.
354
9.12.1 DIFFERENTIAL DIAGNOSIS OF

ACUTE FLACCID PARALYSIS
AD Tewari
Acute flaccid paralysis (AFP) implies paralysis of acute
onset, i.e. less than 4 weeks and affected limb or limbs
are flaccid, i.e. floppy or limp. Tone is diminished as
evidenced by palpation or passive movement of joints.
Deep tendon reflexes are diminished or absent but
sensation is not affected.
Case Definition
A case of AFP is defined as any child aged less than 15
years who has acute onset of flaccid paralysis for which
no obvious cause (such as severe trauma or electrolyte
imbalances) is found, or paralytic illness in a person of
any age in which polio is suspected.
This is the definition taken for surveillance and
should be capable of detecting all cases of AFP due to
polio and non-polio etiology. All cases of AFP, regardless of age should be reported and investigated as
poliomyelitis. Occasionally, poliomyelitis may occur in
older children, therefore, AFP surveillance must focus
on children aged less than 15 years. A high sensitivity of
AFP reporting will ensure that all cases of paralytic
poliomyelitis are detected, reported and investigated,
resulting in preventive control measures to interrupt
transmission of disease.
Experience in other parts of world indicates that at
least 1 case of AFP occurs per year for every 100,000
population of children aged less than 15 years. This is
referred to as background rate of AFP among children and
is accounted for by non-polio causes of AFP, such as
Guillain-Barr syndrome, transverse myelitis, traumatic
neuritis, etc. regardless of whether acute poliomyelitis
exists in the community.
Based on the estimated populations of children aged
less than 15 years, the number of expected AFP cases
that should be detected and reported in each state,
regardless of whether polio is endemic should be
calculated.
The goal of AFP surveillance in India is to have all
states reporting AFP rates of at least 1 case per year per
100,000 population of children aged less than 15 years.
This would ensure adequacy of surveillance.
Figure 9.12.1.1: Virological AFB
Figure 9.12.1.2: Clinical AFB
If AFP rates reported are less than the calculated

figures, then this would suggest that surveillance is not
sensitive to detect all cases of paralytic poliomyelitis, thus
providing regular monitoring of the system.
Classification of AFPPolio vs Non-polio
All AFP cases should be classified as polio or non-polio
based on isolation of virus in the stool specimens (Fig.
9.12.1.1). But for implementing AFP surveillance, a
clinical classification as indicated below must be used so
that true epidemiologic data are collected (Fig. 9.12.1.2).
For this purpose, main causes of AFP include
poliomyelitis, Guillain-Barr syndrome, transverse
myelitis, and traumatic neuritis. They are to be taken into
account first, and then, followed by other causes of
paralysis.
Causes of AFP The main causes and differential
diagnosis of AFP are depicted in Table 9.12.1.1.
355
TABLE 9.12.1.1: The main causes and differential diagnosis of AFP

Polio
GBS
Traumatic neuritis
Transverse myelitis
Etiology
Polio virus type I, II

and III and other
enteroviruses
Likely delayed
hypersensitivityimmunologic
Trauma
Usually unknown;
multiple viruses
Onset of
paralysis
24 to 48 hours
Few hours to ten

days
Few hours to four

days
Few hours to four

days
Fever at onset
High. Always
present at onset of
flaccid paralysis,
disappears later
Not common
Commonly present
before, during and
after flaccid paralysis
Rarely present
Flaccid paralysis
principally proximal
Generally acute,
symmetrical and distal
Asymmetrical, acute,
and affecting only one
limb
Acute, symmetrical,
usually involving lower
limbs
Muscle tone
Reduced or absent in
the affected limb
Global hypotonia
Reduced or absent in
the affected limb
Hypotonia in lower
limbs
Deep tendon
reflexes
Decreased or absent
Globally absent
Decreased to absent
Absent in lower limbs

early, hyper-reflexia late
Sensation
Severe myalgia,
backache
Cramps, tingling,
hypoesthesia of
palms and soles
Pain in gluteus,
hypothermia
Anesthesia of lower
limbs with sensory level
Cranial nerve
involvement
Only when bulbar/

bulbospinal
involvement is
present
Often present,
Miller-Fisher
syndrome
Absent
Absent
Respiratory
insufficiency
Only when bulbar/

bulbospinal
involvement is
present
In severe cases
Absent
Absent
Autonomic signs
and symptoms
Dysautonomia
Frequent blood pressure

alterations, sweating,
blushing and body
temperature fluctuations
Rare
Hypothermia in
affected limb
CSF: WBCs
Protein
High WBCs
Normal or slightly
elevated
less than 10 WBCs

High
Normal
Normal
Normal
Normal or slightly
elevated
Bladder
dysfunction
Absent
Transient
Never
Present
Nerve conduction
values at third week
Anterior horn cell

disease (normal during
the first two weeks)
Abnormal demyelination
Abnormal, suggestive
of axonal damage
Normal or abnormal.
No diagnostic value
EMG at three
weeks
Abnormal
Normal, depending
upon recovery
Normal, depending
upon recovery
Normal
Sequelae at
three months,
and up to a year
Severe, asymmetrical
atrophy, skeletal
deformities
developing later
Symmetrical atrophy
of distal muscles
Moderate atrophy, only

in affected lower limb
Flaccid diplegia,
atrophy after years
Source: Adapted from Field Guide, Ministry of Health and Family Welfare, New Delhi
356
Paralytic Poliomyelitis
Refer to Page 352 Ch 9.12, Table 9.12.1.
Guillain-Barr Syndrome
Transverse Myelitis
Traumatic Neuritis
It is caused by injury to sciatic nerve by injection in
gluteal region, leading to paralysis of lower extremity.
Injection is given for the preexisting febrile illness.
Paralysis is acute and onset occurs within hour to
5 days usually accompanied by pain. Muscle tone is
reduced or absent in the affected limb. Power at hip and
knee is normal. Child walks with footdrop. Knee jerk is
present, but ankle jerk is absent or diminished. Pain
sensation in gluteal region or along with the affected leg
can be diminished. Atrophy may appear 40 to 60 days
later. CSF examination is normal. Electromyography is
abnormal after 3 weeks. Management is rehabilitation,
surgical if indicated.
Prognosis
Atrophy does not reach the same degree as seen in polio.
Differences in calf circumference usually do not exceed
0.15 to 1.5 cm. Child gradually recovers with physiotherapy in 3 to 9 months.
Death occurs due to respiratory muscle failure and

cardiac arrest.
TreatmentIntravenous potassium.
Peripheral Neuropathies
They are caused by:
Drugs
Metabolic defects (diabetes)
Toxins (lipid solvents and fish toxins)
Organophosphate pesticides
Heavy metals (lead)
Hereditary disease (Charcot-Marie-Tooth)
Postdiphtheritic paralysis.
Pseudoparalysis
Nonspecific toxic synovitis
Low-grade fever for several days
Unilateral limp
Hip or knee joints are commonly affected
Swelling of the joint, accompanied with painful
movements.
Scurvy
Age group: 6 months to 2 years

Gradual onset
History of irritability, generalized tenderness
Frog like position of legs, due to pain
Spongy swelling of gums
X-ray knee is characteristic (white line, pencil line
cortex, zone of degeneration).
Other Differential Diagnosis

Non-Polio Enteroviruses
Non-polio enteroviruses are known to cause AFP.

They are coxsackie A virus, coxsackie B virus and
Echo virus, enteroviruses types 70 and 71, and
mumps. Complete recovery occurs in most of the
cases. In some cases, sequelae may resemble paralysis caused by wild poliovirus.
Hypokalemia
History of diarrhea and vomiting for few days prior

to onset of paralysis.
Toxic, irritable.
Weakness affects the limbs first, followed by trunk
and respiratory muscles.
Neckdrop is a usual feature.
Congenital Syphilitic Osteochondritis

Found in early infancy.
Osteochondritis is painful, causing pseudoparalysis.
Diagnosis is by X-ray wrist, elbow, knee, ankle,
showing features of osteochondritis.
The differential diagnosis of AFP is quite extensive.
The clinical must be fully aware of other causes of AFP,
so that he neither misses the diagnosis nor he over
diagnoses polio. The importance of a 60 days follow-up
and stool for viral culture is a paramount.
SURVEILLANCE OF AFP (Fig. 9.12.1.3)

Surveillance means data collection for action. Surveillance is carried out for all cases of acute flaccid paralysis, not just for poliomyelitis. The surveillance data
357
Figure 9.12.1.3: Sequence of action to be taken after detecting a case of AFP
collected and documented must support the principle

that, if polio cases had occurred, they would have been
detected, reported and investigated in an expeditious
manner. The surveillance is critical for achieving the
goal of polio eradication, which is defined as the absence
of clinical cases of poliomyelitis for at least 3 years and
the absence of detectable wild polio-viruses from
communities.
Stool Sample
Two stool specimens should be collected at an interval
of 24 to 48 hours apart and within 14 days of onset of
paralysis. However, when AFP cases are seen late (i.e.
greater than 2 weeks after paralysis onset/stool
specimen may be collected up to 60 days after onset of
paralysis).
The specimen should be placed in a clean container
such as wide mouth plastic or glass bottle with screw on
cap. It need not be autoclaved, but should be cleaned.
At least one thumb sized 8 gm of stool is required.
Stool sample should be adequate and in good condition
accompanied by all details as required by laboratories
(the sample is to be sent to WHO accredited laboratories).
The Ministry of Health has sponsored the formation of a

network of laboratories some of which are located at:
Sanjay Gandhi Postgraduate Institute, Lucknow
National Institute of Communicable Diseases, New
Delhi
ERC, Mumbai
NIV, Bengaluru
BJMC, Ahmedabad
SI, Kolkata
Enterovirus Research Institute, Kasauli
Pasteur Institute of India, Coonoor
King Institute of Preventive Medicine, Chennai and
others are being developed at various places.
Stool samples should be stored in the refrigerator or
any container that can maintain a temperature below 8C,
till they are reached to the laboratory. A vaccine carrier
with frozen ice packs is used for this purpose.
This vaccine carrier should never be used to transport vaccine. Throughout transport, specimen must be
packed to maintain temperature below 8C.
Action
Once a case of AFP has been reported, the following
measures are to be taken:
358
1. All reported cases should be investigated by District

Immunization Officer (DIO) as per the case
investigation form, within 48 hours after notification
by a reporting unit (Fig. 9.12.1.3). A reporting unit
means a center where paralytic cases are brought for
diagnosis, treatment or rehabilitation. The DIO
should send the copy to the state headquarter.
2. The District Immunization Officer should not wait
for laboratory result to conduct immunization. The
decision should be made on the spot, regardless of
whether the laboratory results are available or not.
The DIO should initiate appropriate action for
outbreak response immunization as and when
indicated.
3. The DIO must revisit every case of AFP 60 days after
the onset of paralysis, to confirm the presence or
absence of residual paralaysis. The minimum level
of residual weakness can usually be detected by the
measurements of arm or midthigh circumference as
well as by skinfolds on medial aspect of the thighs.
4. The DIO should take part in active surveillance by
regularly visiting the reporting units and private
practitioners. All health workers, Aanganwadi
workers, traditional birth attendants must be
encouraged to report AFP cases immediately to the
nearest primary health center. The medical officer
must in turn immediately inform the DIO.
5. To strengthen the surveillance system, a Surveillance
Medical Officer (SMO) has been appointed under the
National Polio Surveillance Project whose main task
is to supervise the work of polio related activities in
that district and to act in accordance with the
directions of project from time to time.
Besides medical college hospital, specialized
pediatric hospital, district hospital have been named
as reporting unit (RU). Very popular pediatrician and
quack are made informers. All health service
providers (to whom any of the AFP case have visited
in the past 2 years) are part of network.
If any deficiency is detected, the expansion of
reporting network should be important part of
monthly action plan of the surveillance medical
officer. Efforts should be made to recruit them as
quickly as possible. Active case search (ACS) will be
the most important activity in 2004. The SMO is to
ensure this action by visiting all the department/
unit/wards including medicine, pediatrics, neurology, casualty, emergency, ICU, etc. seeking and
searching all the registers at these places. The SMO is
to meet all the key doctors, including unit heads,

searching the medical record section, asking resident
doctors, nurses and paramedical staff. Telephonic
contacts with RU/informers should be maintained
to whom a visit is not planned that week by the SMO.
6. The progress made: From approximately more than 3.5
lacs cases of polio virus from 125 countries across five
contingents in 1988 to only 677 cases in 2003 (Data as
of 13 January 2004) confined to only five key hot spots
in six endemic countries representing a greater than
99 percent reduction in number of wild poliovirus
the progress made by the eradication initiative is
indeed awesome.
i. The Milestones: 1991Last case of polio in the
Americas (Peru), 1997Last case of polio in
Western Pacific (Cambodia), 1998Last case of
polio in Europe (Turkey). The Americas, Europe,
and Western Pacific regions of the World Health
Organization were certified polio-free in 1994,
2000 and 2002 respectively. More than three
billion people now live in 134 countries and
territories certified polio-free.
ii. The Current Status: Poliovirus is more geographically restricted than every before in
history. Only six countries remain polioendemic.
More than 75 percent of all polio cases
worldwide linked to just five key polio cases
worldwide linked to just five key polio hot spots
within these countries: Kano (Nigeria), Uttar
Pradesh and Bihar (India) and Sindh and North
West Frontier Province (Pakistan).
Importations of poliovirus from endemic to
polio-free areas threaten to derial efforts to
contain the virus. In the 2002-2003 period, for
the first time in history, more countries suffered
polio cases due to importations than were
themselves endemic for the disease.
In 2004, the world has a onetime opportunity to
make good on this global investment by ending
transmission of poliovirus, now and forever. This
only has become possible because of effective
surveillance.
iii. AFP-Surveillance: The country is having an
effective, widely distributed network of an
efficient surveillance system for the very first
time in its history, managed by National Polio
Surveillance Project (Government of India and
WHO). Right now, the country is having a
network of 6 Regional Coordinators (RC), 18

Subregional Coordinators (SRC), and 223
Surveillance Medical Officers (SMOs) spread
over all the nooks and corners of the country.
There are very few vacant posts lying to be filled
and the network is more concentrated in North
Indian states.
iv. Number of Reporting Units (RU) and Informers:
Number of reporting units were 9127 in 2003,
an increase of 2 percent from the last years
number of 8935. However, the numbers of
informers have been increased substantially this
year and their number has gone up from 6952 in
2002 to 9763 this year a 40 percent increase in
their recruitment.
v. All India Non-AFP rates: The whole country
barring few small states is maintaining a healthy
non-polio AFP rate of greater than 1 case per
100,000 population less than 15 years of age. The
exact year-wise figures are provided below:
1.74 in 2003,
1.87 in 2002,
1.76 in 2001,
1.99 in 2000,
1.83 in 1999.
Strengthening of surveillance system to a
level to detect all cases of AFP in children under
15 years of age, is an important element of polio
eradication strategy. The clinicians have an
important role to play in polio eradication efforts,
by detecting AFP, diagnosing the cause of paralysis, management of the cases and timely notification to public health authorities.
BIBLIOGRAPHY
1. Acute flaccid paralysis. IAP Journal of Practical Pediatrics
1997;221-6.
2. Conclusions and Recommendations. The Ninth Meeting
of India Expert Advisory Group for Polio Eradication,
New Delhi, India, November, 2003;18-19.
3. Polio eradications and AFP surveillance, WHO Bulletin,
1997.
4. Surveillance of Acute Flaccid Paralysis Field Guide, Pub.
By MCH division. Department of Family Welfare
Ministry of Health and Family Welfare, 2000.
9.12.2 NATIONAL IMMUNIZATION DAYS

(NIDs) AS A VITAL COMPONENT
OF ERADICATION STRATEGY
Vipin M Vashishtha, Naveen Thacker
In May 1988, the World Health Assembly committed the
member nations of the World Health Organization
359
(WHO) to achieving the goal of global eradication of

poliomyelitis. The polio eradication initiative (PEI) is a
global collaborative effort. WHO, UNICEF, Rotary
International, the US Centers for Disease Control and
Prevention (CDC), and a number of national governments and non-governmental organizations (NGO) are
strongly committed to the initiative. Their generous
financial and technical support has been critical in
achieving the significant progress made to date.
The original targets of GPEI when the initiative was
undertaken in 1988 were:
No cases of clinical poliomyelitis associated with wild
poliovirus, and
No WPV found world wide (including in sewage or
drinking water) despite intensive efforts to do so.
Since than various elaborative modifications were
made to final goal and the most recent published goal is
to ensure
that poliovirus transmission is interrupted globally
through coordinated national and international
action;
that the full humanitarian and economic benefits of
eradication are realized;
that the lessons and infrastructure from its implementation are utilized in the strengthening of health
systems and control of other important diseases.
The new strategic plan has identified four key
objectives and milestones:
1. Interruption of WPV transmission.
2. Achieving certification of Global Polio Eradication.
3. Developing products for the Global OPV Cessation
Phase.
4. Mainstreaming the Global Polio Eradication
Initiative.
The primary strategies for achieving these goals and
objectives are:
1. Attaining high routine immunization.
2. Supplementary Immunization Activities (SIAs)
including NIDs and SNIDs.
3. Surveillance of acute flaccid paralysis (AFP).
4. Mopping-up immunization.
Attaining High Routine Immunization
Immunize every child aged < 1 year with at least 3 doses
of oral poliovirus vaccine (OPV). Paralytic polio can be
caused by any of 3 closely-related strains (serotypes) of
poliovirus. Trivalent OPV (OPV3) provides immunity
360
against all 3 types. Three routine OPV doses should be

received by infants at ages 6, 10 and 14 weeks.
National Immunization Days (NIDs)
Conduct pulse polio immunization (PPI) program by
providing additional OPV doses to every child aged
< 5 years at intervals of 4-6 weeks.
Surveillance of Acute Flaccid Paralysis (AFP)
To identify all reservoirs of wild poliovirus transmission.
This includes AFP case investigation and laboratory
investigation of stool specimens collected from AFP
cases, which are tested for polioviruses in specialized
laboratories.
Mopping-up Immunization
When poliovirus transmission has been reduced to
well-defined and focal geographic areas, intensive houseto-house, child-to-child immunization campaigns are
conducted over a period of days to break the final chains
of virus transmission.
Experience in several of the worlds WHO regions,
where polio has been eliminated, has demonstrated that
the recommended strategies are effective and that global
eradication of polio is feasible.
SUPPLEMENTARY IMMUNIZATION ACTIVITIES
(SIAS): NIDS AND SNIDS
The second part of the four-pronged strategy involves
mass immunization campaigns, known as Supplementary Immunization Activities (SIAs). This includes
both National Immunization Days (NIDs) and Subnational Immunization Days (SNIDs). This mass activity
is also popularly known as Pulse Polio Immunization
(PPI). These supplementary immunization rounds are
intended to complement - not replace - routine immunization. The aim of mass campaigns is to interrupt
circulation of poliovirus by immunizing every child
under 5 years of age with two doses of OPV, regardless
of previous immunization status.
Aims of NIDs/SNIDs
The aim of NIDs/PPI is to flood the community with
OPV within a very short period of time, thereby
interrupting transmission of virus throughout the
community. Intensification of the PPI programme is
accomplished by the addition of extra immunization

rounds, adding a house-to-house search and vaccinate
component in addition to providing vaccine at a fixed
post. The number of PPI rounds conducted during any
particular year is determined by the extent of poliovirus
transmission in the country. In recent years, several
rounds have been conducted throughout the year
especially in the northern states of Uttar Pradesh and
Bihar, which have carried a heavier burden of poliovirusin an attempt to break the last chains of transmission.4
Intensification of PPI requires meticulous program
planning, intensive supervision and monitoring and
extensive social mobilization.
In 2003 for example, 415 million children under five
years were immunized during National Immunization
Days in 55 countries using over 2,2 billion doses of oral
polio vaccine (OPV).
The idea is to catch children who are either not
immunized, or only partially protected, and to boost
immunity in those who have been immunized. This way,
every child in the most susceptible age group is protected
against polio at the same time - instantly depriving the
virus of the fertile seedbed on which its survival depends.
NIDs are conducted in two rounds, one month apart.
Because OPV does not require a needle and syringe,
volunteers with minimal training can serve as vaccinators, increasing the number of vaccinators well beyond
the existing staff of a countrys Ministry of Health. For
example, a recent NID in India deployed two million
volunteers to immunize over 150 million children in just
a few days.
Three to five years of NIDs are usually required to
eradicate polio, but some countries require more time,
especially those where routine immunization coverage
is low. NIDs are normally conducted during the cool,
dry season because logistics are simplified, immunological response to OPV is improved and the potential
damage to heat-sensitive OPV is reduced. For last many
years, NIDs are usually conducted during months of
January and February in India.
Sub-national Immunization Days (SNIDs)
As the name implies, in this activity instead of covering
entire country, only few states/large geographical areas
are included for mass immunization. Rest all other
components remain the same. These rounds are
conducted year round contrary to cool months for NIDs,

depending upon the epidemiology of wild polio viruses.
Since, localization of wild virus in few endemic states in
India, these campaigns have now being used more
frequently and it is not unusual to have even 6 SNIDs
during a single calendar year.
Synchronized NIDs
As the wild poliovirus doesnt distinguish between
borders, neighboring countries are increasingly coordinating, or synchronizing their NIDs. This ensures
children crossing borders for any reason are identified
and immunized. Coordinated planning also allows
health teams to cross borders themselves, to immunize
children on an island which may be less accessible from
the other side, or those in pockets of territory otherwise
isolated by rivers, mountains or other impassable terrain.
This approach was first used between countries of
Eastern Europe and Central Asia, in a successful
campaign called Operation MECACAR. Another
massive synchronized campaign amongst 17 west and
central African countries in autumn 2000 dramatically
reduced wild poliovirus transmission by immunizing 76
million children in the same week. In Angola, Congo,
the Democratic Republic of the Congo and Gabon, 16
million children were immunized during three rounds
of synchronized NIDs in 2001. Finally, similar synchronized efforts have been undertaken along the
borders of Afghanistan and Pakistan, where the
poliovirus freely circulates.
361
activities, modifications in surveillance policies, or

changing approaches to programme communications
and social mobilization.
The NIDs/SNIDs is usually conduced over a week
now. A thorough micro-planning is done at least a
fortnight in advance and services of school children,
teachers, NGOs, paramedical personnel, health workers,
religious leaders, panchayat and municipal board
members are usually utilized. The first day (usually
Sunday) is kept for the booth activity where children
below 5 years of age immunized with OPV at a fixed
venue. Next 6 days are kept reserve for aggressive houseto-house activity to ensure 100% children are reached.
A vigorous IEC (information, education and communication) campaign is run involving all channels of
communication like print media, TV channels, cable TV,
cinema houses, meetings at public and religious places,
rallies of school children, announcements from mosques
and temples, public announcements at village fair, street
plays, distribution of pamphlets, etc to inform
community and motivate them about participating
actively in the campaigns. Mobile booths are also created
at railway stations, bus terminals and other transport
venues to catch mobile population. Oral polio vaccine is
used as the vaccine of choice by administering two drops.
The strict cold chain is maintained at +2 to 8 degree
centigrade by employing icepacks with vaccine carriers
and status is constantly monitored by vaccine vial
monitor(VVM).
Operational Strategy
In India, the India Expert Advisory Group (IEAG),
established in May 1999 as a group of national and
international experts on polio eradication, provide
technical advice to the Ministry of Health and Family
Welfare, Government of India, on immunization and
surveillance activities for polio eradication and also
monitor the quality of immunization activities, AFP
surveillance and laboratory performance. IEAG also
issues guidelines and recommendations to Government
of India to conduct NIDs and SNIDs for the coming
months. The IEAG meets on a periodic basis, the
frequency being determined by the status of polio
eradication in India. Meetings occur more frequently
when urgent decisions must be made regarding matters
such as acceleration of supplementary immunization
The Utility and Impact of NIDs

NIDs and SNIDs have become the main source of polio
immunization in the areas where routine immunization
(RI) rates are poor. Many countries like China, Brazil,
etc, have successfully employed NIDs to rapidly wipe
off wild polio virus transmission from their environs. Its
utility as a potent tool in the armamentarium of
eradication strategies is beyond doubt. This strategy has
also got tremendous use during the post-eradication era
also where any future outbreak of wild virus will be dealt
with, mass immunization.
Since 1988, when the Global Polio Eradication
Initiative (GPEI) was launched, this program has made
tremendous progress in reducing the burden of disease
world-wide. As a result, the total number of wild polio
362
virus cases has declined from an estimated 350,000 to

less than 1,500 in 2007. WHO Regions that have been
certified as polio-free are the Americas (last case in 1991,
Peru; Region certified polio-free in 1994), the Western
Pacific Region (last case in 1997, Cambodia; Region
certified 2000), and the European Region (last case in
1998, Turkey; Region certified 2001).The number of polio
endemic countries has also been reduced from 192 to only
4 in 2008. Wild polio virus type 2 has been eradicated
and last such case was seen in 1999. The remaining
reservoirs of wild polio virus are now largely confined
to sub-Saharan Africa and Indian subcontinent in southeast Asia. India and Nigeria are now the two main
endemic countries responsible for over 90% of wild polio
virus cases world-wide in 2008.
BIBLIOGRAPHY
1. Global Polio Eradication Initiative. Available at: http://
www.polioeradication.org/Accessed on June 20, 2008.
2. Global Polio Eradication Strategy: National Immunization Days. Available at: http://www. polioeradication.
org/content/fixed/national.shtml Accessed on June 20,
2008.
3. National Polio Surveillance Project. Eradication strategy.
Available at: http://www.npspindia.org/Eradication%
20 Strategy.asp Accessed on June 20, 2008.
4. Vashishtha VM, Thacker N. Polio eradication: how near
and how far? Indian J Practical Pediatr 2006;8:220-31.
5. Wild Poliovirus Weekly Update. Available at: http://
www.polioeradication.org/content/general/
casecount.pdf Accessed on June 20, 2008.
6. World Health Organization. Global Polio Eradication
Initiative Strategic Plan 2004-2008. Weekly Epidemiol Rec
2004;79:55-7.
9.13 Diphtheria
Diphtheria is an acute toxin-mediated disease caused by
Corynebacterium diphtheriae. It is one of the oldest recognized infectious diseases. It used to occur in epidemics
and was associated with high mortality. Klebs identified
the organism in 1883 and Loeffler cultivated it in 1884.
The first child was treated with antitoxin on the
Christmas day in 1891. Successful immunization could
be established after Ramon produced the toxoid in 1923.
Etiology
Corynebacterium diphtheriae (Klebs-Loeffler bacillus) is an
aerobic, non-motile, non-encapsulated, non-spore
forming irregularly staining gram-positive pleomorphic
bacillus. The pathogenicity of the organism is due to
release of exotoxin. The toxin inhibits cellular protein
synthesis and is responsible for local tissue destruction
and membrane formation. The toxin is absorbed into the
bloodstream and it is responsible for the major complications like myocarditis, neuritis, proteinuria and
thrombocytopenia. Corynebacterium diphtheriae has three
biotypes gravis, mitis and intermidius. The most severe
disease is associated with the gravis biotype.
Culture of the organism requires selective media
cystine-tellurite blood agar. If isolated, the organism must
be distinguished from diphtheroids, which normally

inhabit nasopharynx and skin.
Epidemiology
The only known reservoir of diphtheria is human being.
The patients or carriers transmit the disease through nasal
discharge or droplets by sneezing, coughing and talking.
Fomites and dust, though uncommon may also serve as
vehicle of transmission. The disease mainly affects the
unimmunized children below 15 years. The peak incidence
of the disease is during autumn and winter months. The
incubation period is 2-5 days (range 1-10 days).
The various sites affected are nasal mucosa, tonsils,
pharynx, larynx, trachea, conjunctiva and vagina. More
than one anatomic site may be involved. The signs and
symptoms depend upon the site of infection, immune
status of the host and the production and systemic
distribution of toxin.
Respiratory Tract
Nasal diphtheria initially resembles common cold. It
usually occurs in infants. There may be mild fever and

nasal discharge more often unilateral. The discharge is
foul smelling and serosanguineous. Careful inspection
may reveal a white membrane on the nasal septum. The
affected nostrils get obstructed and there may be
difficulty in breathing.
Tonsillar and pharyngeal diphtheria is the most
common clinical variety. Initially anorexia, malaise, low
grade fever and difficulty in swallowing are noted. Sore
throat is the universal early symptom. Within 1-2 days a
white pseudomembrane appears on the tonsils. It may
spread to cover the tonsils and pharyngeal walls or
progress down into the larynx and trachea. The pseudomembrane is a dense necrotic coagulum of organisms,
epithelial cells, fibrin, leukocytes and erythrocytes. It is
grey brown in colour and adherent to the base. Removal
is difficult and reveals a bleeding edematous submucosa.
Cervical lymph nodes are enlarged, accompanied by
severe edema causing swollen neck giving an appearance
of Bull neck. Edema is brawny with redness and
tenderness.
The typical features of the leather-like adherent
membrane, extension beyond the faucal area, relative
lack of fever and dysphagia help differentiate diphtheria
from exudative pharyngitis caused by group A streptococcus and epstein-barr virus.
The course of pharyngeal diphtheria depends upon
the extent of the membrane and the amount of toxin
produced. In severe cases, respiratory obstruction and
circulatory collapse may occur. In mild cases, the
membrane sloughs off in 7-10 days and the recovery is
uneventful. Laryngeal diphtheria is usually due to
extension of the membrane from the tonsils and pharynx.
The common symptoms are noisy and difficult breathing,
barking cough, hoarseness of voice and progressive
stridor. If obstruction is not relieved (e.g. by tracheostomy),
the child may succumb to suffocation and heart failure.
Other Sites
Diphtheritic skin infection is a superficial, non-healing
ulcer with grey-brown membrane. In most cases it is a
superadded diphtheria infection over an underlying skin
lesion. Extremities are more often affected. Mucocutaneous
infections at other sites are ear, eye and genital tract.
Complications
a. Cardiac: Myocarditis is caused by the toxin of C.
diphtheriae and it occurs usually during the second
363
week. It occurs in approximately 10-25% of the

patients with diphtheria and is responsible for 5060% of deaths. There is tachypnea, dyspnea, extrasystoles, weak pulse and muffled heart sounds. ECG
shows prolonged PR interval and ST-T changes.
Elevation of serum SGOT closely parallels the severity
of myocarditis. Recovery from myocarditis and
cardiomyopathy is usually complete.
b. Neurological: Neurological complications are multiphasic in onset. Palatal paralysis occurs acutely or in
the second week. Weakness of posterior pharyngeal,
laryngeal and facial nerves may follow causing a
nasal quality of voice, dysphonia and regurgitation
of fluids. Ocular palsies occur in the third week. It
involves muscles of accommodation, ciliary muscles
and lateral rectus muscle causing squint and diplopia.
Generalized symmetric polyneuropathy usually
occurs after 3-6 weeks of illness. This usually recovers
completely. In cases of palatal paralysis frequent
aspiration of secretions, feeding through nasogastric
tube and IV fluids are recommended.
c. Respiratory tract obstruction may require intubation
and mechanical ventilation. Secondary bacterial
pneumonia, nephritis and hepatitis can occur.
Diagnosis
The diagnosis is based on clinical examination and is
confirmed by isolation of bacilli. The material for culture
may be obtained from beneath or part of the membrane
itself. Other supportive investigations include raised
WBC count, raised protein and cells in CSF in cases of
neuritis. ECG may show arrhythmias in the form of block
and ST-T changes indicative of myocarditis.
Treatment
The principles of treatment are as follows:
i. Neutralization of free circulating diphtheria toxin,
ii. Eradication of bacteria by antibiotics,
iii. Supportive therapy.
Specific antitoxin is the mainstay of therapy and
should be administered early on the basis of clinical
diagnosis. Efficacy diminishes with elapsing time. For
neutralization of free circulating toxin, antidiphtheric
serum (ADS) should be given early in proper doses by
IV or IM route after skin sensitivity test. The dose of ADS
depends upon the site of infection. For nasal diphtheria
364
20,000 units, for tonsillar and pharyngeal diphtheria

40,000-80,000 units and for laryngeal lesions 80,000120,000 units are given. Diphtheria immune globulin
(DIG) can be used in place of ADS in a dose of 0.6 ml/kg
body weight.
Antibiotics: Penicillin is the drug of choice, aqueous
crystalline penicillin G (100,000-150,000 U/kg/day).
Alternatively erythromycin (40-50mg/kg/day) can be
used. The antibiotics should be given for 14 days or until
throat culture is negative to prevent the development of
carrier state.
Patients with pharyngeal diphtheria are placed in
respiratory isolation. Supportive therapy includes bed
rest for about two weeks to reduce the risk of cardiac
complications and maintenance of proper hydration and
nutrition. In children with laryngeal obstruction,
tracheostomy is lifesaving.
Prognosis
Early diagnosis, adequate use of ADS/DIG, antibiotics
and good supportive care has reduced morbidity and
mortality. Young age, gravis type of bacteria and
laryngeal diphtheria have poor prognosis. Sudden death
may occur due to respiratory obstruction, myocarditis
and respiratory paralysis.
Prevention
Diphtheria is a notifiable disease. The patient should be
isolated until the course of antibiotics is completed or
until two cultures from throat and nose are negative. The
people in close contact should ensure that they had been
immunized. If not, they should be submitted for throat
culture. If the person is culture negative, then no
treatment is required. If culture positive, then it should
be considered a carrier state and chemoprophylaxis
should be given with oral erythromycin or penicillin.
Diphtheria toxoid is available combined with tetanus
toxoid and pertussis vaccine as DTP, DT, Td and Tdap.
For primary prevention, DPT vaccine should be given at
6, 10 and 14 weeks of age two booster doses at 18 months
and 5 years of age. National EPI schedule advocates DT
instead of DPT as second booster. But over the years
immunity to diphtheria wanes despite three primary and
two booster doses of DPT vaccines. Low dose diphtheria
vaccine combined with regular dose of tetanus toxoid
(Td) is recommended as booster doses in children above
7 years and adults in subsequent immunizations in place
of tetanus toxoid (TT). This should be used in any wound
management and is also safe during pregnancy.
BIBLIOGRAPHY
1. Buescher ES. Diphtheria. In: Kliegman RM, Jenson HB,
Behrman RE, Stanton BF, editors. Nelson Textbook of
Pediatrics. 18th edn. Philadelphia: Elsevier 2007;1153-6.
2. CDC. Diphthera, tetanus and pertussis: Recommendations for vaccine use and other preventive measures.
MMWR 1991;40:1-28.
3. Epidemiology and prevention of vaccine-preventable
diseases. 10th edn. Department of Health and Human
Services CDC. 2007.
9.14 Pertussis (Whooping Cough)

YK Amdekar
Pertussis is an acute highly communicable infection of
the respiratory tract caused by Bordetella pertussis. It may
affect any susceptible host but is more common and
serious in infancy and early childhood. It derives its name
from a latin word perintensive and tussis cough.
Hence, any disease which results in severe cough is often
perceived as pertussis, more so as proof of diagnosis is
difficult to obtain in routine clinical practice. Similar
illness has been known to be caused by B. parapertussis,
B. Bronchiseptica and also adenoviral infections of type
1,2,3 and 5. It should be considered with high index of

suspicion in an unimmunized child presenting with
severe spasmodic cough.
Epidemiology
In India, before the introduction of EPI, there were more
than 2.5 lacs of cases reported in 1974 and 4.5 lacs in 1978.
In 1969, Ashabai et al, reported the incidence of Pertussis
as 15/1000 < 5 years and 85/1000 < 10 years of age. In
1972-75, one hospital based study reported that pertussis

constituted 1.4 percent of total vaccine-preventable
diseases, 0.3 percent of hospital admissions, 0.3 percent
of vaccine-preventable deaths and 0.1 percent total
pediatric deaths. Mortality in pertussis was around 6
percent. Similar high incidence had been reported in 50s
in developed countries; but after the introduction of
vaccine, incidence of pertussis came down significantly.
In India during postvaccination era, there has been a
decline in incidence of pertussis. In 1987, Singh reported
prevalence of pertussis as 3.6 percent in children < 10
years of age as compared to 8.5 percent in 1969. Similar
observations have been made in hospital-based studies.
Risk of acquiring pertussis prior to vaccination has been
estimated 20 times more than that after vaccination.
However in recent years, isolated epidemics continue to
occur all over the world. Epidemics of pertussis are
reported every 3 to 4 years in UK. Most recent estimates
of WHO indicate that 12.9 million children die under 5
years of age, of which 4.3 million die of ARI. Pertussis
accounts for 0.26 million of them, 6.1 percent of ARI
deaths. It is thus clear, that even with decline in pertussis
after vaccination, it still continues to be a major health
hazard. Infants may be susceptible before the age at
which vaccine is immunogenic, postvaccinal immunity
is likely to wane off in older children who may suffer
from mild or modified form of disease that is unrecognizable. Of course, unimmunized children in the
community continue to suffer and spread infection. In
population with higher coverage of pertussis vaccine,
there is a shift in age prevalence of disease and older
children and adults do suffer from pertussis.
Pathogenesis
Organisms spread by droplets from infected untreated
patients. Clinical manifestations depend upon the host
response to antigens associated with capsule, cellwall or
cytoplasm of the organism. Lymphocytosis promoting
factor probably plays an important role in human
infection. Both T and B lymphocytes are involved.
Endotoxin does not seem to contribute in the pathogenesis of the disease. Systemic and local humoral responses
are beneficial in human infection. Pathological changes
are characterized by inflammation of the mucosal lining
of the respiratory tract. Bronchopneumonia develops
with necrosis and desquamation of superficial epithelium of small bronchi. Bronchiolar obstruction and atelectasis result from accumulated secretions. Bronchiectasis may develop and persist. Changes in brain and liver
365
have been noted in severe disease, especially in infants

and are considered to be due to anoxia.
Clinical Features
Unless treated early in the evolution of the disease, it
runs a lengthy course for 6 to 8 weeks, classically through
three stagescatarrhal, paroxysmal and convalescent.
The prodromal catarrhal stage lasts for 1 to 2 weeks and
is characterized by coryza, fever and mild cough, which
progresses to episodic paroxysms of increasing intensity
ending with high pitched inspiratory whoop. Whoop
may be absent in infants and partially immune older
children and adults and hence, makes the diagnosis
difficult to suspect in them. This stage lasts for a variable
period of 2 to 6 weeks or longer. Convalescent stage is
heralded by decreasing intensity and frequency of cough
over 1 to 2 weeks. It is possible to diagnose pertussis only
with high index of suspicion in a child who coughs for
more than 2 to 3 weeks without any other obvious cause.
Complications
Infants and young children are more susceptible to
complications. Respiratory complications include otitis
media, pneumonia due to B. pertussis itself or secondary
bacterial infection, atelectasis, emphysema, bronchiectasis, pneumothorax and pneumomediastinum. CNS
complications result in seizures and encephalopathy and
often seen in paroxysmal stage of the disease in 0.5
percent of hospitalized patients. Severe cough leads to
marked increase in pressure in various compartments
which may result in epistaxis, retinal, subconjunctival
and intracranial hemorrhages, inguinal hernia, rectal
prolapse and rupture of diaphragm. Malnutrition is the
end result of disease in infancy and early childhood due
to protracted course of the illness interfering with
feeding. Pertussis is also known to flare up the preexisting silent tuberculous infection.
Other conditions which may present with an acute onset
of severe cough lasting for more than 2 to 3 weeks include
adenovirus infection, endobronchial tuberculosis,
inhaled foreign body or hyper-reactive airway disease.
Other chronic infections of respiratory tract may also be
considered. Recurrent episodes of cough rule out
pertussis.
366
Diagnosis
Prevention
It is often made on clinical features. In an unimmunized

child in contact with a patient having pertussoid cough,
it may be safe to consider the diagnosis of pertussis.
Marked lymphocytic leukocytosis is a non-specific
parameter and low ESR is often a clue. Specific
diagnosis depends on recovery of B. pertussis from
nasopharyngeal swab or cough plate cultured on BorderGengou medium. Cultures are often positive in catarrhal
and early paroxysmal stage. Direct fluorescent antibody
and counter-immunoelectrophoresis are other methods
for rapid diagnosis. Most of these methods are not
routinely available in clinical practice. At present, no
single test exists which is sensitive and specific enough
for the diagnosis in all the stages.
Strict respiratory isolation is desirable for 4 to 5 days after

starting antibiotic therapy. Chemoprophylaxis with
erythromycin is recommended for close family contacts
especially under 2 years of age. Under the age of 5,
children should be vaccinated as per IAP guide lines.
With availability of safer low concentration vaccine for
older children and adults, it is ideal to offer pertusis
pertusis vaccine (Tdap) to them. Pertussis vaccine is
discussed in the chapter on immunization.
Management
BIBLIOGRAPHY
1.
2.
3.
Respiratory distress, CNS signs and poor intake leading

to dehydration especially in infants are strong indications
for immediate referral to a hospital.
General measures include providing adequate
nutrition and hydration and avoiding factors aggravating
cough such as excessive crying. The antibiotic of choice
is erythromycin given orally in dose of 40 to 50 mg/kg/
day in 3 to 4 divided doses. It does not shorten the course
of illness but does terminate respiratory tract carriage of
B. pertussis, thereby reducing the period of communicability. Complications are managed symptomatically.
4.
5.
6.
7.
Ashabai PV, John TJ, Jayabal P. Infectious disease in a group

of south Indian families. Indian Pediatr 1969;6:645-50.
Centre for Disease Control. Pertussis surveilence. United
States 1989-1991 MMWR 1993;42.
Chaudhari, et al. Impact of National Immunization
schedule on vaccine preventable disease on a hospitalbased study. Indian Pediatr 1992;29:33-8.
Garrene M, Ronsman C, Campbell H. The magnitude of
mortality from ARI in children under 5 years in
developing countries. Wld Hth Statist Quart 1992;45:180.
Grenfell BT, Anderson IM. Pertussis in England and
Wales an investigation of transmission dynamics and
control by mass vaccination. Proc Royal Society London
1989;236:213-50.
Singh et al. Pertussis in rural children. Indian Pediatr
1987;24:553-6.
WHO. EPI in South-East Asia SEARO Regional Health
Papers No. 12, p. 131.
9.15 Tetanus
Tetanus is an acute often fatal, severe exotoxin-mediated
infection caused by Clostridium tetani. Rosenbach in 1886
demonstrated for the first time these slender bacilli. The
disease is characterized by severe muscular spasm.
Epidemiology
Tetanus occurs worldwide and is an important cause of
neonatal death in developing countries. The causative
organism Clostridium tetani is part of the normal flora in
human and animal intestines and is disseminated
through the excreta. In spore form they are hard and long
lasting in soil and dust. As the spores of Clostridium tetani

are ubiquitous, wound contamination is unavoidable.
The contamination of wound, unhygienic and improper
handling of the umbilical cord in newborns, lack of
hygienic habits and aseptic care during and after delivery
in women are the main risk factors for infection. But
tetanus is a preventable disease. It is the only vaccine
preventable disease that is infectious but not contagious
from person to person.
Among the burden of vaccine preventable diseases
world over, tetanus ranks fourth with 13% disease

burden. According to WHO, published in 2008, the
reported cases of tetanus in India in 2006 were 2587, of
which 600 cases were neonatal tetanus. The incidence is
high in tropical countries with humid climate. More cases
are reported from rural than urban areas.
Etiology
The causative organism Clostridium tetani is a grampositive, anaerobic, spore forming organism. It forms
terminal spores resembling drumsticks. The spores are
resistant to boiling, usual antiseptics and chemical agents
like phenol. They can survive autoclaving at 121oC for
10-15 minutes.
Clostridium tetani usually enters the body through
wound. The bacilli itself is non-invasive. The spores
germinate in anaerobic conditions. They produce two
types of toxins tetanospasmin and tetanolysin. Of these,
tetanospasin is a neurotoxin and is responsible for the
clinical signs and symptoms of the disease. Toxins are
disseminated via blood and lymphatics. Toxins act at
several sites within the nervous system.
The incubation period of tetanus is around 10 days (range
3-30 days). On the basis of clinical findings, three different
forms of tetanus have been described. The most common
type (80%) is generalized tetanus. Localized tetanus
produces pain and spasm of the muscles in proximity to
the site of injury. Occasionally this form of disease may
precede generalized form. Cephalic tetanus is a rare form
of the disease seen in children with otitis media.
Generalized tetanus usually presents with a
descending pattern. The first sign is trismus or lockjaw
due to spasm of masseter muscle, followed by stiffness
of the neck, difficulty in swallowing and rigidity of
abdominal muscles. The spasms can be precipitated by
bright light, noise and even touch. Difficulty in
swallowing, restlessness, irritability and headache are
early manifestations. The rigidity of facial muscles leads
to the sardonic smile of tetanus or risus sardonicus, a
typical grinning appearance. Rigidity and spasm of back
and abdominal muscles causes arching (opisthotonos).Laryngeal and respiratory muscle spasm can lead
to airway obstruction and asphyxia. Constipation and
retention of urine may also occur. Hyperpyrexia,
hypertension, excessive sweating, tachycardia and
cardiac arrhythmia can occur due to sympathetic nerve
involvement.
367
Neonatal tetanus typically occurs when the umbilical

cord is cut with an unsterile instrument and manifests
within 3-12 days of birth. It is generalized tetanus, a
serious condition and often fatal. Progressive difficulty
in feeding (sucking and swallowing) with associated
hunger and crying are generally seen. The baby becomes
stiff and spasms develop. Opisthotonos may be extreme
or sometimes absent.
Diagnosis
Diagnosis is mainly clinical. The typical setting is an
injured unimmunized patient or baby born to an
unimmunized mother presenting within 2 weeks with
trismus, rigid muscles and clear sensorium. The organism
can be isolated from wound or ear discharge.
Treatment
The aim of therapy is to neutralize all toxins, eradication
of C. tetani and wound environment conducive to
anaerobic multiplication and supportive care.
Human tetanus immunoglobulin (TIG) 3000-6000
units IM is recommended to be given immediately. TIG
has no effect on toxin which is already fixed to the neural
tissue and doesnt penetrate the blood-CSF barrier. It can
neutralize circulating tetanospasmin. Antitetanus serum
is recommended only when TIG is not available. It can
be given in a single dose of 50,000-100,000 units, half the
dose IM and the rest intravenously after skin test.
Penicillin is the antibiotic of choice for C. tetani.
Penicillin G 200,000 units/kg body weight can be given
intravenously in 4 divided doses for 10-14 days. Local
wound, discharging ears, umbilical cord should be
cleaned and debrided.
All patients with generalized tetanus require
muscle relaxant. Diazepam is preferred as it causes
both muscle relaxation and seizure control. Initial dose
is 0.1-0.2 mg/kg every 3-6 hours given intravenously.
Midazolam, baclofen can also be used. The best
survival rates with generalized tetanus are achieved
with neuromuscular blocking agents like vecuronium
and pancuronium. These drugs produce general
flaccid paralysis which can be managed by mechanical
ventilation.
Meticulous nursing care is imperative. The patient
should be kept in a quiet, dark environment with
minimum auditory or visual stimuli. Maintenance of
nutrition, fluid and electrolyte balance, suctioning of
secretions and cardiorespiratory monitoring should be
done. Provision for tracheostomy should be kept ready.
368
Prognosis
The average mortality of tetanus is 45 to 55 percent. For
neonatal tetanus the mortality is 60 to 70 percent. The
most important factor influencing outcome is supportive
care. Recovery from tetanus doesnt confer immunity;
therefore active immunization of the patients following
recovery is imperative.
Prevention
Tetanus is an entirely preventable disease. Active
immunization is the best method to prevent tetanus. All
children should be immunized with three doses of DPT
at 6, 10 and 14 weeks followed by booster doses at 18
months and 5 years of age. Boosters should be given at
10 years and then every 10 years. Td or Tdap is the
vaccine of choice above 7 years age.
Neonatal tetanus could be prevented by immunizing
the pregnant women with two doses of tetanus toxoid
(preferably Td) between 16 and 36 weeks of pregnancy,
and with only one dose of Td in the subsequent
pregnancies.
Wound Management
All wounds should be cleaned, necrotic tissue and foreign
material should be removed. Wounds which are not
minor require human TIG except those in fully immunized patient. In patients with unknown or incomplete
immunization history, crush, puncture or projectile
wounds, wounds contaminated with soil, saliva or feces,
avulsion injuries, compound fractures, 250 U of TIG
should be given IM. In cases where the wound could not
be properly debrided or wound more than 24 hours old,
500 U TIG should be given. Tetanus toxoid may be
administered immediately depending on the immunization status of the child.
BIBLIOGRAPHY
1. Arnon SS. Tetanus. In: Kliegman RM, Jenson HB, Behrman
RE, Stanton BF, editors. Nelson Textbook of Pediatrics.
18th edn. Philadelphia: Elsevier 2007.p.1228-30.
2. CDC. Diphtheria, tetanus and pertussis: Recommendations for vaccine use and other preventive measures.
MMWR 1991;40:1-28.
Services CDC. 2007.
4. World Health Organization. The high risk approach:
the WHO-recommended strategy to accelerate elimination of neonatal tetanus. Wkly Epidemiol Rec 1996;
71:33-6.
9.16 Measles
Measles is a contagious disease characterized by catarrhal
symptoms, followed by appearance of typical measly
rash. The incidence of measles has come down world
over with effective immunization. But measles is a major
cause of preventable blindness and still the leading
vaccine preventable killer in children. India contributes
27 percent of global measles deaths. WHO has started
the Measles Surveillance Project in India from 2007.
The number of reported cases showed a decline from

1997 to 2005, and then there was a sharp rise in 2006.
According to WHO, published in 2008, the reported cases
of measles in India in 2006 were 60751 and in 2005 it was
52454. As per EPI fact sheet, documented measles
immunization coverage in India was 67% in 2003 in
children less than 1 year of age.
Etiology
Epidemiology
Measles occurs both epidemically and endemically. The
peak incidence is during winter and spring. One attack
of measles confers lifelong immunity.
Among the burden of vaccine preventable diseases
world over, measles ranks first with 38% disease burden.
Measles is caused by measles virus, an RNA virus, of

genus Morbillivirus, of the family Paramyxoviridae. Only
one sero-type of measles is known.
Measles is seen in early childhood in developing
countries. The disease usually occurs below 3 years age.
Infants are usually protected till the age of 4-6 months
369
due to immunity acquired trans-placentally from mother.

Usually these antibodies are undetectable by the age of
9 months but antibodies may persist up to 12 months of
age. The disease runs a mild course in healthy children,
whereas the disease is severe in malnourished children.
Transmission occurs either by direct contact or droplet
spray. The period of infectivity is 4 days before and 4
days after appearance of rash. It is rarely sub-clinical. It
is highly contagious and secondary attack rate is
approximately 90% in susceptible household contacts.
rash appears on feet it starts disappearing from face and

fades down in same pattern. Temperature also suddenly
normalizes once rash starts fading and child suddenly
looks well from sick look. The severity of disease is
directly related to the extent and confluence of rash. In
severe cases rash may become hemorrhagic. The rash
fades in the next 3 to 4 days. As the rash disappears it
leaves behind the brawny desquamation and brownish
discoloration characteristic of post-measles state which
disappears in 7-10 days.
Pathogenesis
Complications
Measles virus enters the human body through the

respiratory epithelium of the nasopharynx. The virus
replicates initially in these cells including the epithelial
cells lining the buccal mucosa and conjunctiva. Later it
spreads to the regional lymph nodes. Further replication
of the virus leads to the primary viremia with seeding of
the cells of the reticulo-endothelial system. Infection of
these cells leads to the secondary viremia, whereby the
measles virus is disseminated through out the body,
coincident with the clinical manifestations of the disease.
Measles can affect various systems in the body resulting

in following complications.
a. Respiratory system Postmeasles bronchopneumonia, empyema, mediastinal and subcutaneous
emphysema and flaring of pulmonary tuberculosis.
b. GIT Diarrheal episodes are quite common after
measles.
c. ENT Otitis media.
d. Systemic Acute malnutrition, secondary bacterial
infections like septicemia with Streptococcus, etc.
e. Cancrum oris, stomatitis nomans at different sites.
f. CNS Measles encephalitis and encephalopathy.
g. Eye Keratitis.
h. SSPE Subacute sclerosing pan encephalitis (SSPE)
is a degenerative disease of the brain caused by a
persistent infection with measles virus. It can manifest
several years (usually 7 years) after measles infection.
The patient develops progressive personality
changes, developmental retardation, myoclonic
seizures and motor disability. Measles virus has been
isolated from the brain tissue of such patients. Their
sera and CSF show a high titer of measles specific
antibodies.
The clinical course of measles can be divided in four
clinical stages incubation, prodromal stage, catarrhal
stage and post-measles stage of complications.
The incubation ranges from 10-12 days. In the later
part of incubation period, the child shows prodromal
symptoms which last for 2-4 days and consist of fever,
malaise, coryza and tracheobronchitis.
At the end of prodromal phase, the child gets fever
which may be high grade. Kopliks spots, which are
pathognomonic sign of measles, are seen on day 2-3 of
fever. These are grayish white or bluish white dots with
reddish areola occasionally they are hemorrhagic. Mostly
seen on buccal mucosa opposite lower molars but may
be seen all over the buccal mucosa. Conjunctival
congestion and photophobia is also classical of measles,
which occurs before Kopliks spots appear. Temperature
rise abruptly as rash appears and often reaches 40C or
higher.
Rash appears on 4th to 6th days of fever. It starts as
faint erythematous maculopapular rash on upper lateral
aspect of neck and typically behind the ears and
increasingly involve face then spreading on to trunks and
then to legs and arms over next 3 to 4 days. By the time
Prognosis
In developing countries measles has a devastating course
with a mortality of 1 to 3 percent which may go up during
epidemics to 5 to 15 percent and a high rate of complications.
Management
Management is mainly supportive. The child may be
given antipyretics, fluids and antihistaminics during
acute phase. No antiviral therapy is available. The child
may be isolated for the period of infectivity. There is
370
inverse correlation between serum retinol concentration

and measles severity. A single dose of vitamin A 100,000
units orally for children 6-12 months of age and 200,000
units orally for more than 1 year of age children reduces
mortality.
Prevention
1. Isolation of the patient From 7th day of exposure to
5 days after rash appearance.
2. Vaccine Measles can be effectively prevented by
measles vaccine. The newborn baby is protected by
transplacentally acquired maternal antibodies. The
antibody gradually wanes and the infant becomes
susceptible to measles starting from 6 months of age.
By 9 to 12 months of age most infants become
susceptible. At this age live attenuated measles
vaccine offer good protections. The preparations of
the vaccine contains 1000 TCID dose of vaccine virus.
Unconstituted vaccine remain viable for 2 years at 28C but once reconstituted it should be used within 4
hours as vaccine does not contain any preservative
or antibiotic. Measles is a potent and effective vaccine
with a seroconversion rate of 95-98 percent. As per
national immunization programme in India and EPI
policy we give measles vaccine at 9 month of age as
0.5 ml subcutaneous injection. MMR vaccine contains
measles, mumps and rubella vaccines. The Global
recommendation now is two doses for MMR and
Varicella Vaccines the first dose at 15 months and
the second at 4-6 years. It will be ideal to administer

the second dose at 5th year along with DTP booster
and OPV. Measles vaccine is contraindicated in
pregnancy, children with primary immunodeficiency, untreated tuberculosis, cancer, organ transplantation or those receiving long term immunosuppressive therapy or severely immunocompromised
HIV infected children.
3. Post exposure prophylaxis (i) Less than 6 months
old child (mother usually immune in India) there is
no need for prophylaxis as child already protected. (ii)
6-12 months unimmunized then vaccinate with
measles vaccine within 72 hrs. (iii) More than 12
months unimmunized then vaccinate with measles or
MMR vaccine within 72 hrs of exposure. (iv) Immunocompromised give 0.5 ml/kg immunoglobulin
(maximum 15 ml) IM irrespective of immunity status.
BIBLIOGRAPHY
1. Bhargava I. Measles. Control of measles, mumps and
rubella. 1 st edn. New Delhi: BI Churchill Livingstone,
1995.
Services CDC. 2007.
3. India EPI fact sheet, 2003, country Fact sheet WHOSE
ARO. 2004.
4. Mason WH. Measles. In: Kliegman RM, Jenson HB,
Behrman RE, Stanton BF, editors. Nelson Textbook of
Pediatrics. 18th edn. Philadelphia: Elsevier. 2007;
1331-7.
9.17 Mumps: Epidemic Parotitis

Ashok Gupta
Mumps is an acute, generalized, virus infection of
children and young adults. Mumps virus, is an RNA
virus of the genus Paramyovirus in the family Paramyxoviridae, which also includes the Parainfluenza viruses,
only one serotype is known. The virus can infect almost
any organ: the salivary glands, the pancreas, the testes
or ovary, the brain, the breast, the liver, the joints and
the heart. Parotitis is the most common illness.
Epidemiology
The mumps virus is endemic worldwide, and its only
known host is the human. In unimmunized population
epidemics tend to occur every 2 to 5 years, throughout

the year but often with a peak in late winter or early
spring.
Natural History
The mumps virus is transmitted via saliva, through
airborne droplets, by direct contact, fomites contaminated by saliva and possibly by urine. The secondary
infection rates in susceptible populations have been as
high as 80 percent. The period of communicability
extends from several days before the onset of symptoms

to several days thereafter, but the virus has been isolated
as early as 6 days before and as late as 9 days, after the
onset of parotitis. Infection with the virus or immunization is thought to confer immunity for life.
The virus proliferates in the upper respiratory tract
epithelium and then enters circulation. It then localizes
in glandular and neural tissue.
After an incubation period of 2 to 4 weeks, average
16 to 18 days, symptoms begin acutely with fever,
malaise, and headache.
Parotitis
Most patients develop parotitis that may appear in one
or both parotid glands. Earache, jaw tenderness with
chewing, and dry mouth are among the presenting
complaints that worsen over the next several days.
Sucking a sour stimulus produces significant worsening
of the pain. The swelling is at the angle of the jaw, and
obliterates the angle, often extending to the lower portion
of the ear, which may be displaced up and out.
Defervescence and resolution of parotid tenderness takes
about a week.
Submaxillary Mumps
Symptoms are similar to parotitic mumps. In the absence
of associated parotid swelling, differentiation from othe
submaxillary swelling is difficult. In all such situations,
examine fauces for the signs of tonsillitis that might cause
cervical adenitis, and laboratory tests are needed for
definite diagnosis.
Sublingual Mumps
The sublingual salivary glands when they swell, they
push up into the mouth below the tongue, forcing it up
against the hard palate, and also down under the chin as
a very tender swelling. It is acutely uncomfortable, often
accompanied by severe general symptoms. It usually
subsides after a few days, and is fortunately uncommon.
Orchitis
Infection can also be established in the testes and
epididymes, particularly in adolescents or adults (25%
of post pubertal males). Orchitis, unilateral in 80 to 85
percent, usually occurs 1 to 2 weeks after parotitis, but it
371
may occur without parotitis. Symptoms begin abruptly

with testicular swelling and tenderness and associated
nausea, vomiting, and headache. The testicle may enlarge
three or four times and become very tender. Later on,
some degree of atrophy develops in nearly half of the
affected organs.
Meningitis and Encephalitis
CNS involvement is characterized by an aseptic meningitis that occurs in 1 to 10 percent of patients with parotitis.
Meningeal symptoms develop anytime between a week
before to several weeks after the parotitis. Lymphocytic
dominance with fewer than 500 cells is usual, but white
cell counts may rise to over 2000 in the spinal fluid. The
spinal fluid glucose is usually normal, and the protein is
normal or slightly elevated. These findings revert to
normal after about a week and sequelae are uncommon.
Encephalitis is rare with an estimated frequency of 3/1000
cases. It can be very serious with seizures and cortical
blindness. High fevers are common. Recovery is usually
complete, but fatalities have been reported. Occasionally
meningitis or encephalitis may occur without manifest
parotitis. Aqueductal stenosis and hydrocephalous have
been associated with mumps infection. Injecting mumps
virus into suckling hamsters has produced similar lesions.
Other Complications
Pancreatitis is another manifestation of mumps and
occurs in approximately 5 percent of the patients.
Infection with mumps virus has been implicated as a
possible cause of juvenile onset of diabetes. There has
been documentation of onset of diabetes within a few
weeks, following clinically diagnosed mumps. An
association has been found between mumps infection
and endocardial fibroelastosis (St. Geme et al. 1972).
There is no evidence of impairment of fertility in
postpubertal females patients with oophoritis reported
in about 7 percent cases. Other complications include
myocarditis, deafness unilateral or bilateral (transient or
permanent), arthiritis, dacroadenitis, optic neuritis,
thyroiditis have been reported.
Diagnosis
The clinical features of acute parotitis are diagnostic.
Laboratory findings are of little value, except that the
serum amylase is elevated in 90 percent of the patients
372
with parotitis and serum lipase levels are normal,

distinguishing mumps parotitis from pancreatitis.
Serologic tests are rarely done, but it is possible to identify
infection acutely by detecting antibodies to the S antigen
by complement fixation antibody titers which rise in first
week of illness, and V antigen by complement fixation
antibody titers that follow with a rise several weeks later,
and may persist at low levels for years. Neutralizing and
hemagglutination inhibiting antibodies appear during
convalescence.
Treatment
There is no specific treatment. Symptomatic treatment
includes simple analgesics. Immune globulin treatment
is not cost-effective and is no longer commercially
available.
Prevention
The live attenuated mumps virus vaccine induces
antibodies in 96 percent of seronegative recipients and has
97 percent protective efficacy with Jeryl Lynn strains of
mumps virus. Immunization is usually given at about 15
months of age in combination with measles and rubella
vaccination and can be given at age of 12 months if child
has not received measles vaccination at 9 months of age.
Second immunization also MMR is recommended at
any time during childhood. Children who have not
received the second dose should be immunized by 11-12
years of age. Women should avoid pregnancy for 30 days
after monovalent vaccine (3 months in case of rubella
vaccine). Neither vaccine nor immunoglobulin has been
shown to be effective in preventing mumps after exposure.

Mumps vaccination is contraindicated in patients with
allergy to vaccine component (anaphylaxis to neomycin),
moderate to severe acute illness with or without fever,
immuno deficiency due to immunosuppressent drugs or
disease but human io deficiency virus positive children
and symptomatic HIV infected children with CD4 count
>15 percent should be vaccinated with MMR vaccine.
BIBLIOGRAPHY
1. Annotation: Mumps embryopathy. Lancet 1966;692-3.
2. Centers for disease control and prevention: Measles,
mumps and rubella vaccine use and strategies for
elimination of measles, rubella and congenital rubella
syndrome and control of mumps. Recommendations of
the advisory committee on immunization practices
MMWR 1998;47 (RR-8):1-57.
3. Christies AB. Infectious; Epidemiology and clinical
practice, (3rd edn) Churchill Livingstone, Edinburgh
1980.
4. Feldman HA. Mumps; In Viral infections of humans
1989;471-91.
5. Gordon JE, Kilham L. Ten years in the epidemiology of
mumps. American Journal of Medicine 1949;218:338-59.
6. Hanshaw JB, Dudgeion JA. In Viral diseases of the fetus
and the newborn. Saunders, Philadelphia, 1978.
7. Kurtz JB, Tomlinson AH, Pearson J. Mumps virus
isolated from a fetus. British Medical Journal 1982;284471.
8. Rima BK. Mumps virus. In Webster RG, Granoff A (Eds):
Encyclopedia of Virology 1994;876-83.
9. Weibel RE. Mumps vaccine. In Plotkin SA, Mortimer
EA (Eds): Vaccines, Saunders, Philadelphia, 1988;223-34.
10. Wolnsky JS, Waxham MN: Mumps virus. In fields BN 9
edn. Virology 1990;989-1011.
9.18 Rubella
Rubella or German measles or third disease is a mild
disease affecting children and adults. Its importance lies
in the fact that if a woman has Rubella during pregnancy,
infection may be transmitted to the fetus across the
placental barrier, resulting in marked teratogenic effects.
Epidemiology
Humans are the only natural host of rubella virus. The
virus is transmitted by droplets via respiratory route from
person to person and transplacentally to cause congenital

rubella syndrome. It replicates in the mucosal cells of
upper respiratory tract and spreads to the regional lymph
nodes, especially the posterior auricular and the
suboccipital group.
Secondary attack rate is 50-60% in family contacts and
almost 100% in closed populations like institution or
military barracks. Virus is shed in nasopharyngeal
secretions, blood, feces and urine during the clinical

illness. Virus can be spread 7 days prior to exanthema
and 7-8 days after its disappearance. Sub-clinical patients
are also contagious.
Etiology
The Rubella virus is a cubical, medium sized (70 nm) virus.
It is an RNA virus of the genus Rubivirus in the family
Togavirus.
Incubation period is 14-21 days. Initial prodromal
symptoms include malaise, headache, mild catarrhal
symptoms and low grade fever. Most characteristic
features are retro auricular, posterior cervical and postoccipital lymphadenopathy. Discrete rose colored spots
on the soft palate (Forchheimer spots) may be seen in
approximately 20% patients before the onset of skin rash.
Skin rash is mostly discrete maculopapular but quite
variable in size and confluence. It starts on face and
spreads rapidly over trunk. Progression is so fast that by
third day it usually clears up. No significant desquamation is seen in rubella. Occasionally conjunctivitis is
present. In women and young girls arthralgia and
polyarthritis may occur. Any joint can be involved but
small joints of hand are affected most frequently. It lasts
few days to few weeks and leaves no sequelae.
In pregnant women, Rubella virus can cross the
placenta and infect the developing embryo or the fetus
resulting in various congenital malformations. The exact
nature and extent of these malformations depend on the
gestational age of the affected fetus. Risk for congenital
defects is greatest with primary maternal infection.
Congenital defects occur in about 90% infants if maternal
infection occurs before 11 weeks of pregnancy and about
10-20% by the end of first trimester. This may result in
spontaneous abortion or birth of a severely malformed
baby. Maternal infection after 16th week is associated
with low risk of congenital defects.
Classically the Congenital Rubella Syndrome (CRS)
includes a triad of malformations cataract, sensorineural hearing loss and congenital heart disease, most
commonly patent ductus arteriosus (PDA). CRS may also
be a disease with multisystem involvement, a wide
spectrum of clinical expression and long postnatal period
of active infection with shedding of viruses. It can also
lead to IUGR, microphthalmia, microcephaly, mental and
motor retardation.
373
Diagnosis
Confirmation is by serology or viral culture. IgM
antibodies are detectable in first few days of illness. Fourfold rise in IgG in paired sera is also diagnostic.
It is often confused with mild variety of scarlet fever or
rubeola. Other viral illnesses like roseola infantum,
infectious mononucleosis, enteroviral infection and drug
rash closely resemble Rubella.
Prognosis
The prognosis of childhood Rubella is good, that of
congenital Rubella varies with the severity of infection
and organ involved.
Treatment
No specific antiviral therapy is available for Rubella.
Antipyretics are used for symptomatic relief.
Prevention
Rubella vaccine is a live attenuated vaccine. The vaccine
is available separately or as triple vaccine MMR that
contain measles, mumps and rubella. Principal goal of
rubella vaccination is to prevent CRS. The Global
Varicella Vaccines the first dose at 15 months and the
second at 4-6 years. It will be ideal to administer the
second dose at 5th year along with DTP booster and OPV.
Special care should be taken in reproductive females
to avoid pregnancy for 3 months after MMR vaccination.
But inadvertent vaccination during pregnancy is not an
indication for termination of pregnancy.
BIBLIOGRAPHY
1. Bhargava I. Measles. Control of measles, mumps and
rubella (1st edn). New Delhi: BI Churchill Livingstone,
1995.
Services CDC. 2007.
3. India EPI fact sheet, 2003, country Fact sheet
WHOSEARO. 2004.
4. Mason WH. Rubella. In Kliegman RM, Jenson HB,
Behrman RE, Stanton BF (Eds). Nelson Textbook of
Pediatrics. 18th edn. Philadelphia: Elsevier 2007;
1337-41.
374
9.19 Staphylococcal Infections

S. aureus are ubiquitous in healthy persons, patients,

animals and fomites. Most neonates are colonized within
the first week of life and 20 to 30 percent of normal
individuals carry S. aureus in the anterior nares at all times.
Coagulase negative Staphylococcus is also ubiquitous on
skin and mucosal surfaces. Transmission of Staphylococcus
occurs by direct contact or by spread of heavy particles
over a distance of six feet or less. Infection may follow
colonization which is favored by antibiotic therapy to
which Staphylococcus is resistant. Coagulase negative
Staphylococcus infection usually follows colonization or
direct inoculation during surgery.
lized skin infection in the form of wound infection,

furuncles, carbuncles, folliculitis and impetigo. Impetigo
is common in children and affects exposed parts of the
body, i.e. face and legs. Children with recurrent
furunculosis should be investigated for nasal carriage,
phagocytic dysfunction and metabolic dysfunction.
Localized infection with diffuse skin rash is seen in the
form of staphylococcal scalded skin syndrome (SSSS) caused
by epidermolytic toxin produced by certain strains of
Staphylococcus aureus most often of phage group 2, type
70/71 or 51. This toxin produces superficial splitting of
skin with level of splitting high in epidermis. It starts as
macular erythema leading to flaccid bullae in 2 days.
Erosions crust and dry and heal with desquamation over
next 4 to 8 days leaving no sequelae. SSSS should be
differentiated from toxic epidermal necrolysis (TEN) in
which split is subepidermal and blisters are hemorrhagic.
TEN, scarlet fever, Kawasaki syndrome and toxic shock
syndrome are other differential diagnosis but all of them
have mucosal involvement.
Cellulits is more deep seated spreading infection of
the skin and needs systemic antibiotics for treatment.
Pathogenesis
Respiratory Infection
Staphylococcus aureus is resistant to heat and drying. Its

pathogenicity depends on various cell wall components,
enzymes and toxins. Catalases, coagulase, hyaluronidase,
lipases and nucleases are cellular products with important
enzymatic actions. They produce a number of toxins, e.g.
exfoliative toxin A and B responsible for bullous impetigo
and scalded skin syndrome; staphylococcal enterotoxins
(Type A, B, C, C2, D, E) if ingested, result in diarrhea,
vomiting and hypotension. TSS toxin-1 is associated with
toxic shock syndrome. The development of staphylococcal
disease is related to resistance of host to infection and to
virulence of organism. Defects in mucocutaneous barrier
by trauma, surgery, foreign surfaces and burns increases
the risk of infection.
Staphylococcus aureus is a rare cause of otitis media and

sinusitis. It is reported to be a cause of pneumonia in 1 to
28 percent of lung aspirates and is more common cause
of pneumonia in neonates.
One of the following manifestations is seen:

Staphylococcal enterocolitis follows use of broad
spectrum oral antibiotics leading to destruction of
normal bacterial flora and favoring staphylococcal
overgrowth.
INTRODUCTION
Staphylococci are gram-positive cocci which grow in
clusters aerobically or as facultative anaerobes. Strains
are classified as coagulase positive, i.e. Staphylococcus
aureus responsible for most clinical problems and coagulase negative (e.g. S. epidermidis, S. saprophyticus, S.
hemolyticus).
Epidemiology
Staphylococcus aureus
Signs and symptoms depend on location of infectionSkin infectionS. aureus is most common cause of loca-
Septicemia and Bacteremia

They may be associated with any localized infection and
are usually seen at extremes of age and in immunocompromised host organisms may subsequently
localize to any site, especially in lungs, heart, joints, bones
and kidney. This may lead to meningitis, osteomyelitis,
arthritis, pyomyositis and acute bacterial endocarditis.
Intestinal Tract

Peritonitis is seen in patients undergoing chronic
ambulatory peritoneal dialysis. Food poisoning is
caused by ingestion of enterotoxins preformed by
Staphylococcus contaminating food. Two to seven
hours after ingestion of toxin, sudden, severe
vomiting and watery diarrhea develops. Symptoms
usually subside within 12 to 24 hours.
Coagulase Negative Staphylococcus (CoNS)
CoNS causes nosocomial infection in patients with
indwelling foreign devices, (e.g. IV catheters, peritoneal
dialysis catheter, etc.) immunocompromised states, and
surgical trauma. Symptoms of bacteremia and septicemia
are seen. Infection may present as endocarditis and
urinary tract infection also.
375
depends on site and type of infection. Coagulase negative

staphylococci infection are treated with methicillin and
in cases resistant to methicillin vancomycin is used.
Toxic Shock Syndrome (TSS)
The term TSS was introduced by Todd et al, in 1978 for a
syndrome characterized by rapid onset of fever,
hypotension, erythroderma (early) and a delayed desquamation 1 to 2 weeks after onset, specially on palms
and soles. Diagnosis depends on clinical manifestations
as given below (Table 9.19.1). There is usually no specific
laboratory test for diagnosis. Multisystem involvement
is shown by increased creatinine, thrombocytopenia,
hypocalcemia, azotemia, hyperbilirubinemia, and leukocytosis. Bacterial cultures usually reveal Staph. aureus.
Diagnosis
Etiology and Epidemiology
Diagnosis of Staphylococcus infection depends on isolation

of bacteria from skin lesion, abscess cavity, blood,
cerebrospinal fluid or other sites of infection. Diagnosis
of food poisoning is made on basis of normal flora,
epidemiological and clinical findings. CoNS may
contaminate blood cultures but bacteremia should be
suspected, if cultures grow rapidly (within 24-hr), when
two or more cultures are positive with same CoNS and
signs, and symptoms of CoNS are present.
It is usually seen in menstruating women between 15 to

25 years of age who use tampons or vaginal devices but
can occur in children and men with wounds, nasal
packing, sinusitis, osteomyelitis. Majority of cases are due
to Staph. aureus phage group 1 which produce number
of extracellular toxins, e.g. TSS 1 and enterotoxins
responsible for systemic manifestations.
Treatment
Patients should be treated with b lactamase resistant

antibiotics for 10 to 14 days. Intravenous vancomycin
show be started. Infected or colonized site should be
Intact skin is a powerful barrier against staphylococcal

infection. Hence, topical therapy with, bacitracin,
mupirocin or fusidic acid is enough for minor skin
infections and impetigo. Large abscesses should be
drained and systemic antibiotics should be administered.
Antibiotic therapy alone is not effective in individuals
with undrained abscesses or with infected foreign bodies.
Cellulitis should be treated with systemic antibiotics.
Since 90 percent of Staphylococcus aureus are resistant to
penicillin, therapy should be started with penicillinase
resistant antibiotics, e.g. methicillin, oxacillin, cloxacillin
or dicloxacillin. In cases resistant to these antibiotics
vancomycin or teicoplanin should be used. Linezolid,
daptomycin, quinupristin-dalfopeistin, vancomycin with
linezolid and gentamycin and vancomycin with
trimethoprim-sulphamethoxazole may be useful for
serious infections. Skin, soft tissue and minor upper
respiratory infection can be treated with oral antibiotics
dicloxacillin, oxicillin or nafcillin. Duration of therapy
Treatment
TABLE 9.19.1: Diagnostic criteria for Staphylococcal Toxic

Shock Syndrome
Major Criteria (all required)
Acute fever (temp >38.8C)
Hypotension (orthostatic shock)
Rash (erythroderma with deep desquamation)
Minor Criteria (any 3)
Mucous membrane inflammation
Vomiting, diarrhea
Liver abnormalities
Renal abnormalities
Muscle abnormalities
Central nervous system abnormalities
Thrombocytopenia
Exclusionary Criteria
Absence of another explanation
Negative blood culture (except for S. aureus)
376
drained and cleaned. Inotropic agents, and corticosteroids may be needed in few cases of severe hypotension.
Overall mortality is 3 percent.
2.
TSS should be distinguished from Kawasakis disease
which usually occurs in children less than five years of
age and manifestations as myalgia, hypotension, and
diarrhea are not seen in Kawasakis disease. Scarlet fever,
leptospirosis and Rocky mountain spotted fever are other
differential diagnosis.
3.
4.
5.
BIBLIOGRAPHY
1.
Dolin R. Staphylococcal infections. In Mandell GL,

Bennett JE, Dolin R (Eds): Principles and Practice of
6.
Infectious disease 4th edn. Churchill Livingstone: New

York 1995;17:5484.
Hussain FM, BoyleVaura S, Bethal CD et al. Current
trend in community acquired methicillin resistant
Staphylococcus aureus at a tertiary care pediatric facility.
Ped Infec Dis J 2000;19:116366.
Jain A, Daum RS: Staphylococcal Infections in children:
Part I. Pediatr Rev 1999;20:18391.
Miles F, Voss L, Segedin E, Anderson BJ. Review of
staphylococcus aureus injections requiring admission to
pediatric care unit. Arch Dis Child 2005;90:1274-8.
Todd J. Staphylococcal infections. In Behrman RE, Kliegman RM, Jenson HB (Eds ): Nelson Textbook of Pediatrics
(18th Edn). Saunders, Elseiver; India, 2007;1123-9.
Tunnessen WW Jr: Practical aspects of bacterial skin
infections in children. Pediatr Dermatol 1985;2:85.
9.20 Pneumococcal Disease and its Prevention

Rohit C Agrawal
INTRODUCTION
Pneumococcal disease is as old as antiquity known to
the human kind which could not be controlled effectively
despite extensive research by the medical science, nor
by the advent of newer and newer antimicrobials. This
is one of the most virulent invasive bacterial disease
under five years of age, though elderly population above
65 years of age are equally affected as well. Pneumococcal
disease is number one vaccine preventable cause of
childhood mortality worldwide.
ETIOLOGY
The causative organism Streptococcus pneumoniae is a
gram positive lanceolate shaped encapsulated
diplococcus having a polysaccharide capsule which is
antigenic in nature and determines various serotypes of
the bacteria.
ETIOPATHOGENESIS
Person contracts the infection through respiratory
droplets and then spread occurs via nasopharyngeal
carriage. Once after gaining access the bacterium
pneumococcus has propensity to inhabitate in the
nasopharynx. From the nasopharynx the bacterium

causes the disease by oppsonising phagocytosis by two
modalities; first by direct spread in the adjoining areas
therby causing nonbacteremic pneumonia, sinusitis and
otitis media, secondly by invading the sterile fluid
compartments of the body like blood and CSF thereby
causing bacteremia, bacteremic pneumonia and
meningitis. The later conditions are known as invasive
pneumococcal diseases (IPD).
CLINICAL SPECTRUM
Most vulnerable and the peak age for the invasive disease
is 6 to 18 months due to low immunity. The incidence
starts declining after 5 years only to rise again above 50
years of age. The children from day care centers, bottle
fed, malnutrited from overcrowdings and slums who are
constantly exposed to pollution and cross infections are
at risk for the disease. According to developed world
standards even an episode of otitis media in past and
the children who have received a course of antibiotics in
past one month are also at risk for this disease. The
children who have chronic lung, liver, heart and kidney
diseases, nephrotic syndrome, diabetes, CSF fistulae and
cochlear implants are at moderate risk for this disease.
377
Prematurity
Cerebrospinal fistula
Existing or cochlear implants
Presumed risk
Age
Child care outside
Children younger
the home
than 2 years old
Multiple courses of
Adults over 65 years
antibiotics in last
of age
3 months
Recurrent AOM
Multicentric IBIS Study done under INCLEN over
4 yrs from 1993-97 over a large no of population (5798
children) published in Lancet 1999 shows the distribution
of the invasive pneumococcal disease as follows
IBIS Study [INCLEN] [1993-97] [N-5798]
Figure 9.20.1: Pleural fluid gram stain

Meningitis
Pneumonia
Septicemia
Peritonitis
Others *
37.3%
29.6%
7.6%
7.3%
18.2%
[*Empyema, Arthritis, deepseated, Abscesses, etc.]
Bacteremia without focus beyond neonatal period is

the most common manifestation of the invasive disease
with a mortality rate of 40-50%. Of the survivors of
meningitis 25-50% are likely to get sequelae like MR,
seizures, hearing loss, blindness, spasticity, tube
placements, LDs, speech and language disorders and
restrictive lung diseases there by rendering the morbidity
a matter of major concern.
Figure 9.20.2: Lanceolate shaped diplococci
Children with sickle cell disease, functional and

anatomical aspleenia and immunocompromised with
HIV or transplants are at very high risk for the disease.
Underlying Medical Conditions
High risk
Congenital or acquired immunodeficiency
Sickle cell disease, asplenia, HIV
Moderate risk
Chronic pulmonary disease
Chronic heart disease
Chronic renal insufficiency, nephrotic syndrome
Diabetes
PNEUMOCOCCAL DISEASE BURDEN

According to a statement made by Dr. Lee Jong Wook
director general of WHO every minute one child dies
of pneumococcal disease across the globe. Out of
estimated 2.0 million deaths annually under 5 years of
age due to pneumonia globally, 0.9-1 million are alone
due to pneumococcal pneumonia out of which about 50%
are contributed by India and five other developing
countries. S. pneumoniae, the causative organism of
pneumococcal diseases is responsible for up to 50% of
CAP, 30-50% AOM, a significant proportion of bacterial
meningitis and bacteremia. It is number one cause of
bacteremia beyond the neonatal age. Although CFR is
only 10-22% versus 70% for pseudomonas, the total
number of deaths caused by pneumococcus exceeds
deaths caused by all other pathogens. Estimated
378
incidences of this disease both invasive and noninvasive

are > 25-100 per 100000 < 5 yrs in developed world and
>250-500 per 100000 <5 yrs in developing world.
The epidemiological disease surveillance in India is
poor, the culture threshold is high and data on prevalence
of pneumococcal disease is scanty. According to IBIS
studies it is estimated that 12-35% of all IPD admissions
i.e. 6.6 million out of 22 million episodes of ARI are mostly
due to community acquired pneumococcal pneumonia
with approximately 0.2-0.4 million deaths. Younger the
age more invasive the disease with a peak between 6-18
months due to low immunity.
PREVENTION
The magnitude of pneumococcal disease burden both
invasive and noninvasive in India and developed world
as well is significant enough to warrant its prevention
on priority basis. The modalities of prevention are either
chemoprophylaxis or by effective vaccination. The
question arises why to immunize when antibiotics have
been shown to work and particularly when penicillin
resistance is been least in India (1.3-12.8%). If we glance
at the rapid emerging penicillin and multidrug bacterial
resistance the picture is as gloomy as follows
First case of penicillin resistance in 1970 in US.
US - 1988 - 4.1%, 1990-15%, 2000-33%.
> 40% - Taiwan, Hong Kong, Sri Lanka.
10-40% - US, SA, Europe, China.
< 10% - Pakistan, Malaysia, Australia.
India: IBIS 1.3%, Multicentric 1 -4%,
ANSORP- 3.8-12.8%
Multidrug bacterial resistance in India is no rosy than
globally, which is evident from the following figures
ANSORP Study (in 11 countries including India)
Average Resistance
35.85 %
IBIS Study
SMX/TMP
56.3%
Erythromycin
4.2%
Chloromphenicol
16.6%
Penicillin
1.3%
Ceftriaxone
0%
Vancomycin
0%
In Mumbai 4% in 1998 and 12% in 2000
Hence in the effective prevention and control of this
dreaded childhood bacterial disease with high mortality
and morbidity, immunization is not only prudent and
must but the only logical solution.
Pneumococci worldwide are developing resistance

to commonly used antimicrobials, including penicillin.
Over the past two decades there has been a rapid
emergence of antibiotic resistant pneumococci posing a
formidable threat to health in developed and developing
countries alike. Emerging antimicrobial resistance
emphasizes the need for preventing pneumococcal
infections by vaccination. Arrival of resistant pneumococci was however long overdue in India given the
inadvertent and irrational use of newer antimicrobials.
Though penicillin resistance is fortunately low and that
too intermediate, it is very likely to rise rapidly in near
future.
Nasopharyngeal carriage is an important factor in the
transmission and propagation of the disease. In a study
at a big public sector hospital in Mumbai 74% children
< 5 yrs of age were colonized with S. pneumoniae. In
ANSORP study on 227 Indian children average nasopharyngeal carriage rate was found to be 43.2% out of
which 12.8% isolates were PRSP. For the effective
prevention and control, a break in the chain of nasopharyngeal carriage is very important, which is only
possible by vaccination.
PNEUMOCOCCAL VACCINES
Historical Backgrounds
Polysaccharide vaccines were available as early as 1940s.
A 14 valent polysaccharide vaccine was used in USA in
1970 and found to be not very effective. A 23 valent non
conjugated polysaccharide vaccine was successfully
launched and licensed to use in US in 1987. However
being a polysaccharide it was B and not T cell
dependent; that is poorly immunogenic below the age
of 2 yrs, has low immune memory, does not reduce
nasopharyngeal carriage and does not provide herd
immunity. It has at best 70% efficacy against prevention
of invasive pneumococcal disease in high risk population
but no protection against non bacteremic pneumonia/
otitis media. It is quite a safe vaccine, but practically
useless < 2 yrs of age, when it is required most. In mid
2000 a conjugated polysaccharide vaccine was introduced in US where the capsular antigens of S.
Pneumoniae were conjugated to a non toxic diphtheria
CRM 197 toxin as carrier protein, and thus rendering it
T cell dependent there by making it potent to be used
< 2 yrs of age.

Serotypes
More than 90 serotypes and 45 serogroups have been
discovered world wide. According to IBIS study 36
serotypes were discovered in Indian subcontinent.
11-12 serotypes are the commonest, responsible for most
of the pneumococcal infections world wide, out of which
seven serotypes 4, 6B, 9V, 14, 18C, 19F and 23F are
commonest in developed countries and additionally 4
serotypes 1, 5, 7, and 3 are commonest in developing
countries. According to IBIS study most common
invasive serotypes in Indian children < 5yrs are 6, 1, 19,
14, 4, 5, 3, 29, 7, 15 and 23. Serotypes 1 and 5 together
constitute 29% of pneumococcal disease in India. The
serotype 1 which is the commonest in India is more
common in blood than CSF and also in children above 1
year of age.
The only one available 7 valent conjugated pneumococcal vaccine containing serotypes 4, 6B, 9V, 14, 18C,
19F and 23F being licensed for universal immunization
since 2000 in US and 19 countries in the developed world,
meets successfully 80-90% coverage in those countries
but only 50-55% in the Indian subcontinent.
Immunogenicity- Safety - Efficacy profiles of PCV
Since this vaccine is used routinely in western and
developed countries, studies pertaining to above profiles
are available from those countries only.
Immunogenicity
PCV7 is a highly immunogenic vaccine. 100% of vaccinees are seroconverted after 3 doses, with protective
antibody correlates of 0.35 mcg/ml. However antibody
levels fall over a period of 1 yr, and after a booster dose
100% vaccinees are sero protected for many years due to
amenestic response on boosting with many fold rise in
GMC.
Safety
In a large study of 18000 vaccinees, barring few
insignificant local reactions like erythema and induration
and systemic reactions like fever > 38C, rashes,
drowsiness, irritability, diarrhea and vomiting, no serious
adverse effects were seen. The side effects were similar
to HIB/MMR/DPaT, and less than DPwT.
Efficacy
Most of the studies available are from US and developed
world. NCKP (North California Kaiser Permanent) and
379
CDC (Center for Disease Control and Prevention)

studies showed an excellent efficacy of 97.4% in vaccine
serotypes, 89% in all serotypes and 65% in HIV positive
children. A whopping reduction in IPD to the tune of
94% was experienced within a span of 4-5 years after
the introduction of this vaccine in US for universal
immunization in the year 2000. Efficacy trials showed
30% reduction in radiologically diagnosed pneumonia,
13.3% in clinically diagnosed pneumonia and 8%
reduction in AOM. A trial in Gambia with this vaccine
showed an overall decline in childhood mortality by
16%. Apart from the direct benefits a significant decline
in pneumococcal disease in unvaccinated contacts of
the vaccinees was noticed following introduction of the
vaccine in the immunization program due to herd effect
resulting from reduced nasopharyngeal carriage
(Fig. 9.20.3).
What are the Qualities of PCV7?
It provides efficacy both against IPD and non IPD in
children < 2yrs.
It contains most of the invasive strains of pneumococci.
It significantly reduces the incidence of nasopharyngeal carriage.
It is efficacious against antibiotic resistant strains.
It induces high avidity antibodies with amenestic
response on boosting.
It is very safe and induces minimal and self-limiting
side effects.
It is compatible with concomitant administration of
other vaccines like OPV/IPV, DTPw, DTPa, Measles,
HIB, HepB, Varicella, HepA, etc.
What are the Flip Points of PCV7?
The burden of pneumococcal disease is the greatest
among malnourished, poor and unprivileged
children in India and thus assumes status of public
health importance and ideally should be available to
all the children. However due to its high cost it is
not. Cost is a big prohibitive factor.
As of current data PCV7 covers only 52-55% of
pneumococcal serotypes in India. Limited serotype
coverage
Though a very small but there is emergence of a
challenge of replacement of serotypes there by
causing increase in the disease by other serotypes like
6A, 19A and 35, which are not cross protected.
380
Figure 9.20.3: Efficacy against invasive pneumococcal disease (Adapted from Black S et al)
Who Should Receive it?
Dose Schedule
High risk
(> 2 yrs)
Healthy Children (PCV Vaccine)
All < 2 yrs of age Children from daycare centers/Bottle

fed
Immuno compromised
children
All > 65 yrs of

Multiple courses of
age (23 valent
antibiotics
non conjugated)
Sickel cell disease,

Functional asplenia
and transplant
patients
Routine Vaccination: 3 doses at 6,10,14 weeks and 1

booster at 15-18 months
Catch up vaccination
6-12 months: 2 doses 4-8 weeks apart and 1 booster
at 15 -18 months
12-23 months: 2 doses 8 weeks apart
24-59 months: single dose
Routine
Special circumstances (>2 yrs )
Children with 1 or
2 recent ear
infections
Ch. Lung, Heart and

Liver diseases, DM
Dose is 0.5 ml IM
High Risk Children (PCV and PPV 23)

If affordable, PCV should be given first. For
children aged less than 5 years follow the schedule

mentioned above. For children older than 5 years a
single dose of PCV is recommended (Currently
available PCV 7 though licensed upto age 9 years,
has been shown to be safe and immunogenic in
children older than 9 years as well).
In children aged 2 years or more, PPV 23 should
also be given as a single dose of 0.5 ml IM. If PCV
has been given earlier, a gap of 2 months must be
maintained between PCV and subsequent PPV 23.
A high-risk child who has received PPV 23 in the
past but not PCV vaccine may be offered a single
dose of PCV vaccine at the time of presentation if 2
months have elapsed since receipt of PPV 23.
Only one repeat dose of PPV 23 is recommended
only for children who have sickle cell disease, hyposplenia, asplenia, congenital/acquired immunodeficiency, those on immunosuppressive therapy, renal
failure and nephrotic syndrome. The repeat dose of
PPV 23 may be given after 3-5 years if the child is less
than 10 years of age and after 5 years if child is aged
more than 10 years.
IAP Recommendations
IAPCOI recommends the use of the currently available
conjugate pneumococcal vaccine (PCV 7) after one to one
discussion with parents in healthy children aged less than
2 years
WHO position (2007) since Pneumococcus is a cause of
significant morbidity and mortality in less than 2yrs,
especially in the developing world, this vaccine should
be treated as one of the child survival strategy and should
be included in national immunization program in all
those countries where under 5 mortality is more than
50, despite its limited coverage.
What Holds Good for India in Future
More valent vaccines should be available. A 10 valent
vaccine by GSK with additional serotypes 1, 5, 7 and a
13 valent vaccine by Wyeth with additional 1, 5, 3, 7, 6A
and 19A are in pipeline. Advanced generation Protein
Based vaccines are in phase-I trials, which might cover
all the serotypes, may appear on horizon in next 5 10
years. For better compliance ideally these conjugated
vaccines should come in better combinations with other
381
vaccines. Not to emphasis, better disease surveillance and

broader epidemiological data should be available in
India.
Treatment - Antimicrobial
Penicillin is still most effective and the drug of choice in
pneumococcal disease. Penicillin resistance in India is
only 1.3-4% and that too intermediate (MIC levels
0.06-1 mcg/ml). The pneumococcus achieves the
resistance by alteration in the penicillin binding protein.
For non invasive pneumococcal diseases
i. Amoxycillin 40 mg/kg/day in 2 to 3 divided doses
for 7 to 14 days.
ii. Ampicillin 100 to 200 mg/kg/day in 4 divided
doses IV.
iii. Penicillin 100000 to 200000 units/kg/ day in 4
divided doses IV.
The problem of intermediate resistance can be
overcome by doubling the dose of amoxycillin to 80 to
90 mg/kg.
For invasive pneumococcal diseases
Since the invasive diseases are dreadful and could be
fatal, the drugs of choice should be 3rd generation
injectable cephalosporins to which pneuomococci are
100% susceptible.
i. Cefotaxime 100-200 mg/kg/day in 3 to 4 divided
doses.
ii. Ceftriaxone 100 mg/kg/day in 2 divided doses.
Incase of high resistance to penicillin is suspected
(MIC level > 2 mcg / ml in CSF and 4 mcg / ml in blood)
or in case of life threatening meningitis drugs like
Vancomycin, Tiecoplanin or Rifampicin may be added.
CONCLUSION
Pneumococcal diseases are serious, common but
preventable.
BIBLIOGRAPHY
1. Black S, Shinefield H, Fireman B, et al. Efficacy, safety
and immunogenicity of hepavalent pneumococcal
conjugate vaccine in children. Pediatr Infect Dis J
2000;19:187-95
2. Black S, Shinefield H, Fireman B, Lewis E, Ray P, Hansen
JR, et al. Efficacy, safety and immunogenicity of
382
3.
4.
5.
6.
7.
8.

heptavalent pneumococcal conjugate vaccine in children.
Northern California Kaiser Permanente Vaccine Study
Center Group. Pediatr Infect Dis J. 2000;19:187-95
Center KJ, Prevenar Vaccination: Review of the global
data 2006. Vaccine 2007; 25:3085-9
Centers for Disease Control and Prevention. Direct and
indirect effects of routine vaccination of children with 7valent pneumococcal conjugate vaccine on incidence of
invasive pneumococcal disease United States, 19982003. Morb Mortal Wkly Rep. 2005;54 (36): 893-897.
Cutts FT, Zaman SM, Enwere G, Jaffar S, Levine OS,
Okoko JB et al. Efficacy of nine-valent pneumococcal
conjugate vaccine against pneumonia and invasive
pneumococcal disease in The Gambia: randomized,
double-blind, placebocontrolled trial. Lancet 2005;
365:1139-1146
Fishman SM, et al. Childhood and maternal underweight. In Ezzati, MA. Lopez A. Rodgers and C. Murray,
eds. Comparative Quantification of Health Risks: The
Global and Regional Burden of Disease Attributable to
Selected Major Risk Factors, World Health Organization,
Geneva, 2004.
Hausdorff WP, Bryant J, Kloek C, et al. The contribution
of specific pneumococcal serogroups to different disease
manifestations: implications for conjugate vaccine
formulation and use, part ii. Clin Infect Dis 2000;30:
122-40.
Hausdorff WP, Bryant J, Paradiso PR, et al. Which
pneumococcal serogroups cause the most invasive
9.
10.
11.
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13.
14.
15.
16.
17.
disease: implications for conjugate vaccine formulation

and use, part 1. Clin Infect Dis 2000;30(1):100-21.
Invasive Bacterial Infection Surveillance (IBIS) Group.
Prospective Multicentre hospital surveillance of
Streptococcus pneumoniae disease in India. Lancet
1999;353(9160): 1216-21.
Jodar L, Butler J, Carlone G, Dagan R, Goldblatt D,
Kayhty H et al. Serological criteria for evaluation and
licensure of new Pneumococcal conjugate vaccine
formulation for use in infants. Vaccine 2003;23:32653272.
Levine O, Cherian T. Pneumococcal vaccination for
Indian children. Indian Pediatrics 2007; 44: 491-96.
Available from: URL:http://www.indianpediatrics.net/
july2007/491.pdf
MMWR September 16, 2005/54 36;893-97.
National Health and Family Welfare Survey3, Ministry
of health and Family Welfare, Government of India, 2007.
Poehling KA, Talbot TR, Griffin MR, Craig AS, Whitney
CG, Zell E et al. Invasive pneumococcal disease among
infants before and after introduction of pneumococcal
conjugate vaccine. JAMA.2006;29:1668-74
UNICEF, Pneumonia, the forgotten killer of children,
2006.
Whitney CG, Farley MM, Hadler J, et al. Decline in
invasive pneumococcal disease after the introduction of
protein polysaccharide conjugate vaccine. N Engl J Med
2003;348(18):1737-46.
WHO, Pneumococcal conjugate vaccine for childhood
immunizationWHO position paper. Wkly Epidemiol
Rec 2007 Mar 23:82:93-104. Available from: URL:http://
www.who.int/wer/2007/wer8281.pdf
383
9.21 Hemophilus Influenzae b Disease

RK Agarwal, Anju Aggarwal
Hemophilus influenzae b (Hib) is an important etiology for
meningitis, pneumonia and other invasive infections in
children younger than five years. Serotype b is
responsible for nearly all episodes of meningitis and most
cases of severe pneumonia caused by Hemophilus
influenzae b.
In the neonate wherein nontypable H. influenzae is

more common the disease manifests as septicemia,
pneumonia, respiratory distress syndrome with shock,
conjunctivitis, scalp abscess or cellulitis, meningitis,
mastoiditis and septic arthritis.
Diagnosis
Epidemiology
H. influenzae type b is a natural organism of upper
respiratory tract. Mode of transmission is person to
person mainly by inhalation if droplets. Incidence of Hib
was very high in the prevaccination era. In USA it
accounted for upto 40 percent of pneumonia and
meningitis. With introduction of Hib vaccine incidence
of invasive Hib disease decreased by 99 per cent.
Although firm figures on incidence are lacking there
is evidence for the presence of both Hib meningitis and
pneumonia in India. The invasive bacteria infections
surveillance (IBIS) group study from six-sentinel centers
across the country during 24 months period revealed:
Of the 58 isolates, 96 percent were due to H. influenzae b,
in children less than five years and 69 percent of these
were due to meningitis. The authors concluded that there
is evidence to show substantial burden of Hib disease in
India. Approximately 20 per cent of the mortality due to
lower respiratory tract infection is believed due to
invasive Hib disease.
Etiology
Hib disease is caused by Haemophilus influenzae b which
are small, nonmotile, gram-negative cocco bacilli. Six
serotypes a, b, c, d, e, and f have been defined. The strains
responsible for invasive symptoms are genetically
capsulated forms of type b, is found in 95 percent of cases.
In infants and young children Haemophilus influenzae b
(Hib) is a major cause of meningitis, pneumonia, sinusitis,
septic arthritis, cellulitis and empyema epiglotitis. It may
also cause purulent pericarditis, endocarditis, conjunctivitis, osteomyelitis, peritonitis and epididymoorchitis.
The diagnosis by immunological tests like latex agglutination, counter immunoelectrophoresis (CIE) coagulation tests are confirmatory in over 90 percent of cases
of pyogenic meningitis. For respiratory infections CIE
has been shown to be better than LA (sensitivity in serum
38%; in urine 22 and 44% in concentrated urine). The
specificity is 90 percent in blood culture in children with
H. influenzae infections. Monoclonal antibody tests are
superior to LA and CIE for rapid diagnosis.
Management
Initial antibiotic therapy in meningitis caused by Hib is
cefotaxime or ceftriaxone. Combination of ampicillin and
chloramphenicol can be used but the resistance is
increasing. Duration of therapy is 10 days. Oral amoxycillin should be used for otitis media and pneumonia for
5-7 days. Combination of amoxycillin and clavulanic acid
should be used if there is lactamase producing strains.
chemoprophylaxis with rifampicin in a dose of 20
mg/kg/day for 4 days as single oral dose not exceeding
600 mg/day eradicates Hib from pharynx in approximately 90 percent of cases.
Prevention
Significant decline has been recorded in the incidence of
Hib disease worldover where Hib vaccine has been
included in the National Immunization Schedule. The
vaccine can be given in monovalent or combination
formulation. In geographical region where the burden
of Hib disease is unclear, efforts are made to evaluate
the magnitude of this problem. In view of the demonstrated safety and efficacy of the Hib conjugate vaccines,
Hib vaccine should be included, as appropriate to
national capacities and priorities, in routine infant
384
immunization program. For further details, refer Chapter

8.3 newer vaccines.
BIBLIOGRAPHY
1. American Academy of Pediatrics. H. influenzae infection.
In 2006 Rec Book: Report of Committee of Infections
Diseases, 27th edition. Elk Grove Village IL: American
Academy of Pediatrics 2006;310-8.
2. Funkhauser A, Steinhoff MC, Word J. Haemophilus
influenzae disease and immunization in developing
countries. Rev Infect Dis 1991;13:S542-54.
3. IBIS (Invasive Bacterial Infectious Surveillance Group).
Invasive Haemophilus influenzae disease in India: A
preliminary report of prospective mutihospital surveillance, Pediatr Infect Dis J 1998;17:S169-71.
4. Levine OS, Schwartz B, Pierce Kane M, Development,

Evaluation and implementation of Haemophilus
influenzae type b vaccines for young children in
developing countries: Current status and priority actions,
Pediatr Infect Dis J 1998;17:S95-113.
5. Petola H. Spectrum and burden of severe Haemophilus
influenzae type b disease in Asia. Bull WHO 1999;77:878-87.
6. Wenger JD. Epidemiology of Haemophilus influenzae
type b disease and impact of Haemophilus influenzae
type b conjugate vaccines in United States and Canada.
Pediatr Infect Dis J 1998;17:S132-6.
7. WHO, Global Programme for Vaccines and Immunization: The WHO position paper on Haemophilus
influenzae type b conjugate vaccines. Wkly Epidemiol
Rev 1998;73(10):64-71.
9.22 Typhoid Fever

YK Amdekar
Salmonella group of organisms are responsible for variety
of manifestations such as gastroenteritis, meningitis,
osteomyelitis and abscesses. Typhoid fever is one of the
most important diseases caused by Salmonella typhi. It is
an acute systemic febrile illness. It is exclusively present
in humans. It is an important public health problem in
India. Recently, it has assumed serious proportions,
especially due to increasing bacterial resistance to
multiple antibiotics.
Salmonella organisms are gram-negative bacilli,
motile and having flagella. They possess flagellar antigen
(H) and somatic antigen (O). There exists many
subgroups of these organisms. Most common pathogen
causing typhoid fever is S. typhi. Other subgroups such
as Paratyphi a and b lead to paratyphoid fever, which is
a milder form of typhoid fever. Paratyphi a infection is
prevalent in India but Paratyphi b is rare. There also occurs
other non-typhoidal Salmonella infections.
Epidemiology
S. typhi infection occurs only in humans. It is endemic in
India. It is transmitted by feco-oral route through
contaminated water or food. Acutely infected patients
excrete bacilli in their stool and urine for a variable period
of few weeks. About five percent of infected adults
become chronic carriers who continue to excrete bacilli
in their excreta for a year or longer. It is the adult carrier

who serves as a reservoir of infection. Food handlers and
cooks are potent sources of infection. Most of the infected
children cease to excrete bacilli within 2 to 3 months and
are rarely chronic carriers. Epidemics occur as a result of
contaminated drinking water supply, poor sanitation and
personal hygiene, overcrowding and poverty. Typhoid
fever was on the decline in the last decade and the
estimated incidence was less than 1/1000 population.
However, in the 90s it has gone up by 15 to 20 times.
This is due to variety of adverse factors including laxity
in immunization against typhoid and emergence of
multidrug resistance. Older children and young adults
are most commonly infected though 10 percent cases
occur below five years of age and 1 to 2 percent even
below two years.
Pathogenesis
Incubation period averages to be around 10 to 14 days.
After oral ingestion, bacilli reach the intestines passing
gastric barrier and attach themselves to the mucosa and
partially penetrate the intestinal wall. They are ingested
by the phagocytic cells where they multiply and finally
enter the bloodstream via lymphatics. After transient
bacteremia, bacilli are seeded in various organs like liver,
spleen, gallbladder and bone marrow where they

multiply further. This phase heralds the onset of clinical
illness. Bile serves as a good culture medium for the
growth of organisms and gallbladder discharges large
number of organisms into the intestines. Peyers patches
and other lymphoid follicles take up the bacilli, get
inflamed and sloughed off to form typical typhoid ulcers,
which may lead to two most dreaded complications
hemorrhage and perforation, especially in absence of
proper treatment.
Clinical Manifestation
The disease starts with an acute onset of fever, which
gradually rises over next 2 to 3 days. During this phase,
diagnosis of typhoid fever can hardly be suspected
clinically. Therefore, persistent high fever, toxic look,
coated tongue, gaseous distended abdomen with gurgling
in the lower part and hepatomegaly merit high index of
clinical suspicion of typhoid fever. Fever is high and
continuous, rarely touching the baseline. By the end of
first week, small soft splenomegaly appears often with
symptoms/signs of mild bronchitis. In 25 to 30 percent
of patients, liver involvement is more pronounced with
tenderness and at times mild jaundice. Right hypochondrial pain and tenderness may be severe indicating
presence of acalculous cholecystitis. Signs of meningism
are at times elicited without accompanying meningitis.
Though every organ in the body may be involved in
typhoid fever, clinical manifestations of pneumonia,
myocarditis, osteomyelitis, meningitis, arthritis, etc. are
rare. In fact, characteristic bradycardia seen in adults in
typhoid fever is lacking in children.
Complications of typhoid fever are fortunately rare
in children. Intestinal hemorrhage has been reported in
one to two percent of patients and perforation in
< 0.5 percent. They occur in second week of the illness,
especially in children who remain untreated without
antibiotics. Sudden drop in fever with signs of shock,
pallor or signs of peritonitis suggests the onset of
complications. Late focal infections such as meningitis
endocarditis osteomyelitis, or pneumonia can occur.
Clinical diagnosis of typhoid fever in a previously
immunized child is not easy as disease may manifest with
atypical presentation and progress. Fever may not be
high and continuous. In fact, any pattern of fever is
possible and child may not appear toxic. Typical
abdominal signs may also be absent, which makes clinical
diagnosis very difficult. It is the persistence of fever
385
beyond a week without any obvious clue that should

raise the suspicion of probable diagnosis of typhoid fever.
Blood culture is the only definite diagnosis of typhoid
fever especially in immunized children as Widals test is
often difficult to interpret due to presence of pre-existing
antibodies.
Diagnosis of typhoid fever in a child who is already
on antibiotic therapy possesses a challenge, as blood
culture sent after an antibiotic administration is often
negative. It is important in general not to start an antibiotic without proper attempt at diagnosis.
Diagnosis
Isolation of organisms from blood culture in the first
week and from stool and urine samples in subsequent
weeks is the ideal confirmative test, which should be
pursued in every case of typhoid fever. Clot culture has
proved to be a useful test. Clot is lysed by streptokinase
and inoculated into culture media as for blood culture.
Serum left over from the sample is used for serological
tests.
Widals test measures antibodies to S. typhi, paratyphi
a and b. It is ideal to perform the test on a paired samples
of sera, one taken in an acute phase of illness at the end
of first week and another one, a week later. Rising titer
of antibodies is diagnostic. Interpretation of a test on a
single sample is unreliable, as the disease is endemic in
India and a baseline antibody titer in the community may
be high. High antibody titer against O antigen may
suggest recent infection. Previous immunization with TA
vaccine may account for the antibodies though oral
typhoid vaccine and VI antigen vaccine do not contribute
to the presence of these antibodies. Anamnestic reactions
are seen, especially with H antigens in patients with
fever of different etiologies unrelated to typhoid fever.
Antibodies rise only at the end of the first week and
Widals test may be negative in early stage of the disease.
It may also be negative if antibiotics are administered
too early in the course of the disease. Hence, Widals test
alone should not be relied upon in the diagnosis of
typhoid fever.
Hemogram shows nonspecific findings but leukopenia with eosinopenia in a typical clinical setting may
be highly suggestive and should be preferably followed
by blood culture prior to starting antibiotic therapy.
Appearance of eosinophils on the follow-up hemogram
heralds the beginning of recovery and is observed early
386
in the course of defervescence of fever. Hepatic enzymes

(SGPT) show mild elevation in most patients and serum
bilirubin levels may be raised in few of them, generally
up to 5 mg percent. Abdominal sonography reveals
presence of acalculous cholecystitis in about 30 percent
of patients.
Management
Since the introduction of chloramphenicol in the
treatment of typhoid fever, defervescence of fever was
usually achieved within one week as compared to natural
course of illness spanning over 3-4 weeks. Mortality also
came down from 10 percent to almost 1-2 percent and
rate of complications was reduced significantly. However
in the last 5 years, with emergence of multidrug resistant
strains of S. typhi the course of illness is altered. In spite
of use of newer antibiotics, clinical course is often
prolonged to more than a week, though fortunately,
mortality has remained low.
Chloramphenicol has been the drug of choice till
recently. It is administered in dose of 50 to 100 mg/kg
body wt/day in three divided doses. It is given orally
except in very sick children in whom it may be given
intravenously. It takes about a week to control fever and
the drug must be continued for another week. Relapse
may occur in spite of proper treatment and carrier state
is not prevented by this drug. Major toxic effect of
chloramphenicol is aplastic anemia and is not dose
related. Fortunately, it is rare. Other drugs useful in the
treatment of typhoid fever are ampicillin, amoxicillin and
cotrimoxazole. Furazolidone has also been used even
though the drug is poorly absorbed from intestines and
thus has mainly a local effect and not a systemic effect.
Hence, this drug alone is not recommended for serious
infection.
Emergence of multidrug resistant typhoid fever has

necessitated use of newer antibiotics like cephalosporins
and quinolones. Oral cefuroxime or parenteral third
generation cephalosporins such as ceftriaxone or
cefotaxime are effective. Quinolones have an advantage
of convenient dosage forms but the probable toxic effect
on the growing cartilage is considered against its routine
use. However, it may be used in case no better drug is
available. Quinolones are efficacious, convenient and
cost-effective. The recent epidemic of multidrug resistant
typhoid fever has forced clinicians to use oral ciprofloxacin with good results. Safety of this drug is reasonably
established if used for a short-time in otherwise normal
patients. This drug has an advantage of preventing
relapse and carrier state.
Supportive management includes bedrest, low
residue normal family diet, adequate hydration and
antipyretics for fever.
Prevention
Proper hygienic measures and consumption of clean
uncontaminated food and water ensures reasonable
prevention. Conventional TA vaccine against typhoid
and paratyphoid has an efficacy of about 70 percent.
Newer vaccines against typhoid are oral TY21 and
parenteral VI antigen vaccine. Both of them have similar
efficacy as that of TA vaccine. Thus, routine immunization with any of these vaccines is recommended after
the age of two years.
For IAP - Infectious Diseases Chapter Protocol on
Enteric Fever, refer to Chapter 36.11.2, Page No. 1528.
BIBLIOGRAPHY
1. Adam D. Use of quinolones in pediatric patients. Rev of
Infect 1989;2:111316.
2. Ashkenazi S, Cleary TG. Salmonella infection. Nelson
Textbook of Pediatrics (15th ed) 1996;78490.
3. Koul PB. Multidrug resistant S. typhi infection: clinical
profile and therapy. Indian Pediatr 1991;28:35761.
387
9.23 Leprosy
Rajeshwar Dayal
Leprosy, also known as Hansens disease, is a chronic
granulomatous disease caused by Mycobacterium leprae.
It particularly affects the skin and nerves besides affecting
all the organs.
According to WHO, out of a total of 2,31,361
registered cases of leprosy in the world in June 2007,
82,801 were residing in India. The global prevalence rate
is below 1/10,000 population. Only 4 countries in the
world - Brazil, The Democratic Republic of Congo,
Mozambique and Nepal have yet to achieve the goal of
eliminating leprosy as a public health program.
India achieved the leprosy elimination target at the
end of 2005. Though the total number of registered cases
of leprosy came down to about 82,800 in India (a
prevalence rate of 0.84 cases/10,000 population ), the new
case detection rate did not reduce concomitantly. A total
of 1,39,252 new cases were detected in the year 2007.
Pediatric leprosy constitutes about 10% of the total
disease burden. The age group most commonly affected
in the pediatric leprosy population is 5-14 years, though
in very high endemic countries, prevalence in age groups
0-4 years is also significant. Leprosy affects males more
than females. It is not a hereditary disease and it was
found that infants born to leprous parents, if separated
soon after birth and protected from the exposure, escaped
from the disease. HIV infection has not been documented
to alter the risk of leprosy in areas of high prevalence.
Achieving eradication of the disease from the
elimination stage is a giant task. It requires, the cases to
be identified at an early stage and treated promptly so
that deformity and spread of infection can be prevented.
For the diagnosis of early and suspicious cases of leprosy
newer diagnostic concepts of molecular biological
approaches like PCR, in situ PCR and in situ Hybridisation have evolved and are the need of the time.
SOURCE OF INFECTION AND
MODE OF TRANSMISSION
The only source of infection is the infected human
being. The capacity of multibacillary leprosy patients
to infect is 4-11 times that of patients with paucibacillary leprosy.
Direct Transmission
For direct transmission, a prolonged and close contact is
required. An Intrafamilial contact with a patient is
more risky than an Extrafamilial one.
Untreated lepromatous patients discharge as many
as 100 million bacilli from their nasal secretions everyday.
These bacilli remain viable outside the human body in
the nasal secretions for several days. Inhalation of these
bacilli, via droplets, is now regarded as the most common
mode of entry of leprosy bacilli into contact person. After
inhalation, these inhaled leprosy bacilli enter the
respiratory system from where they are disseminated by
blood to skin and peripheral nerves where depending
on the host immune response, the disease may manifest
either as tuberculoid leprosy( where there is good cell
mediated immune response to M.leprae) or may manifest
as lepromatous leprosy (where there is anergy to
M.leprae).
Other portals of entry include scratched, abraded or
insect bitten skin which facilitates passage of organism
via the droplets laden with with leprosy bacilli through
the epidermis into the dermis, and ingestion of infected
breast milk.
Indirect Transmission
M.leprae remains viable for several days outside the
human body. Occasionally, leprosy may spread by
fomites being used by a patient suffering from multibacillary leprosy. Localized infection via infected
syringes and tattooing needles have been reported.
Incubation period: This varies from a few months to as
long as 20 years with an average between 2 and 5 years.
Onset of this disease is usually gradual but may be
sudden in highly susceptible people.
Early Signs of the Disease
The early signs include:
A hypopigmented patch in the skin, present for a
long duration, non irritating with loss of sensation
to touch, pain and temperature.
388
Thickening of the skin, more red and shiny in

appearance than the surrounding parts; this is more
prominent on face and hands.
Loss of sensation, numbness, feeling of pins and
needles or crawling of ants, tingling sensation in
any part of the body, especially in hands and feet.
There may be paresis in hands and feet or difficulty
in fine movements of fingers.
Appearance of spontaneous blisters and ulcers,
especially in the fingers.
CLASSIFICATION OF THE DISEASE
According to the classification laid down by Indian
Association of Leprologists, the cases have been divided
into 5 broad groups viz, indeterminate, borderline,
tuberculoid, lepromatous and polyneuritic.The borderline group is further subdivided into BB, BL and BT types.
Indeterminate Leprosy
This type of leprosy is seen in only 10 to 20 percent of
infected individuals and is the earliest detectable form
of leprosy.
This is characterized by presence of a single
hypopigmented macule measuring 2 to 4 cm in diameter,
with a poorly defined border without any erythema or
induration. Anaesthesia may be minimal or even absent.
Biopsy may show a granuloma but bacilli are rarely seen
in the section. In 50 to 75 percent of patients this lesion
heals spontaneously, and in the remaining cases it
gradually progresses to one of the classic forms.
Tuberculoid Leprosy
It is characterized by the presence of single or few
asymmetrical, well defined, hypopigmented, erythematous or copper colored patches with sensory
impairment. The entire patch or only its margins is raised
above the level of the surrounding skin. At times, these
patches may not be raised above the level of the
surrounding skin.
Initially, a single nerve trunk related to the lesions is
affected .The nerve trunk becomes enlarged, hard, tender
and later may form a nerve abscess.
In this form of leprosy, the lepromin test is positive
and there is absence of bacilli in the skin smear. On
biopsy, foci of lymphocytes, epitheloid cells arid
Langhans giant cells are seen.
This form of leprosy is the most common, especially

in children and is relatively benign and stable with a good
prognosis.
Borderline Leprosy
Borderline leprosy is further classified into 3 subtypes,
on clinical and histological criteria.
Borderline Tuberculoid (BT) Leprosy
Here the lesions are greater in number but smaller in
size than in tuberculoid leprosy. There may be small
satellite lesions around older lesions and the margins of
the borderline tuberculoid lesions are less distinct and
the centre is less atrophic and anaesthetic.This form
usually involves thickening of 2 or more superficial
nerves.
Mid Borderline (BB) Leprosy
In this subtype, the lesions are more numerous and
heterogenous.The lesions may become confluent or even
plaques may be present. The borders are poorly defined
and the erythematous rim fades into the surrounding
skin. Hyperanaesthesia is more common than anesthesia.
Borderline Lepromatous (BL) Leprosy
In borderline lepromatous leprosy there are a large
number of asymmetrically distributed lesions which are
heterogenous in appearance. Macules, papules, plaques
and nodules may all co-exist. Usually, the individual
lesions are small unless confluent. Anesthesia is mild and
superficial nerve trunks are spared.
Neuritic Leprosy
This may be of primary or secondary variety. In the
former, the nerves are directly infected without any skin
lesion while in the latter infection spreads up the nerves
from leprous skin lesions. The affected nerves become
thickened and tender, producing sensory motor and
trophic changes in their areas of distribution,This
dysfunction leads to deformities, neuropathic ulcers and
lagophthalmos which may result in serious eye
complications.
Neuritic leprosy most commonly involves the ulnar,
median, lateral popliteal, tibial, great auricular and rarely
radial nerves. lt also affects the V and VII cranial nerves.

Lepromatous Leprosy
Most cases of lepromatous leprosy develop from
borderline leprosy (BB or BL). This form of leprosy is
relatively uncommon in the pediatric age group. There
are two symptoms, which may precede the classical skin
lesions by months or years, and serve to alert the
physician to a possible early diagnosis. They are: (i) nasal
symptoms and (ii) edema of legs. The nasal symptoms
chiefly constitute, stuffiness, crust formation and blood
stained discharge. Edema of legs and ankles is always
bilateral, usually prominent late in the evening and
disappears after overnight rest.
Skin lesions may take the form of macules, papules,
nodules and a combination of them. Numerous symmetrically distributed erythematous or coppery, shiny,
macules with ill defined margins are usually the first ones
to appear. Patients may have a leonine face due to loss
of eyebrows and eyelashes. There is no sensory
impairment in these lesions but as the disease progresses,
many peripheral nerves get symmetrically affected. Due
to enormous bacillary infiltration, nerves are initially
softer and larger than normal and are tender. In advanced
cases, nerves become thin and hard due to fibrosis and
389
result in extreme anesthesia. The skin smear is almost

always positive and the lepromin test is negative.
This form of leprosy (LL) is the most infectious, prone
to lepra reactions and if left untreated, the prognosis is
poor.
The features of these varieties of leprosy are
summarized in Table 9.23.1. As age advances, the disease
moves from tuberculoid end of the spectrum towards
the lepromatous end.
Reactions
Reactions are acute exacerbations due to changes in the
host parasite immune relationship. They are common
during initial years of treatment.
The following types are noted:
1. Type 1: Reversal reaction: This is seen in borderline
cases and consists of acute tenderness and swelling
at the site of lesion. Irreversible nerve injury can occur
if this reaction is not treated immediately.
2. Type 2: Erythema nodosum leprosum reactions (ENL):
This occurs in lepromatous and borderline lepromatous cases as a systemic inflammatory response.
There is high fever, migrating polyarthralgia, orchitis,
TABLE 9.23.1: Clinical aspects of tuberculoid, borderline and lepramatous leprosy

Observation
of tests
Types of leprosy
TT
BT
BB
BL
LL
Number of
lesions
Single usually
Single or few
Several
Many
Very many
Size of lesions
Variable
Variable
Variable
Variable
Small
Surface of lesions
Very dry,
sometimes scaly
Dry
Slightly shiny
Shiny
Shiny
Sensation of
lesions
Absent
Markedly
diminished
Moderately
diminished
Slightly diminished
Not affected
Hair growth
Absent
Markedly
diminished
Moderately
diminished
Slightly diminished
Not affected
AFB in lesion
Nil
Nil or scanty
Moderate numbers
Many
Very many (plus

globi)
AFB in nasal
scrapings or in
nose blows
Nil
Nil
Nil
Usually nil
Very many
(plus globi)
Lepromin test
Strongly
positive
(+++)
Weakly
positive
(+ or ++)
Negative
Negative
Negative
AFB-Acid Fast Bacilli ; TT-Tuberculoid; BT- Borderline Tuberculoid; BB- Mid Borderline ; BL- Borderline Lepramatous; LL-Lepramatous
Leprosy
390
iridocyclitis and lymphadenitis. Tender red papules

or nodules resembling erythema nodosum are seen
characteristically.
DIAGNOSIS
Diagnosis of leprosy is based on the presence of any one
of the following cardinal signs:
1. Characteristic skin lesion with partial or total loss of
sensation in the affected skin lesion or in the area of
the skin supplied by the peripheral nerve involved,
with or without the presence of thickened nerves.
2. Presence of acid fast bacilli in the skin smear.
Smear Examination
Sites of bacteriological examination are usually the most
affected parts of the lesion. If no definite patches or areas
of thickened skin are visible, smear should be taken from
ear lobules and buttock. Smears should be made by slit
and scrape method and stained by Ziehl-Neelsen
staining. Smears are positive in LL, BL and some BB and
BT cases. It is of limited help in TT and indeterminate
lesions and patients with early atypical clinical
presentation.
Histopathology
In some cases of indeterminate lesions it becomes
necessary to carry out a histological examination for the
purpose of diagnosis and classification of the lesion.
Bacillary Index
It is a semiquantitative estimation of the density of bacilli
present in the skin smears and, biopsies and is measured
on two scales, namely the Dharmendra scale and Ridley
scale. It measures the total acid fast bacilli in microscopic
field, which includes both live and dead bacilli.
Patients are labeled as having paucibacillary infection
when there are < 5 skin lesion and no bacilli on skin
smears. They are labelled as having multibacillary
infection when there are > 6 skin lesions and bacilli are
present on skin smears. The bacterial index can range
from 0 (No bacilli in 100 oil immersion field) to 6 (>1000
bacilli per field).
Immunological Methods
Test for Cell Mediated Immunity
Lepromin test: Lepromin test is not a diagnostic test for
leprosy but it has been found to be useful for
classifying the disease. This test is positive in cases of

TT and BT, negative in LL, BL and weakly positive
and variable in BB leprosy. The lepromin negative
contacts have been found to be at a much higher risk
of developing disease, than the lepromin positive
contacts. This test signifies immunity of person, i.e.
cell mediated immunity against Mycobacterium leprae
or its antigen. Two kinds of lepromin are commonly
used (a) crude antigen of Mitsuda, and (b) the refined
antigen of Dharmendra.
Serological Assays
Specific serological tests can detect subclinical infection.
The major serological assays include:
Fluorescent leprosy antibody absorption test (FLA-ABS): This
technique is highly sensitive in detecting the antibodies
against M. Leprae antigen by immune-fluorescent
technique and is useful in identifying healthy contacts
of patients who are at risk of developing disease.
Radioimmunoassay (RIA): It detects antibodies to the cell
wall antigens of M. Leprae.
Enzyme-linked immunosorbent assay (ELISA): PGL-ELISA
was found highly positive in multibacillary cases, but
positivity in paucibacillary and subclinical cases was
quite low.
Further simplified dot ELISA and dipstick ELISA
using a monoclonal antibody targeting PGL-1 have also
been studied.
Serological testing is not useful for diagnosis as it does
not detect most paucibacillary cases and it remains
positive even after treatment of multibacillary patients.
MOLECULAR BIOLOGICAL APPROACHES
Identification of organisms can be done in a more rapid
and specific way, both from culture and directly from
clinical specimen, by recombinant DNA technology.
Based on the gene sequences of M.Leprae, several probes
have been designed in recent years. Our institute has also
studied the probes developed at Agra and found them
to be of immense help for early diagnosis of the disease.
During the recent years, several gene amplification
techniques (PCR) for amplifying M. Leprae specific
sequences from variety of specimens have been published. These have been reported to be highly sensitive
and specific.

In Situ PCR
Our study has shown that in situ PCR, with the added
advantages of providing structural correlates and
permitting concomitant study of tissue pathology,
improves the diagnostic yield especially in early and
doubtful cases of leprosy where the histopathology is
nonspecific.
In Situ Hybridization
Again our pioneer study has shown that in situ
hybridisation improved the diagnostic yield significantly.
In Situ PCR on Slit Skin Smears
Another latest in our series of molecular biological
approaches is the utility of in situ PCR on the slit skin
smears. It was found that with an average positivity of
72%. In situ PCR on slit skin smears was better than that
on skin biopsies (60%). In addition it has the added
advantages of being minimally invasive and less
cumbersome and can be performed even at sites from
where skin biopsy is difficult.
TREATMENT
Leprosy patients should be treated with patience,
perseverance and understanding. Besides the medical
treatment, the patients and their parents need moral
support and reassurance. Parents should be explained
hygienic measures, proper diet and importance of taking
treatment completely and regularly.
391
TABLE 9.23.2: Dosage of antileprosy drugs for children

with paucibacillary leprosy (Indeterminate, TT, BT)
Age group
(Yrs)
Dapsone: Daily dose

Unsupervised (mg)
3-5
6-14
15
25
50-100
100
Rifampicin: monthly
dose supervised (mg)
150-300
300-450
600
therefore, no child will require ethionamide/prothionamide which are potent hepatotoxic drugs. Parents should
be advised to give rifampicin on empty stomach and
clofazimine with meals or with a glass of milk. Red staining of skin and lesions is very common with clofazimine.
Treatment of Reactions
Drugs commonly used in these conditions are antimalarials like chloroquine (given orally), antimonials, e.g.
potassium antimony tartratelV and fantosin IM,
clofazimine, corticosteroids and thalidomide (all the
three given orally). Symptoms like iritis and neuritis
occurring during reactions (or occurring independently)
should be properly treated in order to avoid irreversible
sequalae, i.e. deformities and neuropathic ulcers.
Duration of Therapy
The WHO study group has recommended treatment of
paucibacillary cases for only six months and of multibacillary cases for twelve months.
Multidrug Therapy
Prophylaxis
It is now a well known fact that, simultaneous administration of several different antibacterial agents may
prevent the emergence of drug resistant mutants. The
dosage schedule for children as recommended by WHO,
is shown in Tables 9.23.2 and 9.23.3. In the MDT, it is
assumed that clofazimine is acceptable for children and,
Leprosy vaccine: There is no established vaccine against

leprosy as yet.
The results of 5 to 9 years follow up study conducted
on 1,20,000 randomized individuals in South Africa,
indicate that BCG booster vaccination (2 dose BCG
regimen given at 0 and 3 months) provides 50 to
TABLE 9.23.3: Dosage of antileprosy drugs for children with multibacillary leprosy (BB, BL, Polyneuritic)
Age groups
(years)
Dapsone: Daily dose

unsupervised (mg)
Rifampicin: monthly
dose supervised (mg)
Clofazimine
Unsupervised dose(mg)
Monthly dose (mg)
100 once weekly
100
3-5
25
150-300
6-14
50-100
300-450
150 Once weekly
150-200
15
100
600
50 daily
300
392
75 percent protection against leprosy.The combined BCG

M.Leprae vaccine offered no additional benefit.
In order to accelerate the elimination of leprosy as a
public health problem in India the following activities
should receive high priority: 100 percent MDT coverage
and accessibility,, high treatment completion and cure
rates and inclusion of leprosy in the training curricula of
the general health staff off all categories.
2.
3.
4.
BIBLIOGRAPHY
1. Dayal R, Agarwal M, Natrajan M, Katoch VM, Katoch
K, Singh Kalpna, et al. PCR and in-situ hybridization for
5.
diagnosis of leprosy. Indian Journal of Paediatrics 2007;

74:645-8.
Dayal R, Singh SP, Mathur PP, Katoch VM, Katoch K,
Natarajan M. Diagnostic value of in situ polymerase
chain reaction in leprosy. Indian Journal of Paediatrics
2005;72:1043-6.
Dwight A Powell. Hansen disease (Mycobacterium leprae).
In Kliegman, Behran, Jenson, Stanton (Eds): Nelson
Textbook of Pediatrics, 18th edn. Philadelphia, Elsevier
Saunders, 2008;1255-8.
Leprosy. In Park K (Ed): Textbook of Preventive and Social
Medicine, 19 edition. Bhanot Publishers 2007;264-76.
WHO Health Organisation: Leprosy. Global situation,
Wkly Epidemiol Rec, Nov. 25, 2007;82:225-32.
9.24 Leptospirosis in Children

S Ramesh
Leptospirosis is an acute febrile generalized disease
whose manifestations arise from the effects of generalized vasculitis.
Leptospirosis, an infectious disease that effects
humans and animals, is considered the most common
zoonosis in the world. Leptospirosis is caused by
pathogenic spiral bacteria that belong to the genus
Leptospira. The genus Leptospira was originally thought
to have two species L. interrogans which is pathogenic
and L. biflexa which is saprophytic. More recent work
has identified 7 distinct pathogenic species, which appear
as more than 250 serologic variants or serovars which
have been classified into 25 serogroups.
PATHOPHYSIOLOGY
Human beings become infected through moist and
abraded skin and mucous membranes. The primary
lesion caused by leptospire is damage to the endothelial
lining of small blood vessels with resultant ischemic
damage to the liver, kidneys, meninges muscles, etc.
CLINICAL FEATURES OF
LEPTOSPIROSIS SYNDROME
Leptospirosis can occur as:
Anicteric leptospirosis (common, less severe)
Icteric leptospirosis (rare, but severe).
Anicteric Leptospirosis
EPIDEMIOLOGY
The rat is the principle source of infection. Other
important reservoirs include dogs, cats, livestocks and
wild animals. The infected animals excrete spirochetes
in urine for an extended period of time. Human infection
results from exposure to leptospire contamination of
stagnant water with sewerage.
Recreational activities like swimming, out door sports
played in contaminated water are other reasons to
acquire leptospirosis.
Occurs as a biphasic illness.

The first phase is septicemic phase followed by the
immune phase.
Septicemic phase is associated with the multiplication
of Leptospira in the bloodstream, and immune phase
which follows is characterized by the development of
antibodies to Leptospira.
Septicemic Phase
The child may present with fever of abrupt onset,
associated with muscle pain, headache, nausea,
393
vomiting, abdominal pain, etc. Less common findings

include conjuctival suffusion, a transient skin and
mucosal rash, photophobia, and mild signs of meningism. The septicemic phase lasts 4 to 7 days.
onwards. False-positive results are common. Extrusion

of fibrillar material from RBCs mimics leptospirosis.
Urine samples must be examined within half an hour of
collection.
Immune Phase
2. Detection of Antibodies to Leptospirosis
Immune phase is characterized by circulating antibodies.

There is brief asymptomatic interlude between the
septicemic and immune phase.
The important clinical features are in the Immune
phase are:
A. Fever
B. Aseptic meningitis with abnormal CSF profile is seen
occasionally among children.
C. Hepatitis is characterized by enlargement of the liver,
elevation of bilirubin with a modest increase in liver
enzymes.
D. Renal involvement is characterized by abnormal
findings in the urine analysis (hematuria, proteinuria
and casts), azotemia with oliguria or anuria. Renal
failure is the principle cause of death of fatal cases.
Note: In clinical practice distinction between the
septicemic and immune phase may not be seen.
Icteric Leptospirosis (Weils Syndrome)
Weils syndrome is characterized by liver, kidney, and
vascular dysfunction in addition to the other symptoms
of anicteric leptospirosis. Individuals with Weils
syndrome will usually develop jaundice without
hepatocyte destruction and azotemia by the third to
seventh day of illness. The liver may be enlarged and
there may be right upper quadrant tenderness. With
increasing severity of jaundice, the individual is at greater
risk of developing renal failure, hemorrhage, and
cardiovascular collapse. Uremia, oliguria, and anuria
may occur with the onset of kidney failure unless dialysis
is provided. Fatalities due to icteric leptospirosis are
typically due to renal failure, cardiopulmonary failure,
and fatal hemorrhages.
Laboratory Diagnosis
The following are the tests currently available for routine
diagnosis.
i. Macroscopic slide agglutination test (MSAT): It is a

genus specific test and uses killed leptospira as
antigen.
ii IgM-ELISA and Dipstick test: These tests detect
genus specific IgM antibodies which tend to become
positive early in the disease around 4th day of
illness. The above mentioned tests are sensitive but
not specific, they do not differntiate between
pathogenic and saprophytic leptospira, the infecting
serovar cannot be identified.
iii Microscopic agglutination test (MAT): It is a serovar
specific test and is the gold standard of serological
tests to detect leptospirosis. High specificity is the
hall mark of MAT. The MAT is usually positive 10
to 12 days after symptom onset; although, antibodies
are usually present by five to seven days after
symptom onset. As it involves the use of a battery
of live leptospiral cultures to be used as antigen, it
is done in specialized labs only. The available
antisera may not identify all leptospira serotypes,
specific serotypes commonly seen in the community
are usually identified including the virulent and
serious types. Initial high titer of 1:80 or rising titers
(four fold increase) obtained 2 weeks apart are
diagnostic.
TREATMENT
Initiation of treatment early in the disease before 7th day
shortens the clinical course, penicillin is the drug of choice
and the dose is 250,000 units/kg/24 hr in 4 to 5 divided
doses for a period of 7 days. For penicillin allergic
children, erythromycin, Amoxycillin, Ofloxacin are
alternate choices for children under 8 years and
Tetracycline 10 to 20 mg/kg/day in 3 divided doses for
children beyond 8 years.
Doxycycline is the alternate drug to tetracycline given
in a dose of 100 mg twice for 5 days.
1. Dark Field Microscopy (DFM)
OUTCOME
Used to detect leptospires in blood within the first 10

days of illness and from the urine from the second week
Despite the possibility of severe complications the

disease is most often self limited and non fatal.
394
Mortality is due to renal failure in anicteric

leptospirosis, and due to renal failure, cardiovascular
collapse and hemorrhagic manifestations in icteric
leptospirosis.
BIBLIOGRAPHY
1.
Izurieta R, Galwankar SG, Clem AS. Leptospirosis: The

Mysterious Mimic. J Emerg Trauma Shock 2008: In
print.
9.25 Chickenpox (Varicella)

Chickenpox is a highly infectious viral disease in children
and is characterized by the appearance of successive
crops of typical rash with mild constitutional symptoms.
Etiology
Chickenpox is caused by Varicella-zoster virus belonging
to the herpesvirus family. It is a DNA virus. Varicellazoster virus has the capacity to persist in the body after
the primary infection. It persists in the sensory nerve
ganglia. Primary infection with Varicella-zoster virus
results in chickenpox. Herpes zoster is the result of
reactivation.
Epidemiology
Man is the only known source of infection. Most children
are affected by 15 years of age, with peak incidence
between 5 and 9 years. However, the disease can occur
at any age including neonatal period. In the tropics the
age is often shifted to the right. Epidemics occur in
December to February. Spread of infection occurs either
through person to person contact or droplet infection.
Immunity is lifelong after an infection. Infection rate in
household contacts is almost 85%. Incubation period is
10-21 days. The period of infectivity is 1 to 2 days before
and up to 6 days after the onset of the rash.
Prodromal symptoms are fever, malaise, anorexia,
headache, which may precede the characteristic rash by
24-48 hours. The prodrome is marked in older children
compared to younger children. The rash typically begins
as crops of small, red papules which almost immediately
develop into clear, often oval tear drop vesicles on an
erythematous base. The vesicles are not umbilicated.
Soon they become cloudy and then dry up forming scabs
which fall off in the next 5 to 15 days. These lesions

usually appear in crops for 3 to 4 days and thus various
stages of the rash from macular, papular, vesicular and
crusting may be seen at the same time. Varicella lesions
are intensely pruritic. The rash has a characteristic
centripetal distribution, the lesions being more on the
trunk, back and shoulders with fewer lesions over the
scalp and the extremities. Vesicles may be seen in the
oral mucosa, pharynx, larynx, trachea, conjunctiva and
genitals. Rarely the rash becomes hemorrhagic in
association with thrombocytopenia. The condition
generally improves within 7 days.
Varicella bullosa is an uncommon variant mainly seen
in children less than two years of age. Congenital varicella
may manifest at birth or appear within a few days after
birth in infants whose mothers have an active infection.
It is associated with high mortality in newborn if they
acquire the disease from the mother when she gets
varicella 1 week before or after the delivery. The primary
infection has occurred in intrauterine life.
Congenital varicella syndrome The risk of embryopathy
is determined by the gestational period. It is highest
during embryogenesis, during innervations of limb buds
and maturation of the eyes. Eye and brain involvement
is highest during 16-20 weeks of gestation. The disease
involves mainly the eyes, skin, brain, and lungs.
Dermatomal zig zag scarring known as cicatrix is
diagnostic of congenital varicella syndrome. Aplasia of
brain, cataract and microcephaly may occur occasionally.
Diagnosis
The diagnosis is mainly clinical. The virus may be isolated
from vesicular lesions during the first 2 to 4 days of
eruption. Diagnosis may also be accomplished by
immunofluorescent staining of vesicular scrapings.

Serological tests for diagnosis include latex agglutination
test, indirect fluorescent antibody and enzyme immunoassay.
Complications
Chickenpox is usually a mild disease in children with
few complications. Complications are more common in
immune compromised children. The important complications are as follows:
i. Secondary bacterial infections of skin and mucosal
lesions. Varicella gangrene and necrotizing fascitis
are rare complications.
ii. Varicella pneumonia.
iii. Bleeding into the lesions due to thrombocytopenia
iv. Purpura fulminans due to associated consumptive
coagulopathy.
v. Reyes syndrome.
vi. Bacterial sepsis, arthritis, osteomyelitis, hepatitis and
glomerulonephritis.
vii. Post chickenpox encephalitis is a rare complication;
cerebellar signs are common in this. Myocarditis and
pericarditis are very rare.
viii. Reactivation of latent virus after a primary infection
may result in Herpes zoster later.
Treatment
Treatment is mainly symptomatic and supportive.
Paracetamol is given to control fever. Aspirin should be
avoided as it may increase the risk of Reyes syndrome.
Antihistaminics are advised to reduce pruritus.
Fingernails should be trimmed to prevent scratching.
Acyclovir is an antiviral drug available in tablets and
liquid form. It is safe, effective against Varicella but it is
not routinely recommended in uncomplicated infection
as Varicella is a self limiting disease, there is low risk of
complications in children, treatment has a marginal
benefit and the therapy is costly. Acyclovir is indicated
in immune compromised children. The dose for oral
therapy is 20 mg/kg/dose, maximum 800 mg/dose,
given as four doses per day for 5 days. It is more effective
when treatment is initiated within 24 hours of onset of
disease. There is dubious clinical benefit if initiation of
treatment is delayed more than 72 hours after onset of
exanthem.
395
Disseminated disease requires early IV acyclovir for

7 days. In severely immune compromised children rapid
IV therapy may be needed in a dose of 10 mg/kg/dose 8
hourly for 7 days.
Varicella-zoster immunoglobulin (VZIG) may be
used within 48 hours after exposure for the maximum
protection in high risk groups. These include neonates,
children with leukaemia, on steroid therapy and
pregnant women.
Prognosis
Mortality is 4 times higher in infants and adults have 25
times more chances of dying. Mortality is less in children.
The common cause of death in children is encephalitis,
pneumonia and DIC.
Prevention
Varicella transmission is difficult to prevent because the
infection is contagious 24-48 hours before the onset of
rash and until the vesicles are crusted, which is usually
3-7 days.
Varicella is a vaccine preventable disease. Live
attenuated varicella vaccine is safe and is almost 90%
effective in preventing severe diseases. Approximately
10-20% may have breakthrough varicella, a modified
manifestation of the illness in a mild form. The Global
Varicella Vaccines the first dose at 15 months and the
second at 4-6 years. It will be ideal to administer the
second dose at 5th year along with DTP booster and OPV.
IAP recommends vaccination of children after 12 months
to 13 years with a single dose of Chickenpox vaccine.
Children older than 13 years should be given 2 doses at
one month interval.
BIBLIOGRAPHY
Services CDC, 2007.
2. India EPI fact sheet, 2003, country Fact sheet
WHOSEARO, 2004.
3. Meyers MG, Seward JF, LaRussa PS. Varicella-Zoster
Virus. In: Kliegman RM, Jenson HB, Behrman RE,
Stanton BF, editors. Nelson Textbook of Pediatrics. 18th
edn. Philadelphia: Elsevier 2007;1337-41.
396
9.26 Dengue Illnesses

Ashok S Kapse
At the end of the previous century, the world faced the
resurgence of several infectious diseases, dengue being
one of the most significant in terms of morbidity and
mortality. The dengue virus is transmitted to humans
by the bite of a domestic mosquito, Aedes aegypti being
the prime vector although some other species such as
Aedes albopictus also are of importance. Four viruses,
dengue-1 to 4, classified in an antigenic complex of the
flavivirus genus, family Flaviviridae, are the etiological
agents of this disease. Infection with one of these
serotypes does not provide cross-protective immunity.
Thus persons living in a dengue-endemic area can have
four dengue infections during their lifespan.
ADVENT OF DHF
Over the last two hundred years dengue was known to
the physician as a self-limiting benign febrile condition;
however in the mid 1950s images of dengue illnesses
underwent a drastic change. South East Asian countries
experienced epidemics of a serious disease associated
with dengue viruses. Patients afflicted from this new
illness exhibited two potentially mortal symptoms;
bleeding diathesis and shock. Dengue hemorrhagic feverdengue shock syndrome (DHF-DSS) was the new name
coined for this entity. Since then the disease has spread
to large areas of the world and is posing a progressively
escalating public health problem in the tropics and
subtropics. Today 2.5 billion people live in dengue
endemic areas and disease is reported from over more
than 100 countries. Though the true incidence is not very
well-known, yearly 50 to 100 million cases of dengue
fever (DF) and few lack cases of DHF are estimated to
occur worldwide. In 1998, 1.2 million cases of DF and
DHF were reported to WHO, including 3442 deaths.
DENGUE ON RISE
Two factors directly responsible for the burgeoning
incidence of DF and DHF areproliferation in the density
and geographic distribution of the vector, and marked
increase in the rate and geographic range of virus
transmission. Major global demographic changes such
as uncontrolled population growth, unplanned urbanization resulting in substandard housing, and need for water
storage have greatly aided the vector proliferation. The
increase in air travel allows the movement of the different
serotypes, strains, and even genotypes of virus from one
region to another. Individuals in viremic phase are able
to introduce a new virus into a vulnerable population.
In general, factors that augment the contact between
vector and host favor an increase in dengue transmission.
Climatic changes also influence virus evolution. WHO
has reported that a temperature rise of 1 to 2C could
result in an increase in the population at risk by several
hundred million, with 20, 000 to 30,000 more fatal cases
annually.
In spite of multiple dengue strain endemicity and
countrywide invasion of Aedes aegypti, till very late India
remained a silent zone [free of DHF]. However by late
eighties this scenario started changing, beginning from
Surat in 1988, and sharp outbreaks of DHF have occurred
all over the country. In the last decade many cities
including Delhi, Kolkata, Bangalore, Chennai, Jaipur and
Gwalior have suffered of DHF epidemics.
PATHOPHYSIOLOGY
For years, pathogenesis of DHF has been a matter of
controversy. Some workers argued that secondary
infection was the main factor for the severity of this
disease, whereas others thought that viral virulence was
of prime significance. Today, the majority view is that
secondary infection is the main risk factor for DHF;
however, other factors such as viral virulence and host
characteristics also have important bearings.
DHF occurs as an outcome of a very complex mechanism where virus, host, and host immune responses
interact to give the severe disease in 2 to 4 percent of
individuals with secondary infection.
Taking into account the international experiences, a
basic hypothesis for the development of DHF epidemics
was published in 1987. The intersection of three groups
of factors namely host, viral, and epidemiological
determine the occurrence of a DHF epidemic. The
epidemiological and viral factors are the determinants
for an outbreak of the disease. Individual risk factors such

as sex, race, and chronic diseases are predisposing
elements which determine the occurrence in a certain
race or age group. However, the pre-existence of
antibodies is the most vital individual risk factor.
Antibody Dependent Enhancement
First infection with any of the dengue viruses in a dengue
virgin body results in self-limiting febrile illness and
recovery from this first infection is accompanied by
generation of immunological responses. Epitopes present
on E protein are capable of inducing homologous as well
heterologous neutralizing antibodies. Levels of these
antibodies have a governing role in driving dengue
infection to more or fewer infected cells.
People infected with one serotype maintain a life-long
protective immunity to infection by the homologous
virus. However protective immunity to infection with
heterologous serotypes is transitory. It has been proposed
that neutralizing antibodies down-regulate the severity
of the disease. During a secondary infection with a
different serotype, the presence of low amount of
heterotypic neutralizing antibodies could prevent severe
disease. On the other hand, when no neutralizing
antibodies are present, heterotypic antibodies form
complexes with dengue viruses, which infect mononuclear phagocytes with enhanced efficiency and as a
consequence a higher number of cells are infected. This
phenomenon has been called antibody dependent
enhancement (ADE). Halstead et al in 1970 observed that
DHF occurs in situations where more than one serotype
circulates. Epidemiological and serological studies done
in Thailand and Cuba firmly established that secondary
infection is a major risk factor for DHF.
Children are at higher risk of acquiring DHF than
adults. Age-specific DHF incidence is observed to be
bimodal, with severe cases peaking at about 7 months of
age and again at 3 to 9 years of age. DHF or DSS occurred
in infants almost exclusively during primary dengue
infections. These infants were born to dengue immune
mothers and had acquired maternal dengue antibody
and subsequently experienced a dengue infection. On
the other hand, children 3 to 5 years old have DHF during
a secondary infection. Baseline microvascular permeability in children is supposed to be significantly greater
than that of adults and this partly explains why DHF is
more frequently observed in children.
397
There seems to be no time limit to sensitization after

a primary dengue infection. The 1997 Cuban epidemic
clearly demonstrated that dengue-2 DHF could occur
even after 16 to 20 years of the primary dengue-1
infection. Besides secondary infection, chronic diseases
such as bronchial asthma and diabetes have been
suggested as risk factors for DHF. Finally, whites have
higher risk of developing DHF than blacks.
Cellular Factors and Cytokines
Neutralizing antibodies are key factors in the etiopathogenesis of the disease; however, the cellular
immune response is also of immense significance. Recent
observations suggest a massive T-cell activation due to
interactions with infected monocytes, and release of
pathogenetic cytokines as a consequence of this
interaction. Cytokines such as TNF [tumor necrosis
factor], interferon, interleukin-2 [IL-2], IL-6, IL-8, and IL10 are found to be greatly elevated in DHF. High levels
of TNF could be responsible in part for transient vascular
damage. Recently a protein of 22 to 25 kDa has been
detected in sera of DHF patients, this factor is able to
induce increased capillary permeability in mice, and is
capable of reproducing all the pathological lesions that
are seen in human beings.
Factors Responsible for Bleeding
Several factors such as vasculopathy, prothrombin complex deficiency, thrombocytopenia and platelet
dysfunction are thought to be responsible for hemorrhage
in DHF. However mechanisms that initiates bleeding is
yet to be established. Various reasons for instance, high
levels of platelet-activating factor inducing platelet
consumption, virus-antibody complexes on the platelet
surface and presence of cross reactive IgM antibodies,
causing platelet lysis have been thought to be responsible
for thrombocytopenia in DHF.
Genotype and Disease Severity
In spite of all the existing knowledge, it is still uncertain
what kind of host and virus-specified factors determine
why certain individuals have only mild DF while others
develop DHF. Viral strains, genotypes, mutants, and
sequence of infective strains are important contemplations. Dengue 2 genotype of Southeast Asian origin, is
found to be related to most of the DHF epidemics in
398
Southeast Asia and America. On the other hand, the

American genotype, is only related to DF epidemics in
the American region. Recently, some amino acid changes
on M and E proteins of dengue 2 strains have been found
to be associated with DHF epidemics. The genetic
variation between genotypes could be responsible for
differences in virus interactions with macrophages and
suggest that certain strains are more virulent than others.
Morens and Halstead reported that subtle antigenic
differences affect the degree to which strains form
immune complexes with heterotypic antibodies.
CLINICAL FEATURES
Figure 9.26.1: Distribution of dengue illnesses
Spectrum of Presentations
Ranging from asymptomatic infection, to mild undifferentiated fever, to fatal shock, dengue illnesses have wide
spectrum of clinical presentations. WHO identifies two
types of illnessesdengue fever (DF) and dengue
hemorrhagic fever (DHF). Dengue shock syndrome
(DSS) is a severe subset of DHF (Fig. 9.26.1).
Dengue fever again presents in two ways: classical
dengue fever and undifferentiated febrile illness.
Classical Dengue Fever
Dengue in its classical form produces a characteristic
clinical syndrome, after a short incubation period of two
to seven days. There is an abrupt onset of high grade
fever, which is associated with headache, retro-orbital
pain, photophobia, backache, myalgia and arthralgia. For
these symptoms dengue has acquired an epithet of Breakbone fever. Besides aches and pains, other common
symptoms include extreme weakness, anorexia, constipation, altered taste sensation and colicky abdominal pain.
A transient maculopapular rash may erupt on chest and
back within first few days of fever.
Signs of skin bleeding such as positive tourniquet test,
petechiae, or ecchymosis are observed in some patients.
DF cases with bleeding complications such as epistaxis,
gingival bleeding, gastrointestinal bleeding, hematuria,
and hypermenorrhea can be observed during some
epidemics. Such phenomena tend to vary with different
strains and with age and gender. In general, bleeding
manifestations are more severe in adults. Post-convalescence depression and bradycardia are also common in
adults. Leucopenia and mild thrombocytopenia are two
of the usually observed hematological changes. In
majority of cases fever tends to last for three to seven

days, and terminates into an uneventful convalescence;
however in few cases it tends to recur and hang about
for few more days Saddleback fever.
Undifferntiated Dengue Fever
Unfortunately classical dengue fever is an uncommon
presentation in pediatric age group. Majority of children
present with undifferentiated febrile illness, posing lots
of diagnostic problems. This undifferentiated dengue
fever may present as fever with maculopapular rash
and/or mild respiratory symptoms.
Dengue Hemorrhagic Fever
Plasma leakage is the major pathophysiological feature
observed in DHF and differentiates this from typical DF.
Initial clinical picture of DF and DHF is similar but latter
part of the disease particularly peri- and postdefervescence periods, may show marked differences.
In DHF defervescence coincides with intracellular
viral killing (see pathophysiology) which in turn sets in
process of vasculopathy making capillaries leaky.
Extravasations of plasma, through these leaky capillaries
result in hemoconcentration, hypovolemia and hypotension.
In majority of cases leak is transient lasting for few
hours; once it stops patient quickly stabilizes and
completely recovers. As with DF, convalescence in mild
DHF is swift and uneventful.
In a small number of cases leak is prolific and
prolonged; plasma may continue leaking for two to three
days. Fluid which drips out manifests as generalized

edema and effusions in serous cavitiesuntreated such
patient may develop severe shock. These cases are
designated as DSS, and carry bad prognosis; intensive
and timely IV fluid therapy can only salvage these
patients. After couple of days, when leak is over,
extravasated fluid returns to circulation. This sudden
gush of fluid into circulation may cause circulatory
congestion and sometimes even failure. Thus, course of
disease in DSS has three arbitrary phases: febrile, leaky
and congestive.
SYMPTOMATOLOGY OF MILD DHF
DHF without Shock
Typically a case of DHF has three important findings:
fever, bleeding tendency, and hepatomegaly.
The commonest bleeding manifestation is positive
tourniquet test, and bleeding at venepuncture sites, fine
purpuric rash (Fig. 9.26.2) scattered over trunk, axillae,
face and palate, are usually observed. Epistaxis, gingival
and mild gastrointestinal bleeding may occur infrequently, less than 10% of dengue hemorrhagic fever
patients may have clinically frank and severe bleeding
mainly from gastrointestinal tract.
Liver is usually palpable from early febrile phase,
varies in size from 2-4 cm, and is non-tender. Anorexia,
nausea, vomiting, and vague generalized abdominal pain
are common accompaniments.
Critical stage of the disease starts around defervescence which is often accompanied by circulatory
disturbances as a result of plasma extravasations.
Clinically patients manifest with marked weakness,
irritability, anxiety, restlessness, oliguria and giddiness.
Majority of the patients stabilize at this point and recover
completely within couple of days of defervescence.
Figure 9.26.2: Purpuric rash in DHF
399
SYMPTOMATOLOGY OF SEVERE DHF (DHF/DSS)

Leaky Phase
In a small number of patients capillary leak is profuse
and continues for two to three days. These patients
progressively become oliguric and exhibit signs of
postural hypotension such as giddiness, inability to rise
from recumbent position and need to be helped or carried
for smallest movement. They have typical signs of
circulatory failure: skin becomes cool blotchy and
congested; circumoral cyanosis is commonly observed.
Untreated these patients develop fast and thready pulse,
imperceptible lower limb pulses (dorsalis pedis and
posterior tibialis), narrowed pulse pressure and in an
extreme case unrecordable blood pressure. Severe right
hypochondriac pain and progressive enlargement of liver
coincide with the development of shock. These cases
should immediately be hospitalized for intensive fluid
therapy. Uncorrected shock may head for a complicated
course and develop metabolic acidosis and DIC resulting
in severe bleeding and multiorgan failure. Poorly
managed DSS patients have a high fatality rate of 30 to
40 percent. Besides signs of circulatory failure these
patients also exhibit puffy and swollen face (Fig. 9.26.3),
generalized edema, and polyserositis.
Congestive Phase
After two to three days, leak stops and plasma which
had extravasated during the leaky phase, returns back
to circulation causing vascular congestion. Now patients
start passing copious amount of watery urine and
develop bounding pulse, wide pulse pressure and rise
Figure 9.26.3: Puffy edematous face during leaky phase of DSS
400
Figure 9.26.4: Confluent petechial rash on hand
Figure 9.26.5: Dengue Facies (Measly look)
in blood pressure. Few cases may develop frank

congestive heart failure manifesting with tachycardia,
tachypnea, muffling of heart sounds and basal rales. This
phase may continue for 12-24 hours.
suspicion index is the major reason for this anomaly.

Working in a dengue endemic area for two decades, the
author has observed and tested a clinical finding which
could reliably serve as a suspicion index for dengue
illnessesthis suspicion index could be termed as
erythematous flush.
Convalescence
End of congestive phase heralds the recovery which,
like in DF and DHF, is rapid and complete. Bradycardia,
arrhythmias, and characteristic confluent petechial rash
are the signs seen during convalescence. Bright red
confluent petechial rash erupts along the lateral margins
of soles and palms (Fig. 9.26.4) between eighth and tenth
days of sickness. The rash shows tendency to loose
confluence as it ascends up the limbs and to fade away
above the knee and the elbow. In some cases there are
small round areas of clear skin giving it a name of
annular petechial rash.
ERYTHEMATOUS FLUSH
During their illness dengue patients develop a characteristic erythematous flush. Flush deepens with advancing
disease and imparts peculiar facial feature to these
patients. Dengue facies could be portrayed as suffused and
swollen face, injected eyes, purplish lips and most
importantly reddened malar region and ear lobes. In
other words, patients assume a measly look (Fig. 9.26.5)
devoid of catarrhea. Around eighty percent of patients
suspected as dengue on the basis of this particular finding
were proved to be viroserologicaly positive.
UNUSUAL MANIFESTATIONS
Liver failure and neurological involvements are recently
described with dengue infections. Patients with
neurological manifestations are reported from India,
Indonesia, Myanmar, and Thailand. CNS expressions are
in the form of convulsion, unconsciousness, spasticity
and paresis. Till date there is no evidence for direct
neurological involvement of brain by dengue virus.
SUSPICION INDEX
Serological studies demonstrate that dengue is endemic
in our country, however excepting epidemic situations
dengue is a rarely diagnosed condition. Want of a reliable
LAB INVESTIGATIONS
Platelets and Hematocrit
Rise in hematocrit and drop in platelets are constant
findings in all cases of dengue hemorrhagic fever. These
parameters exhibit a unique time-bound relationship
with the disease. Changes start a little before the
defervescence (4th or 5th day of sickness) and peak
around second or third afebrile day (7th or 8th day of
sickness). Hemoconcentration and thrombocytopenia
represent the pathophysiological hallmark of the disease
viz; capillary permeability and abnormal homeostasis,

and bear a distinct correlation with the severity of the
disease.
Serous Effusions
Leaking plasma gets collected into serous cavities
resulting into development of effusions. Peritoneum is
the first and commonest site. In severe cases patients
develop polyserositis (peritoneal, pleural, and pericardial
effusions); while a mild case may present with only
ascites. Most marked on second to third post-defervescence day, these effusions resolve around tenth or
eleventh day of disease and hardly ever need any
therapeutic intervention.
Turk Reaction Cells
These are transformed lymphocytes. Presence of more
than 20 percent of Turk cells in Buffy coat smear is a
frequent finding for dengue hemorrhagic fever.
A typical plan for clinical diagnosis: Patient presenting with
fever and dengue facies [non-catarrhal measly look]
during or postmonsoon season should raise the suspicion
for dengue illness. A positive tourniquet test (TT)
indicating bleeding tendency augments possibility.
Conduct CBC and platelet count serially, once during
initial period and repeat around fourth to fifth days of
fever. Patient showing rise in PCV and drop in platelets
should be categorized as DHF. Keep this patient under
close observation and monitor him for signs and
symptoms of developing shock. Patient with absence of
thrombocytopenia, and hemoconcentration should be
labeled as DF.
401
Instruct parents to collect childs urine and compare

the output against fluid intake.
Warn parents for bad clinical signs viz giddiness,
restlessness, anxiety, severe abdominal pain and cold
extremities.
Carefully assess every patient exhibiting above
symptoms for signs of shock e.g. poor volume pulse,
imperceptible pulses, narrowing of pulse pressure,
and fall in blood pressure. Patient with these
symptoms need immediate hospitalization for
intensive IV fluid therapy.
Lastly one should bear in mind that DSS sets in with
the defervescence, hence any child deteriorating or
failing to improve with subsidence of fever should
be carefully assessed for signs of shock.
Management of Dengue Shock Syndrome [DSS]
How to suspect DSS and when to hospitalize patients?
A patient of dengue illness showing following signs and
symptoms in peridefervescence period is likely to
develop DSS:
i. Feeling of giddiness (postural hypotension)
ii. Cooler extremities compared to trunk and abdomen.
iii. Oliguria with dark urine
iv. Right hypochondriac pain
v. Increasing liver size.
Patients exhibiting these symptoms should be
carefully assessed for blood pressure and for pulse rate
and volume. Patient exhibiting narrowed pulse pressure,
fast and thready pulse should be considered as having
DSS and must be hospitalized for further management.
MANAGEMENT
Initial Management
Outpatient Management
1. Take two intravenous lines.

2. Collect blood for blood group, Hb, PCV, and platelets.
3. Start with drip of Ringers lactate in a dose of 10 ml/
kg BW/hour (e.g; for 10 kg child 100 ml/hour).
Cases other than the DSS do not require hospitalization

and could be managed at outpatient level. The author
suggests following management plan for such cases:
Keep patient under close clinical observation for
throughout the febrile period and two to three days
beyond the defervescence.
For pain and fever use only paracetomol, avoid
aspirin and NSAID, as they interfere with platelet
functioning.
Give parents a set goal for childs fluid intake (100 to
150 ml/kg BW). Fluids could be water, ORS, milk,
buttermilk, fruit juices, etc.
Continue Ringers lactate till patient passes first urine.

Invariably patient passes small amount of dark and thick
urine only after receiving 20 to 30 ml per kg BW of IV
fluid.
Subsequent Management
Continue IV fluid at same rate; however IV fluids used
should be Ringers lactate, 0.45 saline and Isolyte-P in
402
sequence. IV fluids should be planned for 6 hours

quadrants.
Monitoring of the Patients in the Hospital
The most important aspect of DSS management is
frequent monitoring of these patients. Following
parameters should be monitored at hourly intervals.
Pulse volume
Blood pressure
Abdominal girth
Urine output
Pulse Volume
Pulses to be felt are radial, posterior tibialis, and dorsalis
pedis. Feel of pulse volume is very important; normal
pulse should come and touch palpating fingers without
requiring any pressure. Imperceptible or very weak
pulses indicate more fluid requirement.
Blood Pressure
Remembering blood pressure values according to age is
a difficult task in pediatrics hence it is essential that one
should keep age related blood pressure chart. If one is
unaware of age related blood pressure, then maintaining
good pulse pressure of 30 to 50 should be the management goal.
A narrow pulse pressure less than 30mm of Hg is an
indication for stepping up IV fluid rate.
Majority of patients stabilize with aforementioned

plan of IV fluid rehabilitation, however cases with very
severe leak may require higher doses [15 ml/kg BW]
of IV fluid or even use of colloids like dextran, or
plasma for maintenance of normotension. Such cases
may need CVP monitoring. Obvious clinical bleeding,
or severe internal bleeding as indicated by marked
drop in PCV are other indications for blood or plasma
infusion.
Indication for Platelets
Main reasons for bleeding in DHF are vasculopathy and
coagulopathy; thrombocytopenia does contribute but in
a minor way, therefore patients having thrombocytopenia in absence of obvious clinical bleeding do not
require platelet transfusion.
Use of Vasopressors: (Dopamine and Dobutamine)
Though WHO does not recommend use of vasopressors,
author has clinical experience and scientific reasons for
their recommendation.
Dopamine During hypovolemia bodys compensatory
mechanism shunts blood from peripheral to central
circulation, effecting renal cutaneous and mesenteric
ischemia. The intense pain which DSS patients suffer at
onset of shock phase is likely owing to mesenteric
ischemia. In authors experience DSS patients treated
with dopamine along with IV fluid suffer less of
abdominal pain and GIT bleeding.
Abdominal Girth
In DSS extravasating plasma gets collected into serous
cavities. In postdefervescence period these patients
develop abdominal distension, and when they are put
on IV fluids, their abdominal girth starts further rising.
Expansion of their abdominal girth is directly proportional to severity of leak.
Rapidly expanding abdominal girth is an indication
for higher fluid requirement.
Urinary Output
Urinary output must be measured every six hourly and
amount should be compared with IV fluid given over
six hours quadrant of time. Large gap between IV fluid
intake and urinary output indicates need for advancing
IV fluid therapy.
Dobutamine
In severe cases myocardial engorgement results in a poor
cardiac contractibility. Dobutamine, a drug with strong
ionotropic effect, is a useful remedy in such situations.
Management during Congestive Phase
How to recognize its onset?
After certain time varying between 12 to 72 hours,
depending upon severity of case, DHF leak stops and
fluid which had escaped out returns back to vascular
compartment.
Following changes are likely to occur in monitoring
criteria.
Pulse: Pulse becomes fast and bounding.

Blood pressure: Systolic pressure would go up and
pulse pressure would become wider [>50]
Abdominal girth starts decreasing
Intake/output ratio: The most important signal is
narrowing gap between IV intake and urinary output.
Management of Congestive Phase
As the patient enters into congestive phase, change over
to hypotonic fluid and decrease the rate to 3 to 5 ml/kg
BW/hour, in next few hours patient would pass copious
amount of light colored urine.
In some patients regurgitant fluid may cause cardiac
overload manifesting as cough, tachypnea and tachycardia. Such cases need diuretics and digitalization.
Problem is infrequent and is likely to happen in patients
treated with colloids. Congestive phase may end after
12 to 24 hours heralding recovery.
Reasons for Mortality in DHF/DSS
1. Failing to recognize that patient is in shock.
It is a usual tendency of parents and treating physician
to feel relieved when temperature subsides, however
in dengue patient may pass into shock with defervescence. Instead of feeling of wellbeing, display of
anxiety, apprehension, and giddiness at defervescence should immediately alert treating physician
to possibility of developing shock, failure to
appreciate this is the commonest cause of death in
DSS.
2. Hemorrhages: Though dengue is known as hemorrhagic fever clinical hemorrhages are uncommon, and
are rarely responsible for mortality. Shock effecting
DIC is the major cause for severe hemorrhages.
3. Failing to recognize that patient has entered congestive
phase may cause cardiac overload and consequent CHF
and death.
Though a complex disease, dengue hemorrhagic
fever exhibits a set clinical pattern and observes a
fixed time bound course of events. Awareness and
familiarity with the disease and its course greatly
facilitates diagnosis-making and initiating proper
therapy. With appropriate IV fluid management and
403
frequent monitoring, mortality in DSS should not

exceed more than one percent.
BIBLIOGRAPHY
1. Gamble J, Bethell D, Day NPJ, et al. Age-related changes
in microvascular permeability: a significant factor in the
susceptibility of children to shock? Clinical Science 2000;
98:211-6.
2. Gubler DJ, Kuno G, Waterman SH. Neurologic disorders
associated with dengue infection. Proceedings of the
International Conference on dengue/dengue hemorrhagic Fever; Kuala Lumpur, Malaysia; 1983;290-306.
3. Guzman MG, Alvarez M, Rodriguez R, et al. Fatal dengue
haemorrhagic fever in Cuba, 1997. Int J Infect Dis 1999;
3:130-5.
4. Halstead SB. Antibody, macrophages, dengue virus
infection, shock, and hemorrhage: a pathogenic cascade.
Rev Infect Dis 1989;11(suppl 4):S830-9.
5. Halstead SB. Is there an inapparent dengue explosion?
Lancet 1999;353:1100-1.
6. Kapse AS. A study of an epidemic of Dengue at Surat;
clinico-investigative analysis. In Environment and health
in developing countriess 1998;339-50.
7. Kapse AS. Dengue illnesses. IAP text book of Pediatrics.
2nd edn/2002;239-42.
8. Kliks SC, Nimmanitya S, Nisalak A, Burke DS. Evidence
that maternal dengue antibodies are important in the
development of dengue haemorrhagic fever in infants.
Am J Trop Med Hyg 1988;38:411-9.
9. Morens DM, Halstead SB. Disease severity-related antigenic differences in dengue 2 strains detected by dengue
4 monoclonal antibodies. J Med Virol 1987;22:169-74.
10. Nimmannitya S. Clinical spectrum and management of
dengue haemorrhagic fever. Southeast Asian J Trop Med
Pub Health 1987;20:325-30.
11. Pandey BD, Igarashi A. Severity-related molecular
differences among nineteen strains of dengue type 2
viruses. Microbiol Immunol 2000;44:179-88.
12. Rigau-Prez JG, Clark GG, Gubler DJ, Reiter P, Saders
EJ, Vorndam AV. dengue and dengue haemorrhagic
fever. Lancet 1998;352:971-7.
13. Rush AB. An account of the bilious remitting fever, as it
appeared in Philadelphia in the summer and autumn of
the year 1780. Medical inquiries and observations.
Philadelphia: Prichard and Hall, 1789:104-17.
14. WHO. Dengue haemorrhagic fever: diagnosis, treatment,
prevention and control. Geneva: WHO, 1997.
15. Yang KD, Wang CL, Shaio MF. Production of cytokines
and platelet activating factor in secondary dengue virus
infections. J Infect Dis 1995;172:604.
404
9.27 Infectious Mononucleosis

S Ramesh
The eitological agent for infectious mononucleosis (IMN)
is the Epstein-Barr virus (EBV).
PATHOPHYSIOLOGY
EBV is predominantly transmitted by saliva (oropharyngeal secretions). EBV infection results in a humoral and
cellular response to the virus. The humoral immune
response directed against EBV structural proteins is the
basis for serological tests used to diagnosis EBV infectious
mononucleosis. A rapid and efficient T-cell response
results in control of the primary EBV infection and
lifelong suppression of EBV. Ineffective T-cell response
may result in excessive and uncontrolled B-cell
proliferation, resulting in B-lymphocyte malignancies,
e.g. B-cell lymphomas.
CLINICAL FINDINGS
The classic findings are fever, lymphadenopathy,
pharyngotonsillitis and splenomegaly.
Medical care is sought for the complaints of sore
throat and fever.
Early signs include fever, lymphadenopathy,
pharyngitis, rash, or periorbital edema.
Later physical findings include splenomegaly, uvular
edema, and rarely findings associated with splenic
rupture. Though rare, splenic rupture is a feared
complication. Rupture is commonly related to
trauma, which often may be mild.
The pharyngitis of EBV infectious mononucleosis
may be exudative or nonexudative.
Tonsillar enlargement is common, and massive
tonsillar enlargement may be observed leading to
airway obstruction. Palatal petechiae of the posterior
oropharynx distinguish infectious mononucleosis
from other causes of viral pharyngitis.
Uvular edema is an uncommon finding in infectious
mononucleosis, but if present, it is a helpful sign in
distinguishing EBV infectious mononucleosis from
other causes of viral pharyngitis or from group A
streptococcal pharyngitis.
Lymphadenopathy is predominantly cervical with
the anterior and posterior groups involved.
EBV infectious mononucleosis rarely may result in a

variety of unusual clinical manifestations including
pancreatitis, acalculous cholecystitis, myocarditis,
mesenteric adenitis, myositis, and glomerular
nephritis, autoimmune hemolytic anemia and
thrombocytopenia.
Neurological syndromes include optic neuritis,
transverse myelitis, aseptic meningitis, encephalitis,
meningoencephalitis, cranial nerve (CN) palsies
(particularly CN VII), or Guillain-Barr syndrome.
LABORATORY EVALUATION
Patients with infectious mononucleosis in the
differential diagnosis should have a CBC with a
differential count and an evaluation of the erythrocyte
sedimentation rate (ESR).
Because leukocytosis is the rule in infectious
mononucleosis, the presence of a normal or decreased
WBC count should suggest an alternative diagnosis.
Lymphocytosis accompanies infectious mononucleosis, increases during the first few weeks of
illness, and then gradually returns to normal.
Patients with fever, pharyngitis, and lymphadenopathy are likely to have EBV infectious mononucleosis
if the relative atypical lymphocyte count is equal to
or greater than 20 percent.
Atypical lymphocytes should be differentiated from
abnormal lymphocytes. Atypical lymphocytes are
each different in their morphology as observed on
the peripheral smear, whereas abnormal lymphocytes
are monotonous in their sameness, which readily
permits differentiation on the peripheral smear.
Because of hepatic involvement elevated transaminases is constant finding.
SEROLOGICAL TESTING
EBV infection induces specific antibodies to EBV and a
variety of unrelated non-EBV heterophile antibodies.
These heterophile antibodies react to antigens from
animal RBCs.
Paul Bunnell test: Sheep RBCs agglutinate in the
presence of heterophile antibodies and are the basis
for the Paul-Bunnell test.

Monospot test: Agglutination of horse RBCs on
exposure to heterophile antibodies is the basis of the
Monospot test.
Testing for EBV-specific antibodies is as follows:
EBV induces a serological response to the various
parts of the Epstein-Barr viral particle. IgM and
IgG antibodies directed against the Viral Capsid
Antigen (VCA) of EBV are useful in confirming
the diagnosis of EBV and in differentiating acute
and/or recent infection from previous infection.
EBV IgM VCA titers decrease in most patients
after 3-6 months but may persist in low titer for
up to 1 year. EBV IgG VCA antibodies rise later
than the igM VCA antibodies but remain elevated
with variable titers for life.
Elevated IgM antibody to VCA is the most
valuable and specific serologic test to confirm
acute EBV infection.
Antibodies against Early antigen (EA) and Epstein
Barr Virus Nuclear Antigen (EBNA) are also
employed in the diagnosis of IMN.
405
MANAGEMENT
Rest and symptomatic treatment are the mainstay of
management. Due to the risk of splenic rupture strenuous
physical and athletic activities are not advised during
the first 3 weeks of illness.
Short course of corticosteroids (less than 2 weeks) may
be helpful for the complications of IMV namely airway
obstruction, autoimmune hemolytic anemia, seizures,
meningitis and thrombocytopenia with hemorrhage.
PROGNOSIS
The prognosis for complete recovery is excellent if no
complications ensue during the acute illness.
BIBLIOGRAPHY
1. Burke A Cunha. Infectious Mononucleosis e-medicine
updated May 2006.
9.28 Respiratory Syncytial Virus Infection

INTRODUCTION
RSV is a single-stranded, negative-sense RNA virus and
a member of the paramyxoviridae family. Two
subtypes, A and B, are simultaneously present in most
outbreaks, with A-subtype typically causing more
severe disease. Several distinct genotypes within these
subtypes predominate within a community; the
dominant strains shift yearly, accounting for frequent
reinfections. It causes acute respiratory tract illness in
persons of all ages. RSV causes seasonal outbreaks
throughout the world. In tropical and semitropical
climates, the seasonal outbreaks usually are associated
with the rainy season.
Transmission of RSV is primarily by inoculation of
nasopharyngeal or ocular mucous membranes after
contact with virus-containing secretions or fomites.
Direct contact is the most common route of transmission,
but large aerosol droplets also have been implicated. RSV
can survive for several hours on hands and fomites. Hand
washing and contact precautions are therefore important

measures to prevent nosocomial spread. The period of
viral shedding usually is three to eight days, but it may
last up to four weeks in young infants. The incubation
period ranges from two to eight days.
CLINICAL FEATURES
The clinical manifestations very depending upon the
patients age, health status, and whether the infection is
primary or secondary. Infants and young children with
primary infections usually present with lower respiratory
tract infection (bronchiolitis or pneumonia), whereas
older children and adults typically have upper respiratory tract symptoms [cough, coryza, rhinorrhea and
conjunctivitis] or tracheobronchitis but may develop
lower respiratory tract illness, particularly if they are
elderly (in institutions) or immunocompromised.
Compared with other respiratory viruses, RSV is more
likely to cause sinus and ear involvement.
406
In infants, RSV can cause significant apnea via

unknown mechanisms in approximately 20 percent of
infants admitted to the hospital with RSV and has been
speculated to be associated with sudden infant death
syndrome. Apnea is more likely to occur in young
patients, those born prematurely, those with a history of
apnea of prematurity, and those with more severe
hypoxemia.
RSV causes acute respiratory tract illness in persons
of all ages. Almost all children are infected by 2 years of
age, and reinfection is common. RSV is the most common
cause of lower respiratory tract infection (LTRTI) in
children younger than 1 year. It is also a significant and
often unrecognized cause of LRTI in both elderly and
immunosuppresed. Acute respiratory disease caused by
RSV is not restricted to pediatric and high-risk adult
populations. Healthy adults are infected repeatedly
throughout their lives and typically have symptoms
restricted to the upper respiratory tract.
Though very rarely may be recovered from extrapulmonary tissues such as liver, CSF, or pericardial fluid,
RSV is highly restricted to the respiratory epithelium,
and is shed apically into the lumen of the airways. This
leads to airway obstruction, air traping and increased
airway resistance.
Previous infection with RSV does not appear to
convey complete protection against reinfection, even
when significant specific antibody titers are present.
Individuals affected with subsequent infections of RSV
are usually milder. Transplacentally acquired antibody
against RSV does not protect infants against infection.
A correlation may exist between infection with RSV
during infancy and the later development of reactive
airways. As an example, approximately 25 percent of
infants with severe RSV infection requiring hospitalization subsequently develop bronchospastic disease. RSV
pneumonia leading to respiratory failure can be a
significant cause of acute morbidity and mortality in the
immunocompromised host, with high mortality rates of
70 to 100 percent.
RISK FACTORS
Patients at risk for RSV lower respiratory tract disease
include:
a. Infants younger than 6 months of age, particularly
those who are born during the first half of the RSV
season and those attending daycare.
b. Infants and children with underlying lung disease

such as chronic lung disease (bronchopulmonary
dysplasia).
c. Infants born before 35 weeks gestation, infants and
children with congenital heart disease.
d. Immunocompromised patients (e.g. severe combined
immunodeficiency, leukemia, or bone marrow or
lung transplant).
e. Patients of any age group with significant asthma
f. Residence at altitude >2500 m.
g. Institutionalized elderly.
h. Elderly patients with chronic pulmonary diseased or
functional disability.
DIAGNOSIS
In the appropriate clinical and epidemiologic setting,
diagnosis of RSV infection can be made clinically with
reasonable accuracy. Diagnostic testing for RSV includes
culture, reverse-transcriptase polymerase chain reaction
(RT-PCR), and serology. The laboratory diagnosis of RSV
is made by analysis of respiratory secretions. In healthy
children, a nasal wash usually provides the best yield,
but a nasopharyngeal swab or throat swab may be
adequate if a nasal wash is not possible. In patients who
are intubated or are undergoing bronchoscopy, a tracheal
aspirate or bronchoalveolar lavage should be obtained.
The standard for definitive diagnosis is isolation of the
virus in HEp-2 cells. Identification of typical plaque
morphology with syncytium formation and immunofluorescent staining confirms the diagnosis. Rapid assays
utilizing antigen capture technology that can be
performed in less than 30 minutes are now available. The
sensitivity and specificity of most of these tests exceed
90 percent and they are a mainstay of the diagnostics as
the identification by culture can take from four days to
two weeks.
TREATMENT
In healthy patient with mild respiratory tract infections
who are treated symptomatically as outpatients.
Supportive care for children with RSV lower respiratory
tract infection (LRTI) may include hospitalization,
supplemental oxygen, intravenous fluid and respiratory
support.
Bronchodilators may help to relieve bronchospasm in some
patients, but should not be continued in patients who

fail to demonstrate rapid improvement. Antiviral agents
are available, but their use is not indicated in most
patients. More aggressive therapy, including immunotherapy, or antiviral and immunotherapy with or without
corticosteroids may be warranted for immunocompromised patients.
Corticosteroids may be beneficial in the management of
RSV-associated bronchospasm, particularly in those with
asthma, in whom RSV reinfection may have triggered
an exacerbation.
Ribavirin is a nucleoside with good in vitro activity
against RSV. The routine use of nebulised ribavirin in
infants and children with RSV LRTI is not recommended.
The use of ribavirin administration should be made on
the basis of:
a. Particular clinical circumstances (e.g, underlying
congenital heart disease, lung disease, immunosuppression or need for mechanical ventilation).
b. Clinician experience.
c. Unproven benefits must be weighed against the risk
of occupational exposure and cost of therapy.
In certain adults early use of inhaled ribavirin has
been shown to reduce morbidity and mortality especially
in adult bone marrow transplant recipients who develop
RSV infections. Ribavirin is contraindicated in pregnant
women, and a negative pregnancy test should precede
its use in women of child-bearing age. Ribavirin is a
known teratogen in rodent species.
Passive immunotherapy with neither intravenous
immunoglobulin with a high neutralizing activity against
RSV (RSVIG) [i.e. polyclonal hyperimmune globulin
prepared from donors with high serum titers of RSV
neutralizing antibody] nor monoclonal antibody
(Palivizumab) [i.e. humanized monoclonal antibody
against the RSV F glycoprotein], have proven beneficial
in the treatment of RSV in hospitalized infants and young
children. However ribavirin in combination with passive
immunotherapy and/or corticosteroids may be
warranted in severely ill immunocompromised patients
with RSV LRTI.
PREVENTION
General measures to decrease exposure to RSV and
decrease the risk of acquisition on exposure includes,
avoidance of exposure to tobacco smoke, restricting
participation in child care during RSV season for highrisk infants (if possible) and hand washing in all settings.
RSV is highly contagious and can cause serious
nosocomial infections in infants with congenital heart
407
or lung disease, bone marrow and lung transplant

recipients, and the frail elderly with multiple underlying
conditions. Rapid diagnosis, handwashing, and appropriate
use of gloves are probably the most important infection control
measures, but contact precaution, including surgical mask
and eye protection for health care providers, should be
used when there is a chance of exposure to aerosols of
infectious respiratory secretions. Isolation of patients in
private rooms or in rooms with other RSV-infected
patients (cohorting patients), and limited transport of
patients from their rooms also is recommended. During
outbreaks, personnel caring for RSV-infected patients
should be restricted from caring for uninfected patients
as often as possible. Health care personnel and visitors
with upper respiratory tract infections should be
restricted from contact with high-risk patients as much
as is practical, especially during the peak RSV
transmission months.
PROPHYLAXIS
Infants with high titers of maternally acquired RSVneutralizing antibodies develop less severe RSV disease,
even though antibody does not prevent infections. This
led to the concept of immunoprophylaxis to effectively
decrease the severity of subsequent RSV infections.
Palivizumab as immunoprophylaxis is considered in:
a. Infants and children younger than two years who
have bronchopulmonary dysplasia (BPD) who
require medical therapy within six months of the
anticipated RSV season and/or hemodynamically
significant congenital heart disease.
b. Infants younger than 1 year who were born at 28
weeks of gestation.
c. Infants younger than 6 months of age who were born
between 32 and 35 week of gestation and immunocompromised children.
Palivizumab was preferred to RSVIG because of its
ease of administration and lack of interference with
immune response to MMR and varicella vaccines. The
dose of palivizumab is 15 mg/kg IM once per month for
a total of five doses. The first dose is administered before
the RSV season begins. Once immunoprophylaxis is
initiated, all five doses should be administered, even if
the infant becomes old enough that prophylaxis is no
longer indicated. Immunoprophylaxis also should
continue even if the infant experiences breakthrough
infection. This is because high-risk infants may be
hospitalized more than once during an RSV season and
more than one strain of RSV may cocirculate in a
community.
408
9.29 Rotavirus Disease

Raju C Shah
Acute watery diarrhea resulting in moderate to severe
dehydration still continues to be an important cause of
morbidity and mortality in children. There has been no
appreciable change in the incidence of rotavirus diarrhea
worldwide in the past two decades. The incidence of
rotavirus disease has been observed to be similar in both
industrialized and developing countries, suggesting that
adequate control may not be achieved by improvements
in water supply, hygiene, and sanitation. About 600,000
children die every year from rotavirus infections, mainly
in developing countries, and this figure represents about
5% of all deaths in children younger than 5 years.
EPIDEMIOLOGY IN INDIA
In India rotavirus infection accounts for 26% of all
diarrhea-related hospitalizations. Most cases of diarrhea
(98%) occur during the first 2 years of life, peaking at 911 months of age. Rotavirus-associated diarrhea occurs
year-round but is predominant in winter. If the
estimates of incidence obtained from the population
based study are applied to the total birth cohort of 25
million children in India, then 450,000 hospitalizations
for rotavirus diarrhea would be expected to occur and
will take toll of 100,000 children annually.
ROTAVIRUS
Rotaviruses are 70 nm icosahedral viruses that belong to
the family Reoviridae. Seven rotavirus groups (A to G)
are described, but only groups A, B, and C infect humans.
Group A rotaviruses are the most important from a public
health standpoint. The virus is composed of three protein
shells consisting of an outer and an inner capsid and an
internal core that encases the 11 segments of doublestranded RNA. Rotavirus contains two structural outer
capsid proteins: VP7, the glycoprotein (G protein), and
VP4, the protrease-cleaved protein (P protein). Because
the two gene segments that encode these proteins can
segregate independently, a typing system consisting of
both P and G types has been developed.
Though there is diversity in circulating rotavirus
strains in India, analysis of data from published
epidemiological studies covering 18 Indian cities

performed during 1996-2001 showed that G1 strains had
a greater risk of developing more severe cases of
diarrhea than did children infected with other rotavirus
strains.
Fever, nonbilious vomiting and profuse watery, non-foul
smelling diarrhea are usually the presenting symptoms.
In more than 50% cases fever is the presenting symptom.
Rhinitis, congestion of pharynx and tympanic membrane
may also be present. Irritability, lethargy or shock may
be present depending on degree of dehydration. Infection
lasts 3 to 9 days and disease is self-limiting.
DIAGNOSIS
In most places it is by ELISA and LA assays. Gold
standard of diagnosis is by demonstrating wheel like
virus which can be further subgrouped by serotyping.
MANAGEMENT
Treatment is mainly supportive and consists of management of dehydration as per WHO standard case management guidelines. Oral zinc in a dose of 20 mg twice daily
for ten days can help reducing stool output by 20% and
prevent further attacks of watery diarrhea in next 3
months. Antimicrobial and antisecretory agents have no
role.
PREVENTION
It is believed that diarrhea can be prevented by better
personal hygiene and use of potable drinking water but
rotavirus diarrhea cannot be prevented by such
measures. Research to develop a safe, effective rotavirus
vaccine began in the mid-1970s. The first multivalent
live oral reassortant vaccine, RRV-TV, was withdrawn
from the US market 9 months after its introduction as a
consequence of intussusceptions, a rare but potentially

dangerous adverse effect. Recently a pentavalent
human-bovine (WC3) reassortant (G1, G2, G3, G4 and
P1A [8]) live-attenuated, oral vaccine and a live,
attenuated human rotavirus G1, P1A [8], vaccine (strain
RIX 4414) have been developed (See Chapter 9.3). The
clinical efficacy of both vaccines against severe rotavirus
gastroenteritis is approximately 96 to 98%. There is no
adverse side effect like intussusceptions. Both vaccines
are part of immunization schedule in many countries
and licensed in more than 50 countries by now
Attenuated Human Rotavirus vaccine GlP [8] is licensed
and available in India also (see chapter 9.3).
409
BIBLIOGRAPHY
1. Kosek M, Bern C, Guerrant RL. The global burden of
diarrhoeal disease, as estimated from studies published
between 1992 and 2000. Bull World Health Organ.
2003;81:197-204.
2. Kang G, Kelkar SD, Chitambar SD, Ray P, Naik. T.
Epidemiological profile of rotaviral infection in India:
Challenges for the 21st century. J infect Dis 2005;192
Suppl 1:S120-6.
3. Parashar UD, Gibson CJ, Bresse JS, Glass RI. Rotavirus
and severe childhood diarrhea, Emerg infect Dis 2006;
2:304-6.
4. Shah M, Shah R. Rotavirus-Vaccine and magnitude.
Indian Journal of Practical Pediatrics 2007;9(4):271-9.
9.30 Rabies
Tapan Kumar Ghosh, A Parthasarathy
EPIZOOTIOLOGY AND EPIDEMIOLOGY
Rabies is primarily a disease of animals. All warmblooded animals can be infected by rabies virus. Human
rabies is endemic through the main land and canine
rabies is enzootic world over. Only a few countries and
mostly all islands are free from rabies. Rabies occurs in
all continents except Australia and Antarctica. The
countries like Guyana, Jamaica and Uruguay in Latin
America, Bahrain and Japan in Asia, Great Britain,
Scandinavian countries, Spain and Portugal in Europe,
Fiji and Papua New Guinea in Oceanea are free from
rabies. In India rabies is prevalent all over except
Andaman, Nicobar and Lakshadweep groups of islands.
Bat rabies is not reported from India but it is a major
problem in Latin American countries.
Globally 6 million take postexposure prophylaxis
(PEP); 40,000-60,000 deaths occur due to rabies. In India
more than one million take PEP. According to WHO
sponsored national multicentric rabies survey undertaken in the year 2004 annual incidence of human rabies
deaths came to as 17,137 (14,109 to 20,165 with 95%
confidence). An addition of 20% to include paralytic/
atypical form of rabies provided an estimation of 20,565.
Frequency of human rabies deaths is 1 per 30 minutes
approximately.
Pet dog: man ratio is 1 in 36 and the estimate of pet/
owned/household dog population comes to 28 million.
Frequency of bite is 1 per 2 seconds, annual animal bite

incidence rate is 17.4 per 1000 population. So project
annual incidence is 17.4 million for 1 billion population.
Dogs account for 90 to 96 per cent of animal bites in India.
HISTORY
Rabies and plague are known to affect humans since
ancient times. There are mentions of this disease in
ancient literature, like Vedas. The term rabies is derived
from the Sanskrit word Rabhas which means, To do
violence. Louis Pasteur had developed the first vaccine
against rabies in 1885.
ETIOLOGY AND PATHOGENESIS
Causative virusRabies virus is a bullet shaped, single
stranded RNA virus, and belongs to family Rhabdoviride
and genus Lyssavirus. It causes acute encephalitis in
human being. It cannot penetrate intact skin but can
penetrate intact mucosa. This virus basically infects
animals. Two cycles namely, sylvaic and urban cycles in
the animals help this disease to exist in the world. Unless
both these cycles are totally stopped, rabies will continue
to stay. Apart from dogs, which are the main culprits
other hot-blooded animals like cat, fox, jackals, etc.
transmit rabies. The domestic animals like cow, buffalo,
goat, pig, sheep can transmit rabies after they are bitten
and get infected by rabid animals. Monkey can also
transmit this disease if they are infected. Man to man
410
transmission is rare except in cases of cornea transplant

from donors within diagnosed rabies.
Incubation period 20 to 180 days; peak 30 to 60 days,
extreme 9 days and 1 year. Incubation period is shorter
if the bite is closer to brain.
Clinical typesTwo types of clinical rabies are described:
furious type in 80 percent and paralytic type in 20 percent
(Dumb rabies). Both types are common for human and
canine rabies.
The virus first multiplies in striated muscles, ascends
along axons from periphery to spinal cord and eventually
to neurons in the brains. There is neuronal destruction
in the brainstem and medulla and severest changes in
pons and IV ventricles but cortex is spared.
MODES OF TRANSMISSION AND
CLINICAL FEATURES
Modes of Transmission
Common
Rare
Bite and scratch from infected animals Aerosol transmission

Lick (on broken skin/intact mucus
Organ transplantation
membranes)
Bites by insectivorous bats can also transmit rabies

and rabies can spread also by aerosol infection in bat
infested caves but these are not problems of India.
Clinical Features
As stated earlier furious type of rabies is the most
common (80%) but dumb type of rabies manifested by
ascending paralysis (20%) is also reported. The furious
type of rabies presents with acute neurological phase
characterized by hydrophobia, aerophobia, photophobia and dysphagia. No survival is so far reported in
unvaccinated infected persons in the world literature.
The difference of the presenting features in these 2 types
is shown in Table 9.30.1.
TABLE 9.30.1: Clinical features of rabies

Furious type 80%
paralytic type (20%)
Tingling/numbness at bite site Tingling/numbness at bite site

Nonspecific symptoms
(Fever, malaise, headache,
etc)
Nonspecific symptoms
(Fever, malaise, headache, etc)
Hydrophobia, aerophobia
Photophobia
Ascending paralysis
Coma
Death in 3-5 days

(cardiac and respiratory
failure)
Death in 7-21 days

(Cardiac and respiratory failure)
Detection of antibodies in CSF or serum of unimmunized persons and detection of viral nucleic acid from
infected tissue is also possible. Virus can be isolated from
saliva.
WHO Classification of Bites
Before starting the treatment of animal bite cases in
human being, classification of the exposure is most
important. Table 9.30.2 shows the WHO classification of
animal bites cases.
MANAGEMENT
Treatment following an exposure (bite, scratch or lick
on broken wounds in skin or directly on mucous
membrane, i.e. on oral cavity or on anus by suspected
rabid animal) will consist of the following stages:
1. Proper wound management.
2. Infiltration of rabies immunoglobulin (RIG) in all
category III exposure (see Table 9.30.2) rabies.
3. Antirabies vaccination with modern cell culture
rabies vaccine (CCRV).
4. Antitetanus prophylaxis.
5. Supportive treatment with antipyretic/analgesics,
local and/or systemic antibiotic as required.
For IAP - Infectious Diseases Chapter Protocol on
Management of Rabies refer to Chapter 36.11.4, Page
No. 1534.
The Steps of Management
DIAGNOSIS
Diagnosis is mainly based on clinical signs of hydrophobia and aerophobia in the furious type of rabies.
Confirmation of diagnosis is based on the followings:
1. Detection of Negri body in brain by Sellers stain.
2. Detection of virus antigen by immunofluorescence.
3. Mouse pathogenicity (biological test).
Step I: Wound Management

In wound management, the most important steps are:
i. Through washing of wounds under running tap
water for at least 10 minutes with aim of physical
elimination/shedding of the viral loads and
application of soap/detergent for chemical treatment and changing the pH of the wounds.
411
TABLE 9.30.2: Type of contact, exposure of recommended postexposure prophylaxis

Category
Type of contact
Type of exposure
Recommended postexposure prophylaxis
Touching of feeding of animals.

Licks on intact skin
None
None, if reliable case history is available
II
Nibbling of uncovered skin. Minor

scratches or abrasions without bleeding
Minor
Wound management +
Antirabies vaccine
III
Single or multiple transdermal bites or

scratches, licks on broken skin.
Contamination of mucous membrane
with saliva (i.e. licks)
Severe
Wound management +
Rabies immunoglobulin +
Antirabies vaccine
Note: After carefully assessing the category of exposure, the treating doctor should evaluate the course of action to be taken, based on
the following general considerations. He should also keep in the mind that with the presently available safe cell culture rabies vaccine
(CCRV), it is always safe to offer treatment rather than withhold in doubtful situations
ii. Application of disinfectants like providone iodine,

spirit, household antiseptics, etc. to remove the
remaining virus particles and prevention of
secondary infection.
Step II: Rabies Immunoglobulin (RIG)
Infiltration of bases of wound(s) with rabies immunoglobulin (RIG)Neutralization of the virus and forming
a coat around the virus thus obliterating virus entry into
the nerve ending.
Step III: Antirabies Vaccination (ARV)
A course of postexposure prophylaxis (PEP) either IM
or ID route with modern cell culture ARV (CCRV).
Step IV: Antitetanus Prophylaxis
Administration of tetanus toxoid (TT) and/or tetanus
immunoglobulin (TIG) as required.
It is to be noted that in wound management
application of irritants, cauterization and suturing, i.e.
closing of wounds are to be avoided. If suturing is needed
for the purpose of hemostasis. It can be done only after
administration of RIG.
RABIES IMMUNOGLOBULIN (RIG)
The antirabies serum (ARS)/rabies immunoglobulin
(RIG) provides passive immunity in the form of
readymade antibody to tide over the initial phase of the
infection. Antirabies serum or RIG has the property of
binding to rabies virus, thereby resulting in neutralization of the virus. Two types of RIGs are available.
1. Equine rabies immunoglobulin (ERIG): ERIG is of

heterologous origin raised by hyper-immunization
of horses. Currently manufactured ERIGs are highly
purified and enzyme refined. The dose of ERIG is 40
IU per kg body weight of patient and is given after
testing for sensitivity (Skin test), up to a maximum of
3,000 IU.
2. Human rabies immunoglobulins (HRIG): These are
prepared from the serum of people hyperimmunized
with rabies vaccines. The dose of HRIG is 20 IU per
kg body weight (maximum 1,500 IU). HRIG does not
require any prior sensitivity testing (Skin test).
RIG is to be infiltrated as much as possible into and
around all the wounds; remaining if any is to be given
intramuscularly at a site away from the site of vaccination. All the wounds are to be infiltrated with RIG.
After calculation of the dose of RIG if it is seen that RIG
is insufficient by volume to infiltrate all the wounds, it is
to be diluted with normal saline to make it 2 or 3 times
of its volume.
Antirabies Vaccines
Active immunization is achieved by administration of
safe and potent CCRVs or purified duck embryo vaccines
(PDEV). In India, nerve tissue vaccine or NTV (Semple
vaccine) was used for postexposure treatment in public
sector. However, as this vaccine was reactogenic
(neuroparalyticogenic), the production was stopped in
December, 2004 in all centers. The dosage schedule of
cell culture rabies vaccine (CCRV) is same irrespective
of the body weight or age of the children.
412
The Types of Antirabies Vaccine

1. Cell culture rabies vaccines (CCRV)
i. Human diploid cell vaccine (HDCV)
ii. Purified chick embryo cell vaccine (PCEC).
iii. Purified vero cell rabies vaccine (PVRV).
2. Purified duck embryo vaccine (PDEV) All CCRVs and
PDEV used for postexposure prophylaxis (PEP)
should have potency (antigen content) greater than
2.5 IU per dose.
Reconstitution and storageThe lyophilized prophilised
vaccine should be reconstituted with the diluent
provided with the vaccine immediately prior to use. In
case of unforeseen delay it should be used within 6-8
hours of reconstitution.
Presently liquid human diploid cell (HDCV) vaccine
is also available.
and centers (ARCs) where a handful number of cases of

animal bites/scratches will be available.
The following vaccines have been approved by Drug
Controller General of India (DCGI) currently for use by
intradermal route: (i) Purified chick embryo cell vaccines,
(ii) Purified vero cell vaccine.
As purified duck embryo cell vaccine is a suspension,
its use is not recommended for ID administration,
similarly the liquid and adjuvanated human cell culture
vaccine is not suitable for ID use.
Potency of approved vaccine: The vaccines should have
stated potency of >2.5 IU per IM dose, irrespective of
reconstituted volume. The same vaccine is used for ID
administration as per stated schedule. 0.1 ml of vaccine,
irrespective of reconstituted volume, is administered per
ID site as per schedule below.
ID Vaccine Regimen
Intramuscular (IM) Regimen of Cell Culture

Antirabies Vaccine
The regimens for IM administration are described below.
But the Essen schedule is the only IM regimen to be
practiced in India.
1. Essen schedule: Five dose intramuscular regimen (1-1-11-1) Total five injections, single dose on days 0, 3,7,
14 and 28. Day 0 indicates date of first injection.
2. Zagreb IM Protocol (2-0-1-1)- Two doses on day 0 on
either side of deltoid or anterolateral thigh, 1 dose on
day 7 and one dose on day 21.
Site of inoculation The anterolateral thigh region is ideal
in infants and younger children whereas of older children
can take in deltoid region safely. Gluteal region is not
recommended because the fat present in this region traps
the vaccine, retards the absorption of antigen and hence
impairs the generation of optimal immune response.
Intradermal (ID) Regimen of Cell Culture
Antirabies Vaccine
Intradermal regimens consists of administration of a
fraction of intramuscular dose of CCRVs on multiple sites
in the layers of dermis of skin. The use of intradermal
route leads to considerable savings in terms of total
amount of vaccine needed for full pre- or postexposure
vaccination, thereby reducing the cost of active
immunization. But the regimen will not make any
economic meaning when one or two doses are used in
private clinics. It is better to be used in antirabies clinics
1. Updated Thai Red Cross (Updated TRC-ID) Schedule (22-2-0-2): This is the most ideal ID schedule. This
involves injection of 0.1 ml of reconstituted vaccine
per ID site and on two such ID sites per visit (one on
each deltoid area, an inch above the insertion of
deltoid muscle) on days 0, 3, 7 and 28. The day 0 is
the day of first dose administration of IDRV and may
not be the day of rabies exposure/animal bite. No
vaccine is given on day 14.
2. Thai Red Cross (TRC-ID) schedule (2-2-2-0-1-1): Same
as the above schedule except 0.1 ml single dose is
given on day 28 and day 90, but as the chance of drop
out will increase the first regimen is preferred.
It is very important to learn the technique of giving
ID injection for the staff of antirabies clinics (ARCs).
Pre-exposure Schedule
As rabies is a cent per cent fatal disease and children
constitute a special risk for getting the infection, it may
be advisable to vaccinate children after they attain the
age of 3 years and start playing in the streets and may
come in contact with street or pet dogs. This schedule is
also practiced in persons who are engaged in rabies
research and production of rabies vaccine units, in
municipality workers, in postmen, in persons going to
forests where there are bat infested caves, veterinary
practitioners, taxidermists, etc. It has been shown in
several studies that a course of pre-exposure vaccination
will elicit a good immune response and the memory cells
generated will last for many years. In fact some studies

have also shown that protective levels of antibodies may
persist for at least a decade. If such children are exposed
to rabies by animal bites, 2 booster doses given on day 0
and on day 3 will elicit a rapid and stronger secondary
immune response which will neutralize the virus and
prevents its ascent to the CNS. There is no need for
administration of rabies immunoglobulin in patients who
had taken a complete course of pre-exposure or postexposure course of CCRVs in their previous exposure.
Schedule of pre-exposure vaccination:
Intramuscular: Three doses of any CCRV (1 ml or 0.5 ml
depending on the brand) administered on the anterolateral thigh or deltoid region on days 0, 7 and 28.
Intradermal: The dose (0.1 ml) is same for all vaccine
brands and 0.1 ml is administered intradermally over
the deltoid on days 0, 7 and 28.
ABC-AR Program
Animal birth controlanti-rabies program (ABC-AR
program) is launched in India by Blue Cross to control
stray dog population. All dogs, pet and stray, need
vaccination every year with an effective and potent antirabies vaccine.
persistent attempts to lick, when the dogs are infected

by rabies virus. There is behavior changes, ultimately the
dog develops irresistible tendency to scratch and bite.
The pupils dilate and salivation is increased. The furious
form which show the classical symptoms gives the
concept of mad dogs. Dumb rabies is characterized by
progressive development of paralysis.
It is to be accepted that stray dog population has to
be reduced drastically by initiative to sterilize the male
dogs in stray population and vaccination with modern
rabies vaccines by the government health departments
and NGOs combinedly are needed. Even the pet dogs
must have municipality licenses and they have to be
immunized annually with rabies vaccines. All these will
help to reduce the incidence of human deaths due to
rabies in India.
For IAP- Infectious Diseases Chapter Protocol on
Rabies, refer to Chapter 36.11.4 Page No. 1534.
BIBLIOGRAPHY
1.
2.
3.
WHO Rabies Vaccine Initiative

This is formulated by WHO, vaccine manufacturers,
professional bodies and major funding agencies with the
objective to reduce cost of each effective course of
treatment making it affordable to the downtrodden in
developing countries. Only modern cell culture vaccine
is to be used in pre- and postexposure prophylaxis.
Canine Rabies
All warm-blooded animals even bats are susceptible to
rabies, the incubation period and symptoms had marked
similarities in all of them. The abnormal behavior of the
infected animals are seen commonly. Even rabies is
reported in small percentage of bites by immunized dogs
and also by puppies. The observation period of 10 days
is only true in dog and cat bites.
Dogs are the most important animals in spreading
rabies, responsible for 96% of the cases of human rabies
deaths in India. But for several reasons it is difficult to
control stray dog population in this country. The most
friendly animal to human being, the dog become restless,
move to other places of seclusion, sudden burst of
excessive affection are seen in the early stage with
413
4.
5.
6.
7.
8.
9.
10.
11.
12.
Association for Prevention and Control of Rabies in India.

WHO Sponsored National Multicentric Rabies Survey,
2004. Bangalore: APCRI, 2004;44-5.
Bompart F, Dutta AK, Wood SC, Rabies immunoglobulins in WHO category III bites. Journal of Association
for Prevention and Control of Rabies in India 2001;1(2):
7-11.
Caplan K. Rabies: The Facts Oxford: Oxford University
Press, 1977;53-61.
Ghosh TK. Prevention of rabies by vaccination and
immunoglobulin therapy: Some controversies and
solutions. In: Ghosh TK, ed. Infectious Diseases in
Children and Newer Vaccines. New Delhi: Jaypee
Brothers 2007;330-5.
Ghosh TK. Rabies and its prevention. Pediatr Clin India
2001;36:42-51.
Ghosh TK. Rabies vaccine. In: Shendurnikar N, Agarwal
M, eds. Immunisation for children, 1st ed. Hyderabad,
Bangalore: Paras Publishing 2003;171-82.
Goswami A. Safety and tolerance of equine rabies
immunoglobulin in Indian population. Journal of
Association for Prevention and Control of Rabies in India
2000;1(2):30-4.
Kundu R, Ganguly N, Ghosh TK. IAP Protocols on
Infectious Diseases in Children. Kolkata: IAP infectious
Diseases Chapter 2008;57-71.
Madhusudana SN. Implementing intradermal vaccination: Why delay (Editorial). APCRI Newsletter 2003;3:3.
Meslin FX, Stohr. K. Human Rabies Vaccines. Current
situation and foreseeable Trends. Journal of Association
for Prevention and Control of Rabies in India 2000;1(2):
5-6.
Singh H, Bhatia R. Vaccines: Prospects and Perspectives.
New Delhi: Forward Publishing Company, 1993;282-309.
World Health Organisation. WHO Expert Committee on
Rabies, 89th Report. WHO Tech Rep Ser 1992;8224:
1-84.
414
9.31 Pediatric HIV Disease

Meena Malkani
Acquired Immune Deficiency Syndrome (AIDS) is
caused by human immunodeficiency virus types 1 and
2 (HIV). It is a worldwide problem, but more so in
developing countries like sub-Saharan Africa,
Thailand, India and the rest of the Asia. Ever since the
report of the first pediatric case in 1983, there has been
an alarming increase in the rate of disease. It is
estimated that currently 38.6 million people live with
HIV infection world over of which 2-3 million, i.e.
5-9% are children <15 yrs of age. HIV transmission
occurs by contact with infected cells in blood and body
fluids.
The predominant cells infected are CD4+T lymphocytes, depletion of which causes immunodeficiency.
EPIDEMIOLOGY
The estimated number of children living with HIV/AIDS
in India is 0.17 million (UNAIDS 2004 report), which
means they form about 3.5-5% of people living with HIV
in the country. The pediatric population at risk of HIV-1
infection are infants born to infected mothers, children
given HIV-1 contaminated blood or blood products and
adolescents who acquire infection sexually or by use of
intravenous drugs. Unlike in adults where > 90% of the
time HIV infection occurs through sexual route, in the
developing countries 95% of cases in children occur due
to vertical transmission from their infected parents.
In vertical transmission, HIV can be transmitted
during pregnancy, during childbirth, or breastfeeding.
Without intervention, the risk of transmission from
an infected mother to her child ranges from 15-20% in
developed countries and from 25-45% in developing
countries (Table 9.31.1).
TABLE 9.31.1: Estimated risk and timing of Mother To
child Transmission (MTCT) in the absence of interventions
During pregnancy
During labor and delivery
During breastfeeding
Overall without breastfeeding
Overall without breastfeeding upto 6 months
Overall without breastfeeding upto 18-24 months
5-10%
10-15%
5-20%
15-25%
20-35%
30-45%
VERTICAL TRANSMISSION OF HIV-1

It is an important and unique aspect of pediatric AIDS.
Potential routes of infection include admixture of
maternal fetal blood, or infection across the placenta
antenatally or extensive mucocutaneous exposure to
maternal blood and vaginal secretions intranatally.
Factors which may increase rate of vertical transmission of HIV-1 are:
High viral load in the maternal circulation
Maternal seroconversion just before delivery
Vitamin A deficiency in mother
> 4-hr duration of rupture of membrane
Vaginal delivery
STD in mother
Delivery before 34 weeks
Birth weight < 2.5 kg
Detectable p24 antigen in maternal serum
Absence of neutralizing antibodies in maternal serum
Maternal CD4+ count less than 700/cumm or CD4+/
CD8+ ratio less than 0.6.
BREAST MILK ACQUIRED HIV-I INFECTION
Transmission through breastfeeding seems to be related
to the virus load in the breast milk as well as to length of
time the child is fed. HIV-1 has been detected by culture
and by the PCR method in cellular and acellular
components of breast milk. The colostral viral load
appears to be particularly with HIV-1, such a route is
facilitated by the absence of an acid environment in the
newborn babys stomach that allow HIV-1 to retain its
infectivity.
TRANSFUSION ACQUIRED HIV-1 INFECTION
The risk of transmission to a recipient of HIV-1 infected
blood is at least 95 percent (Table 9.31.2).
TABLE 9.31.2: Differences between perinatal and
transfusion acquired HIV-1 infection
Perinatal
1. Shorter incubation period
Transfusion acquired
1. Longer incubation period
2. LIP common
2. LIP rare
3. Acute HIV syndrome

almost never identifiable
3. Acute HIV syndrome seen

4-6 weeks after transfusion
Figure 9.31.1: The genome of HIV
ADOLESCENT AND HIV

Worldwide data demonstrate that the AIDS pandemic
remains dynamic among adolescents, most of which is
transmitted heterosexually. However homosexual
behavior and sexual abuse is also a major route of
transmission in adolescent population. These are
generally in early stage of HIV infection. Intravenous
drug use and receipt of infected blood products account
for a smaller percentage of transmission while youth who
acquire HIV perinatally account for a small but growing
number of adolescents living with HIV or AIDS. This
group forms advanced stage of the disease.
ETIOPATHOGENESIS
HIV genome is single stranded RNA, 9.8 Kb in size. Both
the ends have identical regions that contain regulation
and expression genes of HIV (Fig. 9.31.1). The remainder
of genome includes three major sections.
The pol region: Produces viral enzymesreverse
transcriptase, protease, and integrase.
The env region: Encodes the viral envelope proteins.
415
HIV selectively binds to cells expressing CD4

molecule on their surfaceprimarily T4 lymphocytes
(CD4+ cells), cells of monocyte-macrophage lineage,
microglia, astrocytes, oligodendrogila and placental
tissue containing villous Hafbauer cells may be infected
by HIV.
The gp120, which has a knob-like structure, interacts
with protruding loop on CD4 protein forming CD4+-gp
120 complex. RNA is released from viral particle. RNA
produces DNA, using reverse transcriptase. The cells
own DNA is broken and the viral DNA, now called
provirus, is inserted. DNA is switched on and copies of
the virus are made, which leave the cell and infect other
cells. With HIV replication, host cell is killed or survives,
but is permanently infected. Monocytes and macrophages are relatively refractory to cell killing and syncytia
formation, and serve as a reservoir of persisting infection.
Since CD4+ lymphocytes are responsible for orchestration of many important immune responses, its inactivation by HIV leads to many defects of monocytes,
macrophages, cytotoxic T-cells, natural killer cells (K) and
B cells. After HIV enters the circulation intense viremia
ensues, resulting in widespread seeding of virus to
various organs, including brain and lymphoid tissue.
CD4+ lymphocytes migrate to lymph nodes where they
become activated and proliferate, causing generalized
lymphadenopathy (acute retroviral syndrome).
Following cellular and humoral response within one
week to three months the level of culturable virus
declines and patient enters a phase of clinical latency,
with lack of symptoms and return of CD4+ cells to only
a moderately decreased level. During clinical latency,
patients undergo gradual deterioration of immune
system with depletion of architecture and degeneration
of the follicular dendritic cell network with loss of ability
to trap HIV particles. This frees the virus to recirculate,
producing high levels of viremia seen during the later
stages of disease. Perinatally infected infants generally
demonstrate a relatively shorter period of clinical latency.
This may be so, if intrauterine infection coincides with
the period of rapid expansion of CD4+ cells in fetus; it
could effectively infect the majority of the bodys
immunocompetent cells causing more severe impairment of immunity than HIV infection in adults.
Protection from Infection
A strong immune response might reduce virus load or
even clear the virus. The frequency of clearance has been
416
reported to range from 2.7 to 6.4 percent. Detection of

HIV-1 envelope specific T-cell response in cord blood of
uninfected newborn of seropositive mother indicates that
clearance may already have occurred in utero. HIV-1
specific cytotoxic lymphocytes and in vitro antibody
production to viral gag and env proteins in apparently
uninfected infants has also been reported.
CLINICAL FEATURES
Pattern of disease expression and progression is quite
variable in HIV-1 infected children. 20 to 30 percent
develop profound immunodeficiency and AIDS defining
illnesses before the first year of life and two-thirds have
more slowly progressive course from 5 to 10 years. Age
of onset of any sign of HIV-1 infection predicts length of
survival.
Revised WHO Clinical Classification 2006
WHO has recently revised the earlier CDC classification
and given the clinical classification (Table 9.31.3, based
on sign and symptoms) and immunological classification
(Table 9.31.4, based on CD4+ counts.)
OPPORTUNISTIC INFECTIONS (OI)
OI occur as CD4+ count declines. Pneumocystic carinii
(PCP) is the most common and lethal opportunistic
infection in pediatric population. Clinically, there is
respiratory distress with cough and hypoxemia. Chest
X-ray radiograph reveals interstitial infiltrates or diffuse
alveolar disease. Diagnosis is made by demonstration of
P. carinii in bronchoalveolar fluid or lung biopsy.
Oral candidiasis is the most common fungal infection.
It may involve the esophagus resulting in vomiting, fever,
dysphagia and anorexia. Intestinal cryptosporidiosis may
result in severe chronic diarrhea and malnutrition.
Atypical mycobacterial infection with Mycobacterium
avium intracellular complex (MAC) has been recognized
increasingly. It presents with fever, weight loss, diarrhea,
TABLE 9.31.3: Revised WHO clinical staging of HIV/AIDS

Clinical stage 1 (asymptomatic):
Asymptomatic
Persistent generalized lymphadenopathy
Clinical stage 2 (mild):
Unexplained persistent hepatomegaly
Papular pruritic eruptions
Extensive wart virus infections
Molluscum contagiosum
Fungal nail infections
Recurrent oral ulcerations
Unexplained parotid enlargement
Herpes zoster
Recurrent upper respiratory tract infections (otorrhea, sinusitis)
Clinical stage 3 (advanced):
Unexplained malnutrition not responding to standard therapy
Unexplained persistent diarrhea
Unexplained persistent fever
Persistent oral candidiasis
Oral hairy leukoplakia
Lymph node TB
Pulmonary TB
Severe recurrent bacterial pneumonia
Lymphoid interstitial pneumonia
Unexplained anemia, neutropenia or chronic thrombocytopenia
Clinical stage 4 (severe):
Unexplained severe wasting
Pneumocystis carinii pneumonia
Recurrent severe bacterial infections
Chronic Herpes simplex infection
Extrapulmonary TB
Kaposi sarcoma
Esophageal candidiasis
CNS toxoplasmosis
HIV Encephalopathy
Cytoegalovirus infections
Cryptococcosis, cryptosporidiosis, isosporiasis
Progressive multifocal leucoencephalopathy
Cerebral or B cell non-Hodgkin lymphoma
HIV-associated nephropathy/cardiomyopathy
TABLE 9.31.4: Revised classification of immune suppression in children based on CD 4+ levels

Classification of HIV
associated immune
deficiency
<11 months
(% CD4)
12-35 months
(% CD4)
36-39 months
(% CD4)
>5 years
(cells/mm3)
Not significant
Mild
Advanced
Severe
>35
30-35
25-30
<25
>30
25-30
20-25
<20
>25
20-25
15-20
<15
>500
350-499
200-349
<200

anemia, granulocytopenia and diagnosed by isolation of
MAC from blood or bone marrow. Other opportunistic
pathogens include Toxoplasma gondii, Mycobacterium
tuberculosis and malarial parasites. Viral infection with
Herpes simplex, Varicella zoster, cytomegalovirus and measles
virus are often seen.
Other common clinical presentation of pediatric AIDS
is lymphocytic interstitial pneumonia (LIP)it is a chronic
lower respiratory tract abnormality. It causes reticulonodular pulmonary infiltrate with or without hilar
lymphadenopathy. The infiltrate is composed of CD8+
lymphocytes. Children with LIP having clubbing,
persistent cough with exertional dyspnea require chronic
oxygen therapy. It may resolve with oral corticosteroids.
Neoplasms are relatively uncommon in pediatric
HIV-1 infection. Non-Hodgkins lymphoma and primary
CNS lymphoma are the most commonly reported
malignant disease.
Recently, multiple soft tissue tumors have been
reported.
DIAGNOSIS OF HIV INFECTION
Detection of HIV-1 antibody (IgG) by ELISA is
extremely sensitive and very specific. It is simple and
inexpensive. However, maternal transplacental IgG in
the infant obscures the usefulness of antibody screening
for diagnosis, except in older children and adolescents.
It may be necessary to wait until 15 to 18 months to
identify an HIV-1 exposed infant by ELISA test. Western
blot analysis measures antibody to specific viral
polypeptides and can be used as a confirmatory test
after six months of age. The presence of IgM or IgA antiHIV in the infants circulation can indicate HIV
infections, as these immunoglobulin classes do not cross
the placenta. However, detectable quantities of IgA antiHIV are not generally produced until 3 to 6 months of
age and IgM anti-HIV are insensitive and nonspecific.
Tests identifying viral presence as HIV-1 culture and
HIV-1 DNA and RNA polymerase chain reaction (PCR)
are more valuable but are very costly. Two types of PCR
are available:
1. HIV DNA PCR: This is a qualitative test that detects
the proviral DNA integrated with the host cell.
2. HIV RNA PCR: This is a quantitative test using
reverse transriptase and thus determines the viral
load.
417
Other Markers of HIV-1 Infection Include

Decreased CD4+ count, increased CD8+ count, depressed
lymphocyte proliferative response to mitogens and
marked hypergammaglobulinemia.
MANAGEMENT
A multidisciplinary team approach is essential for
successful management of pediatric HIV-1 infection.
Specific Therapy
Specific antiretroviral therapy (Table 9.31.5) is believed
to result in extended survival and reduction in
opportunistic infections with improvement in weight
gain and general wellbeing.
Monotherapy
Early trials with ZDV monotherapy were encouraging,
especially regarding improvement in or prevention of
CNS abnormalities. However lack of resistance reduced
the importance of monotherapy. Subsequent studies
documented the benefit of combination NRTI regimens
over monotherapy.
TABLE 9.31.5: Antiretroviral agents
Nucleoside reverse transcriptase inhibitor (NRTI)
1. Zidovudine (ZDV, AZT)
2. Didanosine (ddl)
3. Lamivudine (3TC)
4. Stavudine (d4T)
5. Abacavir (ABC)
6. Zalcitabine (ddc)
*7. Adefovir (ADV)
90-180 mg/m2 every 6-8 hrly

90-150 mg/m2 every 12 hrly
4 mg/kg bid
1 mg/kg q 12 hrly (to 30 kg)
8 mg/kg q12 hrly
0.005-0.01 mg/kg q 8 hrly
Pediatric dose not established
Non-nucleoside RTI (NNRTI)

1. Nevirapine (NVP)
2. Efavirenz (EFV)
3. Delavirdine (DLV)
120-200 mg/32 every 12 hrly

200-600 mg/qd (by wt)
Adolescent/adult 400 mg tid
Protease inhibitor (PI)

1. Ritonavir (RTV)
2. Nelfinavir (NFV)
*3. Indinavir (IDV)
*4. Saquinavir (SQV)
5. Amprenavir
400-450 mg/m2 every 12 hrly

30 mg/kg every 8 hrly
500 mg/m2 every 8 hrly
50 mg/kg tid (under study)
20 mg/kg bid
*WHO directive-pediatric dose not approved
418
In the 2006 WHO guidelines for treatment of infants

and children with HIV, the drugs recommended for
use are:
NRTI (AZT, d4T, 3TC, ABC).
NNRTI (NVP, EFV).
PI (LPV, NFV, SQV).
The recommended first line ARV regimen for infants
and children is:
Regimen of 2 NRTI+1 NNRTI, i.e.
1. AZT + 3TC + NVP/EFV
2. D4T + 3 TC+ NVP/EFV
Under the National AIDS Control Program, specific
fixed dose combination (FDCs) of ARV drugs in
pediatric dosages have been made available at
selected ART countries.
Protease inhibitors are used as second line treatment
in case of treatment failure with first line drugs or
severe adverse reactions to first line drugs.
REDUCTION OF VERTICAL TRANSMISSION
The recommended methods to reduce vertical transmission are:
1. Elective cesarian section
2. Antiretroviral therapy
3. Avoidance of breastfeeding.
However WHO advocates breastfeeding by infected
mothers in developing countries in view of high mortality
related to diarrhea, malnutrition and respiratory disease
in non-breastfed children. Hence, breastfeeding needs
to be decided on individual merit depending on hygiene
and socio-economic factors. Invasive procedures such as
amniocentesis or fetal blood sampling should be avoided
and any sexually transmitted disease in mother should
be adequately treated. AZT is to be included in all
perinatal regimen.
When a pregnant women presents during pregnancy,
she should be given ART as follows (to prevent MTCT):
1. Antepartum: Oral AZT 300 mg BD from 28 weeks
gestation or as soon as feasible.
2. Intrapartum: AZT continued as 300 mg at onset of
labor and 300 mg every 3 hrly till labor.
Also 3TC 150 mg every 12 hrly till labor
Also single dose NVP 200 mg at onset of labor
3. Postpartum: Oral AZT 300 mg BD and 3TC 150 mg
BD for 7 days.
For the baby: NVP single dose 2 mg/kg within 72 hours
of birth and oral AZT 2 mg/kg 4 times a day for 7 days.
PREVENTION OF PCP
PCP prevention is one of the most important goals of
HIV-1 infection management. All infants from 4-6 weeks
of age, either born to HIV-1 infected mothers or proved
to be HIV-1 infected should receive prophylaxis for PCP.
The drug of choice is co-trimoxazole in the dose of 5 mg/
kg/day single daily dose.
Alternatively dapsone 2 mg/kg orally, once a day or
pentamidine or atovaquon may be given.
NUTRITION
Malnutrition is a serious problem, especially if diarrhea
is associated with HIV-1 infection. Dietary supervision
may help to prevent weight loss with adequate calorie
and protein intake.
OTHER INFECTIONS
Prompt treatment of associated bacterial and opportunistic infections with appropriate antiobiotics and drugs
is very necessary.
IMMUNIZATION
All HIV infected children should receive standard
pediatric immunization. However, OPV and BCG in
symptomatic children need to be withheld.
COUNSELING AND SUPPORT
Coping with the complex psychological and social needs
of the family is one of the most important and challenging
aspects of pediatric HIV management.
The child may be the first family member to be
diagnosed and the mother feels an enormous sense of
guilt of having infected her own child. Due to the stigma
attached to diagnosis of HIV, families often feel socially
and culturally isolated. Illness and unemployment can
create financial problems. It is important to establish links
with support agencies in the community, while respecting the familys need for confidentiality. A multidisciplinary team of health professionals who can deliver
coordinated care in a family oriented and child centered
manner, is necessary for the support of the family
afflicted with AIDS. Helping HIV infected children and
their families lead healthier and happier lives must be
one of the biggest and most rewarding challenges of
pediatrics.

FUTURE PROSPECTS
Gene Therapy
Employing inhibitor molecules targeted against CD4+
T-cells indicated that anti-reverse transcriptase antibody
inhibits HIV-1 replication. Gene therapy is defined as
introduction of new genetic material into cells of an
individual with resulting therapeutic benefit. Because
HIV-1 integrates itself into hosts genome, AIDS can be
considered as an acquired genetic disease. This therapy
requires the introduction of anti-HIV-1 genes into cells,
to prevent or inhibit HIV-1 viral gene expression of
function and consequently to limit HIV-1 replication and
AIDS pathogenesis. Gene therapy also down-regulates
HIV-1 gene expression in contrast to conventional drug
therapies.
HIV Vaccine
elicit HIV specific immune responses. The first phase 1

trail of an HIV candidate vaccine was conducted in the
USA in 1987, using gp 160 candidate vaccine.
Subsequently more than 30 candidate vaccines have
been tested in 60 phase 1 or phase 2 trials, involving more
than 10,000 healthy volunteers. But none of the vaccines
have been proved to be effective in preventing HIV
disease in humans so far.
BIBLIOGRAPHY
1.
2.
3.
4.
The development of an efficacious vaccine against HIV

would be the best strategy for controlling the HIV
epidemic. The goal for a preventive HIV vaccine is to
generate both humoral and cellular immunity against
HIV in the host before exposure to the virus. However,
there are many hindrances to the development of an
effective HIV vaccine which includes factors like
antigenic diversity and hypervariability of the virus,
integration of the viral genome into the host cell
chromosome, transmission of disease by mucosal route,
progressive destruction of the immune system of the host,
etc. Several different vaccine concepts have been used to
419
5.
6.
7.
8.
9.
10.
Americal Academy of Pediatrics Committee on Pediatric

AIDS, evaluation and medical treatment of the HIV
exposed infant. Pediatrics, 1997;99.
ARV drugs for treating pregnant women and preventing
HIV infection in resource limited settings; towards
universal access. Recommendations for a public health
approach 2006 version.
Chadwick EC, Yogev R: Pediatric HIV/AIDS, PCNA
1995; 42(4):969-90.
Luzuriaga K, Sullivan JL. Transmission of the HIV from
mother to fetus and infants. AIDS: etiology, diagnosis,
treatment and prevention (4th edition), 1997;167-72.
Nelson Textbook of Pediatrics, 17th edition, Ram Yogev
and Ellen Chadwick 2004;1109-21.
Scarlatti G. Pediatric HIV infection. The Lancet
1996:348:863-8.
Singh S. HIV infection. Frontiers in pediatrics 1996;10215.
The Indian Journal of Pediatrics, Prevention of Mother
to Child Transmission of HIV, March 2004.
The PCNA HIV/AIDS in infants, children and adolescents; Martha A Rogers, February, 2000.
WHO 2006 guidelines on ART in infants and children in
resource limited settings: towards universal access,
recommendations for a public health approach.
9.32 Chikungunya Fever

Utpal Kant Singh, Rajniti Prasad
Chikungunya is a viral fever caused by an alphavirus
and spread by bite of an infected Aedes aegypti mosquito.
The disease was first discovered by Marion Robinson and
WHR Lumsden in 1955 following an outbreak on the
Makonde plateau. The name derives from a Kimakonde
root verb, kungunyala, meaning to dry up or become
contorted, specifically modified in early times to describe
the bent posture of patients. Although primarily African
and zoonotic, it is known chiefly for its non-African large
urban outbreaks, which is transmitted by the same

vectors as those of Dengue viruses. Since 1953, virus
(CHIKV) has caused numerous outbreaks and epidemics
in both Africa and South East Asia, involving hundreds
and thousands of children.
EPIDEMIOLOGY
CHIKV was probably an infection of primates in forests
of Savannahs of Africa maintained by sylvatic Aedes
420
mosquitoes. However, today, CHIKV is also responsible

for extensive A. aegypti transmitted urban disease in the
cities of Africa and major epidemics in Asia. In Africa,
CHIKV is transmitted in the savannahs and forests of
tropical Africa by Aedes mosquito. The vertebrate
portion of the cycle is provided by non-human primates
such as Cercopithecus, monkeys or baboons, which
amplify and maintain virus circulation. It is thought that
endemic circulation and epidemics in troops of primates
are responsible for survival of the virus and local spill
over into human population.
In India, after quiescence of about three decades, an
outbreak of CHIKV is being reported from different parts
of India .The current outbreak in India started in the end
of 2005, when cases of suspected fever were reported
from coastal parts of Andhra Pradesh and Karnataka.
The number of suspected cases reported have varied
from different sources ranging up to a million. The
current outbreak has an attack rate of 4-45%. The
confirmed cases of chikungunya fever have been
reported from all over of country but more so from
Andhra Pradesh, Karnataka, Maharashtra, Tamil Nadu,
Madhya Pradesh and Gujarat states.
CHIKV is commonly transmitted to humans through
the bite of infected mosquitoes of the Aedes genus, which
usually bite during daylight hours. Mother to child
transmission, occupational exposure and occurrence in
a health worker from careless handling a patients blood
has also been reported. In Africa, CHIK virus appears to
be maintained in sylvatic cycle involving wild primates
and forest dwelling Aedes spp. Monkeys and possibly
other wild animals may also serve as reservoirs of the
virus.
A. aegypti, Ae. albopictus and Ae. polynesiensis are
commonly involved in the transmission of virus,
although Culex has also been reported for the transmission in some cases. A. aegypti is the principal vector of
CHIKV in India. This vector species is anthropophilic,
endophagic and bites during the day time. It mainly
breeds in man made containers such as rain water barrels,
cisterns, wells, water storage drums, pots, discarded
bottles, tin cans, motor vehicle tyres, etc. A recent
epidemic in the Indian Ocean islands suggested that
Asian tiger mosquito, A. albopictus was responsible for
spread. A mutation in the envelope protein gene (E1A226V) was found in some strains of CHIKV causing
epidemics on islands in the Indian Ocean. This mutation
is directly responsible for CHIKV adaptation to the Asian
tiger mosquito. Both A. aegypti and Ae. albopictus are

present in the US and the Asian tiger mosquito in Europe.
With the global climate warming, CHIKV could expand
to new geographic locations.
Chikungunya Virus
CHIKV, a positive strand, enveloped RNA virus, is a
member of the Alphavirus genus and belongs to the
Togaviridae family. It is endemic in large parts of Africa,
the Middle East, India, and South-East Asia and is closely
related to Onyong-nyong viruses. Genetic analysis based
on partial E1 envelope glycoprotein gene sequences
showed the presence of three distinct phylogroups. The
first contained all isolates from West Africa; the second
comprised all Central, Southern and Eastern African
strains (CSEA); and the third contained isolates from
Asia. Phylogenetic studies have suggested that the West
African CHIKV cluster was ancestral, the CSEA cluster
diverged from West African ancestors, and the Asian and
Indian Ocean clusters of genotypes had lately and
independently evolved from CSEA variants.
Complete genomic sequence of CHIKV has been
determined and found to have 11,805 nucleotides in
length. Coding sequences consisting of two large open
reading frames of 7,422 nucleotide and 3,744 nucleotide
encoding the non-structural polyprotein (2,474 amino
acids) and the structural polyprotein (1,248 amino acids),
respectively. The non-structural polyprotein is the
precursor of proteins nsP1 (535 amino acids), nsP2 (798
amino acids), nsP3 (530 amino acids) and nsP4 (611
amino acids) and the structural polyprotein is the
precursor of protein C (261 amino acids), E3 (64 amino
acids), E2 (423 amino acids), 6K (61 amino acids) and E1
(439 amino acids).
PATHOGENESIS
CHIKV replicates in various human cells, including
epithelial and endothelial cells, but primarily in
fibroblasts and macrophages. T and B lymphocytes and
monocyte-derived dendritic cells are not susceptible.
Viral entry occurs through a pH-dependent, endocytic
pathway. CHIKV is highly cytopathic for mammalian
cells, inducing apoptosis of infected cells. CHIKV
replication is significantly inhibited by type I and II IFNs.
In humans, CHIKV produces disease about 48 hours after
mosquito bite. Patients have high viremia during the first
2 days of illness. Viremia declines around day 3 or 4 and
421
usually disappears by day 5. Hemagglutination inhibition and neutralizing antibodies can usually be detected
after day 5 with fading viremia. Silent CHIKV
infections do occur, but how commonly this happens is
not yet known. CHIKV infection (whether clinical or
silent) is thought to confer lifelong immunity. A recent
study has suggested CHIKV tropism for muscular
satellite cells, which can act as small reservoirs for virus
or virus-encoded components or both for longer-thanexpected periods.
Chikungunya is an acute infection characterized by
abrupt onset fever and severe arthralgia, followed by
other constitutional symptoms and rash lasting for a
period of 1-7 days (triad: fever, rashes and arthralgia).
The incubation period is usually 2-3 days, with a range
of 1-12 days. All age groups are affected, including
newborns. Fever rises abruptly, often reaching 39-40C
accompanied by intermittent shaking chills. This acute
phase lasts 2-3 days. The temperature may remit for 1-2
days, after a gap of 4-10 days, resulting in a saddle back
fever curve.
The arthralgias are polyarticular, migratory and
predominantly affect the small joints of hands, wrists,
ankles and feet with lesser involvement of larger joints
(Fig. 9.32.1). In acute stage, patients complain bitterly of
pain when asked to move and assume an attitude of
flexion. Pain on movement is worse in the morning,
improved by mild exercise and exacerbated by strenuous
exercise. Swelling may occur but fluid accumulation is
uncommon. Patients with milder articular manifestation
are usually symptom-free within a few weeks, but more
severe cases require months to resolve entirely.
Cutaneous manifestations include flushing of the face
and trunk. This is usually followed by maculopapular
rash. The trunks and limbs are commonly involved, but
face, palms and soles may also show lesions. The rash
may simply fade or desquamate. Petechiae may occur
alone or in association with rash. They are observed
during the acute stage of the illness, and others during
convalescence or thereafter. Pigmentary changes have
been reported to be the most common cutaneous finding
(42%), followed by maculopapular eruption (33%) and
intertriginous aphthous-like ulcers (21.37%). Exacerbation of existing dermatoses, such as psoriasis, and
unmasking of undiagnosed Hansens disease were also
observed.
Figure 9.32.1: Frequency of pain by location during acute

stage of chikungunya infection
Iridocyclitis and retinitis are the most common ocular

manifestations associated with chikungunya, with a
typically benign clinical course. Less frequent ocular
lesions include episcleritis. Other manifestations include
meningoencephalitis (1%), fulminant hepatitis (2%) and
mild hemorrhagic manifestations in 3%.
Most symptomatic patients (93.7%) complained of a
chronic stage of the disease, which is characterised by
pains in joints and/or bones or both. This persisting pain
was continuous (41.3%) or discontinuous with alternation of clinical remission and relapses (58.7%). Some
infected individuals (11.7%) also mentioned fever at this
stage.
Laboratory investigation is critical to establish diagnosis
and initiate specific public health response. Three main
laboratory tests are used for diagnosing Chikungunya
fevers: virus isolation, serological tests and molecular
technique of Polymerase Chain Reaction (PCR). Virus
isolation is the most definitive tests. 2-5 ml of whole blood
is collected during the first week of illness in heparinzed
tube and transported on ice to the laboratory. The CHIK
422
virus produces cytopathic effects in a variety of cell lines

including BHK-21, HeLa and Vero cells. The cytopathic
effects must be confirmed by CHIK specific antiserum
and the results can take between 1-2 weeks. Virus
isolation must only be carried in BSL-3 laboratories to
reduce the risk of viral transmission.
Recently, a reverse transcriptase, RT- PCR technique
for diagnosis has been developed using nested primer
pairs amplifying specific components of three structural
gene regions, Capsid (C), Envelope E-2 and part of
Envelope E1. PCR results can be available within 1-2 days.
For serological diagnosis, an acute phase serum must
be collected immediately after clinical onset and a
convalescent phase, 10-14 days after the disease onset.
The blood specimen is transported at 4C and should
not be frozen to the laboratory immediately. If testing
cannot be done immediately, the blood specimen is
separated into sera that should be stored and shipped
frozen. Serologic diagnosis can be made by demonstration of fourfold increase in antibody in acute and
convalescent sera or demonstrating IgM antibodies
specific for CHIKV. A commonly used test is the
immunoglobulin M antibody (IgM) capture enzymelinked immunosorbent assay (MAC-ELISA). Results of
MAC-ELISA can be available within 2-3 days. Crossreaction with other flavirus antibodies such as Onyongnyong and Semliki forest may occur in the MAC-ELISA;
however, the latter viruses are relatively rare in South
East Asia but if further confirmation is required, it can
be done by neutralization tests and hemagglutination
inhibition assay (HIA). A positive virus culture
supplemented with neutralization is taken as definitive
proof for the presence of Chikungunya virus. PCR results
for E1 and C genome either singly or together constitute
a positive result for Chikungunya virus.
Management
There is no specific treatment for Chikungunya fever.
The illness is usually self-limiting and resolves with time.
Supportive care with rest is indicated during the acute
joint symptoms. Movement and mild exercise tend to
improve stiffness and morning arthralgia, but heavy
exercise may exacerbate rheumatic symptoms. Nonaspirin and non-steroidal anti-inflammatory drugs
(NSAID) are recommended. In unresolved arthritis
refractory to NSAID, chloroquine (10 mg/kg/day) has
proved to be useful. Chloroquine inhibits viral replication
by blocking the pH dependent endocytosis of CHIKV
into host cells. Although chloroquine blocks CHIKV

replication, the therapeutic (antiviral) index of chloroquine in cell cultures is rather narrow thus, one should
be cautious when planning the use of chloroquine as an
antiviral treatment in infected individuals.
Self-resolution occurs with cutaneous lesions. Patients
with hyperpigmentation may be treated with sunscreens
and topical steroids. All patients with only centrofacial
involvement showed complete clearance during followup at 3 weeks. Patients with more diffuse involvement
showed a slower resolution. Aphthous ulcers usually
heal over 7-10 days with local cleaning and topical
antimicrobials to prevent secondary infection. Iridocyclitis and retinitis have a typically benign clinical course.
All the patients respond well to the treatment with
preservation of good vision.
Infected persons should be protected from further
mosquito exposure (staying indoors and/or under
mosquito net during the first few days of illness) so that
they cannot contribute to the transmission cycle.
Prevention and Control
Prevention is entirely dependent upon taking steps to
avoid mosquito bites and elimination of mosquito
breeding sites and include the following.
1. Wear full sleeve clothes and long dresses to cover the
limbs.
2. Use mosquito coils, repellents and electric vapor mats
during the daytime.
3. Use mosquito nets to protect babies, old people and
others, who may rest during the day. The effectiveness of such nets can be improved by treating them
with permethrin. Curtains can also be treated with
insecticide and hung at windows or doorways, to
repel or kill mosquitoes.
4. Drain water from coolers, tanks, barrels, drums and
buckets, etc.
5. Emptying coolers when not in use.
6. Remove from the house all objects, e.g. plant saucers,
etc. which have water collected in them.
7. Cooperating with the public health authorities in antimosquito measures.
Vaccine
The widespread geographic distribution, recurrent
epidemics and infection of military personnel, travellers,
and laboratory staff working with CHIKV have indicated
the need for a safe and efficacious vaccine.

In Thailand, CHIK strain 15561, was used to develop
a small lot of vaccine The vaccine produced no untoward
reactions and was highly immunogenic. The current live
vaccine (Lot 1-85, TSI-GSD-218) was developed in United
States in USAMRIID and was produced at the Salk
Institute, from GMK strain 15561 by serial passage in
MRC-5 cells. The results of phase I and phase II trials
strongly suggest that the live vaccine is safe and welltolerated and produces no severe or frequent symptoms
than found in placebo recipients.
Surveillance
Epidemiological and entomological surveillance should
be intensified. Reporting of fever cases should be
monitored closely. Active surveillance by health workers
using the case definitions for cases presenting with acute
fever associated with arthralgia/arthritis (painful and
stiff joints) to detect new cases early for treatment should
be undertaken. This will help in identifying the affected
areas, so that control measures may be initiated. Vector
surveillance should also be done and will help in
identifying the areas for initiating control measures and
assess the impact of the measures taken. People need to
be educated about the disease, mode of transmission,
availability of treatment and adoption of control
measures. The activities have to be identified particularly
to effect changes in the practice of storage of water and
personal protection.
BIBLIOGRAPHY
1. Queyriaux B, Simon F, Grandadam M, Michel R, Tolou
R, Boutin J. Clinical burden of chikungunya virus
infection. Lancet Infect Dis 2008;1:2-3.
423
2. Chhabra M, Mittal V, Bhattacharya D, Rana U, Lal S.

Chikungunya fever: A re-emerging viral infection. Indian
J Med Microbiol 2008;26:5-12.
3. Chikungunya Fever Fact Sheet - CDC Division of Vector
Borne Infectious Diseases. Available from: http://
www.cdc.gov/ncidod/chikungunya/chickfact.
htm.2006.
4. Edelman R, Tacket CO, Wasserman SS, Bodison SA,
Perry JG, Mangiafico JA. Phase II safety and immunogenecity study of live chikungunya virus vaccine TSIGSD-218. Am J Trop Med Hyg 2000;62(6):681-5.
5. Inamadar AC, Palit A, Sampagavi VV, Raghunath S,
Deshmukh NS. Cutaneous manifestations of chikungunya fever: Observations made during a recent outbreak
in south India. Intern J Dermatol 2008;47:154-9.
6. Khan AH, Morita K, Parquet MC, Hasebe F, Mathenge
EG, Igarashi A. Complete nucleotide sequence of
chikungunya virus and evidence for an internal
polyadenylation site. J Gen Virol 2002;83:3075-84.
7. Lahariya C, Pradhan SK. Emergence of chikungunya
virus in Indian subcontinent after 32 years: A review. J
Vect Borne Dis 2006;43:151-60
8. Mahendradas P, Ranganna SK, Shetty R, Balu R,
Narayana KM, Babu RB, et al. Ocular Manifestations
Associated with Chikungunya. Ophthalmology 2008;
115(2):287-91.
9. Mohan A. Chikungunya fever: Clinical manifestations
and management. Indian J Med Res 2006;124:471-4.
10. Powers AM, Brault AC, Tesh RB, et al. Re-emergence of
Chikungunya and O nyong-nyong viruses: Evidence
for distinct geographical lineages and distant evolutionary relationships. J Gen Virol 2000;81:471-9.
11. Parola P, Lamballerie X, Jourdan J, et al. Novel
chikungunya virus variant in travelers returning
from Indian Ocean Islands.Emerg Infect Dis
2006;12:1493-9.
12. Pialoux G, Gauzere BA, Strobel M. Chikungunya virus
infection: Review through an epidemic. Med Mal Infect
2006;36:253-63.
13. WHO. Disease outbreak news. Chikungunya and dengue
in the southwest Indian Ocean, Geneva 17 March 2006.
9.33 Malaria in Children

Ashok S Kapse
Malaria a, paroxysmal febrile illness is caused by
protozoan microorganisms commonly called as malarial
parasites. Belonging to family plasmodidae malaria
parasites have more than 120 species however only four
of them: P.vivax, P.falciparum, P.ovale and P.malariae are
capable of infecting human beings. P.vivax, and
P.falciparum (P.F.) are commonly prevalent species in our

country. Within the species these parasites tend to differ
in their morphological and clinical characteristics; termed
as strains or isolates these parasitic populations display
distinct biological and antigenic variations.
424
LIFECYCLE OF MALARIAL PARASITES

Spread over two hosts, man and mosquito, malarial
parasites complete their life cycle in two phasesnamely
sporogony and schizogony; sporozoites and merozoites
being the respective end products of these phases
(Fig. 9.33.1).
SCHIZOGONY
While taking blood meal female anopheles mosquito
injects sporozoites in human beings, whereas majority
of these parasites are phagocytosed and destroyed, some
of them succeed in reaching into human liver.
Sporozoites asexually proliferate and multiply into
hepatic parenchymatous cells, after some time hepatic
cells burst and thousands of merozoites are liberated
in to the circulation. These merozoites invade RBCs; using
hemoglobin for their growth merozoites proliferates and
divides into daughter merozoites. Disintegration of
invaded RBC sets merozoites free to attack further RBCs;
this cycle may perpetually carry on, until interrupted by
drugs or immunity.
Sporogony
After few erythrocytic cycles some of the merozoites shift
the line of development and change into the sexual forms;
the male and female gametocytes. Picked up by female
anopheles mosquito during blood meal, these gametocytes
meet and form zygotes inside the mosquito. Going
through various developmental processes termed as
sporogony, zygotes end into formation of sporozoites;

the forms capable of infecting human beings.
Hypnozoites
Some of the p.vivax sporozoites exhibit a different
behavior; after entering hepatic cells instead of entering
into immediate schizogony, they opt to remain dormant
for a long duration of time. Christened as hypnozoites
these parasites awaken at a predestined time and liberate
merozoites in the blood, causing relapse.
MAGNITUDE OF PROBLEM
Discovery of spraying insecticide in 1940 raised vision
for malarial abolition. In 1957, WHO launched a global
campaign for malaria eradication. Program initially
had good progress, but eventually due to technical and
often imponderable factors dithered in late seventies;
paving way for a huge malarial resurgence.
Today malaria is one of the biggest medical
problems with some 1600 million people exposed to
the risk of disease and more than one hundred million
cases occurring annually. The estimated deaths are
between one to two millions per year and majority of
them being children under five years. Barring very few
cases deaths are exclusively attributable to P.
falciparum.
With a striking increase in P. falciparum strain, India
is one of the worst affected countries of this malaria
resurgence. Invasion of new areas and development of
drug resistance are particularly troublesome features of
this resurgence.
MALARIA: A HETEROGENEOUS DISEASE
Malaria presents with marked clinical heterogeneity.
Presentation may vary from severe and fatal illness, to
asymptomatic parasitic circulation in the blood.
Parasitic variations and host immunity are two major
determinants of clinical malarial presentations.
IMMUNITY IN MALARIA
Immunity in malaria could be innate and acquired and
both depend on genetic constitution of the host.
Innate Immunity
Figure 9.33.1: Lifecycle of malaria parasite
Innate immunity is the inherent property of the host,

which being detrimental to the growth and proliferation

of malarial parasites makes a person invulnerable to
malarial infection. This immunity could be absolute or
relative. Following are the examples of this kind of
immunity.
A. Nonexistence of vivax malaria in west Africa due to
absence of Duffy blood group from indigenous
population. (Duffy blood group antigen acts as a
receptor between vivax merozoites and RBCs).
B. Partial protection afforded by certain hemoglobinopathies, e.g. Hb-S, Hb-F, Hb-C and enzymopathies
like G6PD deficiency.
Acquired Immunity
Immunity acquisition in malaria is a slow process
spanning over the years. Biologically malaria parasites
are pleotropic in nature hence only after exposure to
multiple parasitic strains one develops sufficient clinical
invulnerability. Furthermore immunity is invariably
incomplete and needs constant antigenic stimulation for
its sustenance. Presences of antigenicaly variable
plasmodial strains, smokescreen, and down-regulation
of host immune system are some of the postulated
explanations for the slow and incomplete acquisition of
acquired immunity.
Antigenic Variability
In a given locality plasmodium species consist of
antigenicaly distinct races or strains. These races or
strains afford partial cross protection among them. It is
only after a prolonged stay in endemic area that a person
encounters and overcomes each of the plasmodial races
and strains present in his locality and for this very reason
immunity acquisition is a sluggish and a partial process
in malaria.
Smoke Screen Theory
Asexual erythrocytic parasites are the key source of
antigens which provoke nonspecific defense mechanism
as well as induce both species and stage specific,
protective immunity. The effective parasiticidal
immunity is mainly directed against mature schizont or
extracellular merozoites. The parasite material released
during the schizont rupture comprises of loads of
antigens; these antigens come both from the plasmodial
cytoplasm, as well as modified host cell material. A very
small part of this huge antigenic material is protective
merozoite antigen. This inappropriate antigenic material
creates a smoke screen which swamps and blinds the
immune defense system. Consequently a major part of
the immune response is directed towards non-protective
425
antigen, there by negatively influencing the acquirement

of specific protective immunity.
Immunosuppression
Malaria cause significant immune repression. Apoptosis
of mononuclear cells, disturbances into macrophagic
functions and interference with functioning of the
dendritic cells, are some of the important reasons for
malarial immune suppression.
Community Immunity
Like in an individual, malaria varies greatly in its
community presentation. In 1957, Macdonald drew
attention to, two extreme forms of community malarial
presentationshe termed them as stable and unstable
malaria.
High malarial endemicity is categorized into two
forms:
i. Holo-endemicity, and
ii. Hyper-endemicity.
Holo-endemicity and Stable Malaria
In holo-endemic area intense malarial transmission
continues round the year, as a result entomological
inoculation rate (EIR, parasitic bites in a year) is as high
as 100-1,000 bites per annum. Consequentially, infection
rate and fatality rate are high in infancy and early
childhood, but by late childhood due to persistent
antigenic stimulation majority of the children develop
good immunity and are protected from severe and
complicated malaria. Adult population does get
frequent malarial infection, possess circulating
parasitemia, and yet hardly ever suffer from malaria.
This state of clinical immunity in the presence of
parasitemia is called as premunition and this form of
community presentation is termed as stable malaria
(Fig. 9.33.2).
Figure 9.33.2: High EIR = stable malaria
426
Majority of African countries have year long rain

pattern which facilitate high entomological inoculation
rate (EIR) and consequential stable malaria.
Hyper-endemicity and Unstable Malaria
Unstable malaria exists in the area where malarial
transmission has marked seasonal swings; in such areas
entomological inoculation, and consequent high
transmission occurs only in certain parts of the year while
rest of the times transmission is low. In such areas malaria
comes in the form of epidemics and takes a heavy toll in
terms of morbidity and mortality. Community immunity
premunition in this kind of malaria is poor and as a result
all the ages including adults are prone to severe and
complicated malaria. Barring parts of Assam, malaria is
unstable all over our country.
CLINICAL PRESENTATIONS
Malaria poses wide variability in the clinical presentations creating great difficulties in clinical diagnosis and
management.
For clinico-therapeutic purposes malaria could be
divided into uncomplicated and severe-complicated
malaria. Severe-complicated malaria is defined as clinical
situation where malaria has involved bodys vital organ
systems and disturbed its functioning and/or significantly deranged some vital metabolic function.
Excepting stray reports of involvement of P. vivax,
for all practical purposes severe and complicated malaria
is caused by P. falciparum species.
P. FLACIPARUM MALARIA A MICROVASCULAR
DISEASE
P. falciparum has a unique capability of producing microvascular obstruction. RBCs infected with parasites
develop knob like structures on their surface membrane;
these knobs have unique capability of inducing adhesion
molecules like ICAM-1 (intracellular adhesion molecule-1)
on the endothelial surface of micro-capillaries. With the
help of a histidine rich protein, secreted by parasites,
these knobbed-RBCs get adhered to induced receptors
on the endothelial cellscytoadherence is the name given
to this process. Through cytoadherence P. falciparum
parasitized RBCs sequester out of microcapillaries and
complete their life cycle into perivascular compartment.
A similar process of receptor induction also transpires
on the non-parasitized RBCs induced adhesion
Figure 9.33.3: Pathophysiology of P. falciparum malaria
molecules facilitate clumping between parasitized and

non-infected RBCs. This process of clumping is termed
as rosseting. These twin processes of sequestration and
rosseting result into micro-vascular blockade (Fig. 9.33.3),
causing decreased organ blood flow and consequent
organ tissue damage.
There is a varying degree of susceptibility of organ
systems for this microvascular obstruction, brain, lung,
liver, intestine, and bone marrow appear particularly
susceptible. Depending upon predominant organ system
involvement complicated P. falciparum malaria could
clinically manifest as cerebral malaria, renal malaria,
pulmonary malaria, etc. In authors experience prevalence
of these complicated P.F. malarial forms varied from
year-to-year. Differences in predilection for the micro
vasculature involvement among different interspecies
strains could possibly be an underlying reason.
UNCOMPLICATED MALARIA
Clinical Forms and Presentations
Clinical course of uncomplicated malaria is believed to
be consisting of paroxysmal bouts of fever associated
with chills and rigors. However in pediatric age this
intermittent pattern of fever is invariably absent and
instead an irregular fever with respiratory or gastrointestinal symptoms could mark the onset of the disease.
Clinical manifestations vary a great deal in different
pediatric ages. Three arbitrary age groups are identifiable
for their diverse clinical presentations:
1. Neonate to early infancy
2. Late infancy to early childhood
3. Late childhood.

1. Neonates and Early Infancy
In contrast to bacterial infections malaria is invariably
mild in neonates and young infants. Hepatosplenomegaly, anemia, with or without fever are usual
presentations in this age group. Presence of passively
acquired maternal protective antibodies, high number
of Hbf containing senescent RBC, and a milk-diet
deficient in para-aminobenzoic acid are some of the
factors which wield malariostatic influence at this age.
2. Late Infancy to Early Childhood:
(Six Months to Five years)
With the waning of all the malariostatic factors, late
infancy and early childhood has become most susceptible
age for malarial infection. During this age malaria not
only occurs more frequently, it often gets complicated.
Three types of symptom complexes dominate within
this age group:
a. Respiratory,
b. Gastrointestinal, and
c. Convulsive.
a. Respiratory: This is the commonest form of presentation. At the onset, picture simulates flu child
suffers from mild cough and catarrh, while clinical
examination reveals facial and eye congestion. Within
a couple of days, treated or untreated these respiratory
symptoms abate and facial congestion is replaced by
pallor, which is particularly discernible on the ear
lobule and malar area.
b. Gastrointestinal: Marked vomiting and loose stools
characterize this form of malaria. Loose stools
are usually greenish, mucoid and are associated
with abdominal colic and tenesmus. Vomiting and
diarrhea both respond best to antimalarial treatment.
c. Convulsive: Convulsions commonly occur during
malarial fever. Malaria should be considered as first
cause of febrile convulsion in endemic area. Absence
of signs of organic neurological involvement
differentiates these patients from cerebral malaria.
3. Late Childhood
By late childhood malarial presentation starts evolving
into classical paroxysmal pattern. Malarial paroxysm
comprises of three successive stages namely cold stage,
hot stage and sweating stage. Depending on infective
species, paroxysm tends to recur on tertian, sub-tertian
427
or quotidian frequencies, however it is worth knowing

that this paroxysmal form of malarial fever is not a
regular feature of falciparum infection, instead an
irregular pyrexia without any specific pattern is a
common characteristic of falciparum malaria.
Anemia and hepatosplenomegaly are constant
features of all types of malarial infections. A faster and
greater enlargement of the spleen compared to liver is
commonly observed in P. vivax malaria. Conversely liver
enlargement precedes splenic growth and is significantly
more in P. falciparum infection.
DIAGNOSIS
Blood Smear Examination
In 1881, Laveran discovered malaria parasites in the
blood smear of a dying patient, since then demonstrating
parasite in the blood film has remained a cornerstone
for malarial diagnosis.
The procedure consists of collecting a finger-prick
blood sample, preparing a thick and thin blood smear,
staining the smear (most frequently with Giemsa), and
examining the smear through a microscope (preferably
with a 100X oil immersion objective) for the presence of
malaria parasites.
Both thick and thin film examinations are essential,
while thick film facilitates easy detection of parasite, thin
film is necessary for species identification.
Advantages
1. High sensitivity: When used by skilled and careful
technicians, microscopy can detect densities as low
as 5-10 parasites per l of blood, however in field
conditions, the detection capabilities of a typical
microscopist might be just about 100 parasites per l
of blood.
2. Very informative: Parasites can be characterized in
terms of species (P. falciparum, P. vivax, P. ovale, and/
or P. malariae) and life cycle stages (e.g. trophozoites,
schizonts, gametocytes); moreover, the parasite
densities can be quantified (from ratio of parasites
per number of leukocytes or erythrocytes). Such
quantifications are helpful to demonstrate hyperparasitemia and to assess parasitological response to
antimalarial therapy.
3. Relatively inexpensive: Microscopy is inexpensive; cost
estimates are just 4 to 5 rupees per slide in field
conditions.
428
Disadvantages
Microscopy is not without disadvantages. Biggest
problem is its dependence on good techniques, quality
reagents and microscopes and, well trained technicians. Unfortunately these conditions are often not
available, particularly in the more peripheral levels of
the health care system. There are often long delays in
providing the microscopy results to the clinician, so
that decisions on treatment are commonly taken
without the benefit of the results. Rapid detection tests
(RDT) have recently been developed to circumvent
many of these issues.
Rapid Detection Tests
These tests are based on immunochromatographic
detection of antigens derived from malaria parasites in
lysed blood. Tests employ a dipstick or test strip bearing
monoclonal antibodies directed against the target
parasite antigens. Advantages are that tests do not
require any technical expertise and results are available
within few minutes.
RDTs: Targeted Antigens
1. Histidine-rich protein II HRP-II: It is a water-soluble
protein produced by trophozoites and young (but not
mature) gametocytes of P. falciparum. Commercial kits
currently available detect HRP-II from P. falciparum
only.
2. Parasite lactate dehydrogenase (pLDH): Enzyme
is produced by both asexual and sexual stages
(gametocytes) of malaria parasites. Test kits currently
available detect pLDH from all four Plasmodium species
that infect humans. They can distinguish
P. falciparum from the non-falciparum species, but
cannot distinguish between P. vivax, P. ovale and P.
malariae.
RDTs: Test Performance
Test performance of RDTs has been adequately assessed
in diverse clinical situations, in both endemic and nonendemic countries.
RDTs may detect all four Plasmodium species that
infect humans, or may detect only falciparum
depending on the antigens on which they are based.
Present RDTs fail to differentiate reliably between
P. vivax, P. ovale and P. malariae, although research to
develop such a test is continuing.
Compared with expert microscopy, RDTs generally

achieve a sensitivity of >90% in the detection of
P. falciparum at densities above 100 parasites per
l blood, however with low parasitemia (below the
level of 100 parasites per l blood), sensitivity
decreases markedly.
HRP-II tests can remain positive for 7-14 days
following chemotherapy in a substantial proportion
of individuals, even though these patients no longer
have symptoms or parasitemia. Such degrees of
persistent positivity are apparently not encountered
in tests targeting other antigens.
Sensitivity for P. vivax with pLDH kits is comparable
to that for P. falciparum.
RDTs: Advantages
RDTs are easy to perform and interpretation is simple
enough to be grasped even by an illiterate.
There is little difference in interpretation among
individual users.
RDTs do not need any special equipment or training.
Technique can be learnt within few hours with good
retention of skills over a one-year period.
Because RDTs detect circulating antigens, they are
capable of detecting P. falciparum infection even when
the parasites are sequestered in the deep vascular
compartment. In women with placental malaria (as
demonstrated by placental smears), RDTs have
successfully detected circulating HRP-II even though
the blood smears were negative due to sequestration
of P. falciparum in the placenta.
RDTs are relatively robustmost kits can be shipped
and stored under ambient conditions.
RDTs: Disadvantages
Commercially available RDTs targeting HRP-II can
detect only P. falciparum; in areas where other
Plasmodium species are co-endemic (P.vivax in our
country) such kits are likely to miss other infections.
RDTs targeting HRP-II of P. falciparum could give
positive results for fortnight beyond parasite
clearance as confirmed by microscopy. This may
create unnecessary confusion in relation to treatment
failure and drug resistance.
Kits that detect both P. falciparum and non-falciparum
species are unable to differentiate between P. vivax,
P. ovale and P. malariae.

RDTs are not quantitative, hence are useless for
prognostication.
The RDTs are significantly more expensive than
microscopy.
429
function. Restricted activity, exertional dyspnea and

persistent tachycardia rather than arbitrary Hb level,
should form indications for blood transfusion.
OBJECTIVES OF ANTIMALARIAL DRUG USES
MANAGEMENT OF UNCOMPLICATED MALARIA

In uncomplicated malaria following points need due
consideration before starting antimalarial therapy:
1. Hydration status
2. Ability to take oral medication
3. Assessment of prior therapy
4. Anemia.
Hydration Status
Febrile malarial patients are usually dehydrated.
Anorexia, nausea, vomiting, pyrexia and diaphoresis all
cumulatively result in poor hydration and hypoglycemia.
Parents need to be instructed to encourage oral water
and glucose supplements.
Ability to Take Oral Medications
Administration of bitter antimalarial drugs to children
is a pretty difficult task for the parent. Following
measures may prove to be helpful in overcoming this
problem.
a. Antimalarials are better retained if given, after one
or two hours of antiemetic and antipyretic treatment.
b. Formulations containing higher concentrations in
smaller volume are better tolerated.
Patients who are unable to take oral medications
should receive antimalarials parenterally or rectally till
patient could swallow and retain oral drugs.
Assessment of Prior Treatment
History of prior antimalarial drug intake is very
important. Two points need special consideration.
a. Previously taken antimalarial drugs may cause drug
interaction or result in overdosing and toxicity.
b. Persistence of fever and parasitemia, in a patient who
has received antimalarial within last three to seven
days, is an indicator of treatment failure.
Anemia
Anemia is a constant accompaniment of malaria, many
a times it is severe enough to compromise cardiovascular
Antimalarial drugs are used with two main objectives:

1. Complete parasitological cure.
2. Restricting drug resistance development.
Since its introduction chloroquine has been the
mainstay of antimalarial treatment. However for last few
decades P. falciparum had acquired significant resistance
to it. In some instances it might still deliver clinical relief,
but in majority of cases it fails to produce total
parasitological eradication and consequentially patient
is left out with subclinical, submicroscopic parasitemia.
Being a long acting drug chloroquine remains in patients
blood for weeks together in subtherapeutic doses;
exposure of malaria parasites to these subtherapeutic
concentrations of chloroquine fuels the resistance.
Additionally there are evidences that continued use of
chloroquine, in areas with prevalent chloroquine
resistance for that sake any failing drug ensues increased
gametocyte proliferation, this augmented gametogenesis
amplifies infectivity and a resultant drug resistant
malarial spread.
Status of other antimalarial drugs is no betterefficacy
of amodiaquine, sulfadoxin-pyremethamine, quinine
and mefloquine has declined to the level where these
drugs cannot be trusted to affect complete parasitological
cure.
Artemisinine Compounds
Discovery and development of artemisinine derivatives
have equipped world with highly efficient class of
antimalarial drugs. Fortunately this group is yet
unaffected by resistance problem. More over availability
of derivatives in various formats (artisunate as intravenous injections, artemether and artemotil as intramuscular preparations, artisunate and artemether as oral
tablets, and artemisinine as rectal suppository) gives
distinctive freedom to use them at various levels of
medical care, for varied severity of disease.
Artemisinine derivatives act at a very early ring stage
of P. falciparum much before parasites acquire means to
develop pathogenetic excrescence. This unique capability
prevents cytoadherence and rosseting and there by
forestall complications.
430
Artemisinine compounds (AC) also have a very

striking parasiticidal intensity, they reduce parasite
numbers by a factor of approximately 10,000 in each
asexual cycle, which is more than other current antimalarials (which reduce parasite numbers 100- to 1,000fold per cycle). AC diminish parasitemia to such low levels
that very few parasites are left out for gametocytogenesis.
This negative impact on gametocyte formation is greatly
helpful in preventing malarial transmission as well as drug
resistance.
Though drugs posses enough antimalarial properties
on their own, there is realization that drugs need
protection and resistance can be prevented, or considerably slowed down by combining antimalarials; hence
authorities world over ( WHO, NVBDCP, IAP) mandate
that for P.falciparum malaria artemisinine derivatives
must only be used in combination (ACT) with other
effective antimalarial drug.
Recommended ACTs are: Artesunate + mefloquine,

Artemether-lumefantrine, Artesunate + sulfadoxinepyrimethamine, Artesunate + amodiaquine.
Artesunate + mefloquine
Both drugs are available as separate tablets containing
50 mg of artesunate and 250 mg of mefloquine,
respectively.
Recommended therapy
Artesunate 4 mg/kg BW of given once a day for 3 days +
25 mg base/kg BW of mefloquine usually split over two
to three days.
Nausea, vomiting, dizziness, dysphoria and sleep
disturbance are generally associated with mefloquine.
Split doses given either as 15 mg/kg on the second day
followed by 10 mg/kg on third day or as 8.3 mg/kg per
day for 3 days are recommended to diminish MQ related
side effects.
Artemisinine Combination Therapy (ACT)

ACT is clearly superior to monotherapies. Addition of
three day course of artisunate (AS) to monotherapies like
amodiaquine (AQ), mefloquine (MQ) or sulfadoxine
pyrimethamine (SP) results in rapid symptom resolution,
fewer parasitological failures at 28 days and lesser
gametocyte carriage. Shorter courses of ACs (less than
three days), meet with frequent treatment failure,
therefore not recommended.
ACs are eliminated rapidly hence whenever they
are used in combination with short acting drugs
(tetracyclines, clindamycin), a 7-day course is given; on
the other hand shorter course of treatment (3 days) is
sufficient if ACs are given in combination with slowly
eliminated antimalarials. Within three days ACs
drastically decrease parasites in the body. However
complete parasitic clearance depends on partner
medicine which should be effective and persisting at
parasiticidal concentrations until all the infecting
parasites have been killed. Slowly eliminated partner
affords better protection to ACs from resistance
development.
ACT: Available Options
There are minor differences in oral absorption and
bioavailability between the different artemisinine
derivatives however these differences do not have any
bearing on clinical efficacy of ACTs; rather its the
properties of the partner medicine which determine the
value and selection of combination.
Artemether-lumefantrine [A-L]
Combination is available as co-formulated tablets
containing 20 mg of artemether and 120 mg of lumefantrine.
Recommended therapy
A 6-dose regimen of artemether-lumefantrine twice a day
for 3 days calculated as artemether 3.2 mg/kg BW per day.
Lumefantrine absorption needs fatty meal for
adequate GI absorption; inadequate fat intake may result
into poor blood levels and a consequent treatment failure,
so it is essential that patients or care givers are instructed
to take A-L with milk or other fat-containing foodparticularly on 2nd and 3rd day of therapy.
Artesunate + sulfadoxinepyrimethamine [A + S-P]
Combination is available as separate tablets of artesunate
50 mg and sulfadoxine-pyrimethamine co formulation
of 500mg and 25 mg sulfadoxin and pyrimethamine
respectively.
Recommended therapy
Artesunate 4 mg/kg BW given once a day for 3 days
and a single dose of sulfadoxine-pyrimethamine
(calculated as 1.25 mg base/kg BW of pyrimethamine)
on day 1.
Usefulness of this combination is dependent on
efficacy of S-P; in many areas P.falciparum has already
acquired more than 20% resistance to this combination;
continued uses of co-trimoxazole (trimethoprim-

sulfamethoxazole) as chemotherapeutic agent is likely
to deteriorate this situation further.
Artesunate + amodiaquine
Combination comprises of separate tablets containing 50
mg of artesunate and 153 mg base of amodiaquine,
respectively.
Recommended therapy
Artesunate 4 mg/kg BW daily for 3-days and amodiaquine 10 mg base/kg BW, daily for 3-days.
Combination efficacy is already compromised as at
many places amodiaquine 28-day cure rates are already
low and likely to further decrease with continued uses
of chloroquine and amodiaquine as monotherapies
moreover amodiaquine is not freely available.
431
Second-line Treatment
In order of preference following second-line treatments
are recommended:
1. Alternative ACT known to be effective in the region,
2. Artesunate + tetracycline or doxycycline or clindamycin,
Artesunate (2 mg/kg BW once a day)
+
Clindamycin (10 mg/kg BW twice a day) or
Doxycycline (3.5 mg/kg BW once a day) or
Tetracycline (4 mg/kg BW four times a day).
Any of these above combinations should to be given
for 7 days.
3. Quinine + tetracycline or doxycycline or clindamycin.
Quinine Therapy
ACT: Selection
Dose
ACT selection in a given country or area is based on the

level of resistance to the partner medicine. Areas with
higher resistance to amodiaquine, and sulfadoxinepyrimethamine, ACT of choice could be artesunate +
mefloquine or artemether-lumefantrine.
Quinine is used in dose of 10 mg of salt/Kg BW orally

three times daily for a period of 7 to 10 days. For those
who are unable to take drug orally, it can be given intravenously, in the same dose, dissolved in dextrose solution
(1 mg of quinine/ml of dextrose solution, 10 ml/Kg BW,
given slowly over four hours, every 8 hourly).
ACT: Safety
Side Effects
Except for urticaria ACs have remarkably secure profile.

ACTs safety largely depends on partner drug, many of
these drugs are risky in certain situations: tetracycline in
lactating women, S-P in neonates, MQ in infancy.
Clindamycin could be a suitable partner in some of these
conditionspregnancy, lactating women, neonates,
infants.
Quinine therapy is generally crippled with side effects.
AC: Monotherapy
In a rare unfortunate situation when partner drug is
totally unsuitable, ACs could be used as monotherapy;
however in such circumstances, to avoid recrudescences,
ACs should be used for long enough duration (7-days).
ACT: Treatment Failure
Persistence or recurrence of fever and or parasitemia
within two weeks of treatment is considered as treatment
failure. Such patient needs second-line treatment,
although before going for the next line of treatment one
must thoroughly ascertain that patient had completed
previous course.
Mild: A symptom complex of adverse reactions known

as cinchonism occurs in patients taking quinine. This is
characterized by giddiness, light headedness, tinnitus,
transient hearing loss and blurring of vision. Cinchonism
does not necessitate discontinuation of quinine therapy.
Severe: Delayed atrioventricular conduction, bradycardia
and postural hypotension are serious cardiovascular side
effects of quinine therapy. Quinine allergy could manifest
as urticaria, asthma, edema of eyelids and mucus
membrane. It may also result in hemolysis, and
thrombocytopenia.
Induction of hypoglycemia is a particularly troublesome feature of quinine therapy.
Problems with Quinine Uses
Quinine has a rapid schizontocidal action; however it
needs to be used in longer (7-day) course for radical cure
of P. falciparum malaria. This long course creates problems
of compliance resulting in incomplete treatment and
recrudescence.
432
Making Patient Non-infective

Gametocytes are usually formed by the second week of
malaria-infection, and then last in the body for two to three
months. During this period such person remains infective
to mosquitoes and there by help in the malarial transmission
process. Up till now primaquine was the only effective
gametocytocidal drug for P. falciparum species. Patients
treated with quinine should receive single dose of
primaquine (0.75 mg/ kg BW) at the end of quinine therapy.
With ACT gametocyte formation is very minimal.
Moreover it possesses intrinsic gametocytocidal
properties, hence no additional gametocytocidal drug
(primaquine) is needed with ACT.
FEVER MANAGEMENT
Fever is an integral part of malaria. Fever could be
associated with mild constitutional symptoms of nausea,
vomiting, anorexia and body aches but could also cause
seizures.
Antipyretic treatment was found to have higher
parasitic levels and delayed clearance; however a close
scrutiny revealed that it is due to interference with
process of cytoadherence, which in fact is helpful to
patients, therefore there is no reason to deny antipyretic
treatment in malaria.
Round the clock uses of acetaminophen 15 mg/kg
BW every 4 hours given orally is safe and well tolerated.
Ibuprofen (5 mg/kg BW) would be another alternative.
In high fever tepid sponging with tape water could have
an additive effect.
MANAGEMENT OF VOMITING
Vomiting is common in acute malaria and creates
problem with oral medications. Though studies of their
efficacy are lacking being relatively harmless they are
widely used.
MANAGEMENT OF SEIZURES
In children seizures are very common in malaria
particularly with falciparum infection. Most of the times
they are febrile convulsions yet in a few cases they may
be manifestation of cerebral malaria. A convulsing child
must be treated with anticonvulsants, however prophylactic anticonvulsants are needless in otherwise
uncomplicated malaria.
UNCOMPLICATED P. VIVAX MALARIA

Antimalarial Drug Therapy
1. Treatment of Present Malaria Attack
A three-day course of chloroquine is sufficient enough
to terminate P. vivax attack.
Dosages and regimens: Chloroquine is used in a dose of
25 mg of base/Kg BW given over three days. Two
commonly employed regimens are as follows:
a. 10 mg of chloroquine base/Kg BW given as loading
dose on day-1 to be followed by 5 mg of base/Kg BW
after 6 to 8 hours and than 5 mg of base/Kg BW given
on day-2 and day-3.
b. 10 mg of base/Kg BW on day-1
10 mg of base/Kg BW on day-2
5 mg of base/Kg BW on day-3
Though pharmacokineticaly first regimen is superior;
the second one is simpler and in clinical practice has
proved equally effective.
Side effects: In therapeutic doses, given orally, chloroquine
is remarkably safe drug. Taken empty stomach it may
cause nausea and vomiting. Few cases may have
dizziness and blurring of vision. In dark complexioned
adults, pruritis of soles and palms could be a troublesome
side effect; fortunately it is rare in children.
Drug resistant P.vivax: P.vivax is highly sensitive to
chloroquine; still there are occasional reports of chloroquine resistance from different regions of the world
(Indonesia, Papua New Guinea, Myanmar and India).
Except Papua New Guinea, at most of the places resistance
has been transient and did not need change in drug policy.
With sole exception of sulfadoxin and pyrimethamine, P. vivax is sensitive to almost all blood schizontocidal drugs. Chloroquine resistant P. vivax malaria could
be easily managed with quinine, mefloquine, or ACT.
2. Prevention of Relapse in P. vivax
In 1980 it was recognized that sporozoites of P. vivax
infection consists of polymorphic strains. These strains
in varying proportion differentiate into developing
schizonts or into dormant forms known as the
hypnozoites. These hypnozoites for a long time remain
dormant in the hepatocytes and then at a predetermined
time, they awaken, proliferate and produce a clinical

relapse. In an untreated case, relapse continue till all the
hypnozoites are exhausted from liver. These hypnozoites
are sensitive only to 8-aminoquinolines (primaquine,
bulaquine, tafenoquine); a course of primaquin can
destroy these hypnozoites and thereby can prevent
relapses.
Vivax relapses: P. vivax is polymorphic infection; the
frequency and pattern of relapses varies widely from
place to place; whereas 5060% of P. vivax infections in
South-East Asia relapse, rate is just 1520% in Indian
subcontinent.
In terms of time frame relapses have two patterns:
Short-term relapse: Occurring within couple of
months.
Long-term relapse: Occurring over 6-9 months.
Anti-relapse treatment must be set against the
prevalent relapse frequency and pattern.
The curative efficacy of primaquine is dose dependent;
a full course of 14-days therapy (0.25 mg/kg BW)
is mandatory, short course of primaquine widely
recommended (such as 5-day regimens) is inadequate
for prevention of relapses.
There has been debate as to whether primaquine
should be given in high transmission areas. In such areas
there always is a chance for re-infection. Starting a new
cycle needing frequent primaquine courses has poor risk
benefit ratio. Hence certain authorities recommend blood
schizontocidal drugs for every P. vivax attack whether
relapse or reinfection, in high transmission areas. In
countries like ours where transmission is seasonal and
has wide fluctuations, a modified strategy could be
adopted. In India P. vivax infection prevails between
March to October with high transmission between May
to July. Person suffering from P. vivax malaria in high
transmission season may be treated with full course of
chloroquine; supplemented by weekly suppressive
therapy for few months until high transmission season.
Anti-relapse treatment should be deployed for vivax
malarial attack occurring during non-epidemic season
or nearing the end of the epidemic.
Primaquine resistant hypnozoites: A 14-day course of 0.25
mg/kg BW of primaquine is usually sufficient to cure
P.vivax liver stage infection. However in South-East Asia,
particularly Indonesia, and in Oceania vivax hypnozoites
are relatively insensitive to primaquine, needing higher
doses (0.5 mg base/kg BW per day).
433
Primaquine and G6PD deficiency: Glucose-6-phosphate

dehydrogenase deficiency is an inherited sex-linked
disorder where in there is an increased susceptibility to
oxidant hemolysis. Primaquine being a strong oxidant
drug could induce severe hemolysis a G6PD deficient
patient. There is wide community-wise variation in
G6PD deficiency prevalence. Parsees, prajapaties,
sindhies and tribals have much higher incidence.
It is highly desirable to know G6PD status before
prescribing primaquine. In a situation where testing is
infeasible and primaquine is indispensable parents
should be instructed to watch for urine color after
primaquine administration; any change in urine color to
tea color warrants immediate stoppage of drug and
patient should immediately be taken to hospital.
SEVERE AND COMPLICATED MALARIA
Parasitemia and Malaria Severity
In general severity of malaria is in proportion to the level
of parasitemia; however it may not always be so.
Cytoadherence and sequestration are the major pathogenetic determinant of malaria severity. A person with
good anti-sequestration mechanism may not suffer
from complicated malaria; on the contrary higher
sequestration even with low parasitemia may result in
complicated malaria.
Endemic Forms, and Age Distribution of
Severe Malaria
In stable malaria severe and complicated malaria occurs
mainly in nonimmunes and hence it is more common
among infants and children. However in the
communities with unstable, epidemic form of malaria
(as it is in our country) all ages including adulthood are
vulnerable to severe malaria.
As per WHO, following situations are considered as severe
and complicated malaria:
1. Severe prostration
2. Impaired consciousness, altered behavior
3. Multiple convulsions
4. Respiratory distress, acidotic breathing
5. Abnormal bleeding
6. Jaundice
7. Hemoglobinuria
8. Circulatory collapse, shock, algid malaria
9. Hyperpyrexia
10. Severe anemia
434
11.
12.
13.
14.
15.

Hypoglycemia
Acidosis
Renal impairment
Hyperlactatemia
Hyperparasitemia.
Some of these complications such as cerebral malaria,

anemia, hypoglycemia, hyperpyrexia and respiratory
distress are more common in children while others such
as renal impairment, jaundice, and pulmonary edema
are relatively frequent in adults. Assessment and investigations are generally dictated by clinical presentations.
However appraisal of pallor, level of consciousness,
urinary output, and hemodynamic is integral to every
suspected case of severe and complicated malaria.
Similarly, following investigations are also essential in
the management of severe and complicated malaria.
i. Hemogram including platelet count
ii. Smear examination for parasites, (Presence of
P. falciparum schizonts in smear examination is
always an indicator of severe malaria)
iii. Blood sugar level
iv. Serum bilirubin and SGPT
v. Blood urea and serum creatinine
vi. Urine examination, routine, microscopic and
biochemical tests for hemoglobin and urobilinogen.
Complications
1. Impaired Consciousness and/or Altered Behavior
P. falciparum parasites have a special proclivity for
sequestrating into brain microvasculature and hence
neurological syndrome is the commonest form of
complicated malaria. Multiple seizures could portent the
onset of cerebral malaria, generalized hypotonia,
brainstem signs (abnormalities of corneal reflex, papillary
reflex, dolls eye reflex, etc), opisthotonus, and retinal
changes are common neurological elements.
It is vital to realize that besides cerebral malaria there
are other elements which could be causal or contributory
to neurological dysfunctions. Covert epilepticus,
prolonged postictal state and severe metabolic derangement like hypoglycemia, hyperpyrexia, and acidosis can
produce clinically indistinguishable syndrome from
classical cerebral malaria. Managements of these
problems are straightforward with strikingly beneficial
results. Therefore besides frequent evaluation of level of
consciousness; taking rectal temperatures, assessing
blood glucose levels and blood gases assumes equal
importance in such patients. Trial of appropriate
anticonvulsant could also be rewarding in such

conditions. Ruling out meningitis is vital in any patient
presenting with fever and neurological involvement;
proper antibiotic therapy should urgently be instituted
if for some reasons CSF examination is deferred or not
carried out. Frequent startling, nucho-occipital headache
are some of the early warning signals of neuro malaria.
2. Multiple Convulsions
Convulsions are common in malaria, particularly in
P.falciparum infection. Convulsions could be generalized
or focal; some seizures are covert or subtle. Covert
seizures may be suspected if patient manifests with
repeated facial twitching, eye deviation, irregular
breathing and excessive salivation.
Seizures in malaria are multifactorial: microvascular
obstruction leading to altered cerebral metabolism is the
most important element; however other factors like
hypoglycemia, and hyperpyrexia could also be causal or
may lower seizure threshold. It is important to identify
hypoglycemia and hyperpyrexia as they offer relatively
easy management and better outcome.
Repeated seizures carry a poor prognosis; mortality
rates as well long-term sequelae both may increase.
Convulsions should be energetically treated with
benzodiazepines and phenytoin. Phenobarbitone in
doses of 20 mg/kg BW is found to be associated with
better seizure control, yet inexplicable increase in
mortality. Prophylactic anticonvulsant uses are undesirable: it doesnt improve prognosis, conversely it is found
to be detrimental.
3. Severe Anemia
Mild to moderate anemia is an integral part of malarial
clinical presentation. However in certain cases anemia
could be a presenting feature, such patients have low
hemoglobin (Hb less than 7 g/dL, PCV < 20%) and
present with palpitation, tachycardia and dyspnea
(Fig. 9.33.4). Lactic acidosis is a common accompaniment
of severe anemia and adds greatly to respiratory distress;
unless transfused urgently such patients carry very high
mortality.
Causes of Anemia
Anemia in malaria is multifaceted and multifactorial.
Hemolysis, dyserythropoiesis, and deficiency of hematopoietic factors are major contributory factors for malarial
anemia.
435
supplements during malaria endemic seasons are found

to be associated with increased recurrences rate.
4. HemoglobinuriaDark Red Colored Urine
Mild hemolysis is universal with any malaria; nevertheless
massive intravascular hemolysis (Figs 9.33.5 and 9.33.6)
presenting as red smoky urine and jaundice could also be a
feature of severe malaria. Serial estimation of Hb,
reticulocyte count, and LDH are essential to gauze degree
of hemolysis. Evaluation of Coombs test and assessment
of G6PD status should regularly be done in cases presenting
with hemoglobinuria. A repeat G6PD estimation after few
months is mandatory as following massive hemolysis neoRBCs would result into falsely normal G6PD estimation.
Figure 9.33.4: Severe pallor (P. falciparum)
Hemolysis
Mild compensated hemolysis is an integral feature of
malaria pathology. Destruction of parasitized RBC is
important cause of anemia, but RBC destruction is much
beyond the parasitized cells. Immune mediated RBC
damage is a popular theory, but Coombs positivity rates
fail to support it.
Lately it is realized that in malarial infection nonparasitized RBCs develop marked rheological changes
and consequentially loose their deformability. These
poorly deformable RBCs are removed from circulation
by splenic pitting process.
Figure 9.33.5: Hemolytic jaundice
Dyserythropoiesis
In an overtly hemolytic disease like malaria reticulocytosis
should be an essential appearance; conversely despite
considerable anemia many malarial patients have
reticulocytopenia. Bone marrow studies in such patients
typically reveal dyserythropoiesis, these bone marrow
changes persist much beyond the parasitic clearance, and
are largely responsible for lasting anemia. Malarial toxins
are believed to be responsible for bone marrow impairment.
Hematopoietic Factor Deficiency
Deficiency of essential hematopoietic factors also
contribute to malarial anemia. Rapid turn over of RBC
do need folic acid and vitamin B12 supplements,
however except in situations of intravascular hemolysis
there is no iron loss in malaria and iron supplements are
not immediately needed in malaria, contrarily iron
Figure 9.33.6: Hemoglobinuria
436
Blackwater fever frequently described in old African

literature is no more a common occurrence.
5. Jaundice
Jaundice in malaria is not uncommon. Patients suffering
from significant hemolysis do have indirect bilirubinemia
(Fig. 9.33.5) and mild jaundice; on the other hand certain
section of malarial patients has obvious direct bilirubinemia, and impaired hepatic functions; titled as malarial
hepatitis. This complication is more common in older
children and adolescents. Liver biopses done at few
centers reveal parasitic sequestration in billiary canaliculi.
Patients of malarial hepatitis having neurological
element, could have an indistinguishable clinical picture
from hepatic encephalopathy. Presence of asexual
parasitemia differentiates these cases from hepatic
encephalopathy. Identification of this section of cases is
extremely vital as antimalarial treatment in these patients
would provide rewarding therapeutic responses.
6. Respiratory Distress
Malaria could manifest with fever and breathing
difficulty. Deep and rapid breathing devoid of auscultatory chest signs or abnormal radiographic picture is a
common clinical presentation. Metabolic acidosis, with
or without hyperlactatemia is the principal underlying
metabolic disorder.
Associated with cerebral malaria, and/or anemia,
metabolic acidosis may carry a whooping mortality of
35%. Pulmonary edema and ARDS are other dreaded
complications of severe malaria; fortunately they are rare
in pediatric age group.
7. Abnormal Bleeding
Hemostatic abnormalities are uncommon in children,
minor problems like skin petechiae (Fig. 9.33.7), nasal
and gum bleed and subconjunctival hemorrhages are
seen in occasional cases. The major hemorrhages reported
are gastrointestinal and, that has invariably been
associated with steroid therapy.
Prothombin time prolongation and mild to moderate
thrombocytopenia are not unusual to be seen in severe
malaria but without clinical hemorrhages these changes
do not warrant therapeutic consideration.
8. Circulatory Collapse
In majority of malaria patients, because of hypovolemia
and vasodilatation, blood pressure is on the lower side,
Figure 9.33.7: Petechiae
and postural hypotension is pretty common. Manson in

1898 described a malarial complication which was
characterized by syncope, collapse and cold body surface
in the wake of elevated rectal temperature and was
termed as algid malaria. Shock and syncope could be a
manifestation of GI hemorrhage, pulmonary edema and
splenic rupture. Isolation of Gram-negative bacteria in
1987 by Mabey et al from malarial patients presenting
with symptoms of shock and syncope established
another key cause for these cases. Following this
discovery appropriate antibiotic coverage has become
customary in malarial patients presenting with shock.
9. Hypoglycemia
Though anorexia, nausea and vomiting are common in
malaria, yet clinically significant hypoglycemia is unrelated
to glycogen depletion in the liver and instead is caused by
parasitic glucose consumption and quinine induced insulin
secretion. Symptoms of hypoglycemia are varied and
include anxiety, hunger, tremors, sweating, palpitation,
dizziness, headache, confusion, clouding of vision, altered
behavior, convulsion and unconsciousness.
As it is very difficult to differentiate symptoms of
hypoglycemia from that of falciparum malaria and,
hypoglycemia is integral to severe malaria possibility of
hypoglycemia should always be considered, assessed
and treated in severe malaria.
10. Hyperpyrexia
Hyperpyrexia may present as an independent entity or
may complicate course of other forms of malaria, it may
be present from onset or may suddenly develop during
a course of apparently mild attack. Pyrexia above 38.5C
437
may increase the incidence of convulsion and above

40.5C may cause delirium, coma and other neurological
problems. Hyperpyrexia induced neurological changes
may create diagnostic confusion with true cerebral
malaria.
In a shivering malarial patient skin temperature may
be much lower than the core temperature; assessing rectal
temperature is a better practice in such cases.
Severe and Complicated Malaria:

Principles of Management
11. Hyperparasitemia
Severe and complicated malaria is a medical emergency. The chosen antimalarial drug should be able to
achieve effective therapeutic concentrations quickly.
The cinchona alkaloids (quinine and quinidine) and
the artemisinine derivatives (artesunate, artemether
and artemotil) are the only classes of drugs which
are capable of attaining speedy parasiticidal concentrations. Because of extensive resistance chloroquine should
never be used in the treatment of severe and complicated
malaria.
Hyperparasitemia has an increased risk for malarial

severity, most of these patients have vital organ
dysfunction but there are few cases which do not have
any evidence for severe disease. These patients have
symptomatology of uncomplicated malaria; however
they carry a higher risk for treatment failure and may
any time progress to severe malaria.
Defining hyperparasitemia is contentious; although
parasitemia of > 5% in a low-transmission setting and >
10% in a higher transmission settings are generally
agreed levels.
Management of uncomplicated hyperparasitemia is
unsettled. Oral treatment may or may not succeed hence
some authorities suggest initial parenteral treatment.
These cases also need longer duration of therapyseven
days of artemisinine compound + full course of partner
drug.
1. Choice of appropriate antimalarial

2. Supportive treatment
3. Avoidance of harmful and/or useless drugs.
1. Antimalarial Drug Therapy for
Severe and Complicated Malaria
Artemisinine Compounds
Artesunate, artemether, artemotil artemether, and rectal
artemisinine (rectal), all have been used in the treatment
of severe malaria.
By and large complications with P.vivax are uncommon,

nevertheless occasionally P.vivax could create problems
like anemia, mild hemolytic jaundice, hyperpyrexia and
splenic rupture.
Off late reports from Bikaner a city of state of
Rajasthan suggest changing nature of P. vivax. Patients
presenting with various complications like cerebral
malaria, severe anemia, malarial hepatitis, renal
impairment, etc. revealed only P.vivax antigen when
investigated with sophisticated technique of PCR.
Drug of choice: Pharmacokineticaly artesunate is superior

compared to artemether and artemotil. Being water
soluble it could be given either by intravenous or intramuscular injection. Randomised trials comparing
artesunate with quinine from South-East Asia clearly
suggest that artesunate is the drug of choice for treatment
of severe malaria. In a head to head trial, compared with
quinine; it reduced mortality by 34.7%.
Artemether and artemotil have comparable antimalarial properties with artesunate but both suffer from
erratic absorption from intramuscular injection; in severe
malaria there is a possibility of treatment failure because
of such unreliable absorption. Availability of artesunate
as intravenous injection makes it a preferred drug while
treating dire emergency of severe malaria.
Management of Severe and Complicated Malaria
Dosage
Severe and Complicated P. vivax Malaria
Treatment Objectives
Avoidance of death and permanent disabilities are the
most vital goals while treating severe and complicated
malaria. Prevention of recrudescence, transmission, and
resistance development assume secondary importance
in such situations.
Recommended dosages of artesunate are: 2.4 mg kg/BW IV

or IM given at admission time 0 hours, repeat at 12
hours then at 24 hours, and subsequently continue once
a day.
Artesunate is dispensed as a powder of artesunic acid.
This is dissolved in sodium bicarbonate (5%) to form
sodium artesunate. The solution is then diluted in
438
approximately 5 ml of 5% dextrose and given by

intravenous injection or by intramuscular injection to the
anterior thigh.
The solution needs to be prepared anew for each
administration and should not be stored. Artesunate does
not require any dose adjustment in cases with hepatic or
renal compromise.
Recommended dosages of artemether are: 3.2 mg/kg BW IM
given on admission 0 hours then 1.6 mg/kg BW per day.
Follow-on Treatment
After initial parenteral treatment, once the patient could
tolerate oral therapy, it is crucial to continue and
complete treatment with an effective oral antimalarial.
A full course of oral ACT (artesunate + amodiaquine or
artemether-lumefantrine) should be given.
Mefloquine is associated with higher neuropsychiatric complications whenever it is used for cerebral malaria.
Therefore it is worth avoiding it as ACT partner if the
patient had initially presented with impaired consciousness or abnormal behavior.
Quinine
Intravenous quinine is an important drug for severe
malaria. Although artesunate proved better than quinine
in severe malaria in regions with low transmission and
unstable form of community malaria; in settings of high
transmission and stable form of community malaria such
superiority is yet to be established.
Loading dose: To achieve minimal inhibitory concentration
quickly, a loading dose of quinine is necessary. With a
loading dose parasite clearance is found to be faster. The
dose is 20 mg/kg BW of quinine salt given by constant
rate controlled intravenous infusion over 4 hours.
Loading dose should be avoided if patient had earlier
received quinine, quinidine or mefloquine.
Maintenance dose: Maintenance dose is 10 mg/Kg BW of
salt given by intravenous infusion over 4 hours every 8
hourly, till patient is unable to take drugs orally. If after
48 hours of parental therapy patient is still incapable of
taking oral treatment then it is advisable to reduce
maintenance dose by half. Patients with hepatic or renal
failure also need appropriate dose reductions.
Side effects: Hypoglycemia is the commonest side effect
of quinine therapy. Its occurrence is very much related
to rate of quinine infusion, induction of hypoglycemia is
much higher when drug is infused rapidly.
Follow-up oral treatment After two to three days, majority

of the patients are in a position to take a drug orally.
Hepatic clearance of quinine becomes faster during
afebrile phase, accordingly higher doses of quinine are
required to maintain necessary MIC, and hence quinine
doses should not be reduced during recovery period.
During follow on treatment quinine could be
supplemented with either clindamycin or doxycycline,
as per age suitability.
Antimalarial drug therapy for severe and complicated
P.vivax malaria: Antimalarial drugs for severe and
complicated P. vivax malaria are essentially same as that
for P. falciparum malaria. Artesunate is the drug of choice,
artemether and quinine could be other options.
SUPPORTIVE TREATMENT
Patients with severe malaria demand meticulous nursing
care, preferably in an intensive care unit.
Supportive treatment depends on malarial complications. Aspects which need special considerations are
discussed below:
1. Frequent clinical assessment should be made.
Assessment must comprise of:
a. Recording of vital signs
b. Respiratory rate and pattern
c. Coma score
d. Urine output
e. Blood glucose.
2. Convulsions should be treated promptly with
intravenous or rectal diazepam or intramuscular
paraldehyde.
3. Avoid routine use of phenobarbitone (Higher death
rate in patients treated with phenobarbitone).
4. Perform a LP to rule out meningitis; use proper
antibiotic coverage in case CSF examination is
infeasible or is deferred for some reasons.
5. Suspect hypoglycemia in any case showing sudden
deterioration, infuse IV glucose (0.3-0.5 g/kg BW of
glucose) if blood glucose is < 40 mg/l.
6. Measure rectal temperature. Use antipyretic and
cold sponging for hyperpyrexia.
7. Proper management of fluid and electrolyte.Children
with malaria are usually dehydrated and tolerate
fluid boluses quite well conversely adults with
severe malaria are rather vulnerable to fluid
overload and may lend into pulmonary edema
particularly with element of ARF.

8. Consider blood transfusion for severe anemia (Hb
less than 7 g/dL in low transmission zone, less than
5 g/dL in high transmission zone).
9. Consider plasma transfusion, Vit-K supplementation, and avoidance of certain drugs (aspirin) in
malaria with bleeding diathesis.
10. Rule out other causes of hepatobiliary involvement
in malarial patients presenting with jaundice.
11. Consider propped up position, oxygen supplementation and furosemide for pulmonary edema.
12. Consider appropriate antibiotics, fluid replacement,
oxygenation, and dopamine for shock.
13. Management of lactic acidosis. Lactic acidosis has
significantly adverse effect on malarial prognosis,
therefore measures to increase tissue perfusion,
oxygenation and correction of acidosis by sodium
bicarbonate need priority considerations in severe
malaria.
14. Keep a low threshold for antibiotic therapy particularly if patients continue running fever despite
parasitic clearance. Associated salmonella infection
with malaria is pretty common. Secondary
pneumonia in malaria should be treated with a
third-generation cephalosporin; however aspiration
pneumonia in an unconscious patient should receive
penicillin or clindamycin.
AVOIDANCE OF USELESS ANCILIARY TREATMENT
Additional supportive strategies like heparin, prostacyclin, deferoxamine, pentoxifylline, low molecular
weight dextran, urea, high-dose corticosteroids,
acetylsalicylic acid, deferoxamine, anti-tumor necrosis
factor antibody, cyclosporin, dichloroacetate, adrenaline
and hyperimmune have been suggested in severe malaria
yet hardly any of these strategies could prove their
therapeutic utility, on the contrary many of them have
proved harmful.
Corticosteroids
Steroids were in use, in severe malaria, for treatment of
cerebral edema, shock hemolysis, thrombocytopenia and
pulmonary edema. In double blind studies use of steroids
was found to increase duration of coma, incidence of
gastrointestinal bleeding and incidence of secondary
bacterial infection, following these observations steroids
are no more recommended for severe malaria.
Mannitol and Urea
Mannitol and urea were earlier used with an aim to
reduce cerebral edema. But with the realization that brain
439
edema is not a significant feature of neurological malaria

this use is given up.
Dextran
Low molecular weight dextran were recommended to
reduce blood viscosity however due to inevitable anemia.
Blood viscosity is never high in malaria and more over
as dextran can worsen a bleeding diathesis, their use is
unjustified.
For IAP- Infectious Diseases Chapter Protocol for
management of malaria, please see Chapter 36.11.1,
Page No. 1525.
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9.34 Kala Azar (Visceral Leishmaniasis)

Yogesh Jain, Rakesh Lodha
Leishmaniasis refers to a diverse group of diseases that
may affect the viscera, skin or mucous membranes caused
by infection due to the parasites of the genus Leishmania.
Of the various species that cause leishmaniasis, Leishmania
donovani is responsible for the disease in India: Kala azar
and post-kala azar dermal leishmaniasis. Kala azar or
visceral leishmaniasis is the systemic manifestation of this

infection which may be fatal, if untreated. Kala azar is a
major public health problem in certain regions of India.
The disease is endemic in Ganga-Brahmaputra valleys
affecting especially Bihar, West Bengal and Assam.
Epidemics of this disease occur periodically.
441
PATHOGENESIS
DIAGNOSIS
The parasite, Leishmania grows into promastigote forms

inside the insect vector, sandfly (Phlebotomus). These
are injected into a susceptible host by the sandfly. The
parasite multiplies freely in its amastigote form inside
the mononuclear phagocytic cells throughout the visceral
reticuloendothelial system in spleen, liver, bone marrow
and lymphoid tissue. However, infection with L. donovani
is not synonymous with disease. For each case of kala
azar, there are 30 to 100 subclinical infections in an
endemic area. Malnutrition is a significant risk factor that
may precipitate active disease in a child suffering from
subclinical infection.
It is mandatory to make a parasitological diagnosis by

demonstrating the parasite before starting treatment. The
parasite can be demonstrated in various tissue sites as
shown below. It is also necessary to quantitate the
parasite load by counting the number of parasites.
PATHOLOGY
Splenic puncture and bone marrow aspiration are the

commonly employed diagnostic techniques. In presence
of thrombocytopenia, splenic puncture is contraindicated. Additionally, parasite can be cultured on NNN
medium but this is not available everywhere. Polymerase
chain reaction (PCR) can also be used to diagnose this
infection. It is 90 percent sensitive.
Recently antigen detection test (RK-39) has been
found to have high sensitivity and specificity.
Various serological tests for kala azar are available.
The common techniques are indirect fluorescent antibody
test (IFAT), direct agglutination test (DAT) and enzyme
linked immunosorbent assay (ELISA). These tests have
over 95 percent sensitivity and specificity in diagnosis
of leishmanial infection. However, they do not distinguish between asymptomatic infections, past infection
or active kala azar. Therefore, it has limited role in clinical
diagnosis in endemic areas.
Pancytopenia is commonly seen. Anemia is seen in
all cases. Neutropenia is seen in 60 to 70 percent cases
and may be seen early in the course of the disease.
Thrombocytopenia may be seen in 50 to 60 percent of
children. Hypergammaglobulinemia with reversal of
albumin to globulin ratio is commonly seen; aldehyde
test which is based on this, is now obsolete because of its
low specificity and poor sensitivity in the first three
months of the infection.
The bone marrow is hyperplastic but shows some

dyserythropoiesis and maturation arrest. Erythrocytes
are sequestered in the spleen and also undergo
hemolysis. Beside, ineffective erythropoiesis and
immune mediated lysis also contribute to anemia.
Neutrophils and platelets are also sequestered and
destroyed prematurely. The liver and spleen enlarge
because of reticuloendothelial proliferation. There is
variable depression of synthetic functions of the liver
resulting in hypoalbuminemia. However, prothrombin
time is usually normal.
CLINICAL FEATURES
The clinical incubation period is usually 2 to 4 months,
however it may range from 1 month to as long as 2 years.
The clinical features on presentation reflect the chronicity
and the severity of the infection. Fever, hepatosplenomegaly and pallor are seen in more than 95 percent of
cases and thus, are the cardinal features of this illness.
Epistaxis is common early in the disease. A large number
of patients develop darkening of the skin, especially on
the face, hands and the upper torso, that is the feature
which gives the disease its name kala azar.
In some cases of inadequately treated kala azar, a skin
condition called post-kala azar dermal leishmaniasis may
develop as all parasites are not eradicated (See Chapter
31).
Malnutrition may ensue because of the chronic nature
of this disease. Patients may also develop intercurrent
infection of the respiratory and gastrointestinal tract as
manifested by cough and diarrhea.
Kala azar has also been reported as an opportunistic
infection in HIV infected individuals.
Site
Sensitivity
Splenic puncture
Bone marrow
Liver
Buffy coat preparation
Lymph node
95-98 %
54-86%
70 %
70%
60%
COURSE AND PROGNOSIS

If untreated 80 to 90 percent patients die. Intercurrent
infections supervene especially pneumonia, tuberculosis,
dysentery and cancrum oris. However, with treatment,
majority would recover without sequelae. Later, up to
20 percent cases may develop a cutaneous manifestation
of this disease called post- kala azar dermal leishmaniasis
(PKDL).
442
TREATMENT
The objectives of treatment are: (i) Cure the patient of the
leishmanial infection, (ii) Prevent relapse, and
(iii) Treat intercurrent infections. Ultimate cure is clinical
and parasitological cure with no relapse during six months
of follow-up. Parasitological cure is absence of parasites
in bone marrow or splenic aspirate taken after therapy.
Pentavalent antimonials are the fist line drug for this
disease. Sodium antimony gluconate (SAG) and meglumine antimonite are antimonials which are administered
via intramascular or intravenous route. SAG is given in a
single daily dose of 20 mg/kg/day of antimony base for 3
to 4 weeks or 2 weeks after parasitological cure. Some
Indian authors recommend up to 40 days therapy also.
Local injection, site pain, and mild ECG changes are
common adverse effects. Usually, there is improvement
in wellbeing and response to fever occurs in a few days,
hemoglobin starts wising in the second week. The spleen
may not regress totally till one year later. However, bone
marrow /splenic aspirate at the end of treatment should
show parasitological cure. It the treatment is interrupted
or inadequate dose is administered; the response may not
be there. There may be a relapse which is much more

difficult to treat. Relapses usually occur within 6 months.
If antimonials fail to cure the patient, amphotericin B
1 mg/kg/day for 20 days by intravenous infusion or
pentamidine isothionate 4 mg/kg by intramuscular route
on alternate days for 5 to 52 weeks can be given.
Recently, an oral drug miltefosine has been found to
be effective for treatment of kala azar.
CONTROL
Besides case detection and therapy, spraying of sandfly
sites with residual insecticides is vital.
BIBLIOGRAPHY
1. Bhattacharya SK, Sur D, Karbwang J. Childhood visceral
leishmaniasis. Indian J Med Res 2006;123:353-6.
2. Murray HW, Berman JD, Davies CR, Saravia NG.
Advances in leishmaniasis. Lancet 2005;366:1561-77.
3. Wittner M, Tanowitz HB. Lesihmaniasis. In: Feigin RD,
Cherry JD, Demmler GJ, Kaplan SL (Eds): Textbook of
Pediatric Infectious Diseases. Saunders, Philadelphia.
2004;2730-8.
10.1 Anatomical Localization of Neurological Problems: CS Rajput, DP Karmarkar ........................................................................... 444

10.2 Normal Development and Malformations of Central Nervous System: Veena Kalra, Rashmi Kumar ....................................... 448
10.3 Degenerative Disorders of the Central Nervous System: Veena Kalra .......................................................................................... 453
10.4 Seizure Disorders in Children: Veena Kalra ....................................................................................................................................... 455
10.5 Infections of the Central Nervous System: Veena Kalra .................................................................................................................. 462
10.6 Coma in Children: CR Banapurmath, Shobha Banapurmath, G Guruprasad .................................................................................... 470
10.7 Brain Tumors in Children: KS Rana .................................................................................................................................................... 477
10.8 Raised Intracranial Pressure: AD Tewari, Kundan Kumar Mittal ........................................................................................................ 486
10.9 Benign Intracranial Hypertension: AD Tewari, Kundan Kumar Mittal ............................................................................................... 489
10.10 Motor Weakness in Infancy and ChildhoodClinical Approach: Vrajesh Udani ........................................................................ 491
10.11 Floppy Infant Syndrome: R Anandam, D Kalpana .............................................................................................................................. 495
10.12 Muscular Disorders in Children: K Pandian ....................................................................................................................................... 499
444
10.1 Anatomical Localization of

Neurological Problems
CS Rajput, DP Karmarkar
A clear, precise and accurate history of the entire course of
the illness is imperative in neurological disorders. It often
leads to a provisional diagnosis and also helps to guide
the physician towards a more pointed and detailed
neurological examination. It helps to determine the
etiology, etiopathogenesis, course of events and possible
sites of lesions. The onset of disease whether it is acute,
subacute, chronic or acute exacerbation of a chronic illness
is important in clinical neurology. Similarly, the course of
the illness, whether progressive, static, regressive or
showing improvement from the time of insult are
important clues in distinguishing a degenerative brain
disorder from acute acquired insults. Common symptom
groups include delayed neurodevelopment, regression of
neurodevelopment, symptoms such as fits, motor
weakness, gait and tone abnormalities, altered sensorial
states, features of raised intracranial pressure, and sensory
symptoms. History should evaluate the details of each of
the above symptoms and also presence or absence of other
symptom groups. A holistic history is required to assess
the overall status.
Cerebral Lesions
The cerebral cortex functions in an integrated manner, yet
certain functions are more specifically controlled from
various specific sites. In cerebral cortical insults, the
localization or preferential involvement of various lobes
of the cortex can be obtained by history of symptoms
related to higher functions and specific signs as given in
Figure 10.1.1.
Hemiplegia
The clinical evaluation of a child with unilateral motor
symptoms is challenging due to difficulties in performing
a systematic motor examination and retaining the child's
cooperation through the procedure. Hence, history and
functional examination become important management
strategies. The position of the limbs, hands and feet, quality
and range of spontaneous movements, handedness,
involuntary movements, limb asymmetries should be
observed carefully before proceeding for a systematic
examination.
Figure 10.1.1: The effects of lesions of different lobes in cerebrum
Diseases of Central Nervous System
445
Figure 10.1.2: Features of localization of hemiplegia lesions
History of onset of weakness is classified as acute, if

weakness develops within 24 hours of the onset, and it
usually implies a vascular or acute inflammatory etiology.
It is subacute, if it evolves in a few days and is common in
inflammatory or venous vasculopathies, and chronic, if
weeks elapse before full profile is manifest. This is often
due to space occupying lesions, degenerative brain
diseases, or subdural hematoma. The pattern and
distribution of weakness and clinical associations help to
localize anatomic sites of the lesion. The location may be
cortical, subcortical, at corona radiata, internal capsule,
midbrain, pons, medulla or high cervical cord. The clinical
associations at various levels are indicated in Figure 10.1.2.

It is clear that clinical examination must attempt to
determine the site as precisely as possible.
The next important question to answer is the cause of
hemiplegia. Common etiological processes are listed below.
The details are dealt with in subsequent chapters.
Classification of Hemiplegia
Anatomical Classification
This classification helps in localization of the lesion.
1. Cerebral
446
2.
3.
4.
5.
a. Cortical lesion
b. Subcortical lesion
c. Lesion in the internal capsule
BrainstemThis includes midbrain lesions
Pons
Medulla
Spinal
a. Upper cervical
b. Lower cervical
Clinical Classification
Depending upon duration of illness, hemiplegia can be
classified as:
a. Acutewithin 24 hours
b. Subacute2 to 4 days
c. RecurrentCommon causes are vasculopathies,
mitochondrial disorders, embolic episodes, sickle cell
disease, transient ischemic attacks, demyelinating
diseases.
d. Slowly progressive More than 2 weeks duration.
Common causes are intracranial space-occupying
lesions, subdural hematoma, demyelinating diseases.
Depending upon type of tone, It is also classified as:
a. Spastic hemiplegia
b. Flaccid hemiplegia.
Etiopathological Classification of Hemiplegia
Vascular
Thrombosis
i. Arterialarteritis
ii. Venouscortical venous thrombosis
Embolism
Mitral valve disease, subacute bacterial endocarditis
(SABE)
Hemorrhage
Infective
Tuberculosis, pyogenic abscess, encephalitis
Traumatic
Subdural hematoma
Extradural hematoma
Intracranial hemorrhage
Neoplastic
Neurofibroma
Meningioma
Glioma
Leukemia
Demyelinating
Acute disseminated encephalomyelopathy
Multiple sclerosis
Leukodystrophy
Metabolic
Hypoglycemia
Hyperglycemia
Uremia
Postepileptic congenital
AV malformations
Moya-moya disease
Miscellaneous
Hemolytic uremic syndrome
Homocystinuria
Vasculopathies like systemic lupus erythematosus
Hypersensitivity vasculitis
Spinal Cord
Lesions of the spinal cord often lead to paraplegia or
quadriplegia. The onset of weakness, pattern of progression, time taken for evolution of the full profile should
be enquired into. The associated symptoms which need to
be interrogated include history of pain, girdle sensation,
radicular pain, sensory loss including touch, pain,
temperature, pressure and posterior column sensations.
Presence of paresthesias and sensory abnormalities are
often difficult to elicit in children. A definite sensory loss
level is hard to define and thus a useful parameter for
identification of site of spinal cord lesion is not available
in childhood. Involvement of bladder and bowel control,
perianal sensations and sphincteric tone are important.
Presence of cutaneous dimple, lipoma, tuft of hair, spinal
tenderness, perispinal swelling should be examined in
every patient.
The major clinical features that help to localize site of
spinal cord lesions are given in Table 10.1.1. Lesions of
the spinal cord should be differentiated into compressive
or noncompressive myelopathies, and extramedullary or
intramedullary lesions. The clinical features that help in
this regard are listed below.
Lesions Involving the Spinal Cord
and its Localization
Paraplegia It is a symmetric paralysis of both lower
extremities.
Quadriplegia It is paralysis of all four extremities. It is
also called as tetraplegia.
Monoplegia
It is a paralysis of one extremity only.
447
TABLE 10.1.1: Features of localized lesions in spinal cord

Cord
segment
Clinical features
Muscles paralysed
C3-4
Pain in neck and occipital pain

paresthesia and weakness in
upper limbs early,
relative anesthesia of face
Paralysis of 9th, 10th and
11th cranial nerves
Quadriplegia
Lower parts of trapezius,

supraspinatus and infraspinatus,
muscles of upper limbs,
diaphragm
C7
Paraplegia
Triceps and extensors

of wrist and fingers
Triceps (C6-7) lost
C8, T1
Spastic paralysis of trunk and

lower limbs
Paralysis of ocular sympatheticsometimes
Flexors of wrists and

fingers and muscles of
hand
In upper limbnormal,
exaggerated in lower limb
T6
Spastic paralysis of muscles

of abdomen and lower limbs
Intercostals, upper and

lower rectus abdominis,
oblique abdominis
Upper abdominals
and lower abdominals lost
T9-10
Spastic paraplegia
Lower half of rectus

abdominis
Upper abdominals normal

Lower abdominals lost
T12L1
Spastic paraplegia
Lower fibers of oblique

abdominis and transversalis, iliopsoas
L3-4
Spastic paraplegia
Quadriceps, abductors
Knee jerk (L2-4) lost
S1-2
Flexion of hip, adduction of

thigh, extension of knee and
dorsiflexion of foot possible
All other movements in lower
extremities weak
of hip
Glutei, calf muscles,
anterior tibial and peroneal,
small muscles of
foot
ankle jerk + (S1-2)

Knee jerk and
ankle jerk lost,
plantar reflexes lost
S3-4
No paraplegia. Retention of
urine and feces
Paralysis of external
sphincter
Anal and bulbocavernous

reflexes lost. DTR normal
Cauda
equina
1.
Paralysis of lower
limb
Absent deep reflexes
Paralysis of gluteal,
hamstrings and all
muscles below knee
No paralysis of lower
limbs
Knee jerk and

ankle jerk lost
2.
3.
4.
Whole caudaanesthesia
below folds of groin, including
genitals, loss of control
of bladder and rectum
Upper sacral and L5sensory
loss over front and posterior
and outer aspect of thigh
Below S2saddle-shaped
area of anesthesia, incontinence
of urine and feces
S4-5 and coccygeal roots
anesthesia of anus and rectum
Reflexes
All reflexes
in lower limb normal
Paralysis of levator ani
DTRDeep tendor reflex
Cortical causesCortical venous thrombosis, cerebral

palsy, spinocerebellar hereditary spastic paraplegia
Paraplegia in flexion The pyramidal tracts are severely

affected, and there is a lesion of descending spinal pathways. The legs become progressively more flexed at knee
and hip, and stimulation provokes painful flexor spasm.
Spinal causesTransverse myelitis, epidural abscess,

herpes zoster myelitis, GB syndrome, poliomyelitis,
trauma, and tuberculous osteomyelitis of vertebra.
Paraplegia in extension When spinal lesion is incomplete

and affects principally the pyramidal tracts, the tone in
lower limbs is increased in extensor muscles.
Causes of Paraplegia
448

TABLE 10.1.2: Features of cord compression
Extramedullary intradural
Intramedullary (Intrinsic lesions of spinal cord)
Radicular pains rare

Paresthesia occur in all stages
Muscle fasciculations, common
Dissociation of sensations, common
Bladder and rectal disturbances, early
Descending level of sensory disturbances
Persistent Brown-Squard syndrome, very rare

Sacral sparing
Spasticity, less pronounced
Characterized by muscle atrophy
Trophic skin changes, common
No local tenderness of spine
Spinal fluid changes, rare
Radicular pains, common

Paresthesia, rare until late
Muscle fasciculations, rare
No dissociated loss of sensation
Bladder and rectal disturbance, late
Rising level of sensory disturbances as
peripheral tracts are affected more
Brown-Squard syndrome may occur
No sacral sparing
Spasticity and other pyramidal signs pronounced
Little or no muscle atrophy
Trophic skin changes, absent
Vertebral column may be sensitive to local pressure
Spinal fluid changes, frequent
Cord Compression
Table 10.1.2 depicts comparative features of extramedullary and intramedullary cord compression.
Brown-Squard Syndrome
If there is a partial affection of the cord, it might lead to
Brown-Squard syndrome which is characterized by the
following:
1. Loss of motor control (pyramidal tract) below the level
of lesion on the same side
2. Loss of posterior column sensations below the level of
lesion on the same side
3. Loss of pain and temperature sensations on the

opposite side 2 to 6 segments below the lesion.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
Behrman, Kliegman, Arvin: Nelson Textbook of Paediatrics (15th edn) 1996.

Christopher RW, Edwards, Lan AD: Boucher, Davidson's
Principles and Practices of Medicine, 1991.
Chusid IG: Correlative neuroanatomy and functional
neurology (16th edn) 1976.
Patten J: Neurological differential diagnosis.
Walton J: Brains Diseases of the Nervous System
1985.
10.2 Normal Development and Malformations

of Central Nervous System
Veena Kalra, Rashmi Kumar
NORMAL DEVELOPMENT
A thickening of ectoderm occurs dorsally in the first month
of gestation, forming the neural plate. This gets indented
centrally and is flanked by ridges (neural folds). These
fuse in the midline forming the neural tube with apertures
at both endsthe anterior and posterior neuropores. The
anterior and posterior neuropore fuse by the 26th and
29th day of gestation respectively. The rostral segment of
the neural tube develops three regional dilatations or

vesicles, whose cavities eventually form the cerebral
ventricles and aqueduct. These vesicles develop into the
prosencephalon, mesencephalon and rhombencephalon.
The walls of these structures have three layers namely,
the ventricular (or ependymal), the mantle and the marginal layers. The prosencephalon further differentiates into
cerebral hemispheres and diencephalon, while the

rhombencephalon differentiates into mesencephalon (later
pons and medulla) and myelencephalon (later medulla
oblongata). These subdivisions are complete by 36 days
of gestation.
The cerebral hemispheres with subdivisions of limbic
system, basal ganglia and cerebral cortex are distinct by
three months of gestation. Sulcal differentiation starts in
the 3rd month in the Sylvian fissure. By the 5th and 6th
month of gestation, the primary fissures and lobes of the
brain are visible.
MALFORMATIONS
Malformations of the central nervous system may be minor
or major. Most of them have significant clinical
implications, as even minor malformations may be
associated with seizures, focal neurological deficits or
delayed neurodevelopment. Approximately 3 percent of
live newborns and 7 percent of stillbirths have CNS
malformations. Genetic and nongenetic causes may be
responsible, e.g. infections, drugs, maternal irradiation
and other environmental insults. Malformations can be
broadly grouped into:
Dysraphisms and malformations of neural tube closure;
Malformations of embryogenesis and neuronal migration;
Malformations of size and shape of head;
Abnormal CSF dynamics; and
Abnormalities in brain size.
The common ones that require familiarization include
hydrocephalus, microcephaly, neural tube defects, and
disorders of cell migration.
HYDROCEPHALUS
This results from an increased volume of cerebrospinal
fluid due to either increased production, obstruction in its
path or impaired absorption resulting in increased
ventricular size. The ventricles not only become dilated
but the pressure is usually increased, resulting in
increased periventricular white matter pressure, periventricular ooze and blunting of horns of ventricles. When
the ventricles dilate as a compensation for decreased brain,
it is called hydrocephalus ex vacuo (Table 10.2.1).
Pathophysiology
CSF is secreted by the choroid plexus in the lateral
ventricles by plasma ultrafiltration and active secretion.
This involves active transport of sodium and is energy
dependent. The total volume of CSF is about 50 ml in an
449
TABLE 10.2.1: Etiology of hydrocephalus

Congenital
Acquired
1. CSF flow obstruction
1. PostmeningitisTBM,
Aqueductal stenosis
chronic, acute menin-
Arnold-Chiari malformation
Dandy-Walker malformation
2. Intrauterine infections
gitis
2. Posterior fossa tumors
3. Cortical atrophy
3. Intracranial bleeds
(Hydrocephalus
4. Congenital tumors
ex vacuo)
infant, and 150 ml in an adult. About 20 ml of CSF is

produced per hour. It then circulates through the 4th
ventricle and reaches the basal cisterns via the foramina
of Luschka and Magendie, and subarachnoid spaces at
the base and cortex of the brain. The pressure gradient
between the ventricles is about 180 mm of water, and the
veins is about 90 mm of water. The CSF is absorbed mainly
through the arachnoid villi into the vascular system, due
to this hydrostatic pressure. Hydrocephalus resulting
from obstruction within the ventricular system is called
obstructive hydrocephalus, whereas that resulting from
obliteration of the subarachnoid cisterns or decreased absorption is called communicating hydrocephalus.
Congenital Hydrocephalus
Hydrocephalus may be present at birth or develop shortly
thereafter, due to:
1. Aqueductal stenosis It could be inherited as an X-linked
recessive trait or may result from intrauterine infections
such as toxoplasmosis.
2. Arnold-Chiari malformation It is characterized by
cerebellar elongation and downward displacement. It
has varying severity. In the commonest type of Chiari
malformation (type 2), the cerebellum and medulla
oblongata are shifted caudally with distortion and
obstruction of CSF pathways. This malformation is
often associated with myelomeningocele or other
neuronal migration defects.
3. Dandy-Walker malformation This is a cystic malformation of the cerebellum and 4th ventricle, which
occurs due to atresia of the foramina of Luschka and
Magendie. It may also be associated with other brain
malformations.
4. Intrauterine infections, intracranial bleeds, congenital
tumors and many genetic and chromosomal
syndromes, may be associated with congenital hydrocephalus.
450
Acquired Hydrocephalus
This may be communicating or noncommunicating (obstructive). In obstructive hydrocephalus, the CSF flow may
be obstructed at any site along its path. Common sites of
obstruction include aqueduct of Sylvius and fourth
ventricular outflow foramina. In communicating
hydrocephalus, there may be increased production at the
choroid plexus or decreased absorption at the subarachnoid spaces. This commonly follows chronic meningitis including tuberculosis and acute meningoencephalitis.
Obstructive hydrocephalus may be associated with
congenital malformation, tumor, periaqueductal stenosis,
cystic lesions or due to fibrosis, following intraventricular
hemorrhage. The ventricles above the site of obstruction
become dilated, and this helps to differentiate obstructive
from communicating hydrocephalus.
necessary to demonstrate ventricle size, periventricular

ooze (an indication of increased ventricular pressure),
thickness of cortical mantle, coexisting lesions and
possible etiology. Hydrocephalus often gets arrested
spontaneously. Surgical intervention is not required in
all. In established and progressive hydrocephalus or
where vision or life is endangered, surgical intervention
is mandatory. A variety of shunts are available
ventriculoperitoneal, ventriculoatrial, etc. The former is
preferred. Infections, shunt block and child outgrowing
the shunt are some of the commonly encountered complications. The choice should be appropriate and close
follow-up maintained. Medical management should be
instituted if surgery is not indicated. Acetazolamide, 50
mg/kg/day or glycerol may be added for control of
symptoms and raised pressure associated with hydrocephalus.
Clinical Features
A large or rapidly increasing head size with prominent
forehead is the single most important clinical feature. Head
size can increase due to many causes. The sutures and
fontanels remain unduly prominent and have delayed
closure. Macewen's or crackpot sign may be positive and
prominent veins are seen on the scalp. Child may have
impaired upward gaze (sunset sign), cranial nerve palsies,
increased tone in the limbs and brisk tendon jerks may be
detected due to compression of the white matter. The signs
are more severe in lower limbs. Features of raised
intracranial pressure like papilledema, ophthalmoplegia,
bradycardia, abnormalities in respiratory rate and rhythm,
and constipation may occur. Optic atrophy may occur.
Not uncommonly, children experience frequent
headaches, head banging and vomiting due to increased
intracranial pressure. Serial measurement of head size is
an important clinical parameter to be recorded.
It must be remembered that all large heads are not due
to hydrocephalus. Important differential diagnosis include
macrocephaly and megalencephaly, associated with
metabolic CNS diseases, neurocutaneous syndromes,
subdural effusion and large head due to skeletal disorders
like achondroplasias, hemolytic anemias and familial
large heads.
Management
Management includes making a precise diagnosis. Cranial
ultrasound is useful to screen ventricles or subdural space
provided fontanel is open. Subsequently a CT scan is
Prognosis
Prediction of outcome is difficult, based on the size of the
cortical mantle at the time of operation. Hydrocephalic
children have lower intelligence quotients and a higher
risk of developmental disabilitiesespecially in visual,
memory and performance fields than the general
population.
CONGENITAL ABNORMALITIES OF THE SKULL
Normal development The skeletal system develops from
the mesoderm during the 3rd week of gestation. The bones
of the skull are well developed by the 5th month of
gestation and are separated by fibrous sutures and
fontanels.
Microcephaly
It is a condition in which the head circumference is more
than 2 standard deviations below expected norm for age,
sex or gestation. Microcephaly may be primary or
secondary. Except in premature closure of sutures
(craniosynostosis), it reflects a small sized brain. Primary
microcephaly is seen in various genetic and chromosomal
disorders and results from a variety of insults like
migration defects, microgyria, agenesis of corpus
callosum, gray matter heterotopias, etc. It may be familial,
inherited as an autosomal recessive disorder or may result
from an unidentified cause. Microcephaly may also follow
severe insults like CNS infections, metabolic disorders,
intrauterine infections, maternal addictions and other

causes. Secondary microcephaly results from both
perinatal and acquired insults causing destruction of the
brain. The lesions include gliosis, atrophy, cystic
degeneration, porencephaly and encephalomalacia,
depending upon the site and nature of lesion. But primary
and secondary microcephaly result in variable degrees of
mental impairment, hyperkinesia or a broad display of
neurologic disorders. It is important to assess neurologic
development, as some children may have microcephaly
with normal mentality. The cause is often difficult to
establish. Treatment of associated symptoms and
prevention of the preventable causes should be attempted.
Craniosynostosis should be excluded.
Craniosynostosis
It implies premature closure of one or more cranial sutures.
A skull deformity is usually evident and a bony ridge is
felt at the suture. If only one suture is involved, no
neurological deficits are seen and the problems are mainly
cosmetic, but if multiple sutures are fused, brain growth is
restricted and increased intracranial tension may result.
Associated developmental defects of face, orbit and CNS
may be present.
There are some genetic disorders and syndromes associated with craniosynostosis. Crouzon syndrome, an
autosomal dominant disorder, is characterized by
brachycephaly (due to bilateral closure of coronal sutures),
proptosis, maxillary hypoplasia and hypertelorism. Apert
syndrome is associated with premature fusion of multiple
suturescoronal, squamous, sagittal and lambdoid. This
autosomal recessive condition is associated with clover
leaf like skull, syndactyly and mental retardation. Pfeiffer
syndrome is associated with turricephaly, prominent
widely spaced eyes and broad, short thumbs and great
toes.
Diagnosis of craniosynostosis can be confirmed by
plain X-ray skull, which shows hyperostotic bony sutural
fusion. Surgical intervention is required to reduce
intracranial pressure, provide space to the growing brain
and for cosmetic reasons. Other defects of sutural fusion
include scaphocephaly, plagiocephaly, tugonocephaly
and turricephaly depending on the shape the skull
assumes.
451
Neuronal Heterotopias
A defect in radial migration of neurons before the 5th
month of gestation, leads to clusters of subcortical neurons
or heterotopia. These neuronal clusters can be detected in
the white matter pathologically or on MRI scans.
Heterotopias are implicated in patients with partial
seizures and developmental dyslexia.
Lissencephaly (Agyria)
This is a rare disorder, associated with absence of cerebral
sulci and gyri, giving the appearance of a fetal brain. About
15 to 20 percent have deletions of chromosome 17p13.3.
Some infants may have a typical facial appearance with
prominent forehead, bitemporal hollowing and short nose
with upturned nares.
Pachygyria
The gyri are widened and show dense gliosis, detectable
on MRI scan. Clinical features include spasticity, mental
retardation and seizures.
Schizencephaly
This disorder is characterized by unilateral or bilateral
clefts in the cerebral cortex that results from a defect in cell
migration in the first trimester of pregnancy.
Agenesis of Corpus Callosum
Commissural plate damage during early embryogenesis
results in this malformation. The clinical spectrum varies
in severity from profound mental and motor defects with
seizures to an asymptomatic child. Associated migration
defects, porencephalic cysts and hydrocephalus may be
observed and may be associated with trisomies (8,18). The
Aicardi syndrome occurs in females, consists of agenesis
of corpus callosum, resistant seizures, severe mental
retardation, vertebral malformations and ocular
colobomas. CT or MRI scan reveals agenesis of corpus
callosum, laterally shifted frontal horns, and abnormally
high position of the 3rd ventricle, between the lateral
ventricles. Intrauterine diagnosis by ultrasound is feasible.
Prognosis is poor.
DISORDERS OF THE CELL MIGRATION
Porencephaly
These disorders present a wide range of severity, with

minor abnormalities of no clinical significance on the one
hand, and devastating malformations on the other.
This refers to the presence of cysts or cavities within the

brain, which may be developmental or acquired.
Developmental cysts are due to defect in cell migration.
452
They are frequently located in the sylvian fissure area and

communicate with both subarachnoid space and ventricle.
NEURAL TUBE DEFECTS (DYSRAPHISM)
This group of congenital anomalies of the CNS results
from failure of the neural tube to close spontaneously. The
precise cause is unknown. Many factors such as radiation,
drugs and abnormal nutritional status acting at a critical
period of gestation as well as genetic determinants may
be causative.
Spina Bifida Occulta
This is a common anomaly affecting about 5 percent of the
population. Affected persons are usually asymptomatic
but may have a patch of hair, a lipoma or pigmentation of
the low back.
Meningocele
This is a protrusion of meninges through a defect in
posterior vertebral arches. There is no accompanying
neural tissue and thus, no neurological deficit. The fluid
filled sac may be covered by intact skin in which case
surgery may be delayed.
Myelomeningocele
This constitutes the most severe form of dysraphism.
Etiology
Both genetic and environmental factors play a role in
etiology. Recurrence risk after birth, of one affected child
is 1.5 percent and increases to 5 percent after two affected
siblings. Folic acid deficiency is believed to play a role
and some recent studies suggest that daily administration
of folic acid around conception and early gestation,
reduces risk of neural tube defects. Valproic acid given
during pregnancy may increase risk.
Prenatal Diagnosis
Alpha-fetoprotein (AFP), a component of fetal CSF, leaks
out through the open defect and reaches high levels in
amniotic fluid. Its level in amniotic fluid thus serves as an
indicator of dysraphism. False positive and false negative
rates of this test are 0.5 percent and 2.5 percent respectively.
Besides, maternal serum AFP is also elevated in the 2nd
trimester and this serves as a good screening test.
Myelomeningocele can be diagnosed by ultrasound in
pregnancy.
Clinical Features
A sac like cystic midline structure is present on the back,
covered by a thin membrane which may leak. It may be
located anywhere along the neuraxis, but about 75 percent
occur in the lumbosacral region. Neurological deficit is
maximum with thoracic and high lumbar lesions. A variety
of problems are encountered: e.g. variable degrees of lower
motor neuron paralysis of the lower extremities, sensory
loss in the perineal area and lower limbs, sphincter
disturbance and neurogenic bladder and bowel.
Deformities such as hydrocephalus, clubfeet and
congenital dislocation of hips may be associated.
Prevention
The prospective mother should receive 5 mg of folic acid
daily beginning at least 6 weeks before conception and
continued in the first trimester of pregnancy.
Management
Management of myelomeningocele requires a multidisciplinary approach. Parents must be given detailed
information about the disorder, its prognosis and options
available. The decision for vigorous treatment of severely
affected babies has to be individualized. Standard
management includes prevention of infection and timely
closure of the defect. After repair of myelomeningocele, a
shunting procedure for hydrocephalus is required in most
infants.
Management of bladder dysfunction is one of the major
problems. Intermittent catheterization, prophylactic
antibiotics, reimplantation of ureters or external drainage
of bladder are sometimes required.
Prognosis is not satisfactory. It leads to early disabilities
if untreated, and intercurrent problems occur despite
treatment.
Encephalocele
It implies a midline cranial defect with protrusion of either
meninges, or meninges with underlying brain tissue
through it. The infant is born with a fluctuant round midline
mass, protruding through the cranium which is
transilluminant and has a positive cough impulse. It
occurs most commonly in the occipital region, but frontal,
nasal or nasofrontal encephaloceles may also be seen. The
lesion may be covered with skin. Children with meningoceles
have a good prognosis, whereas those with encephaloceles
are at risk of multiple problems, specially in presence of
congenital hydrocephalus, e.g. visual problems, seizures and

mental retardation. Antenatal diagnosis is possible by
ultrasound or AFP levels. Management includes reduction
and closure of the defect and ventriculoperitoneal shunting,
if hydrocephalus is present.
Anencephaly
This is a lethal malformation, commoner in females, in
which both cerebral hemispheres are absent. It may recur
in families. The infant is born with a defect in the cranial
bones with a soft mass of rudimentary brain, covered by a
thin membrane continuous with the skin. A deformed
head, large ears and cranial transillumination provide
diagnostic clues. Most infants are stillborn or die shortly
after birth. Antenatal diagnosis is possible by ultrasound
and raised AFP levels (> 1000 ng/ml) in maternal serum
and amniotic fluid. Anencephalic pregnancies are
commonly associated with polyhydramnios and spina
bifida. A combination of folic acid, riboflavin and ascorbic
acid reduces the recurrence risk.
Holoprosencephaly
There is failure of division of the prosencephalon into two
cerebral hemispheres. Only a single lobe is present with
no sagittal division. The defect arises before 23rd day of
gestation. It occurs more commonly in infants of diabetic
mothers, congenital infections, fetal alcohol syndrome,
453
trisomy 13 and 18, deletions 18p and 13q, ring 18 and

triploidy. Majority of patients have severe developmental
delay, spasticity, failure to thrive and seizures.
Neuroimaging techniques confirm the diagnosis.
Various combinations of median facial defects are
associated with holoprosencephalic brain. These include
cyclopia, ethmocephaly, cebocephaly and premaxillary
agenesis.
Megalencephaly
The brain weight and size are more than 2 standard
deviations above the mean for age and sex. It should be
distinguished from macrocephaly or large head which
does not necessarily mean large brain. A wide variety of
conditions may be associated with megalencephaly,
including neuronal heterotopias and migration defects.
In such cases, mental retardation and epilepsy are usually
present. A large brain may also occur with tuberous
sclerosis and neurofibromatosis, in some patients with
storage disorders such as Tay-Sachs disease and Canavan
and Alexander leukodystrophy. Megalencephaly also
occurs as a benign familial feature, affecting more males
than females. In most cases, one parent usually the father,
was also found to have a large head, suggesting an
autosomal dominant mode of inheritance.
10.3 Degenerative Disorders of the

Central Nervous System
Veena Kalra
Degenerative disorders of the central nervous system are
an important and not infrequently encountered entity in
childhood. Degenerative brain disease (DBD) is defined
as any disorder where there is progressive damage to the
brain with or without systemic involvement. These
disorders are often familial, inherited and need to be
accurately diagnosed and classified. Most are genetic
(autosomal recessive), while few are acquired, e.g. subacute
sclerosing panencephalitis. The importance of diagnosis
of DBD is that possible prevention by genetic counseling
and appropriate intervention is likely. They are clinically
characterized by progressively increasing neurological

incapacitation and loss of acquired milestones and
developmental events. Onset of inherited disease can occur
at any age. Failure to attain any milestones is usual, if
insult occurs perinatally. The common occurs if insult
perinatally. The common presentation is an apparently
normal or nearly normal development followed by
progressive deterioration. This deterioration often follows
specific patterns, and affects different parts of the central
nervous system initially. The progressive course is often
characteristic. The age of onset, pattern of progression of
454
different neurological disease states and the age at

incapacitation provide useful diagnostic clues. A useful
clinical approach is to broadly classify them into degenerations that predominantly affect gray matter versus white
matter. Eventually in both, the entire nervous system tends
to become affected and the end-stage picture of all of them
is generally similar. The initial course of the illness is crucial
and needs to be elucidated carefully. The patterns in both
gray and white matter disorders merge imperceptibly.
APPROACH TO A PATIENT SUSPECTED TO HAVE A
NEURODEGENERATIVE DISEASE
Useful Questions
Till what age was the child normal; type of onset-acute/
insidious/chronic; any precipitating factor; family history:
X-linked inheritanceMenkes, Lesch-Nyhan, Hunter;
courseprogressive/static/improving; development
status prior to onset of symptoms; specific symptoms:
cognition, seizures, behavioral disturbances, speech and
language (gray matter), tone changes, ataxia, gait
difficulties (white matter), visual/hearing problems
(white/gray matter); symptoms pertaining to other
systems and syndromes.
Head circumference; facies; hair; eyes; stature;
hepatosplenomegaly; cardiac dysfunction; hyperacusis,
hearing loss; and hernia.
The gray matter disorders are characterized by
seizures, progressive cognitive or intellectual deterio-
ration, loss of recognition, visual and hearing impairment

which is central in origin rather than of end-organ type.
Different types of variably severe seizures characterize
the early phase of the disease. Motor ability is preserved
better and till later in the course of the diseases. Spasticity
is not very severe (Table 10.3.1).
In white matter degenerations, characteristic early
symptoms include progressive increase in tone, variable
spasticity or rigidity associated with brisk tendon jerks
and clonus. In older children, gait disturbances herald
the onset along with spasticity. Seizures are usually not
an early feature. Dementia and loss of socioadaptive
milestones occur late in the course. Fundus examination
to look for changes in the optic nerve and retina are
frequently useful to distinguish white matter from gray
matter disorders. Advanced stages do not present clearcut distinctive features. Presence of associated
organomegalies, large head, hyperacusis, skin
pigmentation, urine and body odor and physical stigmata
may prove useful clues.
Investigations
Clinical manifestations are often variable and one has to
resort to detailed investigations for precise diagosis.
The important investigations include: EEGbackground changes or spike and sharp waves are more often
associated with gray matter disorders. CT scan reveals
white matter changes suggestive of leukodystrophies.
Characteristically, the central white matter is prominent
with arborizing tentacles towards the periphery. Basal
TABLE 10.3.1: Clinical features of gray and white matters diseases

Gray
White
Dementia
Early
Late
Seizures
Early and prominent
Late
Disturbed tone, gait, reflexes
Uncommon and late
Most prominent feature
Basal ganglia signs and symptoms
Present
Absent
Retinitis pigmentosa
May or may not be present
Absent
Imaging (preferably MRI)
Identifies cortical atrophy,

Good for diseases of basal ganglia,
cerebellar atrophies and mitochondrial disorders
Good diagnostic yield for white matter

disease, demyelinations
Electro retinogram (ERG)

VER
BERA
May be abnormal (NCL)

Usually normal
Normal
Abnormal BERA, Amp of V, Wave III-IV,
interpeak latency

ganglia changes are seen in Wilson, mitochondrial
disorders, Fahrs syndrome, migration disorders etc.
Nonspecific atrophy is a common observation.
Choice of Investigations
Gray matter disease: Bone marrow for storage cells; arterial
blood CSF lactate and pyruvate for organic aciduria inborn
errors of metabolism, mitochondrial disorders; urine
copper, serum ceruloplasmin in suspected Wilson disease;
hair microscopy; skin conjunctival, rectal biopsy or
lymphocytes; enzyme analysis in leukocytes, skin
fibroblasts or tissuelysosomal storage disease; urine
oligosaccharides, skeletal survey and specific lysosomal
enzymes; CSF antimeasles antibodies for SSPE; HIV.
White matter disease: Urinary metachromatic granules,
arylsulfatase A, B and C in parents and patients, conduction
velocity in peripheral motor and sensory nerves; plasmavery long chain fatty acids (VLCFA) for
adrenoleukodystrophy; N-acetyl aspartic acid in urine for
Canavan disease; galactosylceramidase for Krabbe disease.
White matter changes are generalized in metachromatic leukodystrophy and infantile form of Krabbes
disease. The X-linked variety of leukodystrophy called
455
adrenoleukodystrophy has white matter changes that are

more marked round the occipital horns. Evoked responses
visual and brainstem auditory evoked responseprovide
help in distinguishing gray and white matter disorders.
Gray matter storage diseases may be identified by specific
vacuoles in circulating lymphocytes and bone marrow.
Macular changes in the eye, identification of abnormal
storage material in the brain, rectal ganglia, bone marrow
and various organs are useful clues. Leukodystrophies
may reveal abnormal myelin and staining patterns in the
Schwann cells, in peripheral nerves, and in the urinary
sediment in metachromatic leukodystrophy. Enzyme
determinations from white blood cells and fibroblast are
useful to identify etiology of degenerative brain diseases
definitively.
Treatment
Most of them can only be managed symptomatically as
course is relentless. Specific treatment is present only in a
few conditions, e.g. Wilson disease, adrenoleukodystrophy, Leigh disease, Menkes disease. SSPE and HIV.
Enzyme replacement (Gaucher disease) and gene therapy
are possible approaches to treatment.
10.4 Seizure Disorders in Children

Veena Kalra
A seizure is defined as a sudden, paroxysmal electrical
discharge from the central nervous system resulting in
involuntary, motor, sensory or autonomic disturbances
with or without alteration in sensorium. It is a common
symptom in childhood practice. The manifestation of the
seizure depends upon the threshold of the brain to manifest
a clinical seizure. The age and neurodevelopmental
maturity status determine the clinical manifestations and
type of seizure disorders encountered.
Magnitude
Almost 5 percent of children are at risk of experiencing a
seizure. Half of them encounter the first seizure in infancy.
Prevalence is greater in the neonatal period (almost 1% in
term and 20% in preterm). In infancy, febrile convulsions
are the most frequent form.
Etiology
Seizures can be provoked by intercurrent events like
dyselectrolytemia, hypoglycemia, hypocalcemia, hypoxia
and other metabolic disturbances. Common causes of
childhood seizures are listed in Table 10.4.1.
EPILEPSY
It is important to identify provoked seizures as they may
not require long-term anticonvulsant treatment. Seizures
unprovoked when recurrent, are termed, epilepsy. Seizures
may be classified according to: (i) the age at which they
present (neonatal seizures, seizures of infancy, seizures
occurring in childhood), (ii) the type of seizure (generalized or partial), and (iii) underlying etiology (idiopathic
or symptomatic).
456
TABLE 10.4.1: Common causes of childhood seizures

Simple febrile convulsions
Infections of the central nervous system
(i) Acquired bacterial meningitis, tuberculous meningitis, aseptic
meningitis, encephalitis, cerebral malaria, tetanus, mumps encephalopathy, measles encephalopathy and Reye's syndrome.
(ii) Intrauterine infections.
Postinfectious or postvaccinal encephalopathy
Following pertussis vaccination, subacute sclerosing panencephalitis, postmeasles encephalopathy and chickenpox encephalopathy, disseminated encephalomyelopathy.
Metabolic causes
Dehydration, dyselectrolytemia, acidosis, alkalosis, hypocalcemia,
hypomagnesemia and inborn errors of metabolism.
Space occupying lesions in the brain
Neoplasm, brain abscess, tuberculoma, cysticercosis.
Vascular
Arteriovenous malformations, intracranial thrombosis or hemorrhage
and consumptive coagulopathies.
Congenital malformations, migration defects.
Miscellaneous causes
Residua of birth trauma and birth asphyxia, heat stroke, acute brain
swelling, poisoning, lead encephalopathy, hypertensive
encephalopathy, breath holding spells, gray matter degeneration
and storage disorders.
Drugs and poisons
Toxic doses of phenothiazine, salicylate, diphenylhydantoin,
strychnine, carbon monoxide etc.
of spread from one hemisphere to the other is well-known.

Unifocal or multifocal seizures present as rhythmic muscle
movements involving one or multiple parts of the body
without Jacksonian march. Tonic seizures are characterized by extension of extremities and axial muscles.
These may occur in the absence of cortical discharges.
Presence of eye signs provide clue to their epileptic nature.
Myoclonic seizures are uncommon, may be erratic and
often coexist with other seizures. Clonic seizures are
uncommon in neonates.
Diagnosis of neonatal seizures requires a high
index of suspicion and knowledge about their varied
patterns. They may be confused with conditions like
jitteriness, apneic attacks, tremors and benign sleep
movements.
The EEG in neonates is an important diagnostic tool.
It may help to identify a seizure from a non-seizure state.
In neonates, all clinical seizures may not be associated
with EEG discharges because many events are subcortical.
The background activity varies with gestational age and
distinctly different patterns are observed at various
gestational ages. In neonatal seizures, discharges are not
as well defined and may be quite polymorphic. In
premature infants, the EEG findings tend to be more
stereotyped and spikes are uncommon.
Etiology
Major etiological groups of neonatal seizures are indicated in Table 10.4.2.
Management
NEONATAL SEIZURES
Neonatal seizures are distinct from seizures occurring in
childhood. Incomplete myelination, lack of neurotransmitter, poor spread of epileptiform discharge and
lack of brain maturation result in atypical and poorly
organized seizures in the newborn. The etiology,
management, utility of investigations, choice and duration
of anticonvulsant therapy are also distinct in the newborn
period.
Management of neonatal seizures includes exclusion of

metabolic causes peculiar to this age by routine blood
testing for glucose, calcium, electrolytes and magnesium
and also exclusion of hypoxic, infective, neurometabolic
TABLE 10.4.2: Major etiological groups of neonatal seizures
Clinical Profile
In the neonatal period, seizures may be atypical, bizarre,
and fragmentary. They are subtle and may present as
episodes of grimacing, blinking, frothing or apneic spells.
All of these may be missed, if the clinician is not alert. The
absence of generalized tonic-clonic seizures and the failure
Hypoxic ischemic encephalopathy, birth trauma

Intracranial hemorrhage
Metabolichypoglycemia, hypocalcemia (early/late onset),
hypomagnesemia, pyridoxine dependency and deficiency, inborn
errors of metabolism of amino acids, carbohydrate metabolism,
organic acids and urea cycle
Structural malformations
Infections, bacterial meningitis, intrauterine infections, brain
abscesses, septicemia
Drug withdrawalsedatives, anticonvulsants, narcotics
Genetic/familial
Miscellaneous, unknown

pathology. Other metabolic causes should be simultaneously investigated. Therapy algorithm should include
0.5 gm/kg IV of 10 percent dextrose followed by 5 ml/kg
of 5 percent calcium gluconate IV to control seizures. If no
response, then phenobarbitone in a dose of 20 mg/kg of
IV may be given. Diazepam in a dose of 0.3 mg/kg of IV
should be used for immediate control of seizures only.
The subsequent therapy depends on the cause identified.
Neonates with hypoglycemia or hypocalcemia should
receive appropriate metabolic correction and maintenance
therapy.
Maintenance Therapy
Neonates with nonmetabolic seizures, or metabolic
seizures that fail to respond to calcium, glucose,
magnesium require anticonvulsant drug maintenance
therapy. Phenobarbitone in a dose of 3 to 5 mg/kg/day in
1 to 2 divided doses is the preferred anticonvulsant in
neonates. The duration of therapy is variable depending
on normalcy of neurodevelopment, seizure control;
usually 3 months is enough. Therapy may need to be
prolonged up to 2 years if seizures remain uncontrolled
or depending upon the cause identified and presence of

brain damage.
SEIZURES OF INFANCY AND CHILDHOOD
Seizures of infancy and childhood commonly include

Febrile convulsions
Infantile spasms
Age dependent epileptic syndromes (Refer Table
10.4.3)
Seizures due to other causes.
FEBRILE SEIZURES
Febrile convulsions are generalized, tonic-clonic, brief and
self-limited events that occur in the presence of fever and
in absence of underlying neurological diseases. They
generally occur between 6 months to 5 years of age, rarely
last more than 15 minutes. Permanent sequelae are
uncommon. A genetic predisposition is often observed.
They may be classified as simple or complex febrile
seizures. Patients who transgress the above mentioned
criteria are termed complex febrile seizures. Risk of
subsequent afebrile seizures, partial complex seizures or
epilepsy is enhanced if the seizures were atypical,
TABLE 10.4.3: Classification of epilepsy

Generalized
Generalized epilepsy may be
i. Tonic-clonic (grand mal)
ii. Tonic, clonic
iii. Absence, petit mal
iv. Atonic, akinetic (minor motor) or
v. Bilateral epileptic myoclonus.
Syndromes
Idiopathic age related
i. Benign neonatal convulsions
ii. Childhood absence
iii. Juvenile absence
iv. Grand mal seizures on awakening
v. Generalized idiopathic
Cryptogenic
i. West syndrome (infantile spasms)
ii. Lennox-Gastaut syndrome,
epileptic encephalopathies
iii. Myoclonic astatic seizures
iv. Myoclonic absences.
457
i.
ii.
i.
ii.
iii.
i.
ii.
iii.
Undetermined syndromes
i. Neonatal seizures
ii. Severe myoclonic epilepsy of infancy
iii. Epilepsy with continuous spike waves during slow wave sleep
iv.
Acquired epileptic aphasia.
Localized
Simple partial with elementary
sympotms and no impairment
of consciousness with
a. motor, b. sensory, c. autonomic, or
d. mixed symptoms.
Complex partial seizures may be associated with
automatisms and impaired consciousness.
Syndromes
Benign childhood focal epilepsy
with centrotemporal spikes or Rolendic epilepsy
Epilepsy with occipital paroxysms
Juvenile myoclonic epilepsy, etc.
Symptomatic
Chronic progressive epilepsy
Epilepsia partialis continua.
Seizures with temporal, frontal,
parietal or occipital lobe mode
of presentations.
458
associated with neurodevelopmental delay, family history

of epilepsy, etc. Interictal EEG abnormalities are observed
in a small proportion.
Role of Lumbar Puncture
A diagnostic lumbar puncture is indicated if a neuroinfection is suspected or in infants experiencing the first
episode of febrile seizures within the first year. In recurrent febrile seizures, a lumbar puncture is not necessary.
Any febrile illness with temperature more than 38C
can precipitate a seizure. The quickness of rise of temperature is an important factor. Certain fevers have greater
predilection to precipitate a convulsion. Most febrile
seizures occur within the first 2 to 3 days of fever. A genetic
predisposition is strongly observed. The empiric risk of
febrile seizure after one affected child is 10 percent; it rises
to almost 50 percent if one parent had febrile seizure. Most
studies suggest a dominant mode of inheritance with
reduced penetration.
Presence of abnormal neurodevelopment, family
history of epilepsy or persistent neurological deficit should
arouse suspicion of a more sinister process. Subsequent
febrile seizures and epilepsy in later years are more
common in this group, and continuous prophylaxis may
become necessary.
Treatment of a Febrile Convulsion
This includes treatment of fever, management of the acute
episode and prophylaxis against future recurrence.
Treatment of the acute fever includes frequent monitoring
of temperature, use of antipyretics, and hydrotherapy.
Control of seizures can be achieved with diazepam,
lorazepam, etc. Acute treatment involves use of diazepam
by the intrarectal or intravenous route in a dose of 0.3 mg/
kg/dose.
Prophylaxis Against Recurrences
Prophylaxis may be intermittent, during acute febrile
episodes or continuous prophylaxis with anticonvulsant
drugs if intermittent prophylaxis fails and risk factors
suggest possibility of future epilepsy.
Intermittent Prophylaxis
Febrile convulsions are best prevented by intermittent
prophylaxis with diazepam or lorazepam. A solution of
diazepam in a dose of 0.3 mg/kg given twice to thrice daily
for the first 3 days of fever is currently recommended. It

reduces seizure recurrence risk by almost 80 percent. The
benefit is comparable to that observed by continuous daily
prophylaxis with either phenobarbitone or sodium
valproate. The added advantage is reduction of side effects.
The long-term benefit on subsequent afebrile seizures is not
clearly known. Studies with oral intermittent medication
with lorazepam, clonazepam or clobazan suggest similar
benefit. Lorazepam may be better because of longer duration
of action and less sedation.
Continuous Prophylaxis
Phenobarbitone in a dose of 3 to 5 mg/kg/day was the
conventional practice. It reduced recurrence by 80 percent.
Side effects like learning disabilities and hyperactivity were
encountered in almost 20 percent making it an
unacceptable initial choice. Sodium valproate is equally
effective. Phenytoin and carbamazepine have no proven
benefit for febrile convulsion prophylaxis.
The optimal duration of treatment is at least one year
seizure-free or till the age of 5 years. Continuous
prophylaxis may be reserved for patients who do not
respond to intermittent prophylaxis, or have associated
mental retardation, presence of atypical complex febrile
seizures and family history of epilepsy. The choice of
intermittent or continuous prophylaxis should be
individualized on patient's risk factors and acceptance of
occasional febrile seizures.
INFANTILE SPASMS, WESTS SYNDROME
Infantile spasms (Salam seizures) refer to massive brief
flexion or extension spasms that occur usually in early
infancy. They occur in clusters either before sleeping or
during early waking hours. The contractions are often
severe and may be few to several hundreds in a day.
Neurodevelopmental retardation may be present before
or may follow. They occur in early infancy and are often
refractory to the standard anticonvulsant drugs. On followup, the spasms either stop completely, continue to occur
or change their pattern and frequency. Most of the patients
have variable degrees of mental and developmental
retardation. The EEG has a chaotic background with spikes
and slow waves. The spikes often exceed 200 microvolts
hypsarrhythmia. In certain variants, a definite slow wave
background is observed. The outcome in these categories
is often worse.

Etiology
It may be idiopathic, cytogenic or symptomatic. A wide
variety of pre-, peri- and postnatal insults are implicated.
The most frequent associations include hypoxic ischemic
encephalopathy (HIE), intrauterine infections, extreme low
birth weight, structural/migration defects and genetic
syndromes. Cardiorespiratory arrest and neurometabolic
defects have also been implicated. Neuroectodermatosis is
an important entity to exclude. The correlation between
infantile spasms and vaccines particularly do not indicate
any etiological role of the latter. It is probably an age coincidence of two independent factors.
Management
Infantile spasms often respond to use of ACTH or corticosteroids. The dose and schedule of use is not
unanimously accepted. A course of 2 to 12 weeks is
recommended. ACTH gel, 40 units intramuscularly daily
for first two weeks followed by decreasing frequency of
injections up to 12 weeks appears a rational choice. Oral
corticosteroids produce almost similar benefit, at lesser
cost. Pyridoxine is found useful in a few selected patients.
Anticonvulsant drugs like phenobarbitone, carbamazepine, and phenytoin are usually ineffective. Valproic
acid and benzodiazepines including clonazepam,
clobazam, and nitrazepam are useful. Vigabatrine is
emerging as a good initial choice in intractable infantile
spasms and especially in spasms due to tuberous sclerosis.
Coexistence of other seizure types warrants use of other
antiepileptic drugs.
The outcome frequently depends upon etiology and
symptomatic cases have a worse prognosis. Some patients
are quite intractable. Delayed development and mental
retardation are commonly observed in children with
infantile spasms. On follow-up, other types of seizures
may be observed.
EPILEPSY IN CHILDHOOD
Epilepsy can be defined as recurrent seizures of neurological origin. It may be idiopathic, symptomatic or
cryptogenic. Epilepsy is essentially a clinical diagnosis; a
careful, detailed, sequential account of fits remains the
cornerstone of diagnosis. A clear witnessed account is
extremely useful. Clinical examination should include
detection of neurological signs, focal deficits, raised
intracranial pressure, stigmata of neurocutaneous syndromes, neurometabolic disorders, systemic abnormalities
and dysmorphic features. Hyperventilation test should
be done if absence attacks are suspected.
459
Childhood epilepsy is a frequently misdiagnosed

condition. It is confused with breath holding spells, night
terrors, syncopes, vasovagal attacks and cyanotic spells.
Childhood epilepsy can be classified as indicated in
Table 10.4.3 and may occur due to a variety of etiological
factors.
Almost all structural malformations, mental retardation, delayed neurodevelopment, gray/white matter
diseases, neurometabolic disorders and some systemic
diseases may produce epileptic fits. Besides, neuroinfections, neuroinfestations (Taenia solium), migration
abnormalities also result in convulsions. Aftermath of
acute infections, hypoxic states and delayed neurodevelopment states are frequent causes. Drugs, toxins, lead
poisoning and organ failures may all produce seizures.
Investigations
Investigations aim to confirm the occurrence of a convulsion, distinguish it from nonconvulsive states and
establish the cause. Important investigations include the
following:
1. Electroencephalography: EEG helps to document
paroxysmal electrical dysrhythmias, to lateralize or
localize underlying structural lesions and determine the
background rhythm. It is also useful in classification of
epilepsy and epileptic syndromes in childhood.
2. Video EEG helps to correlate clinical ictus with EEG
and also record interictal events. It has utility in presurgical work-up of epilepsy patients and also in distinguishing true from pseudoseizures.
3. Imaging techniques are indicated to identify a possible
underlying anatomical lesion especially in partial seizures,
seizures with focal neurological deficits and raised
intracranial pressure. Magnetic resonance imaging is
superior in identifying structural and migration defects.
Functional scans now available include PET, SPECT,
HmPAO, etc. These help in identifying hypo- and
hypermetabolic zones and correlate functional changes
with anatomic imaging.
4. Specific tests to exclude metabolic causes include blood
sugar, calcium, arterial pH, plasma amino acid screen,
and ammonia.
PRINCIPLES OF ANTICONVULSANT THERAPY
The ideal goal in the treatment of epilepsy is complete
control. If this is not attainable then a reduction in
frequency with minimal side effects is the desired goal.
The following broad principles are useful.
460
Identify the existence of seizures and its type accurately so that proper drug can be selected.
Initiate treatment with a single drug, which is least
toxic, easy to handle, acceptable and economically
affordable. Change to an alternate single drug before
trying polytherapy.
Increase the dosage to maximum tolerated level or
optimal blood concentration before adding a second
drug.
Achieve a steady state of the drug by using at least
4 to 5 times the half life of dose.
Choice of drug in various types of seizures, are indicated in Table 10.4.4. Drug doses and the number of daily
doses should be determined by the half life of the
drug.
Blood levels are not routinely required. They are useful
to check compliance, to determine change in doses of
drugs and to confirm suspected toxicity.
Regularity and compliance is the pillar of success of
epilepsy therapy.
Duration of therapy needs to be individualized as there
is no unanimity in literature. Seizures that are easily
TABLE 10.4.4: Antiepileptic drugs in childhood epilepsy

Drug-preparation
Indications
Dose
Half-life
Side effects
Carbamazepine (tab) 100,

200, 400 mg (slow release
preparations)
Partial, tonicclonic, atonic,

akinetic
1030 mg/kg/day.
Start with low doses
1318 hr
Sodium valproate 5 ml
200 mg and 200, 500 mg
tablets.
Broad spectrum
2030 (up to 80)

mg/kg/day in 3
divided doses
710 hr
Relatively safe. Gastrointestinal

symptoms, hepatitis, skin rash, bone
marrow depression (initial phase
only).
Nausea, vomiting, sedation, weight
gain, and hair loss.
Idiosyncratic/toxic hepatic damage;
potentiates sedatives and,
barbiturates.
5 mg/kg single
daily dose
2080 hr
Drowsiness, hyperkinesia,
dependency
Phenobarbitone 15,30,60 mg Tonic-clonic,

tablets
akinetic, partial,
febrile, seizures
Diphenylhydantoin
(Dilatin, Eptoin)
100 mg tablets
Tonic-clonic, atonic- 5 mg/kg in one or

akinetic
two divided doses
up to 20 hr
Hirsutism, gum hyperplasia. Skin

rash, rickets, megaloblastic anemia.
Toxic symptomsnystagmus,
ataxia, diplopia, drowsiness,
increased seizures.
Ethosuximide (Zarontin)
syrup, 250 mg/ml
Absence attacks
2025 mg/kg in two

divided doses
430 hr
Photophobia, decreased
WBC, nephrosis, rarely
blood dyscrasia.
ACTH gel Inj.

(Synacthen)
Myoclonus, Wests
syndrome
2040100 units/
day for 46 weeks.
Taper dose over 3
months.
Prednisolone
Myoclonus
2 mg/kg/day
Nitrazepam 5,10 mg
tablets
Myoclonus
adjunctive therapy.
0.5 mg/kg/day in 2
divided doses
Excessive sleep, salivation,

hypotonia, ataxia
Clonazepam (Rivotril)
0.5, 1 and 2 mg tablets
Atonic, akinetic
Mixed absence
adjunctive
0.030.1 mg/kg/day
in 3 divided doses
Somnolence, hypotonia,
hypersalivation
Clobazam (Frisium)
5, 10 mg tablets
Add-on drug forMyoclonus, partial

seizures, generalized seizures
0.5 mg/kg/day
Hypercortisolism. Tendency to
infections.
Long. Single daily

dose
Less than other benzodiazepines.

controlled, without underlying structural lesion, neurological deficit or mental retardation generally need a 2 to 3
years seizure-free course. Seizures that are intractable,
juvenile myoclonic epilepsies, seizures in retarded
children and post-traumatic seizures merit long-term
anticonvulsants. Inflammatory granulomas (neurocysticercosis) may not require long-term anticonvulsants.
Almost 80 percent of childhood epilepsies respond to
conventional antiepileptic drugs if the appropriate agent
is used optimally. Careful appraisal and re-evaluation is
necessary in the intractable patients.
In such patients, there is a role of newer antiepileptic
drugs. With greater precision in identification of anatomical sites and improved surgical techniques, epilepsy
surgery is gaining a more important place.
Guidelines regarding choice of antiepileptic drugs in
childhood epilepsy are depicted in Table 10.4.4.
Prognosis
Once the diagnosis is made and treatment initiated it is
imperative to stress regularity of treatment. Drug dosage
may be adjusted as per requirement. The possible need of
other anticonvulsants during course of therapy should be
explained. A seizure-free period of 2 to 3 years is considered
adequate and therapy may be gradually tapered over 3
months. Prolonged therapy more than 3 years is required
if seizures have tendency to recur. Recurrence risk is higher
if onset of epilepsy is early, seizures are difficult to control,
seizures are associated with mental retardation or neurological deficit, and certain specific types of epilepsies. The
prognosis of childhood epilepsy in the rest is good. A
normal lifestyle should be encouraged and optimism in
parental attitude fostered.
STATUS EPILEPTICUS
Status epilepticus is defined as persistence of a seizure for
more than 10 minutes or recurrent seizures without gain
of consciousness. It is a common neurologic emergency.
Prompt medical treatment is required to reduce mortality
and limit the morbidity that accompanies it as a result of
irreversible cerebral damage.
Status epilepticus may occur as a first presentation of
a seizure disorder in the lifespan of epilepsy or
neurologically ill patients, or due to intercurrent illnesses
like inflammatory, traumatic, hypoxic or metabolic causes.
Drug withdrawal is an important precipitant. The cause
may remain undiagnosed. Persistent and prolonged
461
seizure activity causes cerebral edema, hypoxia,

hyperthermia, hypoglycemia and vasomotor instability.
Respiratory depression may ensue from involvement of
respiratory center, or from drugs used for seizure control.
Vomiting and aspiration of secretions also increase
morbidity. Treatment should take precedence over
investigation of cause.
Management
Patients should ideally be hospitalized, an intravenous
line established with 10 percent dextrose and diazepam
0.3 mg/kg given intravenously. It is lipophilic, crosses
the blood-brain barrier and has a quick onset of action by
potentiating the GABA pathways at the postsynaptic
cortical receptors. If seizures do not stop within 5 minutes,
a second dose may be repeated. The half-life is short and
seizures may recur. The more preferred benzodiazepines
include lorazepam 0.1 mg/kg and have added advantage
of prolonged duration of action. Midazolam can also be
used, and it causes lesser respiratory depression. The
benzodiazepines should be followed by intravenous
phenytoin in a dose of 20 mg/kg to maintain prolonged
seizure control. Rate of administration should not exceed
1 mg/kg/minute. If seizures remain uncontrolled,
phenobarbitone 20 mg/kg/intravenous may be used at a
rate of 1 mg/kg/minute.
Intravenous dextrose, mannitol to reduce brain edema,
care of body temperature and prevention of aspiration
and injury are additional measures that should be
attended to.
Noncontrol of seizures with the above regimen of
therapy necessitates other aggressive approaches. The
choice depends on availability of drugs, ventilatory
support and monitoring facilities. Diazepam infusion in
a dose of 0.01 mg/kg /minute may be used in gradually
increasing dose till a maximum of 0.03 mg/kg/minute or
till seizure control. Maintain a seizure-free state for 1012
hours following which the dose may be tapered.
Midazolam infusion, may be used alternatively.
Thiopental 4 mg/kg intravenously or as a slow infusion
may be used till seizure control. Ventilatory
support, respiratory and hemodynamic monitoring are
essential.
Mortality and sequelae are determined by etiology of
status epilepticus, adequacy and promptness of therapy
and presence of secondary complications. Mortality ranges
from 10 to 18 percent and morbidity is even higher.
462
10.5 Infections of the Central

Nervous System
Veena Kalra
Infections of the central nervous system are fairly common
in pediatric practice. The clinical profile is protean. A high
index of suspicion of the treating physician is essential to
make an early diagnosis. The need for early diagnosis is
imperative. Potent antibiotics have reduced mortality, but
do not prevent sequelae specially if therapy is delayed.
The newer rapid diagnostic tests and imaging modalities
have improved holistic management of children with
neuroinfections.
Infections of the central nervous system can be broadly
classified into:
Meningitisacute, subacute or chronic
Encephalitis and infective encephalopathy
Cerebral abscess, granulomas, parasitic infestations
Miscellaneous
TABLE 10.5.1: Etiology agents and initial empiric antimicrobial

regimens for bacterial meningitis in various age groups
Age group
Common bacterial
pathogens
Initial antibiotic
regimens
Newborn
Escherichia coli
Klebsiella pneumoniae
Listeria monocytogenes
Enterococcus sp.
Salmonella sp.
Ampicillin plus
aminoglycoside
or cefotaxime
412 weeks
H. influenzae
S. pneumoniae
Group B Streptococcus
Listeria monocytogenes
Ampicillin plus either

cefotaxime
or ceftriaxone
12 weeks
and older
H. influenzae
S. pneumoniae
N. meningitidis
Ceftriaxone or
cefotaxime or
ampicillin plus
chloramphenicol
MENINGITIS
Meningitis may be:
a. AcuteBacterial, viral
b. Subacute or chronicTuberculosis, fungal, parasitic,
neoplastic, and chemical.
c. Partially treated
Etiology
Common etiologic agents of acute bacterial meningitis
vary with age (Table 10.5.1).
Acute bacterial meningitis, a major cause of morbidity
and mortality in young children, occurs both in epidemic
and sporadic pattern. It may follow septicemia, apparently
trivial illness such as upper respiratory tract infections,
otitis media, pyoderma and minor head trauma. Patients
with diminished host resistance as in diabetes mellitus,
malignancies and patients on immunosuppressive drugs
are more susceptible to develop meningitis.
The World Health Organization (WHO) has estimated
that annually bacterial meningilis causes at least 1.2
million cases worldwide and of those 135,000 deaths.
Neisseria meningitides, Hemophilus influenzae type b (Hib)
and Streptococcus pneumouiae are the triad responsisble for
more than 80 percent of all cases.
Bacterial Meningitis
Bacterial meningitis in the postneonatal age is commonly
caused by N. meningitidis, Streptococcus pneumoniae and H.
influenzae. However, any organism can produce
meningitis. Patients with VP shunt, prolonged hospital
stay, immunocompromised hosts, post-lumbar puncture
or post-trauma patients may have diverse etiology. While
most of the meningitis occurs in sporadic pattern,
epidemics are reported most frequently with H. influenzae
and N. meningitidis.
Bacterial meningitis may follow septicemia, or a septic
focus in the skin, lungs or bones. Trauma, pilonidal sinus,
fracture base of skull, neural tube defects, suppurative ear
and mastoid foci are recognized predisposing causes and
should always be examined for, specially in recurrent
meningitis.
Pathogenesis
The infections spread hematogenously to meninges from
the distant foci of sepsis such as pneumonia, empyema,
pyoderma and osteomyelitis or by contiguous spread.

Trivial head trauma and bacterial sepsis are important causes.
The leptomeninges are inflammed, and exudation
occurs in the subarachnoid space and cisterns. Inflammatory cells are seen in the meninges over the cortex and
perivascularly. The exudates may obstruct CSF flow and
the vascular flow may be compromised by the perivascular
reaction. Cerebral edema may occur (Fig. 10.5.1).
Clinical Features
The onset is usually acute and characterized by irritability, excessive crying, vomiting, headache, neck pain or
stiffness in older children. Patients are usually febrile and
have constitutional symptoms. Alteration in sensorium is
usually not profound, and respiration may be altered. A
full anterior fontanel in a non-crying child is suggestive
of associated raised intracranial pressure. Fundus may
confirm optic disc congestion or papilledema. Seizures
are a common symptom and may occur in early or late
463
phase of the disease. This early seizures may be confused

with febrile seizures, particularly in infancy. Late seizures
usually imply secondary cerebral vascular or other
complications, specially if they are focal. Meningeal signs
include neck stiffness, Kernig's or Brudzinski sign.
Kernig's sign is elicited by flexing the hip of the patient to
90 and also flexing the knee and then extending the knee
beyond 135, which evokes pain in the limb and limitation
of knee extension. Other features including cranial nerve
palsies, seizures, focal deficits, along with increased tone
and brisk reflexes may also be present.
Patients with meningitis should be examined for
evidence of septicemia, pneumonia, suppurative focus, or
septic foci of skin, suggestive of a Staphylococcus meningitis.
Hemorrhagic rash on the skin and hypotension or features
of shock are suggestive of meningococcal meningitis. In
meningococcal meningitis, the child develops an acute
fulminating illness, shock, hypotension, coma and even
death, unless aggressive therapy is given. Presence of
pneumonia or periotitic pathology points to a
pneumococcal etiology.
Clinical features of meningitis may remain masked in
certain situations like severe protein energy malnutrition,
immunocompromised states, malignancies and prolonged
corticosteroid therapy.
Meningitis in neonates: Bacterial meningitis in the
newborn is often asymptomatic or may have subtle clinical
features. It is a common accompaniment of septicemia and
should be suspected in every sick neonate. A lumbar
puncture is essential to rule out meningitis. The features
that should arouse suspicion are irritability, excessive
crying, vomiting, headache, neck pain or stiffness. Presence
of fever, or seizures are suggestive.
Investigations
Figure 10.5.1: Pathophysiology of bacterial meningitis
A lumbar puncture is the single most informative test and is

mandatory where meningitis is a diagnostic possibility.
The contraindications include local skin sepsis and raised
intracranial pressure. In the event of raised intracranial
pressure, the lumbar puncture should be preceded by a
bolus of mannitol. Ideally, lumbar puncture should
evaluate opening pressure of the CSF. Cell count should
be performed within 30 minutes. Differential count of the
type of cells must be done on a stained slide and not on a
chamber while counting the cells in the CSF. Blood sugar
should be taken before performing lumbar puncture, as
the CSF sugar correlates best with blood sugar taken before
the LP. CSF biochemistry should include estimation of
464
glucose and protein. Gram's and other appropriate stains,

and bacterial, viral or other appropriate cultures of CSF,
and blood should also be performed as early as possible.
In acute bacterial meningitis, grossly the CSF is often
turbid and has elevated cell counts, usually in 100's and
cells are mostly polymorphonuclear. Sugar is significantly
reduced and is often below 50 percent of the blood sugar.
Protein is elevated and Gram stain may be positive. Culture
yield can be increased by direct plating of the CSF on
culture media. Gram stain yield can be increased by
centrifuging the CSF.
The rapid diagnostic tests available to detect common
bacterial antigens include latex agglutination,
countercurrent immunoelectrophoresis or coagglutination
tests. These tests carry a sensitivity varying from 65 to 85
percent. The main advantages are that pre-treatment with
antibiotics does not alter the positivity of these and the
results are available quickly. Of these, latex agglutination
test is the most preferred. Another nonspecific test includes
C-reactive protein in CSF. This is raised in the acute phase
of acute bacterial meningitis to a greater extent, than in
viral or chronic meningitis. All these tests may help to
differentiate acute bacterial meningitis from other
etiologies. Polymerase chain reaction is being
increasingly used to detect the etiology of acute and
chronic meningitis.
Neuroimaging is useful in acute bacterial meningitis
to exclude complications like subdural effusion, brain
abscess, hydrocephalus, infarcts and identify presence
of meningeal exudates. It need not be performed in all
patients with bacterial meningitis. Ultrasound is useful
in neonates and infants with bacterial meningitis, for
determination of ventricular size and to serially
evaluate ventricular size and debris, if ventriculitis is
suspected.
Therapy
Therapy of meningitis should be prompt and be initiated
even before a definitive diagnosis is established. A lumbar
puncture with suggestive CSF cytology and Gram stain is
enough to initiate treatment.
General care It includes identification and management
of shock, cerebral edema, seizures and fluid imbalance.
Shock should be treated with fluids, and vasopressors;
respiratory resuscitation may be required. Electrolyte
imbalance may occur due to vomiting and inappropriate
secretion of anti-diuretic hormone (SIADH). Though

SIADH requires fluid restriction, management of shock
should take precedence in management, till circulatory
homeostasis is established. Increased intracranial pressure
should be treated with intravenous mannitol, given in a
dose of 1 g/kg as a 20 percent solution. The administration
should be rapid, within 20 minutes and may be repeated
every 4 to 6 hours. Therapy is usually not required beyond
24 to 48 hours. Anticonvulsant drugs are indicated, if
seizures are present. In the acute phase, diazepam 0.3
mg/kg may be given intravenously. Subsequently,
phenytoin may be given for its prolonged anticonvulsant
effect, and less influence on sensorium permitting better
evaluation of the patient. Prolonged anticonvulsant drug
use is not indicated, if seizures occurred in the early phase
of meningitis and were non-recurrent. In seizures that
occur late in the course of therapy, their causes may be
associated subdural effusion, infarct, abscess, etc.
requiring longer duration of anticonvulsant therapy.
Antimicrobial Therapy
Initial antimicrobial therapy has to be empiric, as early
treatment is essential in meningitis even before a
bacteriologic diagnosis is established. The choice of agents
depend upon the frequency of bacterial pathogen at a
particular age or in the peculiar setting, e.g. epidemic
meningitis. A rational choice based on frequency of
bacterial pathogens is indicated in Table 10.5.1.
Subsequent changes in antibiotic regime may be made
depending upon the bacterial pathogens identified or their
sensitivity patterns or clinical non-response as evidenced
by persistence of fever, meningeal signs, fresh neurological
signs, worsening sensorium or lack of CSF response.
Ampicillin is an important drug for regimes against
meningitis, specially in the first 3 months of life because
of its penetration across blood-brain barrier, and frequency
of gram-negative organisms. It should be given
intravenously in a dose of 200 to 300 mg/kg/day.
Ampicillin should be combined with an aminoglycoside
for neonatal meningitis or with third generation
cephalosporin like cefotaxime or ceftriaxone. Beyond 3
months of age, the conventionally used combination of
ampicillin and chloramphenicol is probably inferior to
the use of cefotaxime or ceftriaxone as a single drug for
meningitis. The latter should be preferred except, if
economic constraints prevent their use. Penicillin in a dose
of 3 mega units/kg/day given every 4 hours, is a good

choice for meningococcal meningitis and during its
epidemics. Meningitis with Staphylococcus, and
Pseudomonas may require specific agents like vancomycin,
and a combination of ceftazidime and aminoglycosides
respectively. Vancomycin has role in therapy of penicillinresistant and cephalosporinresistant meningitis. It is
best used in combination with a third generation
cephalosporin.
The duration of therapy for meningitis is generally 10
to 14 days. Resistant gram-negative organisms, staphylococcal meningitis may require longer course of treatment
up to 4 to 6 weeks. Meningococcal meningitis requires a
shorter regimen. Disappearance of clinical features,
defervescence and acceptable limits of cyto-biochemistry
of CSF should be attained before stopping the therapy.
Repeat lumbar punctures are indicated after 48 hours of
therapy, to look for cytobiochemical improvement and
bacteriological sterilization.
Dexamethasone Therapy
Studies have suggested benefit from dexamethasone in a
dose 0.15 mg/kg/6 hourly for 4 days in certain pyogenic
meningitis. The dose should be administered
intravenously 15 minutes, before the first parenteral
antibiotic dose. It results in reduction of hearing
impairment, specially after H. influenzae infections. The
benefit is mediated through reduction in cytokine mediated
inflammatory damage.
Patients with nonresponse of clinical signs, persistent
fever, recurrent seizures, focal deficits, persistent ICP rise
or vascular episodes merit detailed investigations
including CT imaging. The CT imaging helps to exclude
subdural effusion, cerebral abscess, infarct, ventriculomegaly and other complications.
Outcome
Acute complications include nonresolution of meningitis,
persistence of fever, subdural effusion, abscess, infarcts,
ventriculomegaly, hydrocephalus, ventriculitis, focal
neurological deficit or hearing impairment. A careful
examination including evaluation of hearing should be
conducted before discharge. Antibiotics have certainly
improved survival, but patients may have sequelae of the
disease in almost 30 percent. Common sequelae include
delayed development, mental retardation, hearing loss,
focal motor abnormalities like hemiplegia, cranial nerve
palsies and seizures.
465
Differential diagnosis should include the following:
Meningism
Partially treated meningitis
Acute viral and aseptic meningitis
Acute encephalitis
Subacute meningoencephalitis
PARTIALLY TREATED MENINGITIS
Antibiotic therapy, given to treat meningitis or inadvertently for other suspected infections, is known to alter the
clinical picture and cerebrospinal fluid parameters in
patients with meningitis. Adequate, intravenous
antibiotics render the CSF sterile in less than 24 hours,
alter the nature of cellular response from polymorphonuclear to lymphocytic predominance, reduce the
hypoglycorrhachia within 1 to 2 days. This makes
differentiation of partially treated pyogenic meningitis
from tubercular or aseptic meningitis syndromes rather
difficult. Inadequate treatment, oral medication,
suboptimal dose of antibiotics or antibiotics that do not
permeate blood-brain barrier, may not significantly alter
the CSF cytobiochemical picture within the first 1 to 2
days. The CSF culture is often rendered sterile, even with
inadequate medication. However, if the duration of
antibiotic therapy has been longer, the CSF picture gets
altered and it becomes difficult to decipher the etiology of
meningitis, thereby creating the dilemma of partially
treated meningitis. The clinician has then to resort to other
diagnostic tests. Even after the CSF is rendered sterile, he
can resort to detection of specific bacterial antigens by
rapid antigen detection tests. Many tests are available,
e.g. latex particle agglutination test, countercurrent
immuno-electrophoresis, staphylococcal-A coagglutination test, and enzyme-linked immunosorbent assays.
A wide spectrum of bacterial antigens have to be tested
for. Latex particle agglutination is one of tests that is
sensitive, specific, easy to perform and provides results
within few hours. It can be performed on CSF, urine or
even blood. ELISA though useful, is not easy to perform at
various levels of health care. Detection of bacterial DNA
by polymerase chain reaction is extremely sensitive and
may be useful in culture negative cases.
The important differential diagnosis of partially
treated meningitis include aseptic and tuberculous
meningitis.
466
Nonspecific tests like C-reactive protein, CSF lactate,

lactate dehydrogenase increase to a greater extent in
pyogenic meningitis, than viral or tubercular meningitis.
The sensitivity and specially the specificity of these tests
is limited. Despite all above tests, the clinician is often
faced with a diagnostic dilemma and difficulties in
deciding therapy options. In such situations if the onset
was acute and CSF picture supportive of acute bacterial
meningitis, antipyogenic, regime should be resorted to in
adequate dose and duration. Serial CSF cytobiochemical
changes should be monitored after 48 hours of therapy, to
observe the change in CSF cytobiochemistry. A repeat LP
is frequently informative and helps in decision-making.
In case of nonresponse clinically, and persistence of
lymphocytes in the CSF, the patient should be investigated
for other causes of subacute meningitis. Occasionally in
life-threatening situation a multipronged therapy shall
have to be given.
VIRAL MENINGITIS
Acute aseptic meningitis, is a relatively common illness
caused by a large variety of factors, often difficult to define
and identify except after exclusion of bacterial meningitis.
The precise diagnosis is often difficult as viral cultures
are not possible at most centers. The common viruses
implicated include:
EnterovirusesEcho, coxsackie, polio, rota
Arboviruses
Mumps, measles, rubella, Epstein-Barr, cytomegalovirus, Varicella zoster, influenza, parainfluenza
Lymphocytic choriomeningitis
Mycoplasma pneumoniae, leptospirosis, tuberculosis,
malignancy may also produce an aseptic meningitis
syndrome. Of these, the first two groups comprise the
major offenders.
The onset is usually sudden, preceded by fever of variable
degree and general prostation. Symptoms include
irritability, headache, vomiting, pain in the
neck and back and photophobia. A history of exanthems
or contact with an exanthematous patient is an important
clue. Sensorial loss is usually not severe, examination
reveals nuchal rigidity and variable neurological signs.
When there is an associated encephalitis, the clinical
features of seizures, sensorial loss, raised intracranial
pressure and focal deficits are more obvious.
Laboratory Findings
The cerebrospinal fluid contains variable (few to hundreds
cells/mm3). In the early stage, the cell response may be
polymorphonuclear but changes quickly to a lymphocyte
response. The CSF protein is slightly elevated and sugar
is usually not reduced, except occasionally in mumps
meningoencephalitis. Tuberculous meningitis may pose
a diagnostic problem. Grams stain and bacterial cultures
are negative. Viral cultures should be attempted on CSF,
throat and fecal specimens. Serological diagnosis is
possible, only if rising titers are demonstrated by serial
sampling at onset, and about three weeks after onset.
Treatment
Treatment includes management of symptoms, fluid
therapy and control of raised intracranial pressure.
Seizures and adequate hemodynamic and respiratory
support are indicated. The course is usually self-limited
with variable sequelae. No specific therapy is available.
Trials with corticosteroids, antiviral drugs and interferon
have not yielded satisfactory results.
ENCEPHALITIS
Encephalitis implies an inflammation of the brain and
often occurs in combination with meningitis. Cerebellar
or cord involvement may accompany encephalitis.
Involvement of the brain without a direct inflammatory
invasion is called encephalopathy and occurs in many
diverse states, e.g. typhoid, high fevers, Reye's syndrome,
exanthematous illnesses, Shigella, toxins and druginduced states.
Etiology
Table 10.5.2 identifies common biopathogens. Herpes
encephalitis is particularly important to diagnose, because
of therapeutic implications and severe complications, if
left untreated in the early stages of the disease. It usually
follows HSV-1 in older patients, and HSV-2 in the
newborn. The viral access is usually neurogenic in the
former and hematogenous in the latter, where it may be
associated with a severe, fulminant clinical profile.
Clinical features are variable in type, severity, clinical
course and eventual outcome. The onset is usually sudden
with high fever, headache, vomiting, altered sensorium
and seizures and variable neurological or motor

TABLE 10.5.2: Common pathogens for encephalitis
Viruses
1. Inter human transmission
HerpesH simplex 1 and 2,
Varicella zoster, Mumps,
Measles, Pox-variola
2. Influenza
3. ARBO agentsJapanese B,
eastern/western equine
encephalitis, etc.
4. Rabies, lymphocyte
chorimeningitis
5. CMV
6. Slow viruses
7. Dengue
Nonviral
1. Rickettsia
2. Mycoplasma pneumoniae
3. BacterialTB, others
4. Spirochetal
5. Fungal
6. Protozoal
7. Rare causes
Parainfectious: Typhoid, measles, mumps, Rubella, Pertussis

varicella, vaccinia, hepatitis, etc.
symptoms. The neurological deficits may reveal a static or

quickly progressive course and features of raised
intracranial pressure may supervene. Clinical picture is
variable and often difficult to distinguish from acute
bacterial meningitis. Hence, a very large number of
unexplained illnesses get clumped under this diagnosis.
Diagnosis
A carefully recorded history of the course of events, history
of exanthem, outbreaks in the community, toxic and
environmental factors is important. Recent illness may
provide clues to the possible causes. A carefully examined
CSF for exclusion of other causes listed earlier, is essential.
The CSF is generally under raised pressure, clear with a
cell count varying from zero to several hundred, with no
significant elevation of protein and normal sugar.
Virological work up is essential as in aseptic meningitis
on CSF, stool, blood and throat samples. Samples should
be referred to appropriate laboratories and should include
serological work-up. Sequential blood antibodies to
specific viral agents should be tested. ELISA for IgM on
CSF/serum should be done for arbo/enteroviruses. PCR
is an important test for viral encephalitis, specially herpes.
If skin lesions are present, scrapings should be examined
for multinuclear giant cells and brain biopsy may be
required for confirmation of herpes, identification of
specific features, and intranuclear inclusions. With the
advent of MR imaging, CT and EEG, the need for a brain
biopsy in suspected Herpes has diminished.
467
Treatment
Symptomatic and supportive therapy is required by all
patients. Patients with severe illnesses and acutely
raised intracranial pressure, may require mannitol.
Dexamethasone in a dose of 0.4 mg/kg IV as initial dose,
followed by 0.1 mg/kg IV every 6 hours, is helpful in
reducing cerebral edema. Its potential hazard in permitting
quick viral replication has to be considered.
Specific therapy for herpes infection should be given
early, if the diagnosis is reasonably suspect. Herpes
should be identified and suspected in patients with
lateralizing clinical and EEG signs, imaging criteria
suggestive of lateralization, or if the CSF has RBC's. A
virological confirmation should not be awaited for, as early
therapy is mandatory. Treatment on suspicion of herpes
is justifiable in view of the sequelae that ensue from delay
in therapy. Acyclovir in a dose of 10 mg/kg/dose
intravenously, every 8 hourly for 10 days is preferable.
Adenine arabinoside can also be used. Corticosteroids
should be avoided in herpes.
Tuberculous meningitis: It is dealt with in chapter 9.11
on Neurotuberculosis.
BRAIN ABSCESS
A brain abscess implies a focal free or encapsulated
collection of pus within the brain substance. It may be
located anywhere, but is usually supratentorial. The source
of infection is hematogenous. Predisposing causes include
a remote septic focus, cardiac or pulmonary disease,
specially right to left shunts. Contiguous spread of
infection may result from fracture of skull bones, infections
of the middle ear, mastoid and paranasal sinuses. Abscess
may follow leptomeningitis. Immunocompromised
subjects may also be predisposed.
Etiology
The common organisms include streptococci, staphylococci, bacteroides and pneumococci. Fungal infections
are less common causes. Rarely mycobacteria and
Pseudomonas pseudomallei may cause abscesses. Anaerobes
are frequent offenders.
The exact bacterial etiology is hard to define and choice
of therapy has to be based on circumstantial evidence and
common etiological pathogens. Brain abscess may be
single or multiple.
468
Clinical Profile
Clinical picture can be nonspecific with fever, anorexia,
headache and vomiting. Specific symptoms include
papilledema, lateralizing signs, confusion, cranial nerve
palsies, symptoms of raised intracranial pressure, head
tilt, meningeal irritation, or alteration in sensorium. In
advanced undiagnosed cases, coma, herniation and death
may occur.
Diagnosis
Suspicion of brain abscess in a pyrexia of unknown origin
or in fever with neurological symptoms, may lead to timely
diagnosis. Peripheral blood counts have limited utility.
CSF shows a variable cytobiochemical profile ranging
from pleocytosis with elevated CSF protein to a normal
CSF with elevated pressure. Blood culture may be
noninformative. EEG may show lateralized slow waves.
Neuroimaging is the diagnostic modality of choice and
reveals a mass lesion with contrast enhancement and
perilesional edema. It is also useful for follow-up
evaluation. In cyanotic heart disease subjects, it helps to
distinguish a vascular complication from a brain abscess.
Vascular thromboses are more common below 2 years of
age, and abscess is more common beyond two years.
Treatment
The treatment includes symptomatic, supportive, and
appropriate antibiotics for an adequate period. Antibiotics
of choice include intravenous penicillin G,
chloramphenicol and metronidazole, to cover for
anaerobic infections. Specific agents like methicillin,
vancomycin may be required for resistant staphylococci,
aminoglycosides for pseudomonas; ceftriaxone can be
used. The duration of therapy varies from 4 to 6 weeks
and should be guided by radiologic resolution of the
lesion.
Surgical intervention of the abscess is indicated in case
of nonresponse to antibiotics and impending herniation
in a large abscess. Surgical approaches include aspiration
of the abscess and total excision.
NEUROCYSTICERCOSIS
Neurocysticercosis is the most common parasitic neuroinfestation, common in developing countries, caused by
the larval stage of Taenia solium. Man is both an
intermediate and definitive host for this.
A significant increase in childhood neurocysticercosis

(NC) is clear from the abundance of reports in recent
literature.
Prevalence
One to two percent of hospital-based autopsies
reveal neurocysticercosis. CT scans on all consecutive
recent onset, unprovoked seizures in children more
than 3 years, reporting to our outpatient department for
one month period, revealed inflammatory granuloma in
approximately one-third of patients.
Clinical Varieties
NC can be classified into:
a. Parenchymal
b. Racemose
c. Meningoencephalitic
d. Disseminated
e. Rare intraventricular, throttled ventricles.
Parenchymal is the most common type, more than
95 percent , and consists of a single or few isolated lesions.
The image morphology depends on the stage of the larva.
The low attenuation cyst without perilesional edema
indicates a live parasite and may be missed, unless looked
for. A ring or disc lesion with or without perifocal edema
represents dying larvae and is the most common identified
lesion, as patients become symptomatic in this phase. Ring
lesions are characterized by enhancing margins with a
hypoisodense center. A scolex helps to identify the nature.
Perifocal edema may be variable depending upon larval
stage. While single lesions are most common in India,
multiple lesions are reported more frequently from America
and Thailand. The lesion may heal with no tell-tale evidence,
calcification or atrophy.
Clinical Profile
The disease generally occurs in a previously healthy and
neurologically normal child. Seizures are the most common
mode (more than 90%) of presentation, partial seizures
being more frequent than generalized. It is, however, not
uncommon for a single isolated granuloma to result in
generalized seizures.
Raised intracranial pressure is the other major
symptom (approx. 15%) and may result from multiple
lesions, single lesion with extensive perifocal edema,
obstructive hydrocephalus, throttled ventricles with

intense white matter edema or meningoencephalitis. The
frequency varies in different series. Neurological
examination is normal in the majority. Cranial nerve
paresis, hemiparesis or meningitis or hydrocephalus or
papilledema may be present. Less commonly associated
features include, fever before onset of symptoms, subcutaneous nodules, ocular symptoms due to intraocular
cyst, and behavioral changes due to raised intracranial
pressure. Chance detection also occurs.
Diagnosis
The diagnosis is suspected from the image morphology of
the lesion. The profile, however, varies with the larval
stage and the host response. MRI imaging is more
sensitive. Important differential diagnosis include tuberculomas, chronic pyogenic abscess, localized encephalitis, seizure related vasogenic edema, vascular
malformations and rarely neoplastic cause. The real
practical difficulty in most cases is differentiating
tuberculoma from cysticercus granuloma. Evidence
supporting tuberculomas includes a size more than 20
mm, associated midline shift, irregular often thick walled
outline, absence of scolex and lack of early spontaneous
disappearance. Magnetic resonance imaging does
sharpen the diagnostic capability, by identifying live low
attenuating cyst, and by better resolution of the image
morphology. The characteristic hypointensity on T1 and
extreme hypointensity on T2W image in tuberculoma
contrasted with hypointensity on T1 and hyperintensity
on T2W in cysticercus may be useful. Despite this, the
gray zones in signal characteristics are not uncommon.
Multiple parenchymal lesions do occur and present a
severe diagnostic dilemma.
Supportive diagnostic features: The adult worm and Taenia
ova in stools are not commonly detected associations.
History of subcutaneous nodules were reported in 10
percent patients. Biopsy of the subcutaneous nodule is a
very simple and useful test.
The ELISA test (IgG/IgM) can be performed on the
serum and cerebrospinal fluid. The sensitivity and
specificity varies in different series and with the type of
lesion. In intraparenchymal solitary lesions, it has not
proven to be useful in our series.
Therapy
Treatment of seizures is recommended for at least 12 to 18
months, with a single antiepileptic drug (AED) or longer,
469
if seizures continue. Carbamazepine or phenytoin are the

usual choices. Seizures are well controlled in the majority. The duration of AED required is under review, recent
observations suggest shorter courses may be sufficient.
Symptomatic treatment of raised intracranial pressure
with corticosteroids is recommended in the disseminated
and multiple parenchymal variety in the acute stage, 2
days preceding and 3 days concurrent with phase.
Corticosteroids are also recommended with cysticidal
drugs (5 days) to reduce side effects in single lesions with
extensive perilesional edema.
Role of Cysticidal Therapy
It has undergone considerable metamorphosis and a
categorical answer for its long-term benefit in the outcome
of NC, is awaited. Active lesionsparenchymal cysts
without inflammatory response merit therapy.
Spontaneous remission of such lesions is not expected.
Benefit in lesions with perifocal edema, and contrast
enhancement is controversial. Calcific lesions represent
inactive lesions and do not require cysticidal drugs.
Praziquantel and albendazole are the two commonly
used agents. Praziquantel is an isolated isoquinolone
pirazine which is active against the adult and larval form.
Usual therapeutic dose is 50 mg/kg/day for 15 days. A
strong inflammatory response may occur within a few
days of its administration, resulting in exacerbation of
cerebral edema and clinical symptoms. Corticosteroids
are recommended for the initial phase of therapy. The
radiological resolution was reported to be observed
partially in 73 percent and disappearance in 60 percent
after therapy.
Albendazole is an inidazol carbonic acid methyl ester,
used in a dose of 15 mg/kg/day. The duration schedule
varies from five day to a 28 days regime. A clinical
comparison between praziquantel and albendazole
reveals utility of albendazole as a better choice.
A big issue that has generated recently is, whether a
cysticidal drug is necessary at all for inflammatory
granulomas or not. Spontaneous resolution of the solitary
granulomas was observed in almost one-third. The
resolution rate was not statistically different amongst
patients who received albendazole vs controls in trials in
children.
Active forms require treatment. Presence of intraocular,
intraventricular cysts and meningoencephalitis should
be excluded before therapy.
470
Long-term studies are needed to address the issue of

subsequent epilepsy, whether cysticidal treatment alters
the outcome in relation to subsequent epilepsy.
Environmental intervention is fundamental rather
than a mere treatment of patients. Eradication programs
are necessary and will result from socioeconomic
upliftment, and avoidance of open field defection. Public
education and mass treatment of human and porcine
reservoirs are necessary.
Outcome
Sequelae include seizures, mental retardation, focal
deficits, hydrocephalus, etc. Death may occur in the acute
phase, most often due to severe cerebral edema and
herniation.
For IAP- Infectious Diseases Chapter Protocol on
Pyogenic Meningitis, refer to Chapter 36.11.3, Page No.
1531.
3.
4.
5.
6.
7.
8.
9.
BIBLIOGRAPHY
1. Chavez-Bueno S, McCracken GH Jr. Bacterial meningitis
in children Pediatr Clin North Am 2005;52:795-810.
2. John TJ, Cherian T, Raghupathy P. Haemophilus
influenzae disease in children in India: a hospital
10.
perspective. Pediatr Infect Dis J 1998; 179 (Suppl) S169S171.

Kanegay JT, Soliemanzadeh P, Bradley JS. Lumbar
puncture in pediatric bacterial meningitis: defining the
time interval for recovery of cerebrospinal fluid
pathogens after parental antibiotic pretreatment.
Pediatrics 2001;108:1169-74.
Organisation Mondiale de la Sant. Lutte contre les
pidmies de mningite mningocoque. Guide pratique
OMS 2. WHO/EMC/BAC/98.3.1999.
Prober CG. Central nervous system infections. In:
Behrman RE, Kliegman RM, Jenson HB (Eds): Nelsons
Textbook of Pediatrics (17 edn) Saunders, Philadelphia:
Saimders 2004;2038-47.
Prospective multicentre hospital surveilance of
strepto-coccus pneumoniae disease in India. Invasive
Bacterial Infection Surveillance (IBIS) Group, International
Clincal Epidemiology Network (INCLEN). Lancet 1999;
353:1216-21.
Saez-LlorensX, McCracken JrGH. Antimicrobial andantiinflamatory treatment of bacterial meningitis. Infect Dis
Clin North Am 1999;13:619-36.
Tunkel AR, Hartman BJ, Kaplan SL. PRactice guideline
for the management of bacterial meningitis. Clin Infect
Dis 2004;39:1267-84.
Tunkel AR, Hartman BJ, Sheldon LK, Koufman BA, Ross
KL, Scheld WM, et al. Practice Guidelinse for the
Management of Bacterial Meningitis. Clini Infect Dis
2004;39:1267-124.
Tunkel AR, Sinner SW. Antimicrobial agents in the
treatment of bacterial meningitis. Infect Dis Clini North
Am 2004;18.
10.6 Coma in Children

CR Banapurmath, Shobha Banapurmath, G Guruprasad
DEFINITION
Coma is a state from which a child cannot be aroused by
stimuli (verbal, physical, sensory, etc.) and no attempt is
made to avoid painful stimuli. It is a disorder of
arousability. The degree of response to an environmental
stimulus is reduced which is in contrast to that degree
found in sleep.
Stupor refers to a person who appears to be drowsy or in
light sleep, may be aroused by gentle stimulation and
responds to questions or commands but then lapses into
an apparent drowsy or sleep state when left undisturbed.
Neurological obtundation has similar meaning to
stupor and implies some blunting of cognition.
The condition is a medical emergency. The aim of

management should be to preserve life and to minimize
possibility of irreversible brain injury.
INCIDENCE
The incidence of coma in children under 16 years varies
from place to place. One recent study has recorded the
incidence to be 6 per 100,000 general population.
PATHOPHYSIOLOGY
Normal consciousness is maintained by the integrity of
certain areas in the cerebral cortex, thalamus and part of
reticular formation located in upper pons and midbrain.

Lesions affecting the brainstem, mass lesions in the
supratentorium or diffuse lesions of the cerebral cortex
may lead to disturbances of consciousness.
An alteration of consciousness could occur when there
is toxic or metabolic insult to brain; the toxin or an
alteration in homeostasis interferes with the function of
the brain. The encephalopathies occur when brain is
deprived of blood flow or oxygen or when there is infection
of the CNS.
Hypoglycemia occurs frequently as a manifestation of
metabolic and endocrine diseases and if left untreated, it
has deleterious long-term effects on the CNS.
Hypoglycemia should always be considered in the initial
evaluation of a comatose child.
Increased intracranial pressure in coma decreases the
effective cerebral perfusion pressure (CPP) of the brain.
Cerebral perfusion pressure (CPP) is measured clinically
as mean arterial pressure (MAP) minus mean intracranial
pressure (ICP) and obviously CPP tends to decrease with
systemic hypotension or intracranial hypertension with
consequent impairment in brain function.
CPP = MAP ICP
Infants develop less intracranial hypertension (ICP)
because of sutural separation.
HISTORY
A careful history often provides clues to the diagnosis.
Acute deterioration is associated with ingestion of drugs,
cerebrovascular accidents, trauma, and metabolic
disturbance like diabetes and seizure disorders (Table
10.6.1). Previously well infants and young children discovered comatose or convulsing may have suffered a
prolonged febrile convulsion and may be suffering from
early meningitis or encephalitis. In toddlers and small
children, intoxications are usually the result of accidental
ingestion, whereas in adolescents they are more frequently
deliberate.
Deterioration over days or weeks is more compatible
with CNS infection, chronic intoxication or raised
intracranial pressure. The past medical history may
provide vital clues. A family history of epilepsy or TB may
be discovered, or the report of previous stillbirths or deaths
in infancy may indicate inherited metabolic disease. An
altered state of consciousness in the newborn period
associated with vomiting, failure to thrive and seizures,
suggests an inborn error of metabolism.
471
A child with chronic renal failure associated with

hypertensive encephalopathy, may present with coma. A
child with heart or pulmonary disease may develop coma
as a result of cerebral anoxia and ischemia. Acute
subarachnoid hemorrhage secondary to a bleed from an
arteriovenous malformation, causes sudden alteration in
consciousness.
Physical examination may provide clues to diagnosis.
High fever may indicate infection. Increased respiratory
rate is often mistakenly attributed to pneumonia and may
indicate metabolic acidosis as seen in Reyes syndrome.
The breath should be examined for odour of ketones and
for fetor hepaticus. High blood pressure is seen in
hypertensive encephalopathy associated with acute
nephritis or hemolytic uremic syndrome. The presence of
petechial skin rashes, lymphadenopathy or splenomegaly
usually indicates infection. The fundi should be examined
for papilledema and tubercle follicles. Presence of marked
pallor and bulging fontanel suggests intracranial
bleeding. Presence of petechial hemorrhages and shock
state along with coma should suggests possibility of
dengue shock syndrome. Neurocutaneous markers like
caf-au-lait spots, hypo-and hyperpigmented spots should
suggest neurocutaneous syndromes like neurofibromatosis and, tuberous sclerosis. Presence of jaundice in a comatose child should suggest fulminant hepatic failure and
hepatic encephalopathy.
Pyramidal tract signs like hemiparesis may indicate a
Todds paresis, focal encephalitis or localized hematoma
or abscess formation.
Paroxysmal nystagmus or conjugate deviation of the
eyes, sucking or chewing movements frequently represent
brainstem release phenomena secondary to swelling
of the brain. Midbrain compression from cerebral shifts
causes ophthalmoplegia. It is important to note that
papilledema may be delayed or absent sign, even in
the presence of significantly raised intracranial
pressure. A bulging anterior fontanel, hypertension
and bradycardia may suggest raised intracranial
pressure.
Meningeal signs should be sought remembering that
nuchal rigidity and Kernigs sign may be completely absent
in younger children, and in children pretreated with
antibiotics.
472
ASSESSING THE DEGREE OF COMA
INVESTIGATIONS
The Glasgow coma scale (GCS) is the most widely used

method for objectively grading the degree of consciousness,
although it has serious limitations in infants and young
children, since neither motor nor verbal responses to
commands and eye opening to speech can be assessed.
For young children, the modified children coma scale is
more useful (Table 10.6.2). Sequential charting of the coma
score helps the pediatrician to monitor the course of the
illness. It is more useful to record how the child actually
responds. The verbal response, ocular response and motor
response to each stimulus should be recorded.
The investigations of the child with coma should lead to

specific diagnosis and provide information which will
help to provide optimum supportive therapy.
Investigations must be tailored to the individual childs
illness. The pediatrician should be guided by clues obtained
from the history and examination in the choice of investigations. Gastric aspirate may yield detectable drugs and
toxins. Urine may detect toxic metabolites and drugs
undetected on assay of serum (Tables 10.6.3 and 10.6.4).
In a suspected case of bacterial meningitis, a lumbar
puncture should be done. The contraindications for
TABLE 10.6.1: Causes of coma in children

Infections
Meningitis*
Encephalitis*
Abscess
Intracerebral
Subdural empyema
Epidural empyema
Systemic Infections
Gram-negative septicemia*
Septic shock
Shigella encephalopathy*
Dengue shock syndrome*
Hypoxia-Ischemia
Hypoxia* (normal cerebral blood flow)
Hypoventilation
Methemoglobinemia
Ischemia (decreased cerebral blood flow)
Toxins
Endogenous
Uremia *
Hepatic coma*
CO2 narcosis
Porphyria
Exogenous
Barbiturates*
Tranquilizers*
Opiates
Hyperventilation
Anticholinergics
Tumors
Cerebral
Posterior fossa
Others
* More frequently encountered causes of coma in children
Trauma
Subdural hematoma*
Chronic
Acute
Epidural hematoma
Intracerebral hematoma
Contusion and laceration
Cerebral edema
Electrolyte and acid-base abnormalities*
Na+ ,Ca+, K+, Mg+, P+++
Deficiency states
Thiamine
Niacin
Pyridoxine
Vitamin B12
Cardiac causes
Decreased cardiac output
Arrhythmias
Valvular disease
Generalized fall of blood pressure
Hypovolemic
Vasovagal
Carotid sinus
Vascular causes
Hypertensive encephalopathy*
Polycythemia
Emboli
Thrombosis
Vasculitis
Arteriovenous malformations
473
TABLE 10.6.2: Glasgow coma scale

Response
Form of occurrence
Eye opening
Spontaneous
To speech
To pain
None
Oriented
Confused conversation
Inappropriate words
Incomprehensible sounds
None
Obeys commands
Localizes pain
Withdraws
Abnormal flexion
Extension response
None
Verbal
Best motor
Score
4
3
2
1
5
4
3
2
1
6
5
4
3
2
1
Modified childrens coma scale for infants

Response
Form of occurrence
Eye opening
Spontaneous
To speech
To pain
None
Coos, babbles
Irritable cries
Cries to pain
Moans to pain
None
Normal spontaneous movements
Withdraws to touch
Withdraws to pain
Abnormal flexion
Abnormal extension
None
Verbal
Motor
Score
4
3
2
1
5
4
3
2
1
6
5
4
3
2
1
Source: Trauner DA, James HE, 1985.
performing an LP are raised intracranial pressure where

child may develop transtentorial herniations.
Fundus examination for papilledema is mandatory
before doing an LP. Decerebrate or decorticate posturing,
abnormalities of pupil size and reaction indicate
impending cerebral herniation, so LP should be withheld
(Figs 10.6.1 and 10.6.2).
Investigations which will facilitate supportive therapy
1. Urine examination:
Colorfrank hematuria in glomerulonephritis
Smellmousy odor in PKU
Microscopyfor cells, RBC casts
pH of urine
Sugarreducing substances in diabetes
Ketone bodiesdiabetic ketoacidosis

Ferric chloride test, DNPH testmetabolic causes
2. Blood investigation
Blood sugar
Serum urea, creatinine
Serum electrolytesNa, K, Ca and P
Osmolality
Serum levels of anticonvulsants
Septic workup and complete blood counts
LFT
Coagulation profile
Arterial blood gases
3. Imaging studies
Chest X-ray and ECG
CT scan, EEG, and evoked potentials
474
Figure 10.6.1: A one-year-old child with TB meningitis

having decerebrate posturing and coma
4. Virology studies
Figure 10.6.2: Picture showing six years child with coma following acute food poisoning receiving ventilatory support, eye
care and clinical monitoring
Investigations which might provide a specific diagnosis

Liver function tests
Skeletal survey
CT scan
MRI scan
CSF examination
Toxicology screen
Blood ammonia
Blood pyruvate, lactate
Amino acid profile
Organic acid analysis
Porphyrins
An initial EEG provides valuable information about

cortical function. Focal slow waves may indicate a local
TABLE 10.6.3: Localizing the pathology
Signs and symptoms
Cerebral
Subcortical
Midbrain
Pons and medulla
Consciousness
Normal or akinetic
mutism (bilateral
cingulate gyrus)
Lethargy and apathy

(thalamus); drowsiness
(hypothalamus)
Coma
Coma
Respiration
Normal or posthyperventilation apnea
Cheyne-Stokes
Central hyperventilation
Apneustic or Atactic
Pupils
Normal
Small and reactive
Nuclear: midposition
and pinpoint fixed
3rd Nerve: unilateral
dilated and fixed
Pretectal: Large and
fixed
Horners syndrome
(lateral medulla)
Eye movements
at rest
Roving eye movements,

or look toward
destructive lesion and
away from paretic side
Roving eye movements

or look toward
destructive lesion
3rd Nerve: eye down

and out
Look away from lesion

and toward paretic side
Dolls eye and

Calorie stimulation
Present
Present
Absent or abnormal
response
Absent or abnormal
response
Motor
Hemiparesis
Decortication
Decerebration
(rostral pons)
Decerebration

lesion such as focal suppuration due to a pyogenic abscess.
Characteristic EEG findings include focal EEG signs in
Herpes simplex encephalitis.
CT scan is indicated when there are fundal changes or
other signs of raised intracranial pressure or when initial
investigations have failed to clarify the diagnosis. Real
time ultrasound can be done in infants with open fontanel.
In Reyes syndrome, the most significant abnormalities
are elevated serum transaminases (SGOT and SGPT),
hypoprothrombinemia and hyperammonemia. If Japanese
encephalitis is suspected, a serologic diagnosis can be
made by demonstrating rising antibodies.
In dengue shock syndorme or dengue hemorrhagic
fever, 20 percent or greater increase in hemotocrit value,
thrombocytopenia and decreased prothrombin will be
seen. Definitive diagnosis is established by demonstrating
IgM and IgG antibodies.
In suspected poisoning toxicological analysis of blood
and urine is recommended. Diabetic ketoacidotic coma
must be differentiated from hypoglycemia, uremia and
metabolic acidosis. Diabetic ketoacidosis exists when
glucose is greater than 300 mg/dl.
MANAGEMENT
Sequential Management of the Comatose Child
1. AAirway: Ensure adequate airway, place child in
lateral position gently with slight extension gently
get rid of all secretions by careful suctioning.
2. BBreathing: Ensure patient is breathing well.
Provide oxygen. Get blood gases. Consider artificial
respiration.
3. CCirculation: Record pulse rate, blood pressure
and assess the cardiac volume and output. Look for
signs of blood loss, shock and provide fluid bolus
followed by inotropic support, blood to be arranged.
Secure good IV access, draw blood for random blood
sugar (RBS) using glucometer, CBC, grouping and
crossmatching, electrolytes, and calcium. Reassess
every 10 to 15 minutes till cardiovascular stability
is achieved. Maintain cerebral perfusion pressure
above 50 mm Hg.
If hypotension take
(Dopamine drip, fluids)
Take Mean systolic BP
If hypertension-treat
475
4. DDextrose, Drugs, Dysentery, DIC, Drug ingestion or

accidental.
5. EEpilepsy and electrolyte disturbance: Observe for
seizures or stigmata of seizures like bitten tongue,
urinary and fecal incontinence. Control seizures.
Convulsions should be terminated as early as
possible by intravenous administration of diazepam.
The drug is given slowly in a dose of 0.3 mg/kg IV, or
diphenylhydantoin should be administered for
prolonged effect and if seizures recur.
6. FFever, and Febrile seizures: Check for fever, neck
stiffness, purpuric rash, look for meningococcemia.
Consider viral hemorrhagic fever and dengue fever.
7. GGlasgow coma scale: Record response to each item
(Table 10.6.2).
8. HHerniation: Is there evidence of coning? (Table
10.6.5). Look for hypertensive encephalopathy,
hepatic failure and Reyes syndrome.
9. I-Increased ICP: Intracrainal BP (ICP monitoring) in
any case of coma put on ICP monitor.
Raised ICP: Treat with mannitol, frusemide, hyperventilation, dexamethasone, phenobarbitone,
diazepam, pancuronium, drainage of CSF.
Infections, injury, inborn errors of metabolism,
Intussusception (early), Investigate.
10. JJuggling with the Jigsaw puzzle, do not hesitate to
obtain second opinion.
PROGNOSIS
1. Depends on the etiology for example, diabetic coma
(good), inborn errors of metabolism (bad)
2. SignsGlasgow coma scale <5 (bad)
3. EEGReappearance of normal sleep spindles signals
recovery
4. Neurophysiological studies:
BEAR, BEVR, SEP (Somato-sensory evoked potential)
Most sensitive and reliable method
Normal SEPNormal outcome in 93 percent of cases
Absent SEPBad prognosis in 100 percent of cases
Asymmetrical SEPAssociated with sequelae such
as hemiparesis.
5. Absent extraocular movements, nonreactive pupils
and hypothermia are poor prognostic signs.
476

TABLE 10.6.4: Physical signs that provide clues
I.
II.
Examination of the Head:

a. Bulging fontanelle
b. Positive Macewens sign
c. Small/large head
d. Battle sign
ICP, meningitis
ICP, skull #
Underlying structural CNS malformation.
# base of skull.
Examination of the Eyes:

a. Jaundice
b. Retinal hemorrhages
c. Papilledema
d. Ptosis
Hepatic encephalopathy, FHF.

ICT, hypertensive encephalopathy.
ICP, (Absence does not rule out CN pathology).
III nerve involvement.
III. Pupils
a. Equal
Size
Pinpoint
Small
Midposition
Large
b. Pupils unequal
Dilated
Small
Reaction
Nil
Reactive
Reactive
Fixed
Reactive
Fixed
Condition
Opiate poisoning
Narcotic overdose
Metabolic encephalopathy
Midbrain lesion
Metabolic lesion
Atropine poisoning
Brain death
Unreactive
III nerve palsy

Herniation
Horners syndrome
Reactive
IV. Examination of face

Smell of breath
Tongue laceration
V. Examination of decubitus
Decerebrate posturing
Coarse movements
Marked agitation
Petechial/Purpuric hemorrhages
Hyperpigmentation
VI. Body secretions
Smell of breath
Acetone breath
Ammoniacal odour
Altered GI aspirate
Bilious aspirate
Bloody urine
Bloody stool
Stains of blood on clothing
Among children aged one year to 16 years sufferring

from non-traumatic pediatric coma who were followed
ICP
Brain swelling
Brain swelling
Meningoccemia
Addisons disease, hypoadrenalism
Organophosphorus poisoning
Kerosene poisoning
Diabetic ketoacidosis
Hepatic failure
Stress ulcers, GI hemorrhage
Intestinal obstruction, septic ileus
Acute glomerulonephritis
Shigellosis, intussusception
Injury
up for one year, one-fourth of older children had a fatal

outcome.
477
TABLE 10.6.5: Looking for danger signals in comatose children

Bradycardia, decerebrate posturing and periodic breathing are ominous clinical signs.
Most importantly, signs of coning should be sought.
Look for Coning:
Coning happens when brain substance is forced through a rigid hole.
i. Uncal herniation: The uncus and the temporal lobe of the midbrain is pressed against the bony tentorium.
Clinical signs:
Early: Ipsilateral pupillary changes with ptosis.
Later: Progressive IIIrd nerve palsy ipsilateral
Cheyne-Stokes respiration contralateral hemiparesis (Webers syndrome)
ii. Central herniation:
The cerebrum is pushed centrally through the tentorium. Initially the upper mid brain and later the pons and medulla are compressed.
Clinical signs
Early: Erratic respirations , small reactive pupils increased thumb tone, bilateral extensor plantors.
Later: Fixed dilated pupils, decerebrate posturing.
iii. Downward herniation:
Foraminal
Cerebellar tonsils into foramen magmum (midbrain, pons, and medulla) gets compressed in same order from above
downwards
BIBLIOGRAPHY
1. Nayana Prabha PC, Nalini P, Tiroumourougene Serane
V. Role of glasgow coma scale in pediatric non traumatic
coma. Indian Pediatr 2003;40:62025.
2. Trauner DA, James HE, Evaluation of coma. In: James
HE, Anas NG, Perkin RM (Eds). Brain insults in infants

and children. Pathophysiology and management.
Orlando, Florida, Grune and Stratton 1985.
3. Wong CP, Forsyth RJ, Kely TP and Eyre JA. Incidence,
aetiology and outcome of nontraumatic coma; a population based study. Arch Dis Child 2001;84:19399.
10.7 Brain Tumors in Children

KS Rana
Primary brain tumors in children are a diverse group of
diseases. These are the most common solid tumors and
the second most common malignancy of childhood
following leukemia, accounting for almost 21 percent of
total childhood malignancies. Reported incidence in the
USA has varied from 20 to 50 per 1,000,000 children.
Almost 1500 new cases of brain tumors are diagnosed
annually in the United States. Incidence has increased
approximately 2 percent per year in the last 20 years. Even
the relative frequency of the type of the tumors has
changed. In the early part of 20th century, tuberculoma
was the most common intracranial tumor. Subsequent
survey stressed the preponderance of gliomas. In eighties
and early nineties, the incidence of primitive neuroectodermal tumors (PNET/medulloblastoma) has
increased more than 4 percent per year. Outcome of these

tumors depends upon the histology, location, degree of
resectability, and response to adjuvant therapy. Advanced
surgical modalities like laser and microscopic operating
techniques and adjuvant therapy such as focused
radiotherapy and newer chemotherapeutic agents have
increased the life span and improved the quality of life of
these children.
PATHOGENESIS
Etiology of brain tumors is unknown. However, in the
recent years significant progress has been made in the
field of molecular genetics, implicating molecular
abnormalities in the pathogenesis of these tumors. Two
genetic abnormalities are believed to be responsible for
478
the development of tumors. One is associated with the

activation or over- expression of growth- promoting factors
such as proto- oncogenes, and the other is the result of
loss or inactivation of genes that regulate or suppress cell
growth, the tumor suppressor genes.
Role of viruses in the etiology of brain tumors is
controversial. Choroids plexus tumors and ependymomas express a segment of the gene related to monkey
polyoma virus (SV40) and JC virus.
Varieties of chromosomal abnormalities have been
observed in the cytogenetic analysis of brain tumors.
Astrocytomas and glioblastomas are associated with +7p,
-9p, -1p, and -17p chromosomal abnormalities and
medulloblastoma with -8p and -17p. Incidence of brain
tumors is higher in the relatives of children with these
cytogenetic abnormalities. Primary brain tumors have
increased association with genetic syndromes like
neurofibromatosis, Von-Hippel-Lindau disease, ataxia
telangiectasia and Wiskott- Aldrich syndrome. Primitive
cells have also been blamed for the origin of brain tumors
like craniopharyngiomas from the persistent remnants of
craniopharyngeal pouch and PNET/ medulloblastoma
from areas of maldevelopment. Environmental factors like
high dose radiations and immunodeficiency states like
human immunodeficiency virus infection have also been
implicated in the pathogenesis of CNS tumors.
PATHOPHYSIOLOGY
Neurological symptoms produced by brain tumors are
general and local. General symptoms are from increased
intracranial tension (ICT); that results from progressive
enlargement of tumor in the limited cranial vault,
obstruction of cerebrospinal fluid (CSF) and brain edema.
Local symptoms are due to the effects of the tumor on
contiguous areas of the brain. Small strategically located
tumor can be devastating by compressing the vital
structures. As the tumor enlarges, the intracranial contents,
primarily the ventricles are compressed compromising
CSF circulation. Compression of the large vascular
channels results in cerebral anoxia and in turn produces
vascular dilatation and a further increase in intracranial
volume and pressure. Increased intracranial pressure
further decreases cerebral blood flow when perfusion
pressure (difference between mean arterial and
intracranial pressure) falls to approximately 40 mm Hg.
Expanding mass also produces various herniations by
creating pressure gradient in different compartments.
Cerebellar tonsil herniates through foramen magnum,
uncal and diencephalons through tentorial opening and

cingulate gyrus under falx cerebri. These herniations
produce secondary brain dysfunction because of
overcrowding, stretching and rupturing of blood vessels,
edema and pressure over vital structures, notably cranial
nerves and vital centers in the brainstem.
CLASSIFICATION OF BRAIN TUMORS
Histological Classification
The WHO classification of brain tumors based on
histological criteria is depicted in Table 10.7.1.
Anatomical Classification (Table 10.7.2)
Approximately two thirds of brain tumors are infratentorial
in children between ages of 2 and 12 years, with three
fourths of these located in the cerebellum or fourth
ventricle. Supratentorial tumors seen in adolescents and
children less than two years of age include those tumors
that occur in the sellar or suprasellar region and/or in the
cerebrum or diencephalons.
Classification based on Degree of
Malignancy (Table 10.7.3)
The terms benign and malignant often are misleading
when applied to brain tumors. Malignant tumors are
usually aggressive neoplasms that have the capacity to
disseminate within and occasionally outside the nervous
system, whereas benign tumors grow more indolently.
Malignant tumors such as medulloblastomas may be
curable in up to 80 percent of children who are older than
3 years if radically removed and are not disseminated at
diagnosis. Conversely, some benign tumors can
disseminate (up to 4% of cases in low-grade astrocytomas), and may be quite difficult to eradicate.
CLINICAL FEATURES
Clinical signs and symptoms depend upon tumors
location, size, childs age and obstruction of CSF.
Aggressively growing tumors are associated with early
and severe symptoms, whereas initial signs and
symptoms of slow-growing tumors are subtle. Subtentorial tumors, obstructing CSF pathway present with
features of raised ICT. Intra-axial masses like pontine
gliomas present with features of multiple cranial nerves
palsy. Supratentorial tumors present with seizures and
focal neurological deficit. Brain tumors in younger

TABLE 10.7.1: Histological classification of brain tumors
A. Tumors of neuroepithelial tissue
Astrocytic tumors:
Astrocytoma, Anaplastic astrocytoma, Glioblastoma,
Pilocytic astrocytoma, Peomorphic xanthoastrocytoma,
Subependymal giant cell astrocytoma
Oligodendroglial tumors:
Oligodendroglioma, Anaplastic oligodendroglioma
Ependymal tumors:
Ependymoma, Anaplastic ependymoma, Myxopapillary
ependymoma, Subependymoma
Mixed gliomas:
Oligoastrocytoma, Anaplastic oligoastrocytoma
Choroids plexus tumors:
Choroid plexus papilloma, Choroid plexus carcinoma
Neuroepithelial tumors of uncertain origin:
Astroblastoma, Polar spongioblastoma, Gliomatosis
cerebri
Neuronal and mixed neuronal glial tumors:
Gangliocytoma, Dysplastic gangliocytoma of cerebellum
(Lhermitte-Duclos), Desmoplastic ganglioglioma,
Ganglioglioma, Centralneurocytoma
Pineal parenchymal tumors:
Pineocytoma, Pineoblastoma, Mixed transitional tumors
Embryonal tumors:
Medulloepithelioma, Neuroblastoma, Ependymoblastoma,
PNET, Medulloblastoma.
B. Tumors of meninges
Tumors of meningothelial cells:
Meningioma, Atypical meningioma, Papillary meningioma,
Anaplastic meningioma.
C. Germ cell tumors
Germinoma, Embryonal carcinoma, Yolk sac tumor,
Choriocarcinoma, Teratoma, Mixed
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TABLE 10.7.2: Anatomical classification of brain tumors

Location
Tumors
Infratentorial
Cerebellar astrocytoma, Medulloblastoma,

Brainstem gliomas, Ependymomas,
Choroids plexus papilloma, Dermoids,
Epidermoids, Chordomas, Teratomas
Supratentorial
Craniopharyngioma, Gliomas, Choroids

plexus papilloma, Germ cell tumors,
Teratomas, Pineoblastoma, Pinealomas,
Astrocytomas Ependymomas, Oligodendro
gliomas, PNET, Gangliogliomas, and leukemia
infiltrates
children before sutures are closed manifest as progressively enlarging head size.
Headache
Headache in children with brain tumors result from either
direct or transmitted pressure on cerebral arteries, venous
sinuses, dura, cranial nerves, or from hydrocephalus. Brain
parenchyma is insensitive to pain. About 60 to 65 percent
of children with brain tumors have headache. This may be
the earliest (less than 4 months in 95%) or may be the only
symptom in majority of the children. Headache is mainly
diffuse. Mostly transient, occurring in the morning or
awakening the child at night. Headache of more than 4
months duration with normal ophthalmic and
neurological examination is unlikely to be associated with
brain tumor.
TABLE 10.7.3: Brain tumors based on degree of malignancy

Grade
Prognosis
Intracerebral
Extracerebral
Grade 1: Benign
Favorable with removal only
Gangliocytoma, Plexus papilloma,

Cerebellar astrocytoma,
Hemangioblastoma, Isomorphic
pinealomas
Neurinomas, Meningiomas,
Craniopharyngiomas, Pituitary
adenomas, Ventricular
ependymomas
Grade 2: Semi benign
Favorable, additional
therapy required
Extraventricular ependymomas
Isomorphic astrocytomas
Anisomorphic pinealomas
Polymorphic pituitary
adenomas
Grade 3: Semi malignant
Guarded, additional
therapy required
Polymorphic gangliocytoma
Polymorphic ependymoma
Polymorphic plexus papilloma
Polymorphic astrocytoma
Polymorphic oligodendroglioma
Polymorphic pinealoma
Polymitotic meningioma
Polymitotic neurinoma
Grade 4: Malignant
Poor
Glioblastoma, Medulloblastoma
Meningeal sarcoma
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Vomiting
Visual Symptoms
It is one of the most constant sign of raised ICT, occurring

in 84 percent of patients. It can result from raised ICT or
irritation of the brain stem chemo receptors. Vomiting
usually relieves the headache. It may be associated with
nausea and may not be projectile. It is prominent in the
morning and not related to eating.
Visual problems are seen in around 40 percent of children

with brain tumors. Diplopia usually results from unilateral
or bilateral paralysis of lateral recti muscles and is a
common symptom of posterior fossa tumors. Small
children usually dont complaint of double vision, they
compensate by tilting the head in an attempt to align the
two images. Other symptoms those may suggest diplopia
in small children are frequent falls, scare of walking or
playing use of one eye. Strabismus is most striking in
posterior fossa masses and is prominent in the end of the
day. Blurring of vision is a serious symptom and may
indicate vasoconstriction of cerebral vessels impending
cerebellar herniation. Progressive visual loss and
nystagmus may suggest optic nerve glioma of pituitary
mass.
Hypertension and Bradycardia

When intracranial pressure approaches or equals the
systemic arterial pressure, it causes the systemic arterial
pressure to rise; this is associated with bradycardia and
irregular respiration (Cushing triad).
Ataxia
It is characteristically observed in cerebellar tumors.
Cerebellar vermial tumors produce truncal ataxia that
enhances with sitting, standing and walking. Tumors
arising from cerebellar hemisphere produce ipsilateral
ataxia and dysdiadochokinesia.
Head Tilt and Neck Rigidity
This may indicate tonsillar herniation through foramen
magnum.
Mental Status Changes
Changes in behavior and personality are uncommon in
children. Progressive depression of consciousness
suggests raised intracranial pressure and compression of
ascending reticular activating system.
Papilledema
This is absent in almost half the children with brain tumors,
especially those with a rapid course such as medulloblastoma, supratentorial tumors and in young children
with open anterior fontanel. Separation of cranial sutures
and bulging of fontanel may decompress the intracranial
contents. Trend of decreasing prevalence of papilledema
at the time of diagnosis reflects readily available
neuroimaging modalities to evaluate headache at the
onset. Presence of papilledema makes an intracranial mass
highly probable but its absence in no way excludes such a
diagnosis.
Seizures
Seizures as initial symptoms are seen in less than 15 percent of
supratentorial tumors. Complex partial seizures are the most
common type of seizures seen in intracranial
malignancies. Temporal lobe is the most common site for
tumors producing seizures early in the course of disease.
Focal Neurological Deficits
Focal neurological deficits in the form of hemiparesis are
seen in less than 15 percent of patients as an early
presenting feature of supratentorial brain tumors.
Enlargement of the Head
Progressive enlarging head size is characteristic of long
standing increase in intracranial pressure in infants and
young children and is observed in 76 percent of infants
younger than 2 years of age.
DIAGNOSIS
Neuroimaging modalities have superseded the old
evaluation techniques in the diagnostic evaluation of the
child suspected of brain tumor. CT is the imaging modality
of choice in emergency. Intravenous contrast material assists
in tumor identification. Most tumors demonstrate
enhancement with contrast material. Tumors may appear
hypodense, isodense, or hyperdense or may have mixed
density. CT is effective for imaging the skull base, where
natural contrast of bone, paranasal sinuses, fat and CSF

provides inherent contrast resolution. However tumors
in the posterior fossa and temporal lobe can be missed by
CT imaging.
MRI is better in delineation of benign masses from
malignant growths, inflammatory and infectious
conditions and normal brain tissue. Tumors in the
posterior fossa, temporal lobe, sellar and chiasmatic
regions are best visualized with MRI. An understanding
of the nature of the tumor and its location requires
knowledge of T1, T2, FLAIR and gadolinium enhanced
sequences. It is also sensitive to pick up acute, subacute,
and chronic presence of blood products within tumor
mass. MR angiography and conventional arteriography
using digital subtraction techniques, helps delineate the
blood supply to the tumor and exclude the presence of
vascular malformation.
EEG is less useful in the localization of brain tumors.
Persistent slow wave activity usually associated with
seizures suggests temporal lobe mass in children with
complex partial seizures.
Positronemission tomography (PET) has considerable
potential in delineating brain tumors. Primary tumors
show good correlation between the uptake of labeled
fluorodeoxyglucose (FDG) and the malignancy of tumor.
MR spectroscopy has a role in characterization of brain
tumors, in follow-up and differentiation from other non
malignant conditions.
Plain X-ray skull can suggest an intracranial mass if
there is separation of sutures, erosion or enlargement of
sella turcica and calcification (15-20% of brain tumors).
CT and MRI guided stereotactic biopsy is preferred to
open biopsy in childhood brain tumors involving basal
ganglia, thalamus and midbrain. Accurate diagnosis with
this is possible in 95 percent of cases with morbidity in
the 2 to 5 percent range.
DIFFERENTIAL DIAGNOSIS
Increased intracranial pressure is also observed in other
masses like intracranial hemorrhage, brain abscess,
vascular malformations and, inflammatory granulomas.
In infants brain tumors cause increased intracranial
pressure less commonly than hydrocephalus. In pseudotumor cerebri, raised ICT is elevated in the absence of mass
lesion, but there are no localizing signs and the CSF is
normal. Neuroimaging studies show normal or pinched
ventricles. Lead poisoning can also present like posterior
fossa mass but generalized seizures and encephalopathy
are more common.
481
Treatment
Surgery
Surgery remains the mainstay of treatment for brain
tumors. Total resection cannot be accomplished in many
cases, but partial resection is useful to reduce the bulk of
tumor thus permitting destruction of remaining malignant
cells by irradiation and chemotherapy. Perioperative
administration of dexamethasone at a 0.1 to 0.5 mg per kg
per dose reduces increased intracranial pressure and
perilesional edema. Other medications such as phenytoin
can also be used prophylactically. Goal of neurosurgery
is maximum resection while preserving function. Gross
total resection of both malignant and benign tumors has
been correlated with prolonged survival rates. Advent of
operating microscope, laser beam, and ulterasonographic
methods have made it possible to do safe and complete
resections. Establishing the correct neuropathological
diagnosis of the tumor is critical for subsequent therapy.
This often requires immunohistochemistry, flowcytometry
and electron microscopy. Post-operative serial imaging
studies are important to assess the extent of any residual
tumor/recurrence and to follow-up post operative
abnormalities like edema and bleed.
Radiation Therapy
Radiotherapy can be used either as an adjuvant to surgery
or for definitive therapy. Many pediatric brain tumors are
radiosensitive, but because of radiations toxicity to the
developing brain, delivery methods have been modified
to target the area treated more precisely and, when
possible, to decrease the total volume of the brain that is
irradiated. Volume and radiation dosage vary with
different histological diagnoses. Children with
medulloblastomas, for example, receive radiation to the
entire brain and spine, with a booster dose to the original
tumor area, whereas children with brain stem gliomas
receive radiation only to the tumor area. Limited field
radiotherapy and craniospinal radiotherapy have offered
curative therapy for low grade gliomas, PNET and
germinomas. Some of the most intriguing new methods in
brain tumor treatment are conformal therapy and
stereotactic radiosurgery involving a radiation procedure
called Gamma Knife surgery. This treatment precisely
focuses radiation beams to the tumor, delivering radiation
beams in the exact size and shape of the tumor with the
aid of brain imaging techniques. Advantage of stereotactic
radiosurgery is that the surrounding, healthy tissue
482
receives only a very small dose of radiation compared to

the tumor. Pathophysiology of radiation induced injury
results from damage to vascular endothelium that is more
radiosensitive than neurons, injury to glia and axons and
autoimmune vasculitis. Side effects of radiation can be
acute with in 2 to 6 hours in the form of nausea, vomiting
or develop several weeks later in the form of hair lose,
erythema, sore throat, thrombocytopenia, leucopenia and
anemia. Late effects include impaired cognition, defective
endocrinal function and development of secondary
neoplasia.
Chemotherapy
Chemotherapy is increasingly being used to treat both
malignant and benign tumors, especially in infants, where
it has replaced radiation therapy in the postoperative
period. The addition of chemotherapy to the treatment
regimen has increased median survival rates for highrisk medulloblastoma and high-grade astrocytoma. The
use of low-intensity chemotherapy for low-grade gliomas
(optic/hypothalamic gliomas) has shrunk or stabilized
tumors in up to 70 percent of patients. Newer strategies
have been designed to concentrate chemotherapy agents
directly in to the tumor. One of the proposed strategies is
to implant a self contained delivery pump that
administered the drug. Another approach is the use of
polymer matrix to improve local therapy of malignant brain
tumors. The new plastics enable the drugs to diffuse more
uniformly and continuous in to the tumor. Recent advances
in chemotherapy include primarily supportive-care
measures such as the use of haematopoietic growth factors
and autologous stem-cell harvesting and reinfusion. These
measures shorten the duration of myelosuppression,
allowing administration of higher and more frequent doses
of chemotherapy.
Newer Modalities
These include blocking tumor cell surface receptors, inhibit
transduction, inhibit tumor infiltration, metastasis and
angiogenesis that is essential for tumor survival. Gene
therapy is one of the most promising approaches involving
replacement of defective gene.
SPECIAL ISSUES RELATED TO
THE TREATMENT OF BRAIN TUMORS
Endocrinal Dysfunctions
Endocrine dysfunctions can develop after removing
midline tumor, after craniospinal radiation or chemo-
therapy. Diabetes insipidus is common after resection of a

craniopharyngioma, a germ-cell tumor, or a hypothalamic glioma. CNS radiation is associated with
hypothalamic and pituitary dysfunction. Signs and
symptoms include fatigue and cold intolerance (caused
by hypothyroidism), amenorrhea, decreased libido,
hypotension, coma (Addisonian crisis), and retarded bone
age. Decreased growth velocity has been noted in 30 to
100 percent of children treated with cranial irradiation.
Most common hormonal deficiency is growth hormone.
Children may require steroids, thyroid hormone, and or
growth hormone replacement. Several chemotherapeutic
agents, for example, cyclophosphamide can cause gonadal
dysfunction and later on sterility.
Behavioral and Educational Issues
Immature brain of infants and young children is more
susceptible to ionizing radiation. Children who survive
have a high incidence of intellectual impairment as well
as emotional and behavioral problems. Cognitive deficits
include distractibility, memory impairment, confusion,
personality changes, and lowered IQ. Causes for these
deficits are likely a combination of prolonged hydrocephalus, direct damage by tumors, surgical morbidity,
chemotherapy, and whole brain irradiation. Younger the
child, the greater is the effect. More-affected children often
require special education and supportive services, such
as physical and occupational therapy, speech therapy,
and psychological counseling.
Posterior Fossa Syndrome (Cerebellar Mutism)
This unusual entity can follow posterior fossa surgery.
Child is mute, apraxic, unable to execute complex motor
commands, emotionally labile and has difficulty in
swallowing. Most children lose their speech 12 to 72 hours
after surgery. Parents can be reassured that neurological
function and speech generally return in from 2 to 20 weeks
in most children.
INDIVIDUAL TUMORS
Astrocytoma
These tumors are derived from astrocytic neuroglial cells,
commonly from the vermis or lateral cerebellar lobes. They
are cystic with the neoplasm confined to a small intramural
nodule. It is the most common brain tumor, accounting for
more than half of all primary CNS malignancies. Association
with NF1 is present in 50 to 80 percent of patients with

isolated optic nerve astrocytomas and in as many as 20
percent of those with chiasmal or optic tract tumors.
Ionizing radiation to the head for prior malignancies
causes secondary supratentorial malignant astrocytomas
in a small number of patients. Peak age of presentation is
5 to 9 years.
Histologically astrocytomas can be classified in to four
different subtypes. Pilocytic astrocytomas (WHO
grade I) arise throughout the neuraxis, but preferred sites
include the optic nerve, optic chiasma/hypothalamus,
thalamus and basal ganglia, cerebral hemispheres,
cerebellum, and brain stem. These tumors show low
cellularity, low proliferative and mitotic activity, and
rarely metastasize or undergo malignant transformation.
Most common variety seen in children and constitute two
thirds of cerebellar astrocytomas.
Diffuse astrocytomas (WHO grade II) may arise in any
area of the CNS but most commonly develop in the
cerebrum, particularly the frontal and temporal lobes. The
brain stem and spinal cord are the next most frequently
affected sites, while the cerebellum is a distinctly
uncommon site. These tumors are moderately cellular and
infiltrative, often enlarging, that distorts, but does not
destroy neighboring anatomical structures. They arise from
the white matter and extensively infiltrate the adjoining
grey matter. These are difficult to eradicate surgically.
Anaplastic astrocytoma (WHO grade III) arises in the
same locations as diffuse astrocytomas, with a preference
for the cerebral hemispheres. These tumors show
increased cellularity, marked mitotic activity, and a
tendency to infiltrate through neighboring tissue.
Glioblastoma multiforme (WHO grade IV) tumors
occur most often in the subcortical white matter of the
cerebral hemispheres. Combined fronto-temporal location
with infiltration into the adjacent cortex, basal ganglia,
and contra lateral hemisphere is typical. Glioblastoma is
the most frequent tumor of the brain stem in children, while
the cerebellum and spinal cord are rare sites. These tumors
are highly cellular, with high proliferative and mitotic
activity. Although rapid and extensive invasion of
surrounding tissue is common, distant metastasis within
or outside the CNS is rare.
Cytogenetic abnormalities of childhood astrocytomas
are seen in chromosomal 9,13 and 17. MRI with DTPA
enhancement is generally preferred diagnostic mean.
Pilocytic astrocytomas are hypointense and enhance on
T1 (Fig. 10.7.1) and hyperintense on T2 weighted images.
Principal treatment is gross total resection, whenever
483
Figure 10.7.1: Post gadolinium T1 weighted transverse MRI

image of brain showing a well defined heterogeneously
enhancing mass lesion in the right cerebellar hemisphere.
Biopsy proven case of cerebellar astrocytoma.
possible. Total resection depends upon the location and

grade of the tumor. Patients who develop significant
obstructive hydrocephalus may require ventriculoperitoneal shunt. Post-operative radiotherapy is indicated in
recurrence. Chemotherapy has a limited role. High-grade
astrocytoma and diffuse pontine lesions are treated with
radiation.
Medulloblastoma
Medulloblastoma accounts for 10-20 percent of primary
CNS tumors and approximately 40 percent of all posterior
fossa tumors. It is a highly invasive embryonic
neuroepithelial tumor derived from primitive neurons and
neuroblasts present in the fetal granular layer, a superficial
layer of cerebellar cortex presents at birth. It has the
tendency to disseminate throughout the CNS early in its
course. Morphologically similar tumors arising in the
pineal region are termed pinealoblastomas, and those
arising in other CNS locations are called PNETs. Ataxiatelangiectasia is a known common association. The most
frequent cytogenetic abnormality in sporadic
medulloblastoma and PNETs is loss of heterozygosity for
the short arm of chromosome 17 [i (17q)]. Other common
losses of heterozygositiy involve 8p, 11p, 10p, 11q, 16q,
20q and 20p. Gains have been found at 7q, 17q, 18q, 7p,
13q and 18p. Several biological markers has been studied
484
as prognostic factors in these primitive tumors, of these,

TrkC mRNA, MYC mRNA expression seems to be the most
prognostic factors. Male to female ratio is 2:1 and the peak
age is two to four years.
As the tumor grows, obstruction of CSF generally
occurs, resulting in hydrocephalus. Tumor may spread
contiguously to the cerebellar peduncle, floor of the fourth
ventricle; brainstem, cervical spine, or above the tentorium.
It can also spread to the leptomeninges and spinal cord
through the CSF. Of all the pediatric CNS tumors,
medulloblastoma has the greatest propensity for extra
neural spread, especially to bone and bone marrow. Early
clinical features include unsteadiness and features of
raised ICT.
Macroscopically, these tumors are soft, friable and well
demarcated from remainder of the cerebellum.
Histologically, these are highly cellular. These tumors
express a variety of neuronal and neuro endocrine
markers, including synaptophysin and neurofilament
proteins. Photoreceptor differentiation is identified in 27
to 50 percent of these tumors and glial fibrillary acidic in
13 to 62 percent.
MRI with gadolinium-diethylenethriaminepentaacetic
acid (DTPA) enhancement is generally preferable
diagnostic mean (Fig. 10.7.2). Medulloblastoma is
isointense to grey matter on T2-weighted images. The goal
of treatment is to achieve a gross near total resection with
reduced dose posterior fossa radiotherapy followed by
chemotherapy. The overall event free 5 years survival is
60 to 70 percent. After recurrence, less than 25 percent
children survive for 5 years.
Ependymomas
Ependymomas are the third most common brain tumor
after astrocytoma and medulloblastoma. They account for
6 to 15 percent of childhood brain tumors. These can arise
from any part of the ventricular system, the roof and floor
of fourth ventricle are the most common sites. These tumors
are less infiltrative than astrocytomas. Microscopically,
the tumor is composed of uniform looking cells.
Ependymomas with increased cellularity, pleomorphism,
mitosis and necrosis are termed anaplastic. Paradoxically
calcification in the tumor has poor prognosis.
Chromosomal abnormalities noted are deletion of
chromosome 22, trisomy of chromosome 7 and loss of sex
chromosome. Most of these tumors are hypointense and
enhance on T1 (Fig. 10.7.3) and are hyperintense on T2
Figure 10.7.2: Post gadolinium T1 weighted sagittal MRI image

of brain showing a well defined intensely enhancing mass
lesion expanding the fourth ventricle and dispalcing the brain
stem anteriorlyBiopsy proven case of medulloblastoma.
weighted images. Total resection of the infratentorial

tumor is a favorable prognostic factor, though it is difficult
and dangerous. Complete resection should be followed
by radiation. For incomplete resections, radiochemotherapy is advised. For supratentorial ependymomas,
limited field radiotherapy and chemotherapy are
recommended.
Brainstem Gliomas
They account for 10 percent of childhood brain tumors.
All brainstem gliomas are malignant by virtue of their
location. Morphologically these are nonhomogeneous
group, ranging from the benign well differentiated
astrocytoma to the highly malignant glioblastoma. Mostly
arise from pons, 80 percent are diffusely infiltrative and
50 percent are histologically malignant. The four cardinal
presenting features are cranial nerve palsies, pyramidal
tracts signs, cerebellar signs and usually with out features
of raised ICT. Tumors appear hypointense on T1 (Fig.
10.7.4) and hyperintense on T2. Common differential
diagnosis include, brain abscess, granulomas, dermoid
and epidermoid cysts. Treatment depends upon the
tumors resectability. If resectable then complete resection
with radiotherapy and for infiltrative tumors, radiotherapy
and chemotherapy are the treatment options.
Figure 10.7.3: Post gadolinium T1 weighted coronal MRI image

of Brain showing a well defined rim enhancing lesion in the
3rd ventricleBiopsy proven case of 3rd ventricle
ependymoma.
Craniopharyngioma
It is located in the sellar region and arises from the
remnants of the embryonal Rathkes pouch. Chromosomal
485
imbalances are rare. As it expands forward, it compresses

the optic chiasma, with downward expansion, the
pituitary gland and upward expansion the third ventricle
is compressed. Macroscopically, they are partially or
completely cystic and microscopic picture can vary greatly.
Dystrophic calcification is characteristic. Main clinical
features include, vision defects, endocrine abnormalities,
raised ICT, ataxia and intracranial calcification.
The tumor is readily demonstrated by imaging studies.
Other common space occupying lesions in sellar and
suprasellar areas are optic glioma, chondroma, arachnoid
cyst and meningioma. With microscopic surgical
techniques, total resection of the mass with minimal
neurological, endocrine and visual dysfunction is possible
in 70 to 90 percent of patients. But the resective role of
radical surgery and limited surgery with radiotherapy
continue to be debatable. Therapeutic options include total
resection, subtotal resection with observation, subtotal
resection with radiotherapy, cyst aspiration and
instillation of intracavitary radiation or bleomycin.
Endocrine disturbances are generally exacerbated after
surgery. Most common deficiency (almost 100%) is growth
hormone followed by gonadotropins (93%). Diabetes
insipidus develops in two third cases. Post-operative
obesity and psychological deficits are common and
include, visual perception defects and lack of inhibitory
control.
CONCLUSIONS
Figure 10.7.4: FLAIR Coronal MRI images of brain showing

an ill defined mass lesion expanding the the ponsbiopsy
proven case of pontine glioma.
Progress in treating brain tumors creates a challenge: As

more and more children survive longer, the quality of life
after treatment becomes an increasingly important issue.
The late effects of brain tumor therapy include neurological
and neuropsychological, endocrine, and, rarely, secondary
neoplasm. These conditions create a lasting medical,
emotional, and financial burden, which has a significant
impact on the patient, his family, and society. The present
goal is to continue to improve cure rates and lower death
rates and also to reduce the long-term side effects of
therapeutic interventions. Technical advances in surgical
procedures will allow for safer tumor resections, and new
targeting techniques will permit safer irradiation. Increased
delivery of chemotherapeutic agents by disruption of the
blood-brain barrier also is being studied. The future of
oncological therapy probably lies in a better understanding
of the basic mechanisms of oncogenesis, however, allowing
for more specific and less toxic medications. The combi-
486
nation of immunology and cytogenetics, including

antitumor gene therapy and monoclonal antibodies, are
promising alternatives to standard therapy. An aggressive
approach to supportive care has been instrumental in
decreasing perioperative morbidity and mortality in
children with brain tumors, and pediatricians can play a
crucial role in perioperative care, appropriate management
of infection, nutrition, and overall health maintenance.
4.
BIBLIOGRAPHY
7.
1. Agamanolis DP, Malone JM. Chromosomal abnormalities

in 47 pediatric brain tumors. Cancer Genet Cytogenet
1995;81:125-34.
2. Aicardi J. Tumors of the central nervous system and other
space occupying lesions. In Diseases of the nervous
system in childhood. 2nd edn. Cambridge university
press; 1998;491-533.
3. Albright AL. Pediatric brain tumors. CA Cancer J Clin
1993;43:272-88.
5.
6.
8.
9.
10.
Bernald L Maria, John H Menkes. Tumors of nervous

system. In: John H menkes, Harvey B Sarnat, Bernald L
Maria, (Eds). Child Neurology, 7th edn. Lippincott
Williams and Wilkins, Philadelphia; 2006;729-802.
Cohen ME, Duffner PK. Tumors of the brain and spinal
cord including leukemic involvement. In Pediatric
Neurology principles and practice. 3rd edn. Mosby Inc
volume two; 1999;1049-98.
D Rocco C, Massimi L, Caldarelli M, et al. Cerebral tumors
in children less than one year of age. Neuro-Oncology
2004;6:419.
Dyer S, Prebble E, Brundler M, et al. Genomic imbalance
in high and low grade astrocytomas. Neuro-Oncology
2004;6:405.
Mickle JP. Neurosurgery for pediatric brain tumors.
Semin Pediatr Neurol 1997;4:273-81.
Pomeroy SL, Tamayo P, Gaasenbeek M, et al. Prediction
of CNS embyonal tumors outcome based og gene
expression. Nature 2002;415:436-42.
Richmond IL, Wilson CB. Parasellar tumors in children,
clinical presentations, preoperative assessment, and
differential diagnosis. Childs Brain1980; 7:73.
10.8 Raised Intracranial Pressure

Intracranial pressure (ICP) is defined as pressure within
vault that results from interaction of the brain (80-85%),
cerebrospinal fluid (CSF 10-15%) and the cerebral blood
volume (CBV-5-10%). Monro (1783) and Kellie (1824)
doctrine states that, the alteration in the volume of one
compartment must be compensated for opposite change
in another compartment to keep ICP same. Normal ICP in
children varies with (newborn 3.5, toddler 6.5 and older
6-13 mm Hg). Raised ICP if not treated, results in ischemia,
dysfunction of autoregulation, herniation and death. ICP
cannot rise beyond arterial blood pressure.
Etiopathogenesis
Intracranial pressure fluctuates during day, and is greater
in supine position. Coughing and sneezing are also
known to increase the ICP. Normal brain is capable of
dealing these transient changes. The initial increase in
volume of intracranial contents is compensated by
displacement of CSF in spinal canal, decrease in CSF
production, increase in CSF absorption and displacement
of blood in dural sinuses. The cerebral blood flow (CBF)

must be kept constant to provide oxygen and nutrients to
the brain. The major adaptive mechanisms available to
relieve pressure are compressibility of the brain and rapid
reabsorption of CSF by arachnoid villi. In children the
cranial bones are unfused and hence provide an extraadaptive defence mechanism. Whenever intracranial
volume exceeds the capacity of vault to expand, ICP rises
dramatically. The raised ICP will result in failure of
autoregulation thus increasing CBF (normal 50-60 ml/
min/100 gm of brain). Cerebral blood flow is under
neurogenic control (5-10%) and is also affected by
hypercarbia, hypoxia, CPP, CMRO2, SjO2, MAP and
dividing by Cerebrovascular Resistance (CVR). Once
autoregulation is lost, cerebral perfusion pressure falls
(normal more than 60 mmHg). Cerebral Perfusion Pressure
(CPP) is the difference between MAP and ICP. The mean
arterial pressure (MAP) can be calculated by multiplying
diastolic blood pressure by 2, adding systolic blood pressure and then divide by 3. Under such condition raised

ICP become detrimental to nerve cells. There are three
grades of ICP, mild (15-22.5 mmHg), moderate (22.5-30
mmHg) and severe (37.5 mmHg).
Various etiological factors and mechanisms involved
in raised ICP are:
1. Increased intracranial volume Subdural hematoma,
hemorrhage, tumor and infarction.
2. Acute brain swelling Anoxia, acute hepatic failure,
birth asphyxia, hypertensive encephalopathy, Reyes
syndrome.
3. High venous pressure Cardiac failure, superior
mediastinal obstruction, cerebral vein thrombosis.
4. Obstruction in CSF flow and absorption Hydrocephalus,
meningitis.
5. Increase in CSF production Choroid plexus tumor
6. Benign intracranial hypertension Discussed in chapter
10.9.
7. Causes of raised ICP in PICU Fever, agitation, emotions,
noxious stimulus, head turning, REM sleep, electrolyte
disturbances, volume overload, seizure, hypoxia,
PEEP, hypertension, vasodilator drugs, DKA, free
radical production, encephalitis and expanding
lesions of skull.
Clinical Features
Symptoms and signs of raised ICP are due to secondary
pressure effects and tissue shift and often depend upon
rate of rise in ICP and underlying disease. Various clinical
features of raised ICP are:
a. Headache Persistent headache especially in early
morning often bioccipital or bifrontal is a result of
stretching of dura, venous sinuses and sensory nerves.
b. Vomiting Usually projectile and often present early
in the morning.
c. Increase in head size Seen in children below 2 years of
age.
d. Visual changes It includes enlargement of blind spot,
decrease in visual acuity, diplopia, squint and
papilledema (a reliable sign of increased ICP).
e. Personality changes Irritable, lethargy, apathy and
disturbance in speech.
f. Shrill cry, sunset sign.
g. Herniation syndrome Severe brain edema and pressure
difference in various tissues of brain lead to herniation
during which part of brain get impacted in abnormal
location (transtentorial, central, tonssilar, and angular
herniation).
487
Following features of herniation may be present:

Impaired consciousness
Abnormality of pupil
Irregular respiration
Hypertonicity
Paresis
Decerebrate or decorticate posture
Altered body temperature
Cardiovascular collapse.
h. Systemic effects Cushings triad (irregular respiration,
bradycardia and hypertension due to brain-stem
compression), pulmonary edema, myocardial
dysfunction, GI and urogenital hemorrhage.
Diagnosis
A detailed history and physical examination should be
carried out. Laboratory workup includes acid-blood-gases
(ABG), blood sugar, complete blood counts (CBC), LFT,
serum osmolality, electrolytes, cultures and toxic screen.
Skull radiogram may reveal separation of sutures and
erosion of sellae. CT and MRI studies are done to establish
the etiology. Lumbar puncture is relatively contraindicated.
ICP Monitoring
Various indications of ICP monitoring are GCS less than
8, decerebrate/decorticate posturing, bilateral or unilateral
pupil dilation, CT showing edema and midline shift, head
injury, CNS infections, and intraoperative management.
The relative contraindications of ICP monitoring are awake
patients and coagulopathy. Accurate assessment of ICP
and monitoring is essential. The purpose of ICP monitoring
is to maintain cerebral perfusion, detection of changes in
ICP and to prevent ischemia and herniation of brain.
Monitoring will also help in different therapeutic modalities
and efficacy of treatment of ICP. Various methods of ICP
monitoring are:
a. Invasive methods: Subdural, parenchymal and intraventricular catheters, cerebral oxygen monitoring,
PbCO 2, screw and bolt devices, Ladd devices,
cardiosearch pneumatic sensor, etc.
b. Noninvasive methods: Scalp blood flow monitoring,
pneumoelectronic switch, CT, MRI, tympanic
membrane displacement, transcranial Doppler
ultrasonography, ultrasonic transducers.
488

TABLE 10.8.1: Modalities of treatment
Basic Therapies
1. Maintain ABCs (Airways, breathing and circulation), keep SaO2 100%, PaCO2 30-35, SjVO2 55-75%, MAP (appropriate
for age), Temperature 36-37C, CVP 5-10 mm. Keep ICP less than 20 mmHg. Determine optimal CPP (NB >30, 1mo-1yr > 40, 110yr > 50 and 10-15yr > 60).
2. Head position: CPP will be maximum if head is raised between 15 and 30 to provide venous drainage from brain (there is no
valve) and kept in midline in evolumic patients by putting towel rolls or cervical collor (to avoid distention of jugular veins which
impedes venous outflow thus leading to CBV and ICP). While turning the patient keep hip joint flexed less than 30.
3. Temperature control: Keep normothermic (36-37C) as rise in temperature will increase the metabolic rate, thus result in
CBF, CBV and ICP.
4. Blood pressure: Maintain mean arterial blood pressure in the normal range for age.
5. Seizure control: Seizure increases cerebral oxygen consumption and diminishes the capacity to maintain ICP. Midazolam 0.10.2 mg/kg/IV given every 5 minutes till seizures are controlled, load the patient with phenytoin.
6 Fluid: Keep patient normovolemic, give isotonic fluids (Normal saline). Do not use D5W. Hypotension, if present should be
treated aggressively.
7. Ventilation: Maintain PaO2 more than 80 mmHg and PaCO2 of 30-35 mmHg.
8. Paralysis and sedation: Sedation decreases the sympathetic activity thus reduces hypertension and plays a key role in
management. Paralysis is used during controlled ventilation.
9. Lidocaine: It helps in acute reduction of pressure (1.5 mg/kg). It should also be instilled locally before endotracheal tube
suctioning to avoid coughing.
10. Osmotherapy:
a. Both osmotic and loop diuretics are used. Mannitol in low-dose 0.25-0.5 mg/kg of 20% solution given as bolus
and may be repeated 4-6 hourly. It helps by decreasing CSF production, stabilizing membrane, opens BBB,
decreases blood viscosity thus increasing CBF, increased brain compliance, cerebral vasoconstriction and as an
antioxidant.
b. Furosemide: 0.5-1.0 mg/kg/IV may be given alone or with osmotic diuretics.
c. Oncodiuretic therapy.
11. Steroids: Steroids are used in vasogenic edema (tumor, abscess and organized subdural hematoma). Dexamethasone:
Loading dose 1 mg/kg, then 0.25 mg/kg/IV 6 hourly.
12. Hyperventilation: Maintain mild hyperventilation if required, the effect will start within 30 sec and peak in 8 minutes. This will
lead to vasoconstriction and decrease in cerebral blood flow thus resulting in acute reduction of raised ICP.
13. Prevent external stimulus, monitor signs of over stimulation, keep noise level less than 90 db.
Advanced therapies (ICP monitoring is required)
Barbiturate coma.
Moderate hypothermia (32-36).
Decompressive craniotomy/durotomy/lobectomy.
Operative treatment of mass lesions.
Ventricular drainage/VP shunt.
Neuromuscular blocking agents.
Treatment
It should be started when there is clinical evidence of raised
ICP or sudden increase in ICP, i.e. more than
20 mm Hg for more than 3 minutes or 16 to 20 mm Hg for
more than 30 minutes. Various modalities of treatment
described in brief are shown in Table 10.8.1. Gradual
reduction of therapeutic modalities should be done.
Pupillary response should be assessed periodically.
BIBLIOGRAPHY
1.
Dean JM, Rogers MC, Traystaman RJ. Pathophysiology

and clinical management of the intracranial vault. In
Rogers MC (Ed): Textbook of Pediatric Intensive Care.
Baltimore, Williams and Wilkins, 1987;527-55.
2. Emily L, Dobyn S, Anthony G et al. Current Pediatric
Diagnosis and Treatment. Lange Medical Book, 2003;321.
3. ICP monitoring and treatmentOrland Health Care and
Education-2000.
4. Krishnamoorthy KS, Todres DT. Management of
cerebral edema and intracranial hypertension. The Indian
Journal of Pediatrics 1994;61:27-32.
489
10.9 Benign Intracranial Hypertension

Benign intracranial hypertension or idiopathic intracranial hypertension (IIH) also known as pseudotumor
cerebri (PTC) is characterized by headache, papilledema,
raised intracranial pressure without any cause, normal
CSF components and normal or small ventricle size of
brain on imaging studies. Historically, another term used
for this order is otitic hydrocephalus. However, there are
causes bearing close relationship to PTC but failing to
comply with one or more of the accepted criteria. Therefore, Johnston et al, proposed the term pseudotumor syndrome, to broaden the concept of PTC, to include cases
showing intracranial hypertension without ventriculomegaly and being secondary to a presumed disorder
of CSF circulation. The annual incidence of IIH is 1 per
100,000 population and varies from country to country.
Specific etiology may be found in children below 6 years
of age, while cases seen above 11 years are usually of
idiopathic in nature.
Classification of PTC in children according to Brodsky,
Baker and Hamed is given in Table 10.9.1.
Etiology
Following are the possible causes of pseudotumor cerebri
in children.
a. Drugs: Nalidixic acid, tetracycline, steroid, lead
toxicity, nitrofurantoin, fluroquinolones, lithium,
phenothiazines.
b. Infections: GB syndrome, Roseola infantum, lateral
sinus thrombosis.
c. Metabolic and endocrinal: Hypervitaminosis A, vitamin
A and D deficiency, galactosemia, Addisons
disease, obesity, menarche, hypoparathyroidism,
pseudohypoparathyroidism, hypocalcemia, growth
hormone therapy, chronic CO2 retention, catch-up
growth in nutritionally deprived infants and diabetic
ketoacidosis (treatment).
d. Hematological: Polycythemia, iron deficiency anemia,
hemolytic anemia, leukemia, non- Hodgkins
lymphoma, Wiskott-Aldrich syndrome.
e. Vascular: Obstruction of intracranial venous drainage
and superior vena cava.
f. Traumatic: Minor head injury
g. Miscellaneous: Sydenhams chorea, Lymes disease.

Bells palsy and SLE, DPT immunization, cystic
fibrosis, chronic otitis media, systemic infections.
Pathogenesis
The mechanism of raised intracranial pressure in
pseudotumor cerebri is controversial. Various theories
have been put forth on the basis of CSF dynamics:
Alteration in CSF absorption or production and it may
be due to edema of arachnoid villi and venous
obstruction.
Cerebral edema which is interstitial and cytogenic type
may be due to increase in cerebral blood volume and
impaired CSF absorption.
Decrease cerebral flow and venous obstruction which
result in venous engorgement, elevated venous
pressure and associated elevation of intracranial
pressure.
Why the CSF spaces do not dilate is still unclear?
Clinical Features
Symptoms may be acute or gradual in onset and both sexes
are equally affected. Obesity may be associated with many
cases. Infants and young children may present with
irritability and somnolesence. Headache followed closely
by diplopia are principal symptoms as a result of raised
intracranial pressure. Less common symptoms are transient
visual obstruction, nystagmus, neck stiffness, tinnitus,
ataxia, pulsatile intracranial noise, seizures, movement
disorders, paresthesia and rarely facial paresis.
Neurological examination is normal except for
papilledema with enlargement of blind spot, early optic
nerve atrophy and abducens nerve palsy. Consciousness
is preserved and no focal neurological signs are present.
The anterior fontanel is full in infants and Macewen sign
may be positive in older children. There is no risk of
herniation. Mortality rate associated with PTC is no more
than in general population.
Diagnosis
The diagnosis of pseudotumor cerebri is by exclusion and
usually established when the following modified Dandy
criteria is met:
490
a. Signs and symptoms of raised intracranial pressure,

i.e. headache, nausea, vomiting, transient obscuration
of vision and papilledema.
b. Absence of localized findings on neurological examination except 6th cranial nerve paresis.
c. Absence of deformity displacement, or obstruction of
the ventricular system in otherwise normal
neurodiagnostic studies, except for increased CSF
pressure (> 250 mmH2O), and
d. Alert and oriented patient, no other cause of increased
intracranial pressure present.
The condition should be differentiated from migraine,
AV malformation, aneurysms, cavernous sinus malformation, encephalopathy (toxic or metabolic) and
infectious, inflammatory disease of brain. Laboratory
workup should be based on detailed history and physical
examination.
CT with contrast enhancement should be done prior
to lumbar puncture to rule out other causes. The results of
CT scan and MRI are normal or may demonstrate small
ventricular size and obliteration of normal sulcal marking
due to increased cerebral volume. LP may reveal raised
pressure (0-2 yr 75 mm H2O, 2-5 yr 135 mmH2O and above
5 yr 200 mmH2O). It may be raised falsely in a crying child
thus sedation may be required prior to LP. CSF composition
is normal. The protein contents are usually low. Skull
radiogram may show separation of sutures and erosion
of the dorsum sellae. Electroencephalography shows
excessive slow wave activity of theta range with occasional
paroxysmal burst of high voltage slowing. Visual system
must be assessed.
TABLE 10.9.1: Classification of pseudotumor cerebri

1. Primary pseudotumor cerebri
A. No recognized cause (idiopathic or benign)
2. Secondary pseudotumor cerebri
A. Pseudotumor cerebri associated with neurological
cause
B. Pseudotumor cerebri secondary to systemic diseases
C. Pseudotumor cerebri secondary to ingestion or
withdrawal of exogenous agents.
3. Atypical pseudotumor cerebri
A. Occult pseudotumor cerebri (no papilledema)
B. Normal pressure pseudotumor cerebri
C. Infantile pseudotumor cerebri.
pressure. This may be sufficient to reverse the process in

many cases. Children with raised intracranial pressure
are usually treated with acetazolamide (5 mg/kg/24 hr
or 150 mg/m2/qd) following lumbar puncture. The dose
may be titrated on the basis of clinical response. The risk
of hypokalemia, acidosis and renal calculi (if used above
6 months) must be monitored. In spite of above measures,
if patient still have raised pressure then a course of
prednisolone 2 mg/kg may be given and depending upon
the response the duration is adjusted. Low salt diet and
weight reduction may be tried in adolescents. Digoxin,
glycerol and topiramate have also been tried in
management of IIH.
Lumboperitoneal shunting (LPS) and optic nerve
sheath fenestration (ONSF) are recommended if above
measures fail to relieve symptoms or optic nerve atrophy
supervenes. Visual monitoring is required during followup. In general, the prognosis is very good.
Treatment
Pseudotumor cerebri is usually self-limiting benign
condition, but optic atrophy and blindness are most
important complications. The goals of therapy are to:
Identify and treat underlying cause.
Relieve neurological symptoms, and
Avoid permanent visual loss.
The initial lumbar puncture is both diagnostic and
therapeutic in the management of raised intracranial
BIBLIOGRAPHY
1. Bergman I. Increased intracranial pressure. Pediatr Rev
1994;15:241.
2. Roberto Warman, MD. Management of pseudotumor
cerebri in children. International pediatrics. 2000;15:3.
3. Soler D, Cox T, Bullock P et al. Diagnosis and management of benign intracranial hypertension. Arch Dis Child
1998;78:89.
491
10.10 Motor Weakness in Infancy and

ChildhoodClinical Approach
Vrajesh Udani
The clinical evaluation of motor symptoms in the pediatric
patient is often a challenge. The neurological examination
of an irritable, crying, uncooperative infant can be quite
tiring. The physician has to rely on the parents, who if not
observant, may confuse things further.
A brief outline of the important motor pathways, salient
features on neurological examination and clinical patterns
of motor weakness are discussed.
A description of the upper motor neuron (UMN
supraspinal and spinal motor pathways) and lower motor
neuron (LMNthe motor unit) follows:
Corticospinal Tract (CST)
It has its origin in the motor cortex (MC) situated on the
side of the rolandic fissure. There are contributions from
the premolar and sensory cortices. Lesions in only the
motor cortex result in unilateral weakness mainly in the distal
hand, leg or lower half of the face. The proximal muscles
may become transiently weak, recover fairly quickly due
to supplementary motor area, subcortical and basal
ganglia influences. If area 8 (anterior to the MC) is involved
a transient contralateral gaze paresis is seen. Cranial
musculature is mostly bilaterally represented except for
the lower half of the face. However, there is a lot of variation
in corticospinal tract (CST) when it traverses the
subcortical white matterthe so-called corona radiata and
occupies the posterior limb of the internal capsule where
it lies in close proximity to the basal ganglia. A lesion here
causes dense hemiplegia often associated with dystonia.
The CST when winds its way down in the anterior cerebral
peduncle of the midbrain, close to the IIIrd nerve. Lesions
in the brainstem cause 'crossed hemiplegias' with ipsilateral
cranial neuropathies (IIIrd in the midbrain, VI and VII in
the pons, XII in medulla). Ipsilateral cerebellar
dysfunction may be associated.
When the ascending reticular activating formation is
involved, disturbances of consciousness may result.
Spinal Cord
Anatomically, this has the gray matter in the center
arranged in an H and the white matter surrounds this
in anterior, lateral and posterior columns. The central gray
matter has the anterior horn with the alpha and gamma
motor neurons and the posterior horn has several masses
of nuclei, concerned with sensory input coming through
the dorsal root ganglia. The alpha motor neurons receive
input from major descending tracts and project to the
corresponding myotome.
In clinical practice, lesions involve both systems and
lead to a combination of signs. Hence in complete spinal
cord lesions, one gets lower motor neuron signs at the level of
the lesion in the form of wasting, weakness, hypotonia and
decreased reflexes. Below the lesion, there are signs of
spasticity, weakness, increased deep tendon reflexes,
absent superficial reflexes and bilateral Babinski signs. If
the lesion is acute, there is initial hypotonia with
diminished reflexes. Bladder/bowel involvement is more
common with intrinsic lesions.
The other spinal cord syndrome is the poliomyelopathy syndrome, where only the anteior horn cells are
involved, either segmentally or diffusely with only lower
motor neuron signs without sensory involvement.
Motor Unit
The cranial and spinal motor neurons receive direct or
indirect input from the CST as well as other tracts
(reticulospinal, rubrospinal, vestibulospinal, etc.), which
originate in the brainstem. The alpha motor neurons project
their axons through the ventral roots and the motor nerves
and via the neuromuscular junction to the extrafusal fibers,
which are primarily responsible for muscle contraction.
The gamma motor neurons receive their afferent inputs from
the muscle spindle and regulate tone and length of muscle
with the help of supraspinal influences.
Disorders of the motor unit have varying combinations
of weakness, hypotonia and decreased/absent deep
492
tendon reflexes. Anterior horn cell and ventral root/plexus

diseases cause weakness in specific myotomes, peripheral
nerve diseases generally cause distal more than proximal
weakness and muscle diseases cause more proximal
weakness.
Neuromuscular junction disorders have a predilection for
ocular, pharyngeal and proximal limb muscles. Anterior
horn cell diseases and peripheral nerve diseases have early
loss of reflexes with little correlation with muscle
weakness, while in muscle and neuromuscular junction
diseases, reflexes are lost late and more so in weaker
muscles. Fasciculations indicate anterior horn cell or
peripheral nerve involvement while myotonia is seen
exclusively in muscle disease.
HEMIPLEGIA
Approach
In children, the first step is to make sure that the hemiplegia is due to a corticospinal deficit: It must be
distinguished from hemichorea or hemiataxia.
The acuteness of onset in hemiplegias help in
determining etiology. Hyperacute onset, sometimes associated with seizures, indicate cerebrovascular disease. If
the hemiplegia occurs after seizures the other
consideration is a post-ictal Todds paresis which can
sometimes be prolonged. Status epilepticus can cause a
permanent focal deficit. Onset over a couple of days is
seen with demyelinating disorders while gradual onset
over a few weeks is seen with tumors. Common etiological
factors are listed in Table 10.10.1.
The examination should determine associated deficits.
Aphasia and hemianopias indicate cortical or subcortical
lesionsmore often the latter. Seizures are more often in
cortical lesions. Associated dystonia which usually
develops later, suggests concomitant basal ganglia
involvement. Brainstem lesions have either associated
ipsilateral cranial neuropathies, ataxia or subtle
corticospinal deficits on the opposite side.
Hemiplegic Cerebral Palsy
This is usually secondary to prenatal or perinatal
cerebrovascular disease (CVAs) or cortical malformations
usually disturbances in neuronal migration. Causes of
perinatal ischemic CVAs are different in term and preterm
infants. In the latter, periventricular leucomalacia (PVL)
an ischemic white matter lesion associated with sepsis/
maternal chorioamnionitis is the most common cause of
TABLE 10.10.1: Common causes of acquired hemiplegia

Acute onset
1. Stroke
Arterial ischemic
Venous
Hemorrhagic
2. Acute postconvulsive hemiplegia
3. Traumatic brain injury
4. Infectious Meningoencephalitis
Bacterial, TB, viral, fungal
Acute disseminated encephalomyelitis
Brain abscess
Subdural empyema
Metabolic disease MELAS, homocysticuria
Insidious onset
1. TumorsBrainstem or supratentorial
2. InfectionsSSPE
3. Cervicomedullary junction lesions (spinal hemiplegia)
Atlantoaxial dislocation
Tumors, cysts
4. Metabolic diseasesLeukodystrophies
5. Rasmussens encephalitis
spastic cerebral palsy. Periventricular and intraventricular

hemorrhage occurs often in very preterm babies from the
immature germinal matrix and can cause hemiplegic
cerebral palsy. In the term baby, cerebral infarction due to
cardiac or placental emboli, trauma, thrombosis due to
sepsis and associated disseminated intravascular
coagualtion may be causal. This is usually prenatal.
Hemorrhagic disease of the newborn (Vitamin K deficiency)
can lead to intracranial hemorrhage in the 3rd to 8th week
of life, specially in breastfed infants receiving antibiotics.
Diagnosis rests on demonstration of prolonged PT and often
PTT, and treatment consists of fresh frozen plasma and IV
vitamin K.
Cerebrovascular Diseases (CVAs)Stroke
CVAs are infrequent in children with an incidence of 2.5
in 100,000 in western countries. They may be higher in
developing countries because of infections and rheumatic
heart disease.
Infections Any meningitis can cause stroke either by
involvement of the arteries (tuberculosis, syphilis and
fungal infections), or by involvement of the veinsthrombophlebitis as occurs in bacterial meningitis and
subdural empyemas. Treatment primarily aims at specific
antimicrobial drugs, use of steroidsshort term for
bacterial and longer term for TBM, and management of
complications like hydrocephalus.

Hematologic diseases Sickle cell disease is a major cause
of stroke in western countries with large black populations.
It is seen specially in tribals from central India. Immediate
treatment consists of exchange transfusion to remove the
sickled RBCs and sickle hemoglobin. Recurrence may be
seen in 60 to 70 percent. Transfusions are given
periodically to suppress the marrow and keep the HbSS
below 30 percent. This can be instituted even before clinical
stroke using transcranial doppler. Chelation therapy is
needed to obviate iron overload.
Hypercoagulable states Inherited or acquired deficiencies
of natural anticoagulants are probably common causes of
stroke. Heterozygosity for deficiency of protein C, protein
S, antithrombin III, etc. should always be looked for, as
they may need long-term anticoagulation. Factor V laden
mutation causing resistance to activated protein C is an
important cause. Antiphospholipid antibodies are also
commonly associated with ischemic strokes. Tissue
plasminogen activator (tPA) has not been adequately
evaluated in children so far. Thrombosis is usually venous
and is precipitated by dehydration, surgery, infections
and drugs.
Vasculopathies Moya-moya is an important cause and is
characterized by supraclinoid internal carotid artery (ICA)
occlusion bilateraly. Vasculitis associated with varicella
is increasingly being recognized.
Acute Paraplegia/Quadriplegia
The causes of both are similar. Legs are involved more
often and earlier than the arms. Causes include spinal
cord disorders and disorders of the motor unit. Nonneurological painful disorders with apparent weakness
(pseudoparalysis) are seen in conditions like scurvy,
osteomyelitis and fractures. Acute myositis can also mimic
paralysis. Evaluation of the spinefor deformity (e.g.
gibbus in Potts spine), scoliosis (spinal cord tumor) and
tenderness is critical. Involvement of bladder and bowel
suggests spinal cord lesion. Sensory abnormalities are
difficult to confirm in small children but if present, are
suggestive.
Spinal Cord Disorders
Compressive myelopathy This usually causes subacute or
chronic symptoms. The important causes include
infections, congenital lesions, malignancies, vascular and
other lesions. Important amongst these is tuberculosis,
493
which can cause spinal meningitis, extension of TB spine,

and damage the cord by direct compression, vasculitis,
and ischemic damage. Spinal meningitis is sudden while
TB spine is slowly progressive.
Congenital
This is mostly due to occult spinal dysraphism or
craniovertebral abnormalities. Tethered cord and diastomatomyelia are often associated with scoliosis and
abnormalities on the overlying skin, e.g. tuft of hair and
lipoma. Dermal sinuses might also be present and provide
an avenue for CNS infections. Craniovertebral junction
abnormalities are usually congenital, or caused by trauma,
and include atlantoaxial dislocation, basilar invagination
etc. These may be associated with a short neck, low hairline,
mucopolysaccharidosis or Down syndrome. They usually
come with a more indolent quadriparesis, but can present
acutely with minor neck trauma. Spinal cord tumors can
be causal.
Diagnosis of spinal cord compression rests on plain
radiology of the appropriate spinal level followed by an
urgent MRI of the spine with contrast. A CT myelography
is the next best option. Vascular malformations would
need spinal angiography.
Treatment Initial treatment of even suspected cord
compression should start with intravenous high-dose
methylprednisolone as an antiedema measure. In tumors,
surgical decompression is required for a tissue diagnosis
and therapy. Specific treatment if possible, should also be
given, e.g. appropriate antimicrobials, local radiation and
chemotherapy.
Transverse Myelitis
This is often a misnomer as several segments may be
involved. It may occur alone or as part of a more diffuse
process, e.g. encephalomyelitis. The pathogenesis is
presumed to be immune mediated, precipitated by an
infectious insult. The child gets back pain followed by a
rapidly evolving paraplegia with early onset of bladder
dysfunction. Sensory levels are noted, posterior column
sensations, i.e position and vibration are uniformly
affected. MRI depicts swelling and hyperintensity of the
cord on T2 weighted images, the edema may be severe.
Ischemic myelopathies should be excluded. These usually
have dissociated sensory loss with preservation of
position/vibration sense and loss of pain/temperature
below the level of the lesion. Treatment basically consists
of limiting the damage and supportive care. Pulse
494
intravenous methylprednisolone is the mainstay of

treatment, and is often associated with dramatic
improvement. IVIG is another option.
Motor Unit Disorders
These are more common causes of flaccid para/
quadriplegia than the spinal cord disorders. They may
affect the anterior horn cell as in the polio and enteroviral
infections, the peripheral nerves and roots as occurs in
the Guillain-Barr syndrome (GBS) and its variants, e.g.
acute motor axonal neuropathy (AMAN), neuromuscular
transmission defects as in acute botulism, periodic
paralysis and myasthenic crisis and finally in muscle
disease as in acute infectious myositis and dermatomyositis.
Specific treatment consists of either plasma exchange (PE)

to remove the circulating immune complexes, or IVIGa
total of 2 g/kg over two days, or 400 mg/kg daily for 5
days. IVIG is as effective as PE, if not more and is much
easier to administer. The illness is usually benign. Majority
of children recover on their own. The rapidity of improvement and the persistence of deficit is clearly affected by
the use of the above therapies.
Acute Motor Axial Neuropathy (AMAN)
AMAN is similar to GBS, with the major difference being
that only axons are involved and the myelin is spared.
There is a relation to Campylobacter jejuni infection and
recovery is good despite a prolonged course.
Enteroviral Infections
Guillain-Barr Syndrome
This is probably the commonest cause of acute flaccid
paralysis. It is an immune antibody mediated attack on
the peripheral nerve myelin with a predilection for the
proximal root. It is associated with several anti-ganglioside
antibodies.
Clinically, it presents acutely with leg pains and
stiffness. The child often refuses to walk or starts limping.
Weakness progresses rapidly for about 2 to 4 weeks. There
is symmetric involvement of the legs, trunk, arms and often
cranial nerve involvement of the VII and lower cranial
nerves, giving rise to dysphagia and nasal twang.
Respiratory muscles are invariably affected in severe cases
and are the most common cause of mortality. Autonomic
manifestations include cardiac arrhythmias and fluctuations of blood pressure. The clinical picture along with
characteristic slowing of nerve conduction velocities and
increased CSF protein without a cellular response, suggest
the diagnosis.
Treatment is supportive with prevention of aspiration,
frequent checks on respiratory status and intervening with
intubation and ventilation at the first sign of fatigue.
With the pulse polio program, poliomyelitis is rapidly

diminishing. Clinically, the child has high fever, meningismus, back spasms, leg pain and tenderness. Preparalytic
form is more frequent. The paralysis is usually asymmetric
in the lower limbs, though any muscle can be affected.
Paralysis may be preciptated by the use of intramuscular
injections or by exertion. Respiratory and bulbar
involvement is possible.
CSF shows cells and mildly increased protein.
Pleocytosis is initially polymorphonuclear and later
mononuclear. Stool cultures are positive and an essential
part of acute flaccid surveillance. Paired sera help in
diagnosis.
Treatment is supportive with rest to the muscles and
relief of pain. Respiration may need support.
Coxsackie and ECHO viruses give rise to milder
disease. CPK is elevated. The natural history is one of
rapid improvement and only supportive treatment is
enough.
Vaccine associated poliomyelitis (VAP) is a rare
complication of the live vaccine and gives rise to a milder
disease sometimes in contacts of those given the vaccine.
495
10.11 Floppy Infant Syndrome

R Anandam, D Kalpana
Floppy infant syndrome is the term used to denote infantile
hypotonia. The infant is limp, immobile and is often
compared to a rag doll. Three main clinical features of
hypotonia are:
Maintenance of unusual postures
Increased resistance of joints to passive movements
Increase in the range of movements of joints.
Thus the baby assumes a pithed frog appearance with
the hips abducted and externally rotated with loss of
postural tone. When the infant is examined in ventral
suspension, the floppy infant will have marked head lag
and floppiness of the trunk arms and legs, whereas a normal
infant will have straight back, arms flexed at elbows and
partially extended at the shoulder and partially flexed
knees. In the supine position, traction on the hands to
raise the shoulders off the couch will show marked head
lag. Pectus excavatum is present when the infant has longstanding weakness in the chest wall muscles. Newborns
that are hypotonic in utero may be born with hip
dislocation, multiple joint contractures (arthrogryposis),
or both. Hip dislocation is a common feature of
intrauterine hypotonia.
The maintenance of normal tone requires intact central
and peripheral nervous systems. Not surprisingly,
hypotonia is a common symptom of neurological
dysfunction and occurs in diseases of the brain, spinal
cord, anterior horn cells, peripheral nerves, neuromuscular junction and muscles. One anterior horn cell and all
the muscle fibers that it innervates make up a motor unit.
The term cerebral hypotonia encompasses all causes of
postural hypotonia caused by a cerebral disease or defect.
All motor unit disorders (lower motor neuron disorders)
producing floppiness are characterized by significant muscle
weakness; in contrast to cerebral hypotonia where the weakness
is minimal compared to hypotonia. The baby will be able to lift
the limb off the couch in upper motor neuron disorders. In
infancy and childhood, cerebral disorders far outnumber
motor unit disorders.
Differential Diagnosis of Floppy Infant
1. Upper Motor Neuron Causes
1. Chromosomal
a. Turner syndrome
b. Down syndrome
c. Prader-Willi syndrome
2. Infection
a. Sepsis
b. Meningitis
c. Encephalitis
3. Metabolic/Endocrine
a. Hypocalcemia
b. Hyponatremia
c. Hypoglycemia
d. Hypothyroidism
e. Aminoaciduria
4. Perinatal trauma
a. Perinatal asphyxia (HIE)
b. Hemorrhage
2. Lower Motor Neuron Causes
1. Anterior horn cell
a. Spinal muscular atrophy
b. Poliomyelitis
2. Peripheral nerve
a. Congenital hypomyelinating neuropathy
b. Demyelinating neuropathies
3. Neuromuscular junction
a. Transient neonatal myasthenia gravis
b. Congenital myasthenia
c. Infantile botulism
4. Muscle
a. Congenital myopathy
b. Congenital myotonic dystrophy
c. Congenital muscular dystrophy
d. Metabolic and endocrine myopathies
APPROACH TO DIAGNOSIS
The first step in diagnosis is to determine whether the
disease location is in the brain, spine, or motor unit. More
than one site may be involved.
Cerebral hypotonia in newborns usually does not pose
diagnostic difficulty. The history and physical
examination identify the problem. Many clues to the
diagnosis of cerebral hypotonia exist. Most important is
the presence of other abnormal brain functions: decreased
496
consciousness and seizures. Cerebral malformation is the

likely explanation for hypotonia in an infant with
dysmorphic features or with malformations in other organs.
A tightly fisted hand in which the thumb is constantly
enclosed by the other fingers and does not open
spontaneously (fisting) and adduction of the thigh so that
the legs are crossed when the infant is suspended
vertically (scissoring) are precursors of spasticity and
indicate cerebral dysfunction. The tonic neck reflex is an
important indicator of cerebral abnormality if the
responses are excessive, obligatory, or persist beyond age
6 months. When hemispheric damage is severe but the
brainstem is intact, turning the head produces full
extension of both ipsilateral limbs and tight flexion on the
contralateral side. An obligatory reflex is one in which
these postures are maintained as long as the head is kept
rotated. Tendon reflexes are generally normal or brisk,
and clonus may be present.
FEATURES OF CEREBRAL HYPOTONIA

History of birth asphyxia
Seizures
Dysmorphic features
Persistent fisting of the hands
Malformations of other organs
Normal or brisk tendon reflexes
Scissoring on vertical suspension.
Chromosome Disorders
Despite considerable syndrome diversity, common
characteristics of autosomal chromosome aberrations in
the newborn are dysmorphic features of the hands and
face and profound hypotonia. Eg. Down, Turner, PraderWilli syndromes.
Cerebral Dysgenesis
This may be due to known or unknown noxious
environmental agents, chromosomal disorders, or genetic
defects. In the absence of an acute encephalopathy,
hypotonia may be the only symptom at birth or during
early infancy. Hypotonia is usually worse at birth and
gets better with time. Cerebral dysgenesis should be
suspected when hypotonia is present along with
malformations in other organs or abnormalities in head
size and shape. Magnetic resonance imaging (MRI) of the
head is advisable when cerebral malformation is suspected.
Brain injuries occur in the perinatal period and, less
commonly, throughout infancy secondary to anoxia,
hemorrhage, infection, and trauma. The premature
newborn showing a decline in spontaneous movement

and tone may have an intraventricular hemorrhage.
Hypotonia is an early feature of meningitis in full-term
and premature newborns. Tendon reflexes may be
diminished or absent during the acute phase.
Genetic Disorders
Several genetic disorders cause infantile hypotonia. Many
are syndromic and can be diagnosed by the associated
features. Infantile hypotonia is rarely the only
manifestation of inborn errors of metabolism. Acid maltase
deficiency(Pompes disease) causes a severe myopathy.
The doll like facies and associated cardiomyopathy
clinches the diagnosis. The initial features of pyruvate
carboxylase deficiency are neonatal hypotonia, tachypnea,
and movement disorders. Hypotonia may be the only
initial feature of generalized GM1 gangliosidosis.
Diseases of Spinal Cord
Hypoxic-ischemic myelopathy is an expected outcome in
severe perinatal asphyxia. Affected newborns are
hypotonic and areflexic. Because the injuries are always
associated with a difficult and prolonged delivery,
decreased consciousness is common and hypotonia is
falsely attributed to asphyxia or cerebral trauma. However,
the presence of impaired sphincter function and loss of
sensation below the chest should suggest myelopathy.
MOTOR UNIT DISORDERS
Disorders of the motor unit are not associated with
malformations of other organs except for joint deformities
(Fig. 10.11.1). Tendon reflexes are absent or depressed. In
neuropathy loss of tendon reflexes is early. Depression of
reflexes is proportionate to muscle weakness in myopathy
and the ankle jerk is retained till late in the course of
disease. Muscle atrophy suggests motor unit disease but
does not exclude the possibility of cerebral hypotonia.
Failure of growth and even atrophy can be considerable
in brain-damaged infants. The combination of atrophy
and fasciculations is strong evidence of denervation.
However, the observation of fasciculations in newborns
and infants is often restricted to the tongue, and
distinguishing fasciculations from normal random
movements of an infants tongue is difficult unless atrophy
is present.
497
Congenital myotonic dystrophy is often diagnosed by

demonstrating myotonic potentials in the mother of the
baby.
Studies of nerve conduction velocity are useful in
distinguishing axonal from demyelinating neuropathies;
demyelinating neuropathies cause greater slowing of
conduction velocity.
Repetitive nerve stimulation studies demonstrate
disturbances in neuromuscular transmission.
Muscle biopsy can clinch the diagnosis in congenital
myopathies, spinal muscular atrophy and muscular
dystrophies.
Investigations
Figure 10.11.1: Motor unit disorders
Features of Motor Unit Disorders
Absent or depressed tendon reflexes

Failure of movement on postural reflexes
Fasciculations
Muscle atrophy
No abnormalities of other organs
Evaluation of Motor Unit Disorders

As the DNA based diagnosis is commercially available
for many disorders e.g. Spinal muscular atrophy (SMA), it
is preferred to electrodiagnosis or muscle biopsy. Such
investigations are done only when results of DNA
diagnoses are inconclusive or unavailable.
Serum creatine kinase is elevated in muscular
dystrophies. But can be seen elevated in asphyxiated
newborns.The values may be mildly elevated in congenital
myopathies.
Electrodiagnosis
Needle EMG studies help to differentiate myopathies from
neuropathies.The appearance of brief, small-amplitude,
polyphasic potentials characterizes myopathies; the
presence of denervation potentials at rest (fibrillations,
fasciculations and sharp waves) and motor unit potentials
that are large, prolonged, and polyphasic characterize
denervation.
DNA-based testing
Serum creatine kinase
Electrodiagnosis
Electromyography
Nerve conduction studies
Repetitive stimulation
Muscle biopsy
Serum electrolytes, glucose
Renal function tests
Spinal Muscular Atrophy (SMA)

SMA constitutes a major group of floppy babies. SMA is
classified into 3 types, (1-3) depending on the age of onset
and progression. SMA type 1 is the most severe form and
presents as floppy infant. The symptoms start in utero
with history of decreased foetal movements, marked
hypotonia, poor feeding, difficulty in swallowing and
labored breathing due to involvement of intercostal
muscles. The weakness is more proximal than distal. The
infant is very alert with good cognitive development.
Fasciculations are seen on the tongue. Tendon reflexes
are completely absent. The infants do not survive beyond
2 years and death is by respiratory failure.
Most SMA cases are associated with deletions or
mutations in exons 7 and 8 of the telomeric copy of spinal
musculat atrophy gene (SMN1- survival motor neurone1)
in chromosome 5q11.2-13.3.
DNA diagnosis is now widely available which helps
in prenatal diagnosis. The disease are inherited in an
autosomal recessive fashion.
The diagnosis is often clinical which can be confirmed
by DNA diagnosis. EMG and muscle biopsy are used
when these facilities are unavailable or results
inconclusive.
498
Disorders of Neuromuscular Transmission
proximal muscles. Tendon reflexes are depressed.

Contractures occur in about 50 percent of infants. Variants
of the disease are associated with mental retardations
seizures, joint contractures or visual impairment.
Diagnosis is confirmed by markedly elevated CPK values
and findings of dystrophy in muscle biopsy.
Congenital muscular dystrophy with cerebral and
cerebellar involvement has been recognized in Japan and
later in many countries and is called Fukuyama type of
muscular dystrophy. MRI brain reveals periventricular
white matter changes and cysts in cerebellar white matter.
Familial Infantile Myasthenia
Congenital Myotonic Dystrophy
Several genetic defects in the neuromuscular transmission

can cause congenital myasthenic syndrome. All are
autosomal recessive except for the slow channel syndrome,
which is an autosomal dominant trait. Among the
autosomal recessive forms, the causative mutation in one
is in the choline acetyltransferase gene on chromosome
10q; another maps to chromosome 17. All genetic
myasthenic syndromes are seronegative for antibodies that
bind the acetylcholine receptor (AChR). Both the genetic
and clinical features are the basis for classifying
congenital myasthenic syndromes. Neostigmine test is
often negative.
These infants present as floppy infants with ocular,
bulbar or respiratory weakness which is worsened by
excessive crying, after feeding or activity. The tendon
reflexes are preserved. Some may partially respond to
anticholinesterase drugs.
The newborns present with myopathic facies, hypotonia,

and feeding difficulties. CPK is moderately elevated. The
disease is transmitted in an autosomal dominant fashion,
but in majority of children presents in newborn period,
mother is the affected parent. History of difficulty in
releasing the hand grip of mother clinches the diagnosis.
Myotonia may be demonstrated in needle EMG of mother.
Myotonia is not detectable in the baby, it may develop
later.
Polyneuropathies
Polyneuropathies are uncommon in early infancy as a
cause of floppy infant syndrome. These neuropathies
present with distal muscle weakness with wasting and
sensory disturbances. Only with congenital hypomyelinating neuropathy is infantile hypotonia the initial feature.
The others are more likely to start as progressive gait
disturbance or psychomotor retardation. Rarely Guillian
Barr syndrome can present in infancy.
Transient Neonatal Myasthenia

It occurs in about 10 percent of babies born to myasthenic
mothers and is due to transfer of acetyl choline receptor
antibodies from the mother. The affected infants have weak
cry, difficulty in sucking and swallowing, hypotonia and
muscle weakness. Some may need ventilation and
parenteral neostigmine. The symptoms resolve
spontaneously within a few days.
Muscle Diseases
Congenital Muscular Dystrophies
They are a group of muscle disorders appearing
sporadically, or transmitted as an autosomal recessive
trait. These infants are hypotonic at birth, with proximal
or generalized motor weakness involving face, trunk and
Congenital Myopathies
A variety of congenital myopathies have been recognized
and they present at birth. Inheritance follows autosomal
recessive pattern. Clinical features include hypotonia,
muscle wasting and developmental delay.
Some children have a myopathic facies. CPK is normal
or mildly elevated. Diagnosis is confirmed by muscle histochemistry and electron microscopy. Disease are named
from the appearance of muscle biopsy, e.g. central core
disease, nemaline myopathy, mini core disease and
congenital fiber type disproportion.
Metabolic Myopathies
Glycogenosis type 2 is called Pompes disease. It is
characterized by severe hypotonia, hepatomegaly and
cardiac involvement. Muscle weakness is due to primary
involvement of muscle and anterior horn cell due to
denervation.
BIBLIOGRAPHY
1. Bradley. Neurology in clinical practice. 5th edn. 394-400.
2. Fenichel GM. Clinical Pediatric Neurology: A Signs and
Symptoms Approach, 5th edn. Elsevier, 2005.
499
10.12 Muscular Disorders in Children

K Pandian
Muscle disorders in childhood present a wide spectrum
of handicap and distress in childhood. Most of the
difficulties are insidious in onset and are noted when the
child starts walking or as late as when child goes to school.
Unfortunately, most of the disorders are crippling and are
associated with a shortened life-span. Muscle weaknesses
may be acute or chronic. The chronic disorders comprising
the dystrophies are discussed in this chapter.
Presenting Features of Muscular Weakness in Children
Presenting symptoms
General
Weakness
Fatigability
Frequent falls
Slower than peers
Lower Limb
Abnormal gait
Waddling-hip weakness
Steppage gait-weak dorsiflexors
Toe walking-weak peroneal
Difficulty in climbing up/downstairs
Difficulty in getting up from squattingGowers sign
Upper Limb-difficulty in
Elevation of arm
Grooming hair
Dressing undressing
Weakness of hand grip
Change in handwriting
Head and Neck
Double vision
Difficulty in swallowing chewing, sucking, whistling,
blowing
Alteration of voice
Floppy neck.
Children may appear normal at birth. Most of them

have normal motor milestones. But in retrospect some
children have definitive history of delayed motor
milestones. The weakness starts in the proximal muscles
and more in the lower limbs. Frequent tripping, stumbling
and falling may be the presenting complaints due to
weakness of evertors and dorsi-flexors of the foot.
Abnormal gait such as steppage gait, toe walking and
waddling appear in established weakness. Child has
difficulty in climbing stairs which is due to weakness of
hip extensors and descending stairs due to quadriceps
weakness. Has difficulty in keeping up to the speed of his

classmates and has considerable difficulty in crossing
obstacles. Later there is difficulty in getting up from a
squatting posture to standing up and the child typically
climbs up on his legs, the Gowers sign. Walk becomes
waddling due to weak hip muscles and unstable pelvis.
Weakness of proximal muscles of upper limbs is
manifested as difficulty in reaching up a cupboard,
combing hair, reaching behind to remove dress and later
on, weakness of hands and fingers.
Weakness of muscles of head and neck may present as
difficulty in vision, drooping of eyelids, difficulty in
chewing, sucking, whistling and alteration of speech.
Examination
It is always better to observe the child sit, stand and walk
in any suspected muscle disease with under-garments
only. Prominence of muscles, wasting, atrophy and
contractures are easily made out. Child is made to walk
on toes and heels to make out weakness of gastrocnemius
and anterior compartment muscles respectively. Always
examine neck and ocular muscles for weakness. Look for
contractures, myotonia, strength and tendon reflexes.
MUSCULAR DYSTROPHIES
Muscular dystrophies are a group of progressive
genetically determined disorders predominantly affecting
skeletal muscles resulting in wasting and weakness.
Molecular studies help in establishing accurate diagnosis, detect
preclinical cases, identify carriers and defects. Classification
is mostly by clinical and immunochemistry and gene
typing are useful for sub-typing (Table 10.12.1).
Classification of Muscular Dystrophies
1. Duchenne and Becker muscular dystrophy (DMD,
BMD)
2. Emery-Dreifuss muscular dystrophy (EDMD)
3. Limb girdle muscular dystrophy (LGMD)
4. Congenital muscular dystrophies (CMD)
5. Facioscapulohumeral dystrophy (FSHD)
6. Oculopharyngeal dystrophy
7. Distal myopathies
8. Myotonic dystrophy
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TABLE 10.12.1: Genetic basis of Muscular Dystrophics

Disease
X-linked recessive
1. DMD/BDM
2. EDMD
Autosomal dominant
3. LGMD 1A
4. Myotonic dystrophy 1
5. FSHD
6. Oculopharyngeal
dystrophy
Autosomal recessive
7. LGMD 2A
8. Congenital muscular
dystrophy type 1
gene locus
Protein/gene
product
Xp21
Xq28
Dystrophin
Emerin
5q22-31
19q13.2
4q35
14q
Myotilin
DM/ZFN9
?not identified
Polyalanine
Binding protein
Figure 10.12.1: DMD with calf muscle hypertrophy

15q15
Calpain3
6q21-22
Merosin[laminin-2]
DUCHENNE (DMD) AND BECKER (BMD)

MUSCULAR DYSTROPHY
DMD has X-linked recessive inheritance with a
prevalence of 1/3,500 male births. About one-third of cases
are from spontaneous mutation in dystrophin gene
located in chromosome xp21.
BMD is a milder form of dystrophinopathy than the
more severe DMD phenotype with which it is allelic.
Pathology
Dystrophin, a large cytoskeletal protein is intimately bound
to sarcolemma and provides structural integrity to muscle
membrane. High mutation rate is due to the large size of
the gene. Large deletions or duplications in the gene
account for about 70 percent of cases of DMD. Size of
deletion or its location does not correlate with severity of
lesion. Screening of 19 exons by multiplex polymerase
chain reaction identifies about 98 percent of all deletions.
Clinical Features
Most children appear normal at birth and achieve
satisfactory milestones with slight delay. Frequent falls
are noted as the first manifestation at about 3 to 6 years of
age along with clumsy walk. Proximal weakness is more
than distal and lower limbs are more weaker and involved
earlier. Weakness is present in neck flexors, hip girdle
muscles and then the shoulder girdle. Hypertrophy of calf
muscles is prominent by 3-4 years of age. Vastus lateralis
infraspinatus, deltoid and occasionally gluteus maximus
show hypertrophy. Muscle mass tends to decrease in later

stages especially in leg muscles, and distal muscles of
arms and legs also exhibit weakness as disease progresses.
Most children have prominent calf muscles with toe
walking as classical presentation with increased lordosis
(Fig. 10.12.1).
Knee jerks tend to diminish early in contrast to ankle
jerk which may be elicited for many years. They have
progression of muscular weakness and loss of ambulation and are confined to wheelchair by 12 years of age.
Patients without calf hypertrophy can be identified by
presence of valley sign visible behind shoulders (Pradhan
sign).
Cardiac dysrhythmias, progressive cardiomyopathy
[especially the non-steroid treated group] and cardiac
failure occur late. Gastroparesis and pseudo-obstruction
can occur. The average IQ of these patients is also below
mean. Joint contractures, scoliosis and respiratory
impairment are common in the non-ambulatory stage of
illness. Death occurs mostly from respiratory and cardiac
complications. The mean age of death in untreated group
is around 19-20 years .
The severity of BMD is variable. They are ambulatory
past 15 years of age and slowly progressive with a lifespan
even up to 40 years. This may manifest with myalgias,
cardiomyopathy and asymptomatic elevation of CK.
Investigations
Genetic studies have largely replaced the need for painful
biopsies and ENMG. Serum creatine kinase is markedly
elevated 50 to 100 times normal but can drop in late stages
of disease. [Do not depend on CPK values alone for diagnosis].
Muscle biopsy shows fiber degeneration and regeneration.

Immunochemistry shows absent dystrophin staining on
the muscle membrane. Western blot analysis of quantity
and size of dystrophin present is possible and is presently
the investigation of choice.
Management
Gene therapy and stem cell therapy holds much promise
for children with DMD in the near future.
Obesity can become a issue in ambulation and proper
diet management is necessary especially when started on
steroids.
Medical Management
Drugs
Steroids have been tested widely. They improve the
weakness and the quality of life. They are of no use once
the patient is confined to wheel-chair or bed and
preferably stopped at that stage. Prednisolone 0.75 mg/
kg/day to a maximum of 40 mg/day, is effective in
increasing the function and strength, improves pulmonary
function and helps slowing of the rate of deterioration.
Effects can be seen in two weeks and probably last for 3
years. An alternative high-dose treatment with 10 mg/kg
per week in two divided dose on 2 consecutive days each
week has been tried with effectiveness. Side effects of
prednisolone are risk of infections, cataract, hypertension,
osteoporosis, weight gain and irritability.
Deflazacort an analog of prednisolone at a dose of
0.9 mg/kg/day has been tried with equal effectiveness
and less side effects.
501
Braces are helpful in delaying the eventuality of

wheelchair.
Long leg brace/knee ankle-foot orthroses[KAFO]stabilizes
the knee. Disadvantages include stiff legged gait, useful
on level ground. Standing frames can be used when the
child is no longer able to walk. High top boot with upright
double braces gives excellent stability.
Wheel chairs/hoist- both manual and powered wheel
chairs are now available tailored to suit individual needs
and help in activities indoor and outdoor. Proper wheel
chair sizing, solid back support, and solid seating are
important to prevent spinal deformities.
Surgery Spinal instrumentation and fusion may be
necessary to correct scoliosis. Percutaneous tenotomy of
tendo-achilles, knee flexors, hip flexors and iliotibial
bands helps to a certain extent. Patient should be
monitored during and after surgery watching for cardio
respiratory depression. Avoid depolarizing muscle
relaxants.
Genetic Counseling
Daughters of males with BMD and mothers of affected
children are obligate carriers of mutant gene. Serum CK
can be elevated in female carriers (50%) but not always.
DNA analysis is most reliable method.
Prenatal diagnosis can be made with DNA analysis of
chorionic villi or amniotic fluid cells.
LIMB GIRDLE MUSCULAR DYSTROPHIES (LGMD)
Emerging therapiesThese include creatine, useful in

increasing muscle supply of phosphocreatine 0.1g/kg/
day and glutamine 0.6 g/kg/day; Coenzyme q10;
Myostatin inhibitor which acts on myostatin, a negative
regulator of muscle growth have been tried.
It has equal occurrence in males and females. Autosomal

dominant varieties are classified as type 1 and recessive
forms as type 2. Manifestations can be either like DMD or
BMD. Investigations are non-specific. Immunochemistry
shows normal dystrophin. Staining for sarcoglycans,
merosin and dysferlin are useful to know subtypes.
Supportive Therapy and Appliances
CONGENITAL MUSCULAR DYSTROPHY (CMD)
A group involving neurologist, psychiatrist, physiotherapist, genetic counsellors and the whole family is more
helpful. The aim is to avoid contractures and
physiotherapy to be started as early as possible around 3
to 5 years.
They are a autosomal recessive disorders. Mostly present

with hypotonia, proximal weakness and joint contractures.
Several subtypes are described.
They show absence or marked deficiency of
extra-cellular matrix protein merosin. They are classified
as merosin positive or negative. They are based on clinical,
ophthalmological, radiologic and pathological features.
Serum CK is elevated. Fukuyama type presents with severe
mental retardation, contractures, microcephaly and
seizures.
Assistive devices: Ankle foot orthroses [AFO] at night

combined with day time stretching are useful in ambulatory
stage. They should be applied in daytime also once
ambulation is lost to keep gastrocnemius soleus tendons
stretched.
502
FACIOSCAPULOHUMERAL
MUSCULAR DYSTROPHY (FSHMD)
It is inherited as autosomal dominant linked to
chromososme 4q35.
Age of onset is usually 3 years to adult age. Initial
involvement of facial muscles, shoulder girdle and humeral
muscles is an early sign. Scapular winging occurs due to
weakness of muscles which stabilize the scapula.
Asymmetry of motor deficits, sparing of deltoid, neck flexor
and calf muscles, retinal vasculopathy with telangiectasia,
hearing loss involving high frequencies are added
supportive findings. Wasting of upper arm when
compared to forearm gives the typical appearance. Lower
limbs also develop weakness especially anterior
compartment muscles. CK is moderately elevated.
progresses very slowly to proximal muscles. Myotonia is

prominant in hands. Frontal balding, cataracts, wasting
of facial and masseter muscles are characteristic. Cardiac
abnormalities are common, usually conduction defects.
Involvement of diaphragm and intercostal muscles
common. EMG demonstrates myotonic discharges.
Congenital form is severe and presents with hypotonia,
facial weakness, respiratory and feeding difficulties.
If myotonia is severe phenytoin/mexiletine can be tried.
Cardiac complications need treatment and periodic
pulmonary functions need to be done. Type 2 has later
onset and less cardiac complications.
At present most patients can be accurately labelled as
gene localization and immunochemistry are available.
There is no definitive treatment to alter the mortality and
morbidity. The future of these patients lies in realization
of gene therapy.
EMERY DREIFUSS MUSCULAR DYSTROPHY (EDMD)

BIBLIOGRAPHY
It is caused by mutation in gene xq28 which encodes for
protein emerin.
Three forms X-linked, autosomal recessive, autosomal
dominant are recognized. Features are slowly progressive
muscular atrophy and weakness mostly of
humeroperoneal distribution, contractures at tendoachilles, elbows, posterior cervical muscles, and
cardiomyopathy with conduction defects. Deltoids are
spared and hypertrophy of muscles and facial weakness
do not occur. Contractures [upper extremity precedes
lower extremity] are disproportionate to the degree of
weakness. The disease is slowly progressive till third
decade. Female carriers have cardiomyopathy.
Serum CK may be normal or raised. ECG are useful to
pickup bradycardia and conduction defects.
MYOTONIC DYSTROPHY (DM)
It has an autosomal dominant inheritance. It presents at
any age from infancy. Limb weakness begins distally and
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Emery AEH. Muscular Dystrophy; the facts. Oxford

University Press, 2000.
Emma Ciafaloni. Treatment options for DMD. Current
treatment options in neurology 2008;23.
Gerald M Fenichell. Clinical paediatric neurology. 5th
edn, 2005.
Kenneth F. Swaiman Paediatric Neurology principles and
practice 4th ed, 2006.
Panigrahi I, Mittal B. Carrier Detection and Prenatal
Diagnosis in Duchenne/Becker Muscular Dystrophy,
Indian Pediatrics 2001;38:631-9.
Martin A Samuel. Manual of neurological therapeutics.
7th edn, 2004.
Mukherjee M, Mittal B. Muscular dystrophies. Indian J
Paed 2004;71:161-8.
Neuromuscular diseaseNeurology in practice. splsupplement 2003.
Pradhan S. Valley sign in DMD. Neurol India 2002;50(2):
184-6.
Gupte S. Recent advances in paediatrics; spl vol 9;
Neurology 2001.
11.1 Congenital Heart Disease: General Aspects: NC Joshi .................................................................................................................. 504

11.2 Common Congenital Heart Diseases in Children: Anita Khalil, M Zulfikar Ahamed ...................................................................... 509
11.3 Medical Management of Congenital Heart Diseases: Anita Khalil, Bharat Dalvi ............................................................................ 518
11.4 Surgery for Congenital Heart Diseases: KS Dagar, KS Iyer, Srikanta Basu ................................................................................... 521
11.5 Rheumatic Fever and Rheumatic Heart Disease: Anita Khalil ......................................................................................................... 526
11.6 Congestive Heart Failure in Children: Anita Khalil ............................................................................................................................ 534
11.7 Systemic Arterial Hypertension in Children: Srikanta Basu, S Srinivasan .................................................................................... 538
11.8 Pericardial Diseases and Disorders: S Srinivasan, Srikanta Basu ................................................................................................... 548
11.9 Cardiac Arrhythmias in Children: S Srinivasan, Srikanta Basu ....................................................................................................... 551
504
11.1 Congenital Heart Disease:

General Aspects
NC Joshi
Congenital heart disease is one of the most common birth
defects accounting for 30 percent of total congenital
malformations. The heart is developed during the period
of embryogenesis from a primitive muscles wrapped tube
to a four chambered muscular organ with septa, valves,
conduction system and major vessels originating and
terminating in the heart. Any defect in the orderly and
sequential development leads to structural or functional
malformation.
Congenital heart disease is defined as the structural,
functional or positional defect of the heart in isolation or
in combination, present at birth but may manifest at any
time after birth or may not manifest at all.
Incidence6 to 8 per 1000 live borns have significant
structural cardiac malformation.
About 1 in 10 stillborn infants have a cardiac anomaly.
The eight most common anomalies account for over
80 percent of all lesions (Table 11.1.1) and about 10 to
15 percent have complex lesions with more than one
cardiac anomaly.
Previously diagnosis of the defect involved physical
examination, radiography of chest and electrocardiogram
(ECG), later invasive catheter studies. With the
introduction of ultrasound, echocardiography,
interventional cardiology, and intensive care facilities,
now:
1. Antenatal ultrasound increasingly offers early diagnosis.
2. Most structural heart defects are diagnosed noninvasively by echocardiography.
TABLE 11.1.1: The eight common congenital heart lesions
Acyanotic
VSD 32%
PDA 12%
Pulmonic stenosis 8%
ASD 6%
Coarctation of aorta 6%
Aortic stenosis 5%
Cyanotic
Tetralogy of Fallot 6%
Transportation of great arteries 5%
3. An increasing number of defects are treated nonsurgically, e.g. patent ductus arteriosus.
4. Even complex defects can be corrected completely at
initial operation, e.g. transposition of great vessels at
least in major cities in India.
5. The overall infant cardiac surgical mortality is on the
decline.
In adults a heart disease is mostly acquired in origin,
in children it is mostly congenital. The exception is
rheumatic heart disease.
Etiology
There is a major change in the understanding of etiology
of heart malformations. The prevailing dogma has been
that 8 percent of defects are due to chromosomal defects,
2 percent secondary to environmental teratogens
(intrauterine infections, cytotoxic drugs, radiation during
1st trimester) and the remaining 90 percent are multifactorial that is secondary to combined environmental
and genetic factors.
Based on indirect evidence (animal models) and
studies on human familiar patterns of inheritance, much
greater percentage has been attributed to single gene
mutation (Table 11.1.2).
Classification of Congenital Heart Diseases
There are various elaborate classifications. A simple
classification is into:
i. Acyanotic defect with left to right shunts
ii. Cyanotic defects with bidirectional shunts
iii. Defects that do not have shunt but have obstructive element (Table 11.1.3).
Some cardiac malformations are complex and cannot be described using Table 11.1.1. To simplify the
description of these defects, the sequential segmental
analysis has been developed. The heart is divided into
four segments, the great vein, the atria, the ventricles and
the arterial trunks. Abnormalities are described in each of
these segments and in the connections between them
(Table 11.1.4).
Diseases of Cardiovascular System

TABLE 11.1.2: Etiology of congenital heart disease
I.
Chromosomal abnormalities 8%
Incidence
21 Trisomy-Down
60%
syndrome
18 Trisomy90%
13 TrisomyX0-Turners
syndrome
90%
15%
Type of defect
A-V canal
defect
VSD, PDA,
DORV
Dextrocardia
Coarctation of
aorta
II. Environmental Teratogen 2%

I/U infection Rubella
Mumps
Maternal drugs
Phenytoin
Vitamin D
Alcohol
Maternal disease
Diabetes
Systematic Lupus
Types of defect
PDA, VSD, ASD
Endocardial fibroelastosis
Variable
Supravalvular aortic
stenosis
ASD, VSD
Transposition of great
vessels
Congenital heart block
TABLE 11.1.4: Sequential segmental analysis of the heart

Segment
Examples
Atrial situs
Venous
connections of
aorta
Atrioventricular
connections
Acyanotic defects with left to right

shunt
Ventricular septal defect
Patent/Persistent ductus arteriosus
Atrial septal defect
Relative
incidence
32%
12%
7%
Acyanotic defects without shunt (with obstruction)

Aortic stenosis
Pulmonary stenosis
Coarctation of aorta
5%
5%
5%
Cyanotic defects with bidirectional shunt

Transposition of the great arteries
Tetralogy of Fallot
Double outlet right ventricle
Truncus arteriosus
Pulmonary atresia
Mitral atresia
Tricuspid atresia
Total anomalous pulmonary venous
drainage
6%
5%
1%
1%
2%
1%
1%
1%
It is important to learn this segmental approach

because universally echocardiography analysis is
reported according to this sequential segmental analysis.
Ventriculoarterial
connection
Associated
anomalies
III. Single gene mutation 90%
TABLE 11.1. 3: Classification and incidence of congenital

heart defects
505
Solitus
Inversus
Left isomerism
Right isomerism
Total or partial anomalous
pulmonary venous
connection
Anomalous systemic venous
connections
Concordant
Discordant
Absent left connection (mitral
atresia)
Absent right connection
(tricuspid atresia)
Double inlet left ventricle
Concordant
Discordant
Double outlet right ventricle
VSD
ASD
PDA
Coarctation
Clinical Presentation
Despite a large number of cardiac defects that exist, there
are only limited numbers of hemodynamic alterations
caused by cardiac malformations and symptoms.
i. Mixing of systemic and pulmonary circulation leading to cyanosis.
ii. Inadequate blood reaching the lungs for oxygenation leading to cyanosis.
iii. Inadequate blood reaching the body: growth is
affected.
iv. Increase in volume and pressure load over ventricles leading to congestive heart failure.
v. Abnormal situs leading to positional malformation
dextrocardia.
vi. Dysfunction of intrinsic conduction system leading
to arrhythmias.
Cyanosis
Cyanosis is blue discoloration of the skin, mucous
membranes, nails due to presence of desaturated
hemoglobin more than 5 gm/dl percent in arterial blood.
Those cardiac anomalies in which systemic venous return
reaches systemic circulation without passage through
506
lungs, presents with central cyanosis and clubbing of

fingers.
Cyanosis occurs under following circumstances:
i. Reduced pulmonary blood flow in defects with right
ventricular outflow tract obstruction
ii. Right to left shunts as in tetralogy of Fallot
iii. Discordant ventriculoarterial connections as in
transposition of great arteries, and
iv. Mixing of venous and arterial blood as in truncus
arteriosus or single ventricle.
Heart Failure
When heart cannot supply the blood flow demanded by
tissues, a clinical syndrome of symptoms and signs
manifest from elevated atrial pressure. It manifests with
rapid and labored breathing due to pulmonary edema,
pallor with peripheral cyanosis due to poor cardiac
output, tachycardia and excessive sweating due to
increased sympathetic activity and feeding difficulties.
Heart failure occurs in following situations:
1. Volume overload In all defects, with left to right shunt
like ventricular, atrial septal defect, patent ductus
arteriosus
2. Pressure overload In pulmonary and aortic, valvestenosis
3. Intrinsic myocardial diseases In cardiomyopathies, and
myocarditis
4. Decreased or increased diastolic filling In tachyarrhythmias and bradyarrhythmias.
Heart Murmurs
In older children and in infants, congenital heart disease
presents as a heart murmur detected on routine
examination. The murmurs are produced due to
abnormal pressure gradient across laminar or nonlaminar pathways. The murmur is continuous in patent
ductus arteriosus, pansystolic in ventricular septal
defects, midsystolic in atrial septal defect and pulmonary
stenosis, diastolic in atrioventricular valve stenosis and
to and fro continuous murmur in congenital absence of
pulmonary valve.
Shock
Cardiac malformations resulting in a hypoplastic
ascending aorta, aortic atresia results in low cardiac
output. Child appears extremely ill with cold extremities, diminished pulses, low blood pressure, peripheral
cyanosis and in a semicomatose state.
Hypercyanotic Spells
In cardiac malformations with pulmonary infundibular
stenosis the obstruction is of dynamic variety. Whenever
the muscular outflow tract contracts, blood flow to
pulmonary circuit diminishes and patient gets intense
cyanosis. It occurs in Fallots tetralogy and defects with
Fallots physiology.
Stridor
Malformations leading to compression of trachea and
bronchi obstructing airways, presents with stridor as seen
in vascular rings and in dilated pulmonary artery due to
increased pulmonary blood flow.
Chest Pain
Malformation like anomalous origin of left coronary
artery, severe aortic stenosis leads to myocardial ischemia and patient presents with episodes of screaming,
pallor and chest pain.
Recurrent respiratory tract infections In cardiac defects
with left to right shunt, as seen with ventricular septal
defect and patent ductus arteriosus, there is a decreased
lung compliance which leads to frequent respiratory tract
infections.
Growth Failure
Growth failure is a very common manifestation of heart
defects due to poor oxygen saturation in the growing
tissues, persistent heart failure, and frequent respiratory
infections with undernutrition.
Diagnostic Investigations
The investigative tools that are available for diagnosis of
congenital heart diseases include chest radiography,
electrocardiography, echocardiography, cardiac catheterization, cineangiography and cardiac MRI. All tests
except ECG and radiography are expensive.
Radiography of Chest
If there is a suspicion of heart disease on the basis of
history and physical examination, radiography which
complements clinical findings should be obtained.
Interpretation of chest radiograph involves evaluation
of cardiac size and classical cardiac contours, lung
vasculature, individual cardiac chambers, aortic arch and
abdominal situs (Fig. 11.1.1).
Figure 11.1.1: The position of transducer and orientation of

the scanning for parasternal long axis image of the heart
507
Figure 11.1.2: Position of transducer for subcostal four

chamber image of the heart
Electrocardiogram
Like radiography, electrocardiogram also complements
clinical findings. The electrocardiogram gives valuable
information about
1. Hemodynamic status of the defect
2. Severity of the defect
3. A few electrocardiographic patterns are suggestive
of certain lesions.
Normal values of the various ECG parameters are
available and for interpretation age of the child should
be kept in mind. In newborns, normal ECG and radiograph do not rule out serious cardiac defect as it takes
few days to evolve.
Echocardiography (Figs 11.1.1 to 11.1.5)
With the advent of real-time echocardiography imaging,
an elegant elaboration of intracardiac anatomy of all
structural defects of heart became possible. Doppler
echocardiography can evaluate hemodynamic data
regarding pressure differences across the aortic and
pulmonary valves, detection of shunt flows, semiquantification of valve insufficiency. It has almost replaced
invasive cardiac catheterization and at some centers
surgical correction of lesions like PDA, ASD (ostium
secundum) is possible without catheterization.
Figure 11.1.3: Normal pressures and oxygen

saturation in heart and big vessels
Cardiac Catheterization
The classical invasive tool pertaining to pediatric
cardiology remains cardiac catheterization. As mentioned above, echocardiography has reduced diagnostic
508
Figure 11.1.4: Normal X-ray chest showing structures that

form right and left side of the heart
Figure 11.1.6: Position of transducer for apical four chamber
ii. Blade and balloon atrial septostomy

iii. Nonsurgical closure of PDA and ASD
iv. Catheter ablation of arrhythmogenic focus,
pacemaker implantation.
Management of Congenital Heart Defects
Figure 11.1.5: Position of transducer for imaging aortic arch
value of cardiac catheterization but interventional

therapeutic catheterization procedures have increased its
therapeutic value (Fig. 11.1.6).
Indications
Preoperative anatomical definition of the lesion
Preoperative physiological assessment of pulmonary
artery pressures, pressure gradients, etc.
Therapeutic interventional procedures
i. Balloon dilatation of stenotic valves and coarctation of aorta
Management is divided into medical management,

interventional management and surgical management.
Medical management is mainly concerned with prevention and treatment of medical problems.
i. Nutritional support including treatment of anemia
ii. Antibiotic treatment for
1. Frequent pulmonary infections in lesion with
L R shunt.
2. Infective endocarditis prophylaxis and treatment
3. Cerebral abscess commonly seen in cyanotic
heart diseases.
iii. Treatment of stroke seen in cyanotic heart defects
iv. Prevention and treatment of hypercyanotic spells
v. Antiarrhythmic treatment in arrhythmias
complete congenital heart block
paroxysmal SVT
vi. Use of prostaglandin E1 in shunt dependent congenital heart defects.
Surgical Strategies
1. Palliative surgeries mitigates symptoms or extends life
without addressing basic pathophysiology of cardiac
lesion.

Examples
509
BIBLIOGRAPHY
1. Systemic and pulmonary artery shunt

2. Pulmonary artery banding.
Corrective surgery when they are intended to
completely or nearly completely
1. Separate pulmonary and systemic circulation
2. Restore adequate quantities of appropriately oxygenated blood to capillary beds
3. Reduce volume and pressure overloads towards
normal.
1. HO SV Baker EJ, Rigby ML, Anderson RH. Color Atlas

of CHD. London, Mosby Wolfe 1995.
2. Jordan SC, Scott O: Heart Disease in Pediatrics (2nd edn)
1981;3:7.
3. Nora JJ. Causes of congenital heart disease: Old and new
modes. Am Heart J 1993;125:140919.
4. Skinner J, Alverson D, Hunter S. Echocardiography for
neonatologist. London, Churchill Livingstone 2000.
5. Walters HL. Congenital cardiac surgical strategies and
outcome: Hearts, Pediatric Annals 2000;29(8):48998.
11.2 Common Congenital Heart

Diseases in Children
Anita Khalil, M Zulfikar Ahamed
ACYANOTIC CONGENITAL HEART DISEASE
ATRIAL SEPTAI DEFECT (ASD)
Prevalence
ASD (ostium secundum defect) occurs as an isolated defect
in 6 to 10 percent of all congenital heart diseases. It occurs
twice as commonly in females than males. ASDs occur in
1 child/1000 live births.
Pathology
Three types of ASDs exist; secundum, primum and sinus
venosus defects (Fig. 11.2.1).
1. Ostium secundum defectIt is the most common

defect, accounting for 50 to 70 percent of all ASDs.
This defect is present at the site of fossa ovalis,
allowing left to right shunting of blood from LA to
RA.
2. Ostium primum defects30 percent of all ASDs.
3. Sinus venosus defectoccurs in about 10 percent of
all ASDs, most commonly located at the entry SVC
into RA.
Infants and children with ASD are usually asymptomatic.
Rarely, ASDs in infants are associated with poor growth,
recurrent lower respiratory tract infection and heart
failure.
Figure 11.2.1: Unlabeled arrow right superior

pulmonary vein
On auscultation (Fig. 11.2.2) A widely split and fixed S2

and grade 2 to 3/6 ejection systolic murmur are
characteristic findings of ASD in older infants and
children with a large L-R shunt, a mid-diastolic rumble,
resulting from relative tricuspid stenosis (TS), may be
audible at left lower sternal border.
These typical auscultatory findings may be absent in
an infant.
510
Figure 11.2.2: Cardiac findings of ASD. Heart murmurs with solid borders are the primary murmurs, and those without solid
borders are transmitted murmurs or those occurring occasionally.. Expexpiration, lnspinspiration
Figure 11.2.3: Tracing from a 5-year-old girl with secundum-type ASD
Electrocardiography (Fig. 11.2.3)

Right axis deviation (RAD) of + 90 to + 180 degrees. Right
ventricular hypertrophy (RVH) and right bundle branch
block (RBBB) with rSR pattern in VI are typical.
X-ray Studies (Fig. 11.2.4)
1. Cardiomegaly with right atrial and right ventricular
enlargement. (cardiothoracic ratio> 0.5).
2. Prominent main pulmonary artery may be seen in
large shunts.
3. Prominent pulmonary vascular markings.
Echocardiography (Fig. 11.2.5)
1. Two-dimensional echo-study is diagnostic. The study
shows the position as well as size of defect, which
can be seen best in subcostal four chamber view.
Figure 11.2.4: PA and lateral views of chest roentgenogram

from a 10-year-old child with ASD. The heart is mildly enlarged
with involvement of the RA (best seen in PA view) and the RV
(best seen in the lateral view with obliteration of the retrosternal
space). Pulmonary vascularity is increased and the
MPA segment is slightly prominent
In ASD secundumA dropout can be seen in mid atrial

septum.
511
Figure 11.2.5: Diagram of two-dimensional echo of the three types of ASD. The subcostal transducer position provides the most
diagnostic view. (A) Sinus venosus defect. Defect is located in the posterosuperior atrial septum, usually just beneath the orifice
of the SVC. This defect is often associated with partial anomalous return of the right upper pulmonary vein, (B) Secundum ASD.
Defect is located in the middle portion of the atrial septum. (C) Primum ASD. Defect is located in the anterointerior atrial septum,
just over the inflow portion of each AV valve
In ASD primumIt is a defect in lower atrial septum.

Sinus venosus defect (SVC type)Defect in posterosuperior atrial septum.
Coronary sinus ASD- communication at level of
coronary sinus.
2. Flow velocity is increased depending upon the shunt
which brings about dilatation of pulmonary artery and
enlargement of right atrium and right ventricle.
3. Pulsed Doppler examinationA characteristic flow
pattern with the maximum left to right shunt occurring
in diastole.
Color flow mappingIt evaluates the hemodynamic
status of ASD.
Doppler examinationIt estimates ressures in right
ventricle and pulmonary artery.
5. M-mode Echo may show increased right ventricular
dimension and paradoxical motion of the interventricular septumIt signifies RV volume. In older
children and adolescents transesophageal echo (TEE)
may be necessary to visualize the defect. Associated
Partial anomalous pulmonary venous connection may
be picked up by this method.
Natural History
i. In ASD less than 3 mmSpontaneous closure occurs
in 100 percent before one and half years of age. But if
the defect is more than 8 mm or age is more than 2
years it rarely closes spontaneously
ii. Most of the children remain active and asymptomatic, though CHF may rarely develop during
infancy
iii. If untreated, pulmonary vascular disease leads to
hypertension and subsequent CHF develops in the
3rd and 4th decades.
iv. Infective endocarditis does not occur in isolated

ASDs; therefore, prophylaxis against subacute
bacterial endocarditis (SBE) is unnecessary.
v. Onset of atrial fibrillation may occur and less
commonly atrial flutter occurs with increasing age.
Management
Medical
1. No exercise restriction is indicated.
2. In infantsCHF should be treated urgently because
of possibility of spontaneous closure.
3. Nonsurgical closure indicated nowadays by
clamshell or buttoned devices in uncomplicated
and smaller defects. But now Amplatzer Septal
occluder (ASO) is the only FDA approved device for
ASD closure.
Surgical Indications
1. Left to right shunt with a QP/QS ratio of more than 1.5
2. Some consider a smaller shunt to be an indication,
because of danger of paradoxical embolization and
cerebrovascular accident. High pulmonary vascular
resistance (PVR) (i.e. more than 10 units/rn2) is a
contraindication to surgery.
3. Device closure is not feasible or has failed
Timing and procedure Surgery is usually delayed till 2 to 4
years, because of the possibility of spontaneous closure.
But if CHF in infancy does not respond to medical
management, then surgery is indicated. The defect is
repaired under cardiopulmonary bypass with either a
simple suture or a pericardial or a teflon patch.
512
Complications and mortality: In the immediate postoperative

period, arrhythmias and cerebrovascular accidents may
develop. Fewer than 1 percent of patients die; however,
there is a greater risk for small infants or those with high
PVR.
Postoperative follow-up: Atrial or nodal arrhythmias occur
in 7 to 20 percent of the postoperative patients.
Occasionally, sick sinus syndrome may supervene,
especially when a sinus venosus defect is repaired. This
eventuality may require antiarrhythmic drugs or
Patent Ductus Arteriosus (PDA) patent ductus arteriosus (PDA) is the persistence of the duct which connects
the pulmonary artery to aorta during foetal life.
Prevalence
PDA occurs in 5 to 10 percent of all CHDs accounting
for 1 in 2000 live births excluding premature infants. It is
more common in females than males (M:F1:3).
Pathology
1. There is persistence of patency of a normal fetal
structure, between the left pulmonary artery (PA) and
the descending aorta (i.e. 5-10 mm distal to the origin
of the left subclavian artery).
2. The ductus is usually cone shaped, with a small orifice
to the PA, which is restrictive to blood flow.
Patients are usually asymptomatic when the ductus is
small. A large shunt PDAis accompanied by tachypnea, hyperdynamic circulation and poor weight gain.
It might be associated with repeated chest infections, and
CHF.
1. Hyperactive precordium with a systolic thrill at the
upper left sternal border. Bounding peripheral pulses
with wide pulse pressure are other characteristic
feature of hyperdynamic circulation. On auscultation,
P2 may be loud in presence of pulmonary hypertension.
2. Aloud and harsh 4/6 continuous machinery murmur
is best heard at the left infraclavicular area.
Electrocardiography
In small to moderate sized PDANormal or left
ventricular hypertrophy (LVH), large PDA combined
ventricular hypertrophy. In reversal of shunt-RVH
develops.
X-ray Studies
1. Small shunt PDAnormal X-ray.
2. Cardiomegaly of varying degrees occurs with
enlargement of left atrium (LA), left ventricle (LV) and
ascending aorta.
Echocardiography
1. PDA can be imaged in most of the patients by 2-D echo
in a high-parasternal or a suprasternal notch view.
2. The dimensions of LA and LV provide an indirect
assessment of the magnitude of the left to right shunt.
Natural History
1. Unlike PDA in preterms, spontaneous closure of the
PDA does not occur; PDA in term infants, results
because of structural abnormality of the ductal smooth
muscle.
2. If the shunt is large, recurrent chest infection and CHF
develop.
3. Reversal of shunt takes place, if a large PDA remains
untreated and pulmonary hypertension develops.
4. SBE may supervene, more frequent with small PDA
than large ones.
Management
Medical
1. No exercise restriction in absence of pulmonary
hypertension.
2. Indomethacin oribuprofen is ineffective in term infants.
3. SBE prophylaxis indicated in presence of small PDA.
4. Catheter closure of ductus with different devices
Infants more than a few months of age with ductus
< 3 mm in diameter occluding coils, one or two.
Treatment of choice for larger PDAs, < 12 mm in
diameter. Amplatzer duct occluder is device of choice.
For PDAS > 12 mm, septal closure devices are indicated.

Surgical
Anatomic existence of PDA, regardless of size is an
indication for surgery, but before that reversal of shunt
has to be ruled out. Surgical procedure is performed any
time between 6 months to 2 years, or any time in an older
child. Surgery remains the treatment of choice for
premature infants and children with very large PDAs.
Procedure Ligation and division through left posterolateral thoracotomy, without cardiopulmonary bypass.
This is a safe procedure; death occurs in less than
1 percent of patients.
Ventricular Septal Defect (VSD) (Fig. 11.2.6) VSD is
the most common form of CHD and accounts for 20
percent of all CHDs. Incidence is 1.5-3.5 per 100 term
infants and 4.5-7 per 1000 premature infants.
Pathology
1. The ventricular septum may be divided into a small
membranous portion and a large muscular portion.
The muscular septum has three componentsthe
inlet, the trabecular septum and the outlet (infundibular) septum. The trabecular septum has three
components: central, marginal and apical.
A VSD may be classified into: perimembranous,
inlet, outlet (infundibular), central muscular, marginal
muscular and, apical muscular defect
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2. Defects vary in size ranging from a tiny defect to a

large defect with accompanying CHF.
3. Bundle of His, is related to posteroinferior quadrant
of perimembranous defect and superoarterior
quadrant of inlet muscular defect.
VSD Classification
1. Perimembranous: most common -80% of surgical or
autopsy series.
2. Outlet -5-7% of surgical and autopsy series. Situated
just beneath the pulmonary valve (supracristal,
infundibular etc).
3. Inlet 5-8%. Posterior and inferior to perimembranous defect.
4. Muscular: 5-20%
a. Central mid muscular- may have multiple
apparent channels on RV side and coalesce to a
single defect on LV side.
b. Apical- multiple apparent channels on RV side
and single defect on LV side as in central defect.
c. Marginal along RV septal junction.
d. Swiss cheese septum large number of
muscular defects.
History
1. Small VSDThe patient is asymptomatic and growth
is normal.
Figures 11.2.6A and B: (A) The four major components of the ventricular septum seen from the right ventricular aspect. The
membranous septum is contiguous with portions of the outlet septum, the trabecular septum and the inlet septum (B) Possible
sites of ventricular septal defect
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Figure 11.2.7: Tracing from a 3-month-old infant with large VSD, PDA, and pulmonary hypertension.
The tracing shows CVH with left dominance. Note that V2 and V4 are in standardization
2. Moderate to large VSDrepeated pulmonary

infections, easy fatiguability, decreased exercise
tolerance, failure to thrive, pulmonary hypertension.
3. If VSD not operatedpulmonary hypertension
develops cyanosis appears and level of activity is
decreased.
1. Small VSDThe child is well-developed and
acyanotic.
2. Large VSDtachypneic child, repeated chest infection, poor weight gain, and CHF, prominent
precordial bulge.
3. Reversal of shuntcyanosis, clubbing (Eisenmengers
complex) respiratory distress. SI and S2 are well-heard.
P2 may be single and loud in presence of PAH.
Pansystolic murmur, i.e. 3 to 5/6 is heard at left sternal
border.
Electrocardiography (Fig. 11.2.7)
1. Moderate sized VSD volume overload LVH with or
without LAH.
2. Large VSD-combined ventricular hypertrophy (CVH)
3. Eisenmengers Complex-RVH.
X-ray Studies (Fig. 11.2.8)
1. Cardiomegaly of varying degrees depending on the
size of VSD and magnitude of L-R shunt. The
pulmonary vascular markings are increased in central
and peripheral fields.
2. When reversal of shunt takes place, hilar PA enlarges
and peripheral lung fields become oligemic.
Figure 11.2.8: PA view of chest roentgenogram in VSD with

large shunt and pulmonary hypertension. The heart size is
moderately increased, with enlargement on both sides. PVMs
are increased, with a prominent MPA segment

Two dimensional and Doppler echo can identify the
number, size and exact location of defect, estimate PA
pressure by using modified Bernoulli equation, identify
other associated defects and estimate the magnitude of
the shunt.
Natural History
1. Spontaneous closure in 30 to 40 percent of cases with
membranous and muscular VSDs, especially when
they are small.
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Figure 11.2.9: Diagrammatic representation of different parts of the ventricular septum seen a various two-dimensional views.
(A) parasternal long-axis view. (B), (C) and (D) Different levels of the parasternal short-axis view. (E) and (F) a subcostal fourchamber views, respectively (G) and (H) apical and subcostal five-chamber views, respectively
2. CHF develops in large VSD, after 8 weeks of age.

3. In a large VSD, the shunt may reverse as early as 6 to
12 months of age, but Eisenmengers syndrome does
not get established till the teenage years.
4. Infective endocarditis more common compared to other
lesions.
5. In large VSDs, infundibular stenosis may develop
which decreases the magnitude of L-R shunt
(acyanotic TOF).
Management
Medical
1. No exercise restriction in the absence of pulmonary
hypertension.
2. Maintenance of good dental hygiene, antibiotic
prophylaxis against infective endocarditis is very
important.
3. Treatment of CHFwhen poor feeding, sweating
easy fatiguability, tachypnea- leading on to failure to
thrive. It has to be treated with decongestive therapy
(digoxin and diuretics) and ACE-inhibitors indicated.
4. Frequent feeding of high calorie formulaAnemia has

to be corrected by iron therapy or blood transfusion
5. Umbrella closure of selected muscular defects is
possible but, has still not been established.
Surgical lesions
1. Small defects need not be operated.
2. Large VSDsIf CHF responds to decongestive
therapy, then surgery is delayed. If CHF does not
respondthen the VSD should be closed within the
first 6 months of life.
3. After one year of age, significant L-R shunt with QP/
QS of at least 2:1 indicates surgical closure.
4. Older infants with large VSDs and increased
pulmonary resistance should be operated immediately
5. Small VSD with no CHF and QP/QS less than 1.5:1,
should not be operated.
6. Surgery is contraindicated in presence of predominant R-L shunt or PVR-SVR is more than 0.5.
7. VSD with aortic crisp prolapse should be operated
immediately to prevent further aortic regurgitation.
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Mortality Surgical mortality 2 to 5 percent after the age of 6

months. It is higher in smaller infants, less than
2 months or with associated defects.
Complications
1. Incomplete closure.
2. Different degrees of heart blocksRBBB, left anterior
hemiblock or even complete heart block.
3. Aortic regurgitation.
Postoperative follow-up
1. Activity not to be restricted, unless postoperativecomplications are present.
2. SBE prophylaxis may be discontinued 6 months after
surgery, if no complications occur.
3. In presence of heart blocks, pacemaker implantation
may be indicated.
2. Perimembranous ventricular septal defect.

3. Dextroposed and overriding of aorta.
4. Right ventricular hypertrophy.
Other associated features are:
1. Right aortic arch in 25 percent of cases.
2. Pulmonic annulus and main pulmonary artery are
hypoplastic in some patients.
3. In about 5 percent of patient abnormal coronary
arteries are also present.
Prevalence of TOF ranges between 0.48-0.8 per 1000 live

births.
TOF occurs in 3.5-9 percent of all CHDs. This is the
most common cyanotic CHD, seen beyond infancy.
Symptoms vary widely depending on severity of

pulmonary stenosis.
1. Most cases of TOF are mildly cyanosed at birth.
Exertional dyspnea, squatting and hypoxic (cyanotic)
spells develop later on in life.
2. Acyanotic TOF with a large VSD will present with
CHF.
3. Presence of severe cyanosis at birth signifies
pulmonary atresia with VSD.
4. Squatting characteristic Symptom of TOF. Typical
posture after exertion to get relief from dyspnoea.
5. Hypoxic (cyanotic) spell- episode characterized by
paroxysmal, tachypnoea, deepening cyanosis,
limpness, syncope, occasional convulsion or death,
feeding, crying or defecation precipitates the episode.
Pathology (Fig. 11.2.10)
The four components of tetralogy of Fallot include:

1. RV outflow tract obstructionInfundibular pulmonic
stenosis.
1. Varying degrees of cyanosis, clubbing and tachypnea

are present.
2. S2 is usually single in pulmonary area because aortic
component is heard due to dextroposed and overriding of aorta. A loud 3 to 5/6 ejection systolic murmur
is heard at the upper left sternal border. The more
severe is the PS, softer and shorter is the murmur.
3. The only indirect evidence of VSD is the presence of
cyanosis.
4. In acyanotic TOF (VSD with mild P.S.)Long pansystolic murmur resulting from VSD and ejection
systolic murmur due to inendibular stenosis is heard
in pulmonary area. Cyanosis is absent.
CYANOTIC CONGENITAL HEART DISEASE

Tetralogy of Fallot (TOF)
Prevalence
Electrocardiography
Figure 11.2.10: Apical four-chamber view with LV outflow tract
(apical five chamber view) in a patient with perimembranous
VSD (arrow), AV arotic
1. RAD (+120 -+ 180 degrees) in cyanotic form. In

acyanotic cases QRS axis is normal.
2. RVH tall R in v1 and prominent S in V5 and V6.
Figure 11.2.11: A posteroanterior view of chest roentgenogram

in TOE The heart size is normal, and pulmonary vascular markings are decreased. A hypoplastic MPA segment contributes
to the formation of the boot-shaped heart
X-ray Study (Fig. 11.2.11)

1. Normal sized heart with oligemic lung fields
2. Typical presentation-concave MPA segment with
upturned apex giving boot shaped heart or coeur
en sabot appearance.
3. Right atrial enlargment and right sided aortic arch
may be present in 25 percent of cases.
4. Acyanotic TOF X-ray findings are no different from
that of a VSD, but patients with TOF have RVH rather
than LVH on ECG.
Two-dimensional echo and Doppler studies can make the
diagnosis and quantitate the severity of TOF
1. A large perimembranous infundibular VSD and
overriding of the aorta are visualized in long
parasternal view.
2. RV outflow tract (RVOT) obstruction with pulmonary
valve and annulus, MPA and the branches are smaller
than normal.
3. Doppler studies estimate the pressure gradient across
RVOT.
4. Anomalous coronary artery distribution can be
imaged or suspected.
Natural History
Infants who are acyanotic at birth, become cyanosed by 8
to 12 weeks of life.
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Figure 11.2.12: Parasternal long-axis view in a patient with

TOF Note a large subaortic VSD (arrow) and a relatively large
(AO) overriding the interventricular septum (IVS) AVaortic
valve, MVmitral valve
1. Hypoxic spells may develop, depending upon severity

of RVOT and thereby growth retardation may
supervene in future.
2. Brain abscess, cerebrovascular accidents and SBE are
occasional complications.
3. Since central cyanosis predisposes to polycythemia,
iron deficiency anemia and coagulopathy should be
remembered as potent complications.
Management
Medical
1. Physician should recognize and treat the hypoxic
spell. Parents have to be educated to recognize it and
palliative procedures to be carried out.
2. Oral propranolol therapy 1-4 mg/kg 4 times a day
given in hypoxic patients to prevent hypoxic spells
3. Balloon dilatation of RV outflow tract and pulmonary
valve has been attempted to delay surgical repair
4. Relative iron deficiency anemia should be detected
and treated since it is very common in polycythemic
children.
Surgical
Palliative shunt procedures (Fig. 11.2.13) Shunt procedures are performed to increase pulmonary blood flow.
Indication are the following, especially in the poorer
nations where primary repair is difficult.
1. Neonates with TOF and pulmonary atresia.
2. Infants with hypoplastic pulmonary annulus and
hypoplastic PAS.
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procedure of choice for an infant, more than 3 months
of age.
2. Gore-Tex interposition shuntplaced between
subclavian artery and ipsilateral PA, is ideal for infants
less than 3 months.
3. Waterston shunt and Potts operation have been
abandoned because of high percentage of complications.
Conventional repair surgery Timings vary depending upon
the patient, but early surgery is always preferred.
Indications and Timing
Figure 11.2.13: Palliative procedures that can be used in

patients with cyanotic cardiac defects with decreased PBF.
The Glenn procedure (anastomosis between the superior
vena cava and right PA) may be performed in older infants
with hypoplastic RV, such as is seen with tricuspid atresia
3. Severely cyanotic infantsyounger than 3 months and

those who have medically unmanageable hypoxic
spells.
1. Symptomatic infants who have favorable anatomy of

RV outflow tract and PASAn early repair is advised,
any time after four months of age.
2. Mildly cyanotic children who have had shunt
surgerytotal repair ito 2 years after shunt operation.
Procedure: Brocks procedure Total repair of the defect is
carried out under cardiopulmonary bypass and circulatory
arrest. For uncomplicated TOF, mortality is between 2 to 5
percent, during first 2 years.
Complications
The Shunt Procedures

1. Classic Blalock-Taussig shuntAnastomosis between
subclavian artery and ipsilateral pulmonary artery -
1. RBBB on ECG occurs in 90 percent of patient

2. Complete heart block is rare.
11.3 Medical Management of

Congenital Heart Diseases
Anita Khalil, Bharat Dalvi
Advances in perinatal management has resulted in
identifying a large number of babies with congenital heart
disease. With the improvements in surgical techniques and
understanding of cardiopulmonary bypass, more and
more babies with congenital heart disease survive till late
childhood, adolescence and even adulthood. Therefore, it
is important to understand the broad principles of medical
management of these children both during the pre- and
postoperative periods. The details of drug dosages and
schedules have been omitted, and the technical intricacies
of nonsurgical interventions were considered beyond the

scope of this chapter.
Congenital heart disease may broadly be classified
in to 2 main groups. Cyanotic and acyanotic. The medical
management of any congenital cardiac disorder, whether
cyanosed or acyanosed should be on following lines:1. Congestive cardiac failure.
2. Cyanosis
3. Prevention of Infestive Endocarditis.
4. Catheter Intervention procedure.
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CONGESTIVE HEART FAILURE
CYANOSIS
Congestive heart failure in children with congenital heart

disease is related to varied mechanical problems like
valvular regurgitation, myocardial failure or excess
pulmonary blood flow and usually requires surgical
correction. The broad principles of non-surgical
treatment are as follows: Important general measures
include reducing physical activity and restriction of
dietary sodium (e.g. potato chips, wafers, papad, pickles,
etc.) intake. Supplemental oxygen should be administered in patients with pulmonary edema. Pharmacological treatment involves use of drugs to improve the
pumping function of the heart (digoxin, sympathomimetic amines such as dopamine, dobutamine, epinephrine, isoprenaline and amrinone), and control of
excessive salt and water retention (diuretics). If the
combination of these two groups of drugs is not effective,
vasodilators (ACE inhibitors, hydralazine, prazosin or
nitroprusside) should be added. Due to wide variations
in individuals response to digoxin, its dose should be
tailored to individual patients clinical response.
Although digoxin toxicity is uncommon in children as
compared to adults, they should be closely observed for
gastrointestinal symptoms, arrhythmias and electrocardiographic evidence suggestive of toxicity. Serum
digoxin levels can also be monitored. Intravenous
sympathomimetic amines are useful in the perioperative
period or during life threatening low-output states
associated with cadiogenic shock.
The most commonly used diuretic in pediatric
practice is frusemide, and to a lesser extent, chlorothiazides. Spironolactone when used in conjunction has a
potassium sparing effect. While using frusemide in a dose
greater than 2 mg/kg, it is prudent to add potassium
sparing diuretic to the prescription. Volume depletion,
hypokalemia, hyponatremia, metabolic alkalosis and
hyperuricemia are the known, complications which need
to be monitored in patients on long-term diuretic therapy.
A pure venodilator would be desirable when symptoms
are related to systemic or pulmonary venous congestion,
whereas an afterload reducing agent is preferred in
patients with increased peripheral vascular resistance.
Most agents have both the effects and are best suited for
patient with advanced heart failure. Ventilatory support
and ventricular assist devices (e.g. extracorporeal
membrane oxygenator-ECMO) have an important role
particularly in the perioperative management of patients
with severe cardiac failure.
Most cases of cyanotic congenital heart diseases that

require early intervention for cyanosis have a resting
saturation of less than 80% and do not increase
saturations to above 90% on giving 100% oxygen
inhalation. Some cases of common mixing (e.g. total
anomalous pulmonary venous connection and double
inlet left ventricle) can have higher saturations.
Cyanotic Spell
Cyanotic spell is a life threatening emergency characterized by progressive increase in rate and depth of
respiration, deepening cyanosis culminating into lack of
consciousness and occasionally a hypoxic seizure may
also take place. Peak incidence is between 6 months to
2 years of age and it occurs mostly precipitated by crying,
feeding or straining on defecation.
Management
1. Posture child should be put in knee-chest position.
2. Sedation Inj Morphine relieves anxiety and
sensation of suffocation.
3. Beta blockers- Inj. Propranolol or metaprolol reduces
heart rate and relieves the infundibular spasm.
4. Oxygen inhalation mandatory to increase oxygen
saturation.
5. Parenteral administration of sodium bicarbonate to
treat metabolic acidosis more IV methoxemine.
6. In severe cases resistant to these measures general
anesthesia with assisted ventilation is advisable.
7. Correct anemia.
Use of Prostaglandins
Availability of prostaglandins has revolutionized the
management of congenital heart diseases in the neonatal
period, because of its role in keeping for maintaining duct
patent for maintaining pulmonary blood flow. Today,
the obstructed form of total anomalous pulmonary
venous drainage is the only truly cardiac surgical
emergency. In all the other duct dependent circulation
in cyanotic congenital heart disease and left sided
obstructive lesions, the ductal patency can usually be
maintained with prostaglandin infusion to stabilize the
patient so as to permit surgery on a semi urgent basis.
Some indications of prostaglandin infusion include duct
dependent pulmonary circulation as in case of pulmonary atresia with intact ventricular septum or transposition of great arteries with intact ventricular and atrial
520
septum condition in neonates with hypoplastic left heart

syndromes. Prostaglanding E1 is available as intravenous
infusion, whereas prostaglandin E2 can be given orally
as well as parenterally. Side effects include apnea and
hypotension.
Use of Indomethacin or ibuprofen
Oral or intravenous indomethacin has been used
successfully for nonsurgical closure of patent ductus
arteriosus (PDA). Results are gratifying when used in
first 10 days after birth and in pre-mature infants. Second
course may be indicated if the clinical signs of ductus
reappear after the initial closure. Indomethacin should
not be administered in infants with renal dysfunction,
overt bleeding, shock, necrotizing enterocolitis or
electrocardiographic evidence of myocardial ischemia
Ibuprofen is being used with similar results.
Management of Eisenmenger Syndrome
Eisenmenger syndrome refers to patients with congenital
heart defects who have a systemic level of pulmonary
artery pressure and high pulmonary vascular resistance
with right to left or bidirectional shunting. Congestive
heart failure may occur which responds to digitalis and
diuretics. Anticoagulants have been recommended to
prevent in situ thrombosis in lungs. Hemoglobin
concentration at 20 g/dl commensurate for the patients
degree of resting desaturation. Repeated phlebotomies
or erythrophoresis may be required in a polycythemic
patient. Oral iron therapy should be used to treat
hypochromia and microcytosis. Vasodilators are
generally not recommended. Pregnancy is absolutely
contraindicated because of high maternal and fetal
morbidity and mortality.
Treatment of Intercurrent Infections
Intercurrent infections in children with congenital heart
disease (e.g. pneumonias in patients with large left to
right shunts, cerebral abscess in cyanotics or infective
endocarditis) needs to be searched diligently and treated
with specific antimicrobial therapy. For suspected
infections, initial empiric antibiotic coverage should be
given sufficiently broad to treat the most likely
pathogens. Delay in accurate diagnosis could lead to
fulminant progression of infection or worsening of
hemodynamics. Infective endocarditis prophylaxis
should be given within 60 minutes prior to the start of an
invasive procedure and should be directed towards the

common organisms involved.
Treatment of Infective Endocarditis
It is imperative that the selection of antibiotic regimen be
guided by blood cultures to demonstrate persistent
bacteremia as well as antibiotic sensitivity testing.
Treatment should begin on clinical suspicion while
awaiting results to treatment. The duration of therapy
varies from 4 to 6 weeks depending on the organism
isolated and on the underlying premorbid condition.
Surgical intervention is necessary if there is progressive
worsening of congestive heart failure, embolic episodes,
nonresponse to treatment or prosthetic valve dysfunction.
Interventional Catheterization in Management of
Congenital Heart Diseases
Therapeutic catheterization has added a new dimension
to the management of congenital heart disease and in some
conditions provide an effective alternative option or
supplement the surgical management. Interventional
procedures can be grouped into four general types:
1. Atrial septostomy,
2. Valve dilations,
3. Vessel dilations, and
4. Occlusion procedures.
These procedures are performed in catheterization
laboratories by trained pediatric interventional cardiologists and require a large inventory of catheters and
devices.
Atrial Septostomy Procedures
Atrial septostomy procedure is indicated for palliation in
congenital heart lesions in neonates and young infants in
whom all systemic, pulmonary or mixed venous blood
must travel a restrictive interatrial communication in order
to return to the systemic circulation. This includes
complex defects associated with hypoplastic right or left
ventricles and infants with total anomalous pulmonary
venous drainage. The procedure involves withdrawing
an inflated balloon catheter rapidly across the atrial
septum so as to create a nonrestrictive atrial septal defect.
In infants older than 1 month, a blade septostomy catheter
is recommended to achieve the same result due to the thick
septum. These procedure are emergent in nature and can
be performed in catheterization laboratory under
fluoroscopy control or in intensive care unit under
echocardiography guidance.

Balloon Valve Dilation
Stenotic valves can be opened by the use balloon catheters.
The pressure created by the balloon wall as it expands
across a stenosed valve leads to opening of the valve by
splitting the commissures and dilation of the valve
annulus. The balloon is rapidly inflated to a recommended
pressure, till the waist in the balloon disappears. Pressure
gradients are recorded before and after the dilations to
assess the results. These procedures have been successfully used for aortic and pulmonary stenosis. Dilation of
the right ventricular outflow tract in patients with
tetralogy of Fallot with a view to palliation is an emerging
indication. Availability of low profile balloons have
significantly reduced the vascular access complications.
Avoidance of thoracotomy and cardiopulmonary bypass
with their inherent risks and morbidity are definite
advantages of these procedures.
Vessel Dilations and Vascular Stents
This procedure utilizes a catheter with a small, cylindrical,
fixed-maximal-diameter balloon mounted on it. The
balloon catheter is passed over a guide wire, positioned
across the area of stenosis and inflated with relatively
high pressure. This stretches the area of stenosis to the
predetermined diameter of the balloon. Current indications for vessel dilation include postoperative coarctation of the aorta and native coarctation. Branch pulmonary
artery dilation can be done successfully using high
521
pressure balloons. Systemic and pulmonary vein dilation

have also been performed. Intravascular stents provide
the necessary scaffolding to prevent recoil and restenosis
following balloon dilatation. These are being particularly
used in branch pulmonary arteries, aorta and pulmonary
veins.
Occlusion Procedures
These procedures have been used to occlude abnormal of
persistent intracardiac (e.g. atrial and ventricular septal
defects) and extracardiac (e.g. PDA and arteriovenous
fistulas) shunts. The occlusion devices are delivered
selectively through specially designed catheters to occlude
the shunts. Rashkind double umbrella device, PDA coils
are amongst the various devices available for closure of
ductus arteriosus. Recent modifications of amplatzer
occluding device and cardiorenal device have shown
encouraging results in cases of ASD closure. Limited
success has been achieved in closure of ventricular septal
detects using clamshell double umbrella device. Newer
devices with different geometries aimed at achieving
procedural ease, complete occlusion of the shunts and
reducing device embolization rates are being continuously
developed.
BIBLIOGRAPHY
1. Emmanouilides GC, Allen HD: Moss and Adams Heart
Disease in Infants, Children, and Adolescents (7th edn).
Baltimore: William and Wilkins, 2008.
11.4 Surgery for Congenital Heart Diseases

KS Dagar, KS Iyer, Srikant Basu
Since its inception in the 1950s surgery for congenital heart
disease has evolved to its present stage where most defects
can be corrected with a mortality of less than 1 percent. In
the early years, prohibitive mortality and morbidity
concurrent to the bypass run initiated the concept of two
stage repairs, with an initial palliative procedure (which
avoided cardiopulmonary bypass early in infancy)
followed later by a corrective procedure. The scenario has
dramatically changed since with the thrust being on early
total corrective repair where possible, because clinical and

experimental data have shown that early intervention
protects the heart from the adverse effects of volume
loading or hypertension as the case may be. In cyanotic
children, early operation reverses or at least halts the insult
to the cardiopulmonary and other organ systems because
of the attendant ischemia and polycythemia. With increasing age the cardiac response changes from mostly
hyperplasia of myocytes and coronary angiogenesis to
522
only hypertrophy without angiogenesis. In the light of

this, repair during the early hyperplastic phase of cardiac
growth is expected to yield normal or near normal left and
right ventricular function. Early repair also decreases the
potential for electrical instability.
An important fraction of lung development and
maturation occurs after birth, particularly within the first
1 to 2 years. The presence of congenital heart defects have
an adverse impact on this phase of lung development.
The obvious inference is that early interventions to
address congenital heart defects are likely to result in
the optimal opportunity for normal development of lung
vasculature and gas exchange apparatus.
Conventionally, depending on the pathophysiology,
the congenital lesions are segregated into cyanotic or
acyanotic defects. The former may be cyanosed due to
diminished pulmonary flows like tetralogy of Fallot,
ventricular septal defect (VSD) with pulmonary stenosis,
pulmonary atresia, Ebstein's malformation or due to
obligatory mixing of the systemic and pulmonary return
to produce cyanosis, e.g. TAPVC, truncus arteriosus,
single ventricle without pulmonary stenosis. However,
because of anatomic and hemodynamic variations in
each subset, treatment modalities have to be tailored for
each individual patient.
The principles of management of the common lesions
are detailed below.
Atrial Septal Defects
Atrial septal defects (ASDs) are surgically repaired
optimally at 1 to 2 years of age or at the time of diagnosis
thereafter. Direct closure by suturing the margins is
reserved for oval defects located in the fossa ovalis area.
The rest are closed with a patch which may be autologous
pericardium or synthetic material like dacron or GoreTex.
Repair of sinus venosus defects entails closure of the
ASD in such a manner that the pulmonary venous return
is directed across the ASD into the left atrium. This is
achieved using a patch sutured around the pulmonary
venous opening into the SVC and then extending the
patch around the right atrial wall to the ASD margin. The
SVC return flows into the right atrium anterior to the patch.
Percutaneous catheter techniques are still undergoing
standardization and are reserved for defects less than 15
mm with good margins. In this the ASD is closed using
a prosthetic device which is delivered through a catheter
passed through the femoral vein under fluoroscopic or

echo guidance.
Ventricular Septal Defects
Infants with large ventricular septal defects (VSDs), heart
failure, significant growth failure or respiratory symptoms
during the first 6 months of life need prompt repair of the
VSD. Elective operation may be deferred in the first 3
months of life in infants without serious symptoms or
medically controlled congestive heart failure because the
VSD may narrow or close spontaneously. Other associated
cardiac anomalies are repaired simultaneously where
appropriate. Exceptions are made for the rare infant with
Swiss cheese septum and those with straddling
atrioventricular valve. In these settings pulmonary artery
banding is indicated to protect the pulmonary bed from
high pressures and flows. If no band related complications
occur, definitive repair is executed at 3 to 5 years of age.
When patients are first seen after infancy, surgical
decision is based on the extent of their pulmonary vascular
involvement. Except for small VSDs with the left to right
shunt of less than 1.5:1, all VSDs merit closure. With
pulmonary vascular resistance greater than 8 units/m2
operation is advisable only if it falls below 7 units/m2
after special measures like isoproterenol infusion. A
decrease in postexercise QP/QS is also a contraindication
for surgery.
Juxta-arterial VSDs should be repaired promptly
irrespective of size to obviate the development of aortic
incompetence. When aortic incompetence occurs, it is an
absolute indication for VSD closure. The VSDs are closed
surgically using a patch of woven dacron or PTFE. A right
atrial approach may be used almost exclusively as it
obviates a right ventricular scar with its higher incidence
of ventricular dysfunction and arrhythmias. Juxta-arterial
VSD may be closed transpulmonarily or a combination of
transatrial and transpulmonary approaches may be
utilized for optimal exposure.
Atrioventricular Septal Defects
Atrioventricular septal defects (AVSDs) represent a
spectrum from the mild ostium primum defects to the
complete forms with atrial and ventricular septal defects
associated with a single atrioventricular valve with
abnormal leaflets. Indications for surgery depend on the
form of the atrioventricular canal defect.
523
For the symptomatic patient with complete form of

defect, surgical intervention may be indicated as early as
the first few weeks of life. Complete repair, entailing
closure of the primum ASD and the VSD with a patch and
reconstruction of two competent atrioventricular valves,
is the procedure of choice. Pulmonary artery banding is
considered for unusual situations like multiple muscular
VSDs or uncertainty over the degree of ventricular
imbalance. In the asymptomatic patient elective repair is
undertaken by 6 months of age. This is to guard against
the development of increased pulmonary vascular
resistance which if sufficiently high may render the case
inoperable.
Patients with partial defects should undergo elective
corrective surgery preferably at or before one year of age.
Presence of atrioventricular valve regurgitation is an
absolute indication for intervention at the time of
diagnosis irrespective of symptomatology to obviate the
possibility of development of valve leaflet deformity
precluding a repair at a later date.
Left Ventricular Outflow Tract
Left ventricular outflow tract (LVOT) obstruction is a term
for a wide spectrum of defects which have in common an
anatomic impediment for left ventricular ejection. Before
intervention is contemplated the feasibility of a
biventricular repair should be assured and the entity
distinguished from the spectrum of hypoplastic left heart
syndrome for which the Norwood operation is indicated.
The criteria favoring the more extensive operation include
a mitral valve area less than 4.75 cm2 per m2, left ventricular
inflow dimentions < 25 mm, transverse cavitary and aortic
annular dimentions of 6 mm or less. In patients suitable
for a biventricular repair, the indications for surgery
include gradients more than 75 mm Hg, moderate gradients
with symptomatic status, i.e. NYHA class III or above.
Symptoms of angina or syncope always indicate severe
stenosis.
In the localized form of subaortic stenosis, resection of
the stenotic segment (with or without associated
myectomy) through the aortic orifice usually provides
adequate and long-lasting relief of LVOT obstruction. In
the diffuse form, a more aggressive approach is mandatory
and is best managed by the integrated approach as
depicted in Figure 11.4.1.
Figure 11.4.1: Flow chart depicting surgical approach to

left ventricular outflow tract (LVOT) obstruction
Coarctation of Aorta
Surgery is indicated in all situations where there is
evidence of decrease in the luminal diameter approaching 50 percent at the site of coarctation, as it indicates a
significant lesion. A resting gradient of 20 mm Hg or
more is also an indication for surgery. Elective coarctation
repair is best performed at 3 to 6 months of age and repair
in symptomatic patients should be undertaken at the time
of diagnosis. When it is found with more complex
intracardiac disease, the timing and type of surgery is
largely dictated by the intracardiac lesion.
The neonate presenting in extremes requires urgent
intervention with prostaglandin E1 (0.01-0.1 g/kg/min)
to reopen the ductus and thereby support the lower body
circulation. Other supportive interventions include
muscle paralysis and mechanical ventilation along with
inotropic support and correction of acidosis.
At the present time the authors believe that either a
resection with end-to-end anastomosis for discrete lesions
or the extended resection and anastomosis for associated
524
arch hypoplasia is the procedure of choice. Standard

subclavian flap aortoplasty and patch aortoplasty may
be preferable over resection and anastomosis in situations
of previous surgery and scarring limiting circumferential
dissection. Balloon dilatation is an acceptable modality
in the postneonatal period and also for the management
of restenosis.
Tetralogy of Fallot
The diagnosis of tetralogy of Fallot (TOF) is generally an
indication for repair. When severe symptoms develop
in the first 2 to 3 months of life an initial shunt, modified
right BT shunt preferably, followed within 12 months
by repair is a reasonable alternative. When diagnosed
later than 3 months and the infant is importantly
symptomatic, prompt primary repair is considered with
low risk of repair at less than 5 percent.
This approach has the advantage of performing the
repair before irreversible effects of long-standing right
ventricular hypertension, cyanosis and polycythemia
induce secondary myocardial and pulmonary changes.
However, the two-stage repair is probably prudent in cases
where the coronary artery crosses the right ventricular
outflow tract in association with a hypoplastic annulus,
unusual circumstance of severe stenosis of the distal
pulmonary trunk and important multiplicity of VSDs.
The surgical plan consists of establishing an unrestrictive passage from the right ventricular to the pulmonary
artery with closure of the VSD. The former is achieved
by resecting the stenotic infundibular bands and splitting
the pulmonary annulus when hypoplastic and extending
the incision into the pulmonary artery until normal
caliber vessel is reached. In instances where the
pulmonary annulus is divided the defect is filled in with
a pericardial patch extending from the right ventricle
across the annulus into the normal caliber pulmonary
artery. The infundibular resection and VSD closure can
be achieved via the right atrium or a combination of
transarterial and transpulmonary approach. A right
ventriculotomy is best avoided to protect against right
ventricular dysfunction and arrhythmias in the postoperative period.
TOF with Pulmonary Atresia
Most patients who have tetralogy of Fallot with pulmonary atresia (TOF PA) and a duct dependent circulation have sufficiently large (pulmonary artery index
>150 cm2/m2) and confluent (right and left arteries
connected to each other) pulmonary arteries, that they
can be successfully repaired at low operative risks with

good late hemodynamic and electrophysiologic results
using the principles outlined for TOF pulmonary stenosis
with transannular patch. The subset of patients with
diminutive pulmonary arteries and large aortopulmonary
collateral artery (APCA) that supply a variable number of
bronchopulmonary segments or nonconfluent pulmonary
arteries pose a therapeutic challenge.
The repair is staged through early relief of right
ventricular outflow tract obstruction and establishment
of RV to pulmonary artery continuity using outflow tract
patch of pericardium or conduit, leaving the VSD open.
Whenever indicated unifocalization procedures, that join
the multifocal sources of pulmonary blood supply (true
pulmonary artery and one or more nonredundant
collaterals) into a single source are added. Definitive
repair entails patch closure of the VSD and establishment
of continuity between the RV and the pulmonary artery
using either a valved homograft or valve patch repair.
All systemic shunts including redundant collaterals are
retrieved at the time of surgery.
Pulmonary Stenosis with Intact
Ventricular Septum
The cyanosed and critically ill neonate with severe
pulmonary stenosis is initially stabilized on the PGE1.
Thereafter the RVOT relief may be accomplished by
percutaneous balloon valvotomy or open surgical
valvotomy on CPB. The percutaneous technique is
preferred except where the pulmonary annulus is
severely hypoplastic or there is severe reduction of right
ventricular cavity size. The latter is managed with the
insertion of a transannular patch and concomitant
construction of a systemic to pulmonary artery shunt.
Presentation at a later age is managed almost exclusively
by balloon pulmonary dilation.
Pulmonary Atresia with Intact
Ventricular Septum
After medical stabilization of the patient on PGE1,
ventilation and pharmacological support, surgical
intervention aims at stabilization of a reliable source of
pulmonary blood flow and decompression of the RV so
that the cavity can grow towards the fulfillment of an
ultimate biventricular repair. Patients should undergo
RV decompression employing a transannular patch with
systemic to PA shunt to augment pulmonary blood flow
till improvement of RV compliance facilitates antegrade

flow across the opened right ventricular outflow tract. This
approach is contraindicated in patients with a right
ventricle dependent coronary circulation or massive
tricuspid regurgitation. In these patients, palliation is
exclusively with a systemic to pulmonary artery shunt.
In select patients with non-RV dependent right
ventricular coronary fistula, tricuspid valve closure in
addition to the systemic pulmonary artery shunt is done
to prevent coronary steal. The atrial septal defect is left
open to prevent systemic venous hypertension. In nonRV dependent coronary flow anatomy, the patients with
a Z value of tricuspid valve greater than 2 ultimately have
a biventricular repair. The rest are segregated to a Fontan
limb or a one and a half ventricular repair. In this the
superior vena caval return is directed to the pulmonary
bed as a bidirectional glenn bypassing the right ventricle,
and the inferior vena caval blood is ejected by the diminutive right ventricle into the pulmonary artery.
Fontan Procedure
A variety of complex congenital heart defects consisting
of a functional single ventricle are managed under the
tenants of the Fontan principle. The Fontan procedure
and its modifications separate the systemic and
pulmonary venous return and create a passive direct
connection between the systemic venous return and the
pulmonary arteries devoid of a functioning pulmonary
ventricle. The elevated systemic venous pressure becomes
the principle driving force to maintain both adequate
pulmonary blood flow and systemic ventricular preload.
Most centers favor performing a modified Fontan
procedure between 2 and 3 years of age. The timing for
each patient must be individualized to allow time for
adequate growth and development of the pulmonary
circulation but to avoid excessive delays that may lead to
compromise of ventricular function or development of
raised pulmonary vascular resistance which would
preclude a Fontan procedure. For inadequate blood flow
in the neonatal period, a systemic to pulmonary artery
shunting procedure on the side opposite the patent duct
is preferred. Beyond 4 to 6 months of age a bidirectional
glenn is performed wherein the SVC is divided and the
distal end is anastomosed to the right pulmonary artery
with closure of the right atrial end.
In situations of excessive blood flow, a pulmonary
artery banding is done to reduce volume load on the
systemic ventricle and treat CHF and also protect the
525
pulmonary artery against the adverse effects of high

pressures leading to high pulmonary vascular resistance.
Truncus Arteriosus
The presence of truncus is an absolute indication for
surgery. Repair should be undertaken in the neonatal
period or as soon as the diagnosis is made. Eisenmenger's
physiology is the only absolute contraindication to
correction. Early repair appears to greatly reduce the
incidence of pulmonary vascular hypertensions and
pulmonary hypertensive crises in the postoperative
period.
The surgical approach should include closure of the
VSD, use of a valved allograft conduit for the right ventricle
to pulmonary artery reconstruction and retain patency of
the foramen ovale. In limited subsets autologous tissue
flaps may be used to re-establish right ventricular and
pulmonary artery continuity with the aim to avoid later
reoperations.
D-transposition of Great Arteries
Currently infants are initially palliated with a balloon
atrial septostomy to increase mixing of blood and to
increase the saturations and also to decompress the left
atrium in the presence of a patent ductus. This is followed
by the arterial switch during the neonatal period, up to 4
weeks and preferably by 2 weeks, when the left ventricle
is still prepared to support the systemic circulation.
Even in patients with D-TGA VSD, the arterial switch
operation (ASO) is recommended shortly after the
diagnosis is made to prevent the development of raised
PVR and protect against the adverse effects of VSD closure.
In ASO, the aorta arising from the RV is transferred along
with the coronary buttons to the LV and the PA is
reconnected to the systemic ventricle. The early hospital
mortality in case of both simple TGA and TGA, VSD is
about 2 to 5 percent.
Patients with D-TGA IVS presenting later in infancy
where the LV preparedness is questionable, a rapid twostage arterial switch is probably recommended over an
atrial switch. The rapid two-stage repair consists of
pulmonary artery banding, to achieve a LV pressure that
is approximately 75 percent of systemic, with a systemic
to PA shunt followed within 7 to 10 days by debanding,
closure of shunt and an arterial switch.
The other situations are managed by an atrial level
switch like Senning or Mustard operation. In these
526
procedures, the atria are partitioned in such a manner

that the pulmonary venous blood is tunnelled across the
tricuspid valve to be ejected by the RV into the aorta.
Concurrently, the systemic return is channelled across

the ASD through the MV to be ejected into the PA by the
LV.
11.5 Rheumatic Fever and

Rheumatic Heart Disease
Anita Khalil
RHEUMATIC FEVER
Acute Rheumatic Fever (RF) occurs as a result of complex
interaction between group A streptococcus(GAS), a
susceptible host and the environment. An abnormal
immune response to a GAS infection leads to an acute
inflammatory illness that most commonly affects the
joints, brain, heart or skin. Although the other manifestations may resolve without any sequelae. Carditis may
result in significant morbidities and mortality. The acute
rheumatic cardiac involvement may resolve or persist
and evolve into chronic rheumatic valvular disease with
cardiac symptoms developing later. There is a strong
relationship with streptococcal infection of the throat,
and it is possible to prevent further attacks of rheumatic
fever by preventing throat infection.
Prevalence
RF continues to be a major public health problem in
developing countries, where it is the most common cause
of the aquired heart disease in children and young adults.
The prevalence of rheumatic fever in the most vulnerable
age group (5-15 years) is 5.3/1000 in school children, and
there appears to be no obvious decline. Though it has
been almost eradicated from the western countries, a few
outbreaks have been reported from the United States.
Etiopathogenesis
1. Though etiology of rheumatic fever is unknown, it is
believed to be an immunological lesion that occurs
as a delayed sequel of group A beta hemolytic
streptococcal infection of the pharynx and not of skin.
The common strains responsible are M-1, 3, 5, 6, 18
and 24. The attack rate of acute rheumatic fever

following acute streptococcal infection varies with the
severity of the infection ranging from 0.3 to 3 percent.
2. The most common age group involved is 5 to 15 years,
peak incidence being at 8 years and both the sexes
are equally affected.
3. Predisposing factors include low socioeconomic
status, which predisposes to overcrowding, poor
nutrition, and poor hygiene leading on to low
immunological status and, thereby, increasing the
susceptibility. A mendelian recessive pattern has also
been suggested as a genetic predisposition.
Considerable evidence now suggests that the
rheumatic fever is an antigen-antibody reaction, and
patients suffering from streptococcal throat infection
produce antibodies against streptococcal cell wall and
cell membrane proteins. The streptococcal antigen and
human myocardium appear to be identical antigenically.
These antibodies react with human connective tissue of
cardiac muscle, striated muscle and vascular smooth
muscle, and the antibodies have been demonstrated to
be attached to the sarcolemma of the cardiac muscle.
Mitral valve is the most commonly affected, more
frequently in females followed by aortic valve which is
more commonly affected in males. Tricuspid valves are
also involved but pulmonary valves are almost never
affected. Presence of Aschoff bodies in the atrial
myocardium is the hallmark of rheumatic fever. These
are inflammatory lesions associated with swelling with
fragmentation of collagen fibers.
Streptococcal products against which antibodies can
be demonstrated are streptolysin, hyaluronic erythrogenic toxin, streptokinase, deoxyribonucleases and
several others, and these are utilized for the identification
of a previous streptococcal infection.
527
TABLE 11.5.1: Guidelines for diagnosis of initial attack of

rheumatic fever (Jones criteria updated 1992)
Major Manifestations
Minor Manifestations
Carditis
Polyarthritis
Chorea
Erythema marginatum
Subcutaneous nodules
Clinical
Fever
Arthralgia
Laboratory findings
Elevated acute phase reactants
(erythrocyte sedimentation rate)
C-reactive protein)
Prolonged P-R interval
Plus
Supporting evidence of antecedent group A streptococcal infection

Positive throat culture or Rapid streptococcal antigen test
Elevated or rising streptococcal antibody titer
Figure 11.5.1: Antigenic structure of streptococcus 1Capsule

(hyaluronic acid), 2(A): Peptidoglycan (cell wall rigidity), (B):
Carbohydrate (group specific), (C) : Lipoteichoic acid fimbriae,
3Cytoplasmic membrane, 4Cytoplasm, and 5Pili covered
with lipoteichoic acid
1. Five major manifestations

2. Minor manifestations
3. Supporting evidence of an antecedent group A
streptococcal infection.
History
Streptococcus is a bacterium which has a hyaluronic

acid capsule which prevents phagocytosis (Fig. 11.5.1).
Underneath the capsule, there are hair like fimbriae
which are made up of lipoteichoic acid as well as MT and
R proteins. Lipoteichoic acid provides mucosal attachment
and MT, and R proteins dipoteichoic are responsible for
typing of Streptococcus. Each strain of Streptococcus has a
type-specific M protein. The carbohydrate in the streptococcal cell wall is N-acetyl glucosamine which is group
specific and is also present in human connective tissue.
N-acetyl glucosamine is immunologically active and crossreacts with antiserum against human connective tissue.
Thus, rheumatic fever appears to be the result of the hosts
unusual response to Streptococcus both at the humoral and
cellular level. Human leukocyte antigen (HLA) studies
suggest association with HLA-DR3 and serum 833, a Bcell alloantigen identified in 85 percent of rheumatic
patients. These findings favor a genetic susceptibility to
rheumatic fever which is probably inherited as a
mendelian recessive pattern.
Acute rheumatic fever is diagnosed by the use of revised
Jones criteria. These criteria were put forward by Dr. T.
Duckett Jones in 1944, which were revised in 1965 and
later updated once again in 1992.
The criteria are three groups of important clinical and
laboratory findings (Table 11.5.1).
1. Streptococcal pharyngitis, 1 to 5 weeks (average 3

weeks) before the onset of symptoms is common. This
latent period may be as long as 6 months in case of
chorea.
2. Pallor, malaise, easy fatiguability and other history
such as epistaxis (5-10%) and abdominal pain may be
present.
3. Family history of rheumatic fever may be present.
Major Manifestations
Carditis occurs in 50 percent of the patients. The signs of
carditis include some or all of the following in increasing
order of severity:
1. Tachycardia (out of proportion to the degree of fever)
is common. Its absence rules out myocarditis.
2. Pericarditis (friction rub, pericardial effusion, chest
pain and ECG changes) may be present.
3. Valvulitis (a murmur indicating MR and/or AR) is
always present, and if not present then carditis should
not be diagnosed. Now echocardiographic examination helps in confirming and evaluating the severity
of myocarditis, the presence and severity of MR and
AR and the presence of pericardial effusion.
4. Cardiomegaly on chest radiograph indicates pancarditis, pericarditis or congestive heart failure.
5. Clinical signs of CHF (gallop rhythm, distant heart
sounds, cardiomegaly) are indications of severe
carditis.
528
Arthritis
The common manifestations of acute rheumatic fever (70%
of cases) usually involves large joints (knee, ankles, elbows,
wrists). Often, more than one joint, either simultaneously
or in succession is involved with a characteristic migratory
nature of the arthritis. Swelling, heat, redness, severe pain,
tenderness, and limitation of motion are common. The
arthritis responds dramatically to salicylate therapy; if
the arthritis does not respond within 48 hours the
diagnosis of rheumatic fever is probably incorrect.
Sydenhams Chorea
Sydenhams chorea (St. Vitus Dance) is found in
15 percent of the patients with acute rheumatic fever. It
occurs more often in prepubertal girls (8-12 years). It
begins with emotional lability and personality changes
and loss of motor coordination invariably appear.
Characteristic spontaneous purposeless movements
develop, followed by motor weakness. The adventitious
movement, weakness and hypotonia continue for an
average of 7 months (up to 18 months) before slowly
waning in severity.
Erythema Marginatum
Erythema marginatum occurs in fewer than 10 percent of
the patients with acute rheumatic fever, and it is very rarely
seen in Indian subcontinent. The characteristic nonpruritic
serpiginous or annular erythematous rashes are most
prominent on the trunk and inner proximal portions of
the extremities, but never seen on face. The rashes
disappear on exposure to cold and reappear when covered
with a warm blanket.
Subcutaneous Nodules
Subcutaneous nodules are found in 2 to 10 percent of the
cases. They are hard, painless, nonpruritic, freely mobile
and less than 2 cm in diameter. They are distributed
symmetrically, singly or in clusters over the extensor
surfaces of large and small joints, scalp and along the
spine. They last for weeks and are significantly associated
with carditis.
Minor Manifestations
1. Arthralgia refers to a joint pain without the objective
changes of arthritis.
2. Fever (with a temperature usually of at least 39C)

generally is present early in the course of rheumatic
fever.
3. In laboratory findings, acute phase reactants (elevated
C-reactive protein levels and ESR) are objective
evidences of an inflammatory process.
4. A prolonged P-R interval on electrocardiogram is
neither specific for acute rheumatic fever nor an
indication of active carditis.
Evidence of Antecedent Group A
Streptococcal Infection
1. A history of sore throatunsubstantiated is not
adequate evidence of recent group A streptococcal
infection.
2. Positive throat swab cultures or rapid streptococcal
antigen tests for group A streptococci are less reliable
than antibody tests, because they do not distinguish
between recent infection and chronic pharyngeal
infection.
3. Streptococcal antibody tests are the most reliable
laboratory evidence of antecedent streptococcal
infection capable of producing rheumatic fever. The
onset of the clinical manifestations of acute rheumatic
fever coincides with the peak of the streptococcal
antibody response.
a. Antistreptolysin 0 (ASO) titer is well standardized
and therefore is the most widely used test. It is
elevated in 80 percent of the patients and low ASO
titer does not exclude acute rheumatic fever. If three
other antistreptococcal antibody tests (antideoxyribonuclease B, antistreptokinase and
antihyaluronidase tests) are obtained, at least one
antibody test titer is elevated in 95 percent of the
patients.
b. The streptozyme test is a relatively simple slide
agglutination test, but it is less standardized than
other antibody tests. It should not be used as a
definitive test for evidence of antecedent group A
streptococcal infection.
Other Clinical Features
1. Abdominal pain, rapid, sleeping pulse rate, tachycardia out of proportion to fever, malaise, anemia,
epistaxis and precordial pain are common but not
specific.
2. A positive family history of rheumatic fever may
heighten the suspicion, but cannot be used as a definite
diagnostic manifestation.

Diagnosis
The revised Jones criteria (1992) are used for diagnosis of
rheumatic fever (Table 11.5.2). Only the major and minor
criteria and evidence of an antecedent group A streptococcal infection are included in the criteria, although other
findings play a supporting role. A diagnosis of acute
rheumatic fever is highly probable when either two major
manifestations or one major and two minor manifestations
with evidence of antecedent streptococcal infection are
present. The absence of supporting evidence of a group A
streptococcal infection makes the diagnosis doubtful.
Juvenile rheumatoid arthritis
Other collagen disorderssystemic lupus erythematosus, reactive arthritis, infectious arthritis, serum
sickness.
Acute arthritis due to viruses, e.g. rubella, parvovirus,
hepatitis B virus, herpes virusesmore common in
adults.
Hematologic disorderssickle cell anemia, leukemia.
TABLE 11.5.2: Guidelines for diagnosis of initial attack of
rheumatic fever (Jones criteria updated 1992)
Major manifestations
Minor manifestations
Carditis
Polyarthritis
Chorea
Erythema marginatum
Clinical
Fever
Arthralgia
Laboratory findings
Elevated acute phase reactants
(erythrocyt sedimentation rate)
C-reactive protein)
Prolonged P-R interval
Plus
Supporting evidence of antecedent group A streptococcal infection

Positive throat culture or Rapid streptococcal antigen test
Elevated or rising streptococcal antibody titer
Management
Investigations
When rheumatic fever is suspected by history and physical
examination, the following investigations as elaborated
above have to be carried out:
1. Complete blood counts.
2. Acute phase reactantserythrocyte sedimentation rate
(ESR) and presence of elevated C-reactive protein.
3. Throat swab culture.
529
4. Antistreptolysin O titer (In presence of chorea, another

antibody titer has to be estimated).
5. Chest radiograph might show cardiomegaly and
pulmonary congestion if carditis is present.
6. Electrocardiogramfirst or second degree heart block.
PericarditisT wave inversion and reduction QRS
voltages.
7. Echocardiographychamber dilatation, valve
abnormalities, presence of pericardial effusion and LV
dysfunction.
Treatment
Bedrest depending on the severity of the manifestation. In
isolated arthritis, it is recommended for one to two weeks
and in presence of severe carditis, ambulation is not
recommended till all evidences of activity have subsided,
i.e. may be up to two to three months, especially in presence
of congestive heart failure.
Diet
A nutritious high calorie, high protein diet supplemented
with vitamins and minerals is recommended. Salt
restriction is advised only in presence of congestive heart
failure due to carditis.
Penicillin
After throat swab cultures have been obtained, penicillin
is recommended to eradicate streptococci. Initially
procaine penicillin G is administered intramuscularly at
40,000 units/kg once a day for 10 days, following which
long acting Benzathine penicillin is given once in 2l days,
6,00,000 units for children up to 6 years and 1.2 mega
units for those who are older. This prophylaxis is
recommended till the age of 25 to 30 years.
Counseling
Once the diagnosis of rheumatic fever is confirmed, the
patient and the parents have to be educated about need to
prevent further streptococcal infection through
continuous, antibiotic prophylaxis. In presence of cardiac
involvement, prophylaxis against infective endocarditis
is also recommended.
Anti-inflammatory Therapy
Anti-inflammatory or suppressive therapy should not be
started until a definite diagnosis is made. The antiinflammatory drugs include aspirin (salicylates) or
steroids. The clinical response to steroids is faster in
530
comparison to aspirin and so, a few guidelines are

followed so as to decide which anti-inflammatory drug
should be administered.
1. The untreated rheumatic fever subsides in 12 weeks
so the duration for anti-inflammatory therapy should
also be 12 weeks.
2. In carditis with congestive heart failure, use of steroids
is mandatory.
3. In carditis without congestive heart failure, use of
steroids is preferable but has to be monitored closely.
4. In arthritis only aspirin is to be given.
Salicylates
Soluble aspirin is the most commonly used salicylate,
administered in a dose of 90 to 100 mg/kg in four to six
divided doses. The full dose is given for 2-3 weeks or till
the symptoms have subsided, then to 60-70 mg/kg/day
to complete a total duration of 12 weeks. Else, give aspirin
in a dose of 20-60 mg/kg/day for 12 weeks. Blood
salicylate level should be maintained at 20 to 25 g/dl.
Phenobarbitone 15 to 30 mg every 6 to 8 hours.

Haloperidol 0.5 to 2 mg every 8 hours.
Chlorpromazine, diazepam carbamazine or sodium
valproate are sometimes used steroids.
Prognosis
Presence or absence of permanent cardiac damage
determines the prognosis. The development of residual
heart disease is influenced by the following factors.
1. Cardiac status at the initial periodthe more severe
the cardiac involvement initially, the greater is the
incidence of residual heart disease.
2. Recurrence of rheumatic feverseverity of valvular
involvement increases with each recurrence.
3. Regression of heart diseaseevidence of cardiac
involvement in the first attack may disappear in 25
percent of patients if anti-inflammatory therapy is
given in adequate dosage and also for a required
duration and not stopped early. Valvular heart
disease resolves more frequently when prophylaxis
is followed.
Steroids
The commonly used steroid is prednisolone.
Dose 2 mg/kg per day.
Indications
1. In carditis with congestive heart failure given in full
doses for the first 6 weeks and tapered off slowly for
the next 6 weeks.
2. In carditis without congestive heart failure, their use
is controversial but in Indian children, because of low
immunologic status, steroids are recommended in full
doses for first 4 weeks and tapered off slowly for the
subsequent 8 weeks. Aspirin may be added as the
steroids are being tapered off.
During the full course of anti-inflammatory therapy,
antacids are added to overcome irritation to gastric mucosa.
Management of Chorea
Sydenhams chorea is a late manifestation of rheumatic
fever, when acute phase reactants may be normal.
1. Physical and emotional stress should be reduced.
2. Injection of benzathine penicillin for prophylaxis
indicated as in other rheumatic patients.
3. Anti-inflammatory drugs not needed in isolated
chorea.
4. For severe cases, any of the following drugs may be
used.
Prevention
Secondary Prevention
Patients with documented histories of rheumatic fever,
heart disease and also isolated cases of chorea must
receive prophylaxis.
Duration
Ideally prophylaxis should be given to patients
indefinitely. Chance of recurrence is highest in the
subsequent 5 years after the first attack, so, prophylaxis
is recommended every 3 weeks till the age of 25 to
30 years. After the age of 30 years, rheumatic fever is not
known to occur.
Method
The method of choice is long acting benzathine penicillin
6,00,000 units to be given to patients weighing 27 kg or
less and 1.2 million units for patients weighing more than
27 kg. It is given intramuscularly after every 21 days. If a
patient is sensitive to penicillin, then alternative drugs
are given although not as effective. They are:
1. Erythromycin 40 mg/kg/24 hours to be given once a
day.
2. Oral sulfadiazine0.5 g once a day for less than
27 kg and I g once a day for those more than 27 kg.
531
Primary Prevention
Electrocardiography
To eradicate rheumatic fever, primary prevention is what

is required. For this, we have to isolate the population
at-risk which consists of families of low socioeconomic
status living in overcrowded areas. Throat swabs from
children between 2 and 15 years living in these areas are
taken and cultured for beta hemolytic Streptococcus.
Rapid laboratory isolation of streptococcus will isolate
the children at-risk and prophylaxis as detailed above
has to be given for primary prevention. It is necessary to
educate the community regarding the consequences of
streptococcal sore throat.
In mild cases, ECG is normal, but in most cases, there is

left ventricular hypertrophy (LVH) or left ventricle (LV)
dominance. Atrial fibrillation (AF) is a common finding
in adults but is rare in children.
RHEUMATIC HEART DISEASE
Radiographic Study
The left atrium (LA) and LV are usually enlarged in
varying degrees. Pulmonary vascularity is usually within
normal limits, but a pulmonary venous congestion
pattern may develop if CHF supervenes.
Echocardiogrpahy
The most commonly seen sequel of acute rheumatic fever

in the pediatric age group are mitral, aortic and tricuspid
valve disease. Mitral valve involvement is seen mainly
as mitral regurgitation and less commonly as mitral
stenosis. Aortic and tricuspid valve disease are mostly
seen as regurgitation. Tricuspid stenosis is known to
occur though very rarely, and rheumatic aortic stenosis
manifests only after the age of 20 years.
Two dimensional echo shows dilated LA and LV

depending on the severity of MR. Color flow mapping
of regurgitant jet into LA and Doppler studies can assess
the severity of the regurgitation.
Patients with MR are stable for a long time and in
some, mitral stenosis supervenes because of fibrosis,
infective endocarditis is a rare complication and LV
failure and pulmonary hypertension may develop in
adult life.
MITRAL REGURGITATION
Management
Mitral regurgitation (MR) is the most common valvular

involvement in children with rheumatic heart disease.
Mitral valve leaflets are shortened because of fibrosis
vhich leads to dilatation of mitral valve ring, because of
which mitral regurgitation is produced.
History
Patients are usually asymptomatic during childhood
because of the initial phase of MR, pulmonary congestion
is rare. Barely fatigue (due to reduced cardiac out put)
and palpitation (due to atrial fibrillation) manifest. On
examination in severe MR, hyperdynamic apex heat is
palpable. The heart sounds (S1 and S2) are mostly
diminished, and S3 is present and loud. The hallmark of
MR is a prolonged blowing regurgitant murmur starting
with the first sound (sometimes drowning it), and being
transmitted with equal intensity to the axilla and back,
and is best heard in the left decubitus position.
Occasionally, a short low density diastolic rumble is also
heard at the apex.
Medical
1. Preventive measures, e.g. dental hygiene against SBE
and prophylaxis against further recurrence of
rheumatic fever is important and should be carried
out.
2. In mild cases, activity is not restricted, and salt
restricted diet is advised.
3. Decongestive measures, e.g. diuretics and digoxin are
provided if CHF develops.
Surgical
Indications for mitral valve surgery include:
1. Intractable CHF
2. Progressive cardiomegaly with symptoms
3. Pulmonary hypertension.
Mitral valve repair or replacement is performed
under cardiopulmonary bypass. In children, valve repair
is preferred over valve replacement because their valve is
pliable, has a low mortality rate (< 1%) and anticoagulation is not necessary. If the valve is thick, scarred and
grossly deformed, then the valve has to be replaced.
532
Frequently used low profile prostheses are the Bjork-Shiley

tilting disk or the St. Jude pyrolite carbon valve. If prosthetic
valve is used, anticoagulation is compulsory The
mortality rate of valve replacement varies between 2 and 7
percent.
MITRAL STENOSIS
Although mitral stenosis (MS) is rare in pediatric age group
(it takes 5 to 10 years from the initial attack), it is commonly
seen in patients less than 15 years of age in the third world
countries where rheumatic fever is prevalent.
In MS, the leaflets are thickened with fusion of
commissures and calcification sets in resulting in
immobilization of the valve. The left atrium (LA) and right
ventricle (RV) become hypertrophied and dilated, and
severe pulmonary changes take place in the form of
pulmonary congestion, venous and arterial hypertension,
fibrosis of alveolar walls and loss of lung compliance.
Exertional dyspnea is the most common symptom. In
severe cases, paroxysmal nocturnal dyspnea, palpitation
and orthopnea are common. On examination, precordium
may be prominent with palpable RV impulse. Peripheral
pulses are weak and neck veins may be distended. The
hallmark of mitral stenosis is loud S1 with closely split S2
and a loud audible P2 (if pulmonary hypertension is
present). An opening snap is followed by a low frequency
mitral diastolic rumble. A crescendo presystolic murmur
may be audible at the apex.
Electrocardiography
There is left atrial hypertrophy (LAH) and right ventricular
hypertrophy (RVH). Atrial fibrillation is rare in children.
Chest Radiography
LA and RV are usually enlarged and main pulmonary
artery (MPA) segment is prominent. Lung fields show
pulmonary venous congestion, interstitial edema as
Kerleys B lines in the upper lobes.
Echocardiography
This is the most accurate noninvasive tool. M-mode shows
a diminished E-F slope and 2D shows thickened mitral
valve leaflets with doming and dilated LA, MPA, RV and
RA. Doppler studies can estimate the pressure gradient
across mitral valve and level of pulmonary artery (PA)
pressure.
Management
Medical
Prophylaxis against recurrence of rheumatic fever and
good dental hygiene and antibiotic prevention against
SBE are important.
Salt restriction and restriction of activity depending
upon severity.
Balloon valvulotomy is an alternative to closed surgical
commissurotomy and delays valve replacement.
Surgical
Indications Exertional dyspnea with paroxysmal
nocturnal dyspnea or pulmonary edema. The other relative
indications may be recurrent atrial fibrillation, hemoptysis
and thromboembolic phenomenon.
Procedure
1. Closed mitral commissurotomy. Mitral valve repair is
ideal for a pliable mitral valve without calcification or
mild MR.
2. Valve replacement indicated in calcified valves and
with severe MR. Prosthetic valves (Starr-Edwards
Bjork-Shiley, St. Jude) are for longer durability, but
require lifelong anticoagulant therapy.
Complications
Postoperative CHF, arterial embolization and bleeding
diathesis are known.
AORTIC REGURGITATION
Aortic regurgitation (AR) is less common than MR. The
semilunar cusps of aortic valve are deformed and
shortened, thereby, the aortic valve ring gets dilated and
the cusps fail to appose tightly.
In mild AR, the patients are asymptomatic but in severe
AR, there is exercise intolerance and breathlessness.
On examination, precordium is mostly hyperdynamic with a laterally displaced apical impulse. A
wide pulse pressure and a bounding water hammer pulse
is present in severe AR. On auscultation, the heart sounds
are diminished in intensity and a high pitched soft
diastolic decrescendo murmur is best heard at the left 3
to 4th intercostal space and radiating down the left
sternal border. The longer the murmur, the more severe
is the AR
533
Cardiomegaly with dilated LV is common. A prominent

aortic knuckle is frequently seen. Pulmonary venous
congestion is seen in presence of LV failure.
Sometimes it becomes difficult to decide whether it is

organic or functional. Most of the time, TR is associated
either with mitral stenosis or regurgitation. If the TR is
associated with severe MS, then it is mostly functional
because of associated pulmonary hypertension, but if the
TR is associated with pure or dominant MR, then TR
probably is organic in origin because severe pulmonary
hypertension does not develop only due to MR.
Echocardiography
Aortic valve and LV are dilated. Color flow and Doppler

are used to assess the severity of aortic regurgitation. The
patient with aortic regurgitation remains asymptomatic
for a long time, but once symptoms appear e.g. angina,
palpitation, etc. develop, the patient deteriorates rapidly.
There are no specific symptoms of tricuspid regurgitation.

Physical examination shows some specific signs, e.g.
1. Prominent V waves in jugular veins.
2. Systolic pulsation of liver.
3. Pansystolic murmur in lower left sternal border
which increases on inspiration.
Electrocardiography
In severe cases, LVH is the usual manifestation.
Chest Radiography
Management
Medical
1. Good oral hygiene and prophylaxis for SBE as well
as prophylaxis for recurrence of rheumatic fever.
2. Salt restricted diet and restricted activity in presence
of CHF.
3. If CHF develops, then digoxin, lasix, potassium
supplementation and ACE-inhibitors as and when
indicated should be administered.
In addition to signs of TR, there may be signs of

pulmonary hypertension and mitral stenosis.
Electrocardiography
ECG shows severe RVH.
Echocardiography
Color flow and Doppler can quantitate the severity of
TR.
Surgical
Management
Indication for aortic valve replacement

1. When symptoms such as angina or exertional
dyspnea have appeared.
2. In asymptomatic patients when either cardiothoracic
ratio is more than 55 percent or left ventricular
ejection fraction is less than 40 percent.
All patients of TR have to be treated with digoxin, lasix

and potassium supplements. If TR is associated with MS,
then it will disappear following balloon mitral valvotomy. If associated with MR. then mitral valve replacement is indicated.
Procedure
Aortic valve replacement is performed under cardiopulmonary bypass. The antibiotic sterilized aortic
homograft has been widely used and appears to be the
device of choice. The other alternative procedures are
porcine heterograft or Bjork-Shiley and St. Jude prosthesis
which require lifelong anticoagulation therapy and are
also not suited for children.
TRICUSPID REGURGITATION
Tricuspid regurgitation (TR) is frequently seen in 20 to 50
precent of all patients with rheumatic heart disease.
BIBLIOGRAPHY
1.
Guidelines for the diagnosis of rheumatic fever. JAMA

1992;73:268-85.
2. Kumar V, Narula J, Reddy KS, et al. Incidence of rheumatic
fever and prevalence of rheumatic heart disease in India.
Tnt J Cardiol 1994;221-8.
3. Mccarty M. Streptococci. In Davis BD, Dulbecco R, Eisen
HN, Ginsberg HS (Eds): Microbiology (4th edn).
Singapore: Harper and Row Publishers 1990;525-38.
4. Park MK. Pediatric Cardiology for Practitioners (3rd edn).
St. Louis: Mosby Year Book 1996;302-19.
5. Veasy LG, Wiedmeier SE, Garth SO, et al. Resurgence of
rheumatic fever in intermountain areas of United States.
N Engl J Med 1987;316:421-7.
534
11.6 Congestive Heart Failure in Children

Anita Khalil
Congestive heart failure (CHF) is defined as a state in which
the heart cannot maintain the cardiac output required to
sustain the metabolic needs of the body, without evoking
certain compensatory mechanism, at rest or during stress.
Pathophysiology
Cardiac output is determined by preload, myocardial
contractility, afterload and heart rate. Myocardial
contractility is directly proportional to the filling volume
(Frank Starling principle), which depends on the preload.
However, dilatation beyond a certain limit does not
further increase the cardiac output. Neurohormonal
excitation is the pathophysiological hallmark of
congestive heart failure evident by activation of
vasopressor and sodium retention forces, i.e. sympathetic
and renin angiotensin system and also sodium excretory
forces, i.e. increased plasma natriuretic factor and
prostaglandins. There are physiological responses aimed
at restoring perfusion of the vital organs. Retention of
sodium and water leads to increased circulating volume
which in turn, causes increased venous return and
increased preload. Increased sympathetic activity causes
tachycardia and increased systemic vascular resistance
(afterload), which, in turn, increases the work of
ventricles, causing a vicious cycle of failure begetting
failure. Thus, in CHF there is increased preload, afterload
and heart rate, attempting to maintain tissue perfusion.
There is also a decrease in number of beta-I receptors in
myocardium, probably due to high catecholamine levels
in CHF. The causes of CHF at different ages are listed in
Table 11.6.1.
In infants, poor feeding, tachypnea, with intercostal and
subcostal recessions, excessive sweating, wheezing or
mild cyanosis may occur. In older children, fatigue,
anorexia, pain in the abdomen and dyspnea on exertion
are the presenting complaints. On examination,
tachycardia, tachypnea, and enlarged and tender liver
are found. Jugular venous pressure is raised, but is
difficult to appreciate in infants and young children.
Edema or anasarca may appear in older children but are

rarely seen and are ominous in infants. Severely ill patients
may be in cardiogenic shock. One should look for
precipitating events for CHF, i.e. anemia, fever, respiratory
infection, infective endocarditis, rheumatic activity or
arrhythmia.
The chest radiograph reveals cardiomegaly cardiothoracic ratio more than 60 percent in newborn and 55
percent in older children. Changes due to the underlying
cardiac lesion as well as state of the lung parenchyma
help in arriving at diagnosis. Electrocardiogram may be
helpful in the diagnosis of underlying heart disease.
Echocardiography is very useful in assessing
ventricular function (Normal LVEF 55-65%) and detection
of underlying heart disease. Serum electrolytes and arterial
blood gases may be altered in critically ill patients. The
serum sodium may be low, even though, the total body
sodium and water are increased.
MANAGEMENT OF CHF
Management can be broadly categorized as follows (Table
11.6.2) :
1. General supportive measures
2. Increasing cardiac output
3. Treatment of the underlying cardiac abnormality
General Measures
A very sick child should rest in a propped-up position.
Morphine 0.1 to 0.2 mg/kg is beneficial in sedating an
anxious patient with pulmonary edema. Restriction of
activity is monitored according to the patients condition.
Oxygen may be given by a hood at the rate of 8-10
L/min.
In an acutely sick child, intravenous fluids or
nasogastric feeding may be mandatory with restriction of
fluids to 75 ml/kg. In chronic CHF, there is no need for
very low sodium formulas as they are poorly tolerated
and also cause malnutrition. Normal, more palatable
formulas with chronic diuretic administration are
preferable. Infants and children should receive no added
salt diets.
535
TABLE 11.6.1: Causes of CHF at different ages
TABLE 11.6.2 : Guidelines for the management of CHF
1. Fetus
Severe anemia (hemolysis, fetomaternal transfusion supra
ventricular or ventricular tachycardia, Complete heart block
2. Neonates
a. Birth to I week
Birth asphyxia, hypoglycemia, sepsis, transposition of
great vessels (TGA), coarctation of aorta, neonatal
myocarditis
b. 1 week to 1 month
TGA
Large shunts (VSD, PDA)
Viral myocarditis
Cor pulmonale
Large mixing cardiac defects
Fluid overload
TAPVC (obstructed)
3. Infant
a. 1 to 3 months
TGA
Anomalous pulmonary venous drainage
b. 3 to 6 months
Supraventricular tachycardia
Large VSD, FDA
TGA
c. 6 to 12 months
Large VSD, FDA
AV communication
Pulmonary venous anomaly
4. Toddlers
Large VSD, PDA
Supraventricular tachycardia
AV malformation
Metabolic cardiomyopathy
Acute hypertension
Anomalous origin of left coronary artery
Myocarditis
5. Older children and adolescents
Rheumatic carditis
Infective endocarditis
Viral myocarditis
Cardiomyopathydilated
Thyrotoxicosis
Constrictive pericarditis and pericardial effusion
Drugs, e.g. adriamycin
Hemosiderosis
Cystic fibrosis
1. Rest, propped up position

2. Humidified oxygen
3. Salt restricted diet
Diet for InfantsInfants in CHF lack sufficient strength for
effective suckling due to rapid respiration and fatigue.
Nasogastric feeding with calorie dense formula (0.8 cal/ml) is
recommended to reduce fluid intake and to provide extra
energy to meet the enhanced metabolic requirement.
4. Precipitating and aggravating factors for CHF include anemia,
electrolyte imbalance, infective endocarditis, hypertension,
arrhythmia and pulmonary embolism which must be looked
for and treated.
5. Drugs
Digoxin a potent inotropic drug
Diuretics added to complement action of digoxin:
Vasodilator, angiotensin converting enzyme inhibitors
recommended in selected situations
Increasing Cardiac Output

The cardiac output may be increased using a combination
of inotropic drugs, diuretics and vasodilators.
Inotropic Agents
Digitalis
It is argued that stimulating the failing myocardium by
inotropic agents may further damage it. The heart is
already exposed to potent inotropic agents in CHF. On
the other hand, an increase in available contractility
decreases the preload and reflexly the afterload with a
consequent diminished oxygen consumption which is
beneficial for the failing myocardium.
Digitalis withdrawal in patients may cause deterioration
of symptoms. It was found to be superior to captopril in
improving the quality of life. Digoxin depresses
conductors in the SAandAV nodes. Digoxin is reported
to be useful in treatment of cases with CHF both in
normal sinus rhythm, in atrial fibrillation and
supraventricular tachycardias.
Digoxin is an important drug to control CHF. It has a
half-life of 36 hours, an initial effect after 30 minutes and
a peak effect at 2 to 6 hours. Absorption is up to 60 to 80
percent from oral route, is not affected by meals, and 60
to 70 percent is excreted unchanged in the urine. Rapid
digitalization is achieved at 24 hours by giving
intravenously. One-half to threefourths of the total
536
digitalizing dose initially, and the remaining half in two

divided doses 8 to 16 hours later. Slow digitalization in a
less sick child maybe achieved in 7 to 10 days by
maintenance dose daily, i.e. one- fourth to one-fifth of
the total digitalizing dose.
First degree heart block in the form of prolongation
of P-R interval and ST and T wave changes may occur
with digoxin and do not necessitate stopping the drug.
Development of new arrhythmias, when on the drug
should be considered to be digoxin related, until proven
otherwise. Digoxin has a low therapeutic margin, and
blood levels should be maintained between 0.08 and
0.16 pg/dl.
Sympathomimetic agents These drugs combine inotropism with peripheral vasodilatation.
Dopamine
It has inotropic and vasodilatory action up to 5 g/kg/
min. This dose causes increased renal blood flow and
diuresis. Higher doses may cause vasoconstriction and
are not useful for control of CHF. Side effects are
tachycardia, arrhythmia and increased myocardial
oxygen demand. It is a precursor of noradrenaline and
especially useful in chronic CHF with acute deterioration
where the myocardial catecholamine stores are absent.
It is used in cardiogenic shock, asphyxia and postsurgical
situations.
Milrinone
It has been tried orally for prolonged use, and it increases
exercise capacity and cardiac output. However, studies
showing an increased long-term mortality in patients
receiving the drug have precluded its routine use.
Other drugs like devosimeudan has also been used
and tried in CHF in adults with encouraging results,
however, their use in children has not been evaluated.
Diuretics
Diuretics are generally used along with digoxin. They
decrease the circulating blood volume and preload and
relieve pulmonary congestion and dyspnea. However,
the benefit is at the expense of stimulation of the reninangiotensin aldosterone system, causing vasoconstriction
and increased afterload. Long-term diuretic use causes
hypokalemia and alkalosis. Vigorous use can decrease
cardiac output by diminishing the filling pressure. This
may result in lower renal blood flow and lead to an
increase in blood urea nitrogen. When used judiciously
(start with low-dose and titrate slowly), diuretics are
useful in the management of CHF Frusemides, spironolactone and chlorthiazide are some of the commonly used
diuretics. Torasemide - loop diuretic with antialdosterone properties less hypokalemic effect.
Vasodilators
Dobutamine
It has similar actions with lesser side effects. A dose of
5 to 10 g/kg/min is appropriate.
The drugs including adrenaline and noradrenaline
are not recommended.
Phospho-diesterase Inhibitors
1. Combine inotroprism with peripheral vasodilationreduce afterload.
2. Decrease mycocardial oxygen demand.
Amrinone
It is an inotropic drug with peripheral vasodilatory action.
The drug is administered in a dosage of 0.75
mg/kg intravenously initially and then by an infusion
of 5 to 10 g/kg/minute. Side effects include hypotension
and reversible thrombocytopenia. The drug is useful in
acute CHF, but causes intolerable side effects on longterm use.
Venodilators
They increase venous capacitance (preload) and relieve
pulmonary and systemic venous congestion. Patients
with pulmonary edema due to mitral or aortic valve
regurgitation and postoperative patients with CHF
respond well to venodilators. If the initial filling pressure
(pulmonary wedge pressure or LVEDF) is low, venodilators can cause hypotension and reflex tachycardia and
should be selected carefully.
Nitrates (Nitroglycerine)
Tolerance to nitrates is one of the majors factors limiting
their use. Depletion of the sulfhydryl group has been
postulated as the mechanism for tolerance. Major and
rapid kemodynamic effects of nitroglycerine limit its use
to ICU settings. Only intravenous preparation is
available.
537
Arteriolar and Mixed Dilators
Angoitensin II Receptor Blocking Agents
They decrease systemic vascular resistance (afterload) and

increase cardiac output without altering the heart rate,
blood pressure and myocardial oxygen consumption.
Losartan Potassium- Haemodynamically same effects as

Ace-inhibitors and can be added to Ace-inhibitors in
chronic CHF for better results.
Hydralazine
Beta-adrenergic Blockers
Being primarily an arteriolar dilator, it also relaxes

venous vessels. It is also used in hypertension. It has
diverse side effects including precipitation of a lupus like
syndrome. The oral dose is 0.5 to 7.5 mg/kg/day in three
divided doses.
They are controversial agents and generally contraindicated in congestive heart failure. However, they are
being tried in some chronic CHF conditions, based on the
concept that prolonged exposure to adrenergic stimulation
in CHF causes desensitization i.e. decreased activity of
adrenal cyclase due to down regulation of beta receptors.
Beta blockade will cause reversal of this, normalization of
receptors density and restoring the maximum response to
adrenergic stimulation. The adrenergic blockade also
protects the myocardium from cardiotoxic effects of
catecholamines and inhibits tachyarrhythmias and renin
angiotensin activity. The results of trials of these drugs in
dilated cardiomyopathies are still preliminary, through
carvedilol is prescribed in children with dilated
cardiomyopathy.
Angiotensin Converting Enzyme (ACE) Inhibitors

They are more effective than vasodilators alone, as they
decrease the cardiac adrenergic drive and improve renal
sodium and water handling, correct intracellular
electrolyte abnormalities, prevent arrhythmia and
progress of left ventricular dysfunction. The sulfhydryl
group of captopril has many theoretical benefits. It
increases the levels of endothelium derived relaxing factor
and vasodilatory prostaglandins. It can also serve as free
radical scavenger in high doses. Captopril is absorbed 95
percent orally. It decreases generation of angiotensin II
and consequently the afterload. It is used in the dose of 0.5
to 0.6 mg/kg/day in two to four divided doses. Side effects
are hypotension rash (in 5-8% patients), neutropenia and
proteinuria. Enalapril is another ACE inhibitor,
successfully used in adults, so far trials regarding its safety
in children are not available. These drugs are contraindicated in renal vascular disorders. Dry cough is a major
side effect because of Bradykinine release.
Prazosin
It is an blocker and a mixed vasodilator. It is administered
orally in the dose of 25 g/kg/day initially and increased
slowly over a few days to 25 g/kg/day 6 hourly with
blood pressure monitoring.
Nitroprusside
Nitroprusside which is a mixed vasodilator can also cause
hypotension. If used for long, or in high-doses
(> 5 g/kg/min.), it can cause thiocyanate or cyanide
poisoning. Thiocyanate toxicity begins at plasma levels
of 5-10 g/dl. Nitroprusside is photosensitive and
degenerates in light, within six hours. This drug is reserved
for critically ill-patients and should be used for the shortest
possible time.
Treatment of Underlying Cardiac Abnormality

Congestive heart failure is basically the manifestation of
an underlying disease. After the CHF has been treated
symptomatically, the underlying abnormality should be
identified and treated, if possible.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
6.
7.
Adam DT. A new look at digoxin in CHF and sinus

rhythm. Postgrad Med I 1989;65:715-7.
Alarcon SD, Wakin KG, Worthington JW, et al. Clinical
and experimental studies on the hydralazine syndrome
and its relationship in systemic lupus erythematosus.
Medicine 1967;46: 1-33.
Armstrong PW, Walker DC, Burton JR, et al. Vasodilator
therapy in acute myocardial infection. Circulation
1975;52:1118-22.
Artom M, Grahom T. Guidelines for vasodilator therapy
of congestive heart failure in infants and children. Am
Heart J 1987;113:121.
Bain DS. Effect of amrinone on myocardial energetics in
severe congestive heart failure. Am J Caro 1985;56:168.
Behrman RE. The cardiovascular system. In Behrman
RE, Kleighmen RM, Nelson WE, Vaughan VC (Eds):
Textbook of Pediatrics (13th edn). Philadelphia: WB
Saunders Company, 1992;1212-5.
Bristow MR. Myocardial beta adrenergic receptor down
regulation in heart failure. Tnt J Cardiol 1984;5:648-51.
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8. Francis GS. Neurohumoral mechanisms involved in

congestive heart failure. Am J Cardiol 1985;55:15A-21A.
9.
Freidman WF. The intrinsic physiological properties of

the developing heart. Cardiovasc Dis 1972;15:87-91.
10.
Friedman WE, George BL. Treatment of congestive heart

failure by altering, loading conditions of the heart. J
Pediatr 1985;106:697.
11. Grinstead CW, et al. Discontinuation of chronic diuretic

therapy in stable congestive heart failure patients.
Circulation (Suppl) 1992;1:1-808.
12. Hayes CJ, Butler VP Jr. Gersony WM. Serum digoxin

studies in infants and children. Pediatrics 1973;52:561- 64.
13. Lejemtel TH, Sonnenblick EH. Should the failing
myocardium be stimulated? N Engl J Med 1984;310:1384.
14. Loggie JMH, Kleinman IT, Van Maanen EF. Renal function
and diuretic therapy in infants and children. I Pediatr
1975;86:657.
15. Packer M, et al. Comparison of vasodilatation and ACE
inhibition (Enalapril) on exercise capacity and quality of
life in chronic CHF. N Engl J Med 1987;317:799.
16. Packer M, et al. Prospective randomized milrinone survival
evaluation (PROMISE). N Engl J Med 1991;325: 1468.
11.7 Systemic Arterial Hypertension in Children

Srikanta Basu, S Srinivasan
Systemic hypertension is an important condition in
childhood, with estimated population prevalence of 1-5%
in the developed countries. Nutritional surveys, in the
USA show a significant secular increase in systolic and
diastolic blood pressures. The causes for increase in blood
pressure are attributed to increasing obesity, change in
dietary habits, decreased physical activity, increasing
stress and growing awareness of this disease. Similar data
is lacking from India; small surveys in school children
suggest a prevalence ranging from 2-5%. There is evidence
that childhood hypertension can lead to adult
hypertension. Hypertension is a known risk factor for
coronary artery disease (CAD) in adults, and the presence
of childhood hypertension may contribute to the early
development of CAD. Patients with severe cases of
childhood hypertension are also at increased risk of
developing hypertensive encephalopathy, seizures,
cerebrovascular accidents, and congestive heart failure.
Both hypertension and prehypertension have become a
significant health issue in the young because of the strong
association between high BP and being overweight and
the marked increase in the prevalence of overweight
children. Based on these observations, early detection of
and intervention in children with hypertension are
potentially beneficial in preventing long term complications of hypertension.
Definition, Staging and Measurement of Hypertension
Systemic hypertension is defined as the systolic blood
pressure (SBP) or diastolic blood pressure(DBP) more
than 95th percentile. The percentiles used for pediatric

hypertension are based on sex, age, and height. BP
measurements need to be taken on 3 separate occasions. If
percentiles of systolic and diastolic pressures are different,
the higher percentile is used for defining and staging
hypertension. The classification of pediatric hypertension
as proposed by the Pediatric Nephrology group of the
Indian Academy of Pediatrics is the endorsement of the
fourth report of the National High Blood Pressure
Education Program (NHBPEP) Working Group on High
Blood Pressure in Children and Adolescents. The
committee has classified pediatric hypertension into four
groups:
Normal: SBP and DBP less than< 90th percentile;
Normatine data from the fourth report and second
report are to be used in defining hypertension in
children more than 1 year and infants less than 1 year,
respectively.
Prehypertension: SBP or DBP greater than or equal to
90th centile but less than 95th percentile or BP levels
greater than or equal to 120/80 mmHg.
Stage 1: SBP or DBP from 95th percentile to 99th plus
5 mm of Hg
Stage 2:SBP or DBP greater than 99th percentile plus
5 mmHg.
Screening for Hypertension
It is recommended that all children more than 3-year-old
should have their blood pressure measured, who are seen
in clinics or hospital settings. Blood pressure should also
be measured in at-risk younger children with: (i) history
of prematurity, very low birth weight or interventions in

NICU; (ii) malignancy, post organ transplant; (iii) recurrent
urinary tract infections, known renal or urological
diseases, hematuria or proteinuria; (iv) family history of
congenital renal disorders; (v) congenital heart disease;
(vi) conditions associated with hypertension, e.g.,
neurofibromatosis, tuberous sclerosis and ambiguous
genitalia. Blood pressure should be measured in patients
who present with features of kidney or heart disease,
seizures, altered sensorium and headache or visual
complaints. The preferred method for blood pressure
measurement is auscultation. Accurate techniques for
measurement of blood pressure are necessary for its
diagnosis, staging and follow up.
Measurement Devices
Mercury sphygmomanometer: Normative values for blood
pressure are based on sphygmo-manometry, which
continues to be the preferred method for blood pressure
estimation. By convention, an appropriate cuff size
(Table 11.7.1) is one with an inflatable bladder width that
is at least 40 percent of the arm circumference at a point
midway between the olecranon and the acromion. The
cuff bladder length should cover 80 to 100 percent of the
circumference of the arm. An oversized cuff can
underestimate the blood pressure, whereas an undersized cuff can overestimate the measurement. If an
appropriate cuff size is not available, the next larger size
is used. Blood pressure should be measured in a
controlled environment after five minutes of rest in the
seated position with the right arm supported at heart
level. With the stethoscope on the brachial artery, the
mercury column is lowered slowly (2 mm per second).
Systolic blood pressure is the point when Korotkoff
sounds are first heard (K1) and disappearance of sounds
(K5) is the diastolic pressure. If Korotkoff sounds persist,
the measurement is repeated with less pressure on the
TABLE 11.7.1: Dimensions for blood pressure cuffs
Age
Width
(cm)
Length
(cm)
Circumference
(cm)*
Newborn
Infant
Child
Adolescent
Thigh
4
6
9
10
20
8
12
18
24
42
10
15
22
26
52
*Calculated so that the largest arm would still allow the bladder
to encircle the arm by at least 80 percent.
539
stethoscope head. If the sounds persist at low intensity,

then K4 (muffling of sounds) is recorded as the diastolic
pressure. Blood pressure recordings should be expressed
to the nearest 2 mm Hg. A high reading should be
confirmed after the child has rested for 5 minutes and
the average of 2-3 readings is taken as the value for that
occasion. If the blood pressure is greater than the 90th
percentile, the blood pressure should be repeated twice
at the same office visit to test the validity of the reading.
Oscillometric devices: These devices are increasingly used
in infants (in whom auscultation is difficult) and in
intensive care settings when frequent blood pressure
measurements are needed. However, neither are most
oscillometric devices validated for children, nor are there
normative data based on these readings. Blood pressure
values on oscillometry, which exceed the 90th percentile
must therefore be confirmed by sphygmomanometry.
Aneroid and other devices: These instruments, based on
spring-based technology require frequent calibration and
validation. The use of aneroid devices and wrist or finger
band oscillometry for blood pressure measurements is
discouraged. Direct intra-arterial BP monitoring is used
in intensive care setting and is the most accurate method
of measuring blood pressure.
Ambulatory blood pressure monitoring (ABPM): Continuous
recordings over 12- or 24-hr are believed to reflect true
blood pressures accurately, are more reproducible and
correlate with target organ damage. A lack of availability
of these instruments and normative standards has
limited the utility of ABPM for the diagnosis of hypertension in children.
TABLE 11.7.2: Causes of childhood hypertension

according to age group
Age
Causes
One to six years Renal parenchymal disease; renal vascular

disease; endocrine causes; coarctation of the
aorta; essential hypertension
Six to 12 years Renal parenchymal disease; essential hypertension; renal vascular disease; endocrine
causes; coarctation of the aorta; iatrogenic
illness
12 to 18 years Essential hypertension; iatrogenic illness;
renal parenchymal disease; renal vascular
disease; endocrine causes; coarctation of the
aorta
Note: Causes listed in order of prevalence.
540

TABLE 11.7.3: Classification of hypertension in children and adolescents, with measurement of
frequency and therapy recommendations
Frequency of BP
measurement
Therapeutic
lifestyle change
Pharmacologic
therapy
Normal
Recheck at next
scheduled physical
examination
Encourage healthy diet,

sleep and physical activity
Prehypertension
Recheck in 6 months
Weight management
counseling if overweight;
introduce physical activity
and diet management**
None useless compelling

indications such as chronic
kidney disease, diabetes
mellitus, heart failure or
left ventricular hypertrophy exist
Stage 1 hypertension
Recheck in 1 to 2
weeks or sooner if the
patient is symptomatic;
if persistently elevated
on two additional occasions, evaluate or refer
to source of care within
1 month
Weight management
and diet management**
Initiate therapy based on

indications*** or if compelling indications(as shown
above) exist
Stage 2 hypertension
Evaluate or refer to
source of care within
1 week or immediately
if patient is symptomatic.
Weight- management
and diet management
Initiate therapy++
(Based on The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.
Pediatrics 2004;114:560).
**parents and children to modify their eating plan to the dietary approaches to stop hypertension after consultation with a nutritionist.
***indications for antihypertensive drug therapy in children include symptomatic hypertension, secondary hypertension, hypertensive
target organ damage , diabetes( types 1 and 2), and persistent hypertension despite nonpharmacologic measures.
++more than one drug may be required.
Etiopathogenesis
Most childhood hypertension in children is often
secondary to an underlying renal disease; approximately
60-70% patients have renal parenchymal disorders and
5-25% has reno-vascular disease(Table 11.7.4). Coarctation of aorta is an important cause during infancy.
Adolescents usually have primary or essential hypertension making up 85 to 95% of cases. Essential hypertension is rarely found in children younger than 10 years
and is diagnosis of exclusion. Significant risk factors for
essential hypertension include family history and
increasing BMI. Hypertension may be transient in certain
conditions, e.g., acute glomerulonephritis, acute intermittent porphyria, Guillain Barre syndrome, raised
intracranial pressure, corticosteroid administration,
anxiety and hyperthyroidism. Therapy for hypertension

may be required in some of these cases (Table 11.7.2).
Persistence of elevated blood pressures requires detailed
evaluation.
Pathogenesis
Systemic arterial blood pressure is determined by the
cardiac output (COP) and the peripheral arterial resistance
(PVR) (BP= COP PVR). Any factor, which results in the
increase of anyone of these two parameters without a
reciprocal decrease in the other factor, will result in arterial
hypertension.
The predisposing high-risk factors such as obesity,
stress, heredofamilial disposition, excess dietary intake
of sodium chloride, abnormal lipid profile, alcohol and
tobacco smoking or use, use of oral contraceptives play a
well-known role.

TABLE 11.7.4: Conditions associated with persistent
(chronic) hypertension
Renal
Chronic pyelonephritis
Chronic glomerulonephritis
Reflux nephropathy
Obstructive uropathy
Hydronephrosis
Polycystic kidney
Congenital dysplastic kidney
Renal tumors
Renal trauma
Postradiation renal dysfunction
Post-transplantation renal rejection
Renal involvementcollagen vascular diseases:
Systemic lupus erythematosus
Vascular
Renal artery stenosis
Renal artery thrombosis
Renal vein thrombosis
Renal artery compression (extrinsic)
Aortoarteritis (Takayasu)
Systemic vasculitidis syndromes
Endocrine
Congenital adrenal hyperplasia (deficiency of 11
Hydroxylase or 17 Hydroxylase)
Cushing's syndrome: adenoma/carcinoma
Hyperthyroidism
Hyperaldosteronismprimary hyperparathyroidism
Pheochromocytoma
Neuroblastoma
Neurological
Intracranial tumors
Intracranial hypertension
Miscellaneous (Drugs, toxins, metabolic, etc.)
Corticosteroids, oral contraceptives, licorice, lead/mercury
poisonings; porphyria, and Riley Day syndrome (familial
dysautonomia)
Essential Hypertension
Low renin hypertension
Normal renin hypertension
High renin hypertension
Increased sympathetic activity of whatever etiology,

e.g. anxiety, increased ventricular preload secondary to
increased blood volume (excess salt intake, infusion of
large volumes of fluid, excess mineralocorticoid states
and others) will result in increased cardiac output.
541
Increased peripheral arterial resistance is due to

arteriolar vasoconstriction, which follows alpha adrenergic receptor stimulation. Angiotensin stimulation of
medulla oblongata, baroreceptor reflex overactivity,
hypothalamic or cortical stimulation of sympathetic
nerve activity, increased levels of circulating catecholamines as seen in pheochromocytoma/neuroblastoma,
excess glucocorticoids are known factors which increase
the peripheral vascular resistance. Increased renin levels
play a significant role in some cases of hypertension,
including the cases of essential hypertension. Salt
sensitive vessel wall changes have been identified to be
a factor in some cases of hypertension.
Clinical Features
Most patients with pre-hypertension and hypertension
are asymptomatic or have non-specific symptoms.
Infants may show irritability, failure to thrive, vomiting,
feeding problems, seizures or respiratory distress. The
occurrence of epistaxis is rare.
Hypertensive crises: Patients with stage 2 hypertension are
at risk for hypertensive crises, which are classified as
emergencies or urgencies, based on the respective
presence or absence of acute end organ damage (e.g.,
hypertensive encephalopathy, intracerebral bleeding,
acute left ventricular failure and renal failure). The
occurrence of these complications is related to the rate
of rise and duration of hypertension, rather than absolute
blood pressure values.
Hypertensive encephalopathy is characterized by lethargy,
dullness, headache, seizures and visual disturbances
including blindness. Cerebral infarction, hemorrhage and
facial nerve palsy may occur. Neuroimaging shows
features of white matter degeneration in the parietooccipital area (posterior leukoencephalopathy), which are
reversible with treatment. Examination of the retina
might shows hemorrhages, exudates or papilledema.
While hypertensive emergencies require reduction of
blood pressure within hours, the same can be achieved
over 2-3 days in patients with hypertensive urgencies.
Chronic Complications (target organ damage)
Left ventricular hypertrophy (LVH) is the most
prominent clinical evidence of end organ damage in
childhood hypertension. Data show that LVH can be seen
in as many as 41 percent of patients with childhood
542
hypertension. Acute left ventricular failure is another lifethreatening complication of severe hypertension.
Sustained hypertension can also results in changes in
eyes (hypertensive retinopathy),kidneys (albuminuria),
brain and blood vessels (increased initimal and medial
thickness). There is evidence that these changes are
common, even in patients with long standing stage 1
hypertension.
Evaluation
Once hypertension has been confirmed, an extensive
history and careful physical examination should be
conducted to identify underlying causes of the elevated
blood pressure and to detect any end-organ damage.
With the appropriate information, unnecessary and often
expensive laboratory and imaging studies can be
avoided. A child with primary hypertension often has a
positive family history of hypertension or cardiovascular
disease. Other risk factors including metabolic syndrome
and sleep-disordered breathing . It is helpful to remember
that secondary hypertension is more likely in a younger
child with stage 2 hypertension, thus data about systemic
conditions( specially renovascular) associated with
elevated blood pressure should be elicited. History is
taken for dietary habits, abdominal trauma, physical
activity, and symptoms related to renal, cardiac or
thyroid disorders. Infants are assessed for history of
oligohydraminos and invasive procedures in NICU (e.g.,
umbilical artery catheterization). Family history is taken
for hypertension, diabetes, dyslipidemia, obesity,
premature cardiovascular or cerebrovascular disease and
renal disorders. A medication history should include any
use of over-the-counter, prescription, and illicit drugs
because many medications and drugs can elevate blood
pressure. The physician should also ask about the use of
performance-enhancing substances, herbal supplements,
and tobacco use. Physical examination should include
calculation of BMI because of the strong association
between obesity and hypertension. Obtaining blood
pressure readings in the upper and lower extremities to
rule out Coarctation of the aorta also is recommended.
Examination of the retina should be included to assess
the effect of hypertension on an easily accessed end
organ. In the majority of children with hypertension,
however, the physical examination will be normal.
Investigations
Laboratory testing and imaging in a child with hypertension should screen for identifiable causes, detect co
morbid conditions, and evaluate end-organ damage
Screening tests (Table 11.7.5) should be performed on all
children with a confirmed diagnosis of hypertension.
Decisions about additional testing are based on
individual and family histories, the presence of risk
factors, and the results of the screening tests. Young
children, those with stage 2 hypertension, and those in
whom a systemic condition is suspected require a more
extensive evaluation because these children are more
likely to have secondary hypertension. The child who is
older or obese, with a family history of diabetes or other
cardiovascular risk factors, will require further work-up
for the metabolic abnormalities associated with primary
hypertension.
A cause for hypertension is suggested in most instances
based on clinical features and initial evaluation.
Confirmation of the diagnosis requires specific
investigations tailored to specific needs (Table 11.7.6).
Occasionally, the cause for hypertension may not be found
despite detailed evaluation. Hormone levels and 24-hour
urine studies are readily available to most physicians, but
more specialized tests such as renal angiography often
require referral to a center with pediatric radiology,
nephrology, and cardiology services. When renovascular
disease is strongly suspected, conventional or intra-arterial
digitally subtracted angiography are recommended.
Scintography with or without angiotensin-converting
enzyme (ACE) inhibition also can be used. These older
TABLE 11.7.5: Screening work up of children with
hypertension
Evaluation for cause
Hemogram
Blood urea, creatinine, electrolytes
Fasting lipids, glucose, uric acid
Urinalysis, culture
24-hr urinary protein or spot protein to creatinine ratio
Chest X-ray
Renal ultrasonography
Screen for target organ damage
Retinal fundus examination
Urine: microalbumin, spot protein to creatinine ratio Chest
X-ray, ECG, echocardiography

TABLE 11.7.6: Specific diagnostic tests for
sustained hypertension
Condition
Diagnostic investigations
Glomerulonephritis
Complement (C3), ANA, ANCA, antidsDNA, renal biopsy
Reflux nephropathy
Micturating cystourethrogram, DMSA

scintigraphy
Renovascular
hypertension
Doppler flow studies, captopril

renography
Angiography (MR, spiral CT, digital
subtraction or conventional)
Renal vein renin activity
Echocardiography, angiography
Endocrine causes
Thyroxine, thyroid stimulating hormone

Plasma renin activity, aldosterone
Plasma and urinary cortisol
Plasma and urine catecholamines;
MIBG scan, CT/MR imaging
imaging techniques are quite invasive. Data on newer

studies such as magnetic resonance angiography and 3dimensional or spiral computed tomography in children
are limited, but documentation of their usefulness is
increasing. Documenting LVH is an important component
of the evaluation of children with hypertension. Because
echocardiography is noninvasive, easily obtained, and
more sensitive than electrocardiography, it should be part
of the initial evaluation of all children with hypertension
and may be repeated periodically.
543
Weight Reduction
Achievement of ideal body weight is important. Weight
reduction is the primary therapy for obesity-related
hypertension. Obesity increases the occurrence of
hypertension threefold while favoring the development
of insulin resistance, hyperlipidemia, and salt sensitivity.
Significant obesity also increases the likelihood of LVH
independent of blood pressure level. Weight loss is
associated with increased HDL cholesterol and decreases
in triglycerides and body fat. When increased physical
activity is combined with weight loss, the antihypertensive
effect may be greater than that with weight loss or exercise
alone. A reduction in BMI by 10% is reported to lead to 812 mm Hg fall in systemic blood pressure. Weight
reduction is achieved by regular physical activity and diet
modification. Regular moderate aerobic activity for 30-60
minutes on most days and limiting sedentary activities to
less than 2 hours per day is recommended. While children
often find defined physical exercises (aerobics, tread mills)
boring, they are likely to continue activities incorporated
into their routines, e.g., walking or cycling to school, playing
with friends outdoors and swimming. Adolescent girls in
our country should be specifically targeted, since they
spend considerably less time than boys in outdoor sport.
Participation in competitive sports is avoided in
patients with stage 2 hypertension or target organ damage,
until blood pressure is controlled satisfactorily. Strength
training (isometric) exercises (e.g., weight lifting,
gymnastics, karate and judo) should be avoided.
Management
The first step in the treatment process is to distinguish
between essential and secondary hypertension. Management of childhood hypertension is directed at the cause of
the elevated blood pressure and the alleviation of any
symptoms. End-organ damage, comorbid conditions, and
associated risk factors also influence decisions about
therapy. Nonpharmacologic and pharmacologic treatments are recommended based on the age of the child, the
stage of hypertension, and response to treatment
(Table 11.7.3).
Nonpharmacologic Treatment
Non pharmacologic therapy is generally recommended
in any child with hypertension or prehypertension and
usually consists of two important lifestyle changes: weight
reduction and dietary modification. Cessation of smoking
and abstinence from alcohol is also recommended.
Dietary Recommendations
Dietary modification should be strongly encouraged in
children and adolescents who have BP levels in the
prehypertensive range as well as those with hypertension.
Recommendations for daily sodium intake in children
range between 1-1.5 g (45-65 mEq sodium, 2.6-3.8 g salt).
Dietary sodium restriction is associated with small
reductions in blood pressure in children. A no added salt
diet is a satisfactory approach to restrict salt intake. Intake
of food products high in sodium (processed and canned
foods, items prepared in fast food shops including pizzas,
pickles and salted potato chips) should be avoided.
Increased potassium intake, through vegetables and fruits,
is associated with modest reduction of systolic and
diastolic blood pressure in adults with essential
hypertension.
544

TABLE 11.7.7: Treatment of hypertensive emergencies
Drug
Dose/Route
Onset/Duration of Action
(After Discontinuation)
Comments
Sodium
nitroprusside
0.25-10 mcg/kg/min in 5%
dexotrose) by continuous infusion;
maximal dose for 10 min only
protects Infusate from light
Immediate/2-3 min after

infusion
Cyanide poisoning in patients with

renal failure, nausea, vomiting;
methemoglobinemia acidosis;
thiocyanate intoxication with
prolonged use; bags, bottles, and
delivery sets must be light-resistant
Labetalol
0.2-1 mg/kg/dose by bolus

over 2 min period
or
0.4-3 mg/kg/hr
Max: 40 mg/dose or
300 mg/total dose
By cont IV infusion
5-10 min/15-30 min
Contraindicated in CHF, diabetes

mellitus and asthma
Bronchoconstriction, heart block,
orthostatic hypotension
Hydralazine
0.1-0.5 mg/kg/dose
Max: 50 mg/dose
IV, IM
Onset:10-20 min IV;

20-30 min IM
Duration:/>1hr (IV);
4-6 hr (IM)
Tachycardia, flushing,salt retention.
Diazoxide
1-5 mg/kg/dose q5-15 min IV

Max:150 mg/dose
Glyceryl
trinitrate
1-3 mcg/kg/min
2-5 min/5-10 min
Headache, tachycardia, vomiting,

flushing, methemoglobinemia;
requires special delivery system due
to drug binding to plastic tubing
Esmolol
50-300 g/kg/min by infusion
1-5 min/15-30 min
First-degree heart block, congestive

heart failure, asthma
Pain at injected vein,sodium

retention,use with diuretics
Onset: 2 min
An increased intake of fresh vegetables and fruits,

whole grains and non-fat dairy is recommended. These
foods are low in sodium and saturated fat and rich in
minerals (potassium, calcium, magnesium) and fiber. The
IAP Consensus Committee on Obesity and the Nephrology chapter expert group on hypertension recommends
the daily food composition in the form of a thali, where
half (50%) is vegetables, salads and fruits, a quarter (25%)
is cereals (rice and/or chapattis), and the remainder is
protein based (legumes, milk, egg, animal protein). The
intake of fried foods, snacks and sweet dishes should be
limited.
Pharmacologic Therapy
Drug therapy is indicated in patients with symptomatic
hypertension; (i) acute or chronic complications of
hypertension, including evidence of target organ damage,

(ii) secondary hypertension, (iii) stage 2 hypertension, (iv)
stage 1 hypertension that persists despite 6-months of
lifestyle modifications, and (v) pre-hypertension or stage
1 hypertension with comorbid conditions (diabetes,
chronic kidney disease or dyslipidemia). The goal for
treatment is the reduction of blood pressure to levels <95th
percentile, unless comorbid conditions or target-organ
damage is present, when it should be lowered to <90th
percentile. Therapy is initiated with one agent, at an
appropriate dose and the dose is increased until the
desired blood pressure is achieved. If the highest dose is
not effective or if there are side effects, a drug from a
different class is added or substituted. Medications with
a longer duration of action (once, twice daily dosing) are
preferred for better compliance and less side effects. Dose
545
TABLE 11.7.8: Oral pharmacologic treatment of chronic hypertension in children

Drug
Dosage and
frequency of dosage
Comments
Diuretics
Monitor for hypokalemia, hyperglycemia and

hyperuricemia
Hydrochlorothiazide
1-3 mg/kg/day;qd
Furosemide
1-6 mg/kg/day; qd-bid
Bumetanide
Spironolactone
0.015-0.1 mg/kg/dose (max. 10 mg/day)

1-3 mg/kg/d; qd-bid
Metolazone
0.2-0.4 mg/kg/day qd
Aldosterone antagonist
Distal tubular blockade of Na:K
exchange
Inhibition of reabsorption of Na+
Vasodilators
Hydralazine
Minoxidil
1-8 mg/kg/day; qid

0.1-1 mg/kg/day; qd-bid
Tachycardia, headache, lupus synd.

Hirsutism, salt-water retention
- Adrenergic Antagonists
Prazosin
0.05-0.5 mg/kg/day; bid-tid
First dose hypotension
Calcium Channel Blockers

Nifedipine
(extended release)
Amlodipine
Isradipine

0.05-0.5 mg/kg/day; qd-bid
0.1-0.8 mg/kg/day; bd-tid
Tachycardia, headache, flushing, dizziness
- Adrenergic Antagonists
Propranolol
Atenolol
Labetalol+
Metoprolol
1-4 mg/kg/day; tid

1-4 mg/kg/day; bid-tid
1-6 mg/kg/day; bid-tid
Hypoglycemia, bronchospasm
Longer duration
Hypercalciuria, Ototoxicity
Ototoxicity; Loop diuretics
+ 1:4 alpha:beta blockade
Angiotensin-Converting Enzyme Inhibitors

Captopril
0.02-2 mg/kg/day bd-tid (neonates)
0.5-6 mg/kg/day bd-tid (children)
Enalapril
0.1-0.6 mg/kg/day bd-qid (max 40 mg/day)
Adolescents
2.5-5 mg/24 hr (max 40 mg/day)
Lisinopril
0.06-0.6 mg/kg/day; qd
Ramipril
6 mg/m2; qd
- Adrenergic Agonists
Clonidine
0.005-0.025 g/kg/day bd-qid

(max. 0.9 mg/day)
GFR; Platelets and neutrophils;

K+; Angioedema; cough
Caution- use in renal artery stenosis
Drowsiness and rebound hypertension

Angioedema,cough, headache, dizziness
Angiotensin receptor blockers

Irbesartan
4-5 mg/kg/day
Losartan
0.7-1.4 mg/kg/day; qd
adjustment of antihypertensive medications need not be

made more frequently than every 2-3 days. The choice of
initial drug therapy is largely at the discretion of the
physician. Diuretics and beta blockers have documented
safety and effectiveness in children. Commonly used
medications in children include ACEI, calcium channel
blockers (CCB), angiotensin-receptor blockers (ARBs),
Anemia, neutropenia, dry cough infrequent
vasodilators, beta blockers and thiazide diuretics

(Tables 11.7.7 and 11.7.8). It should be noted that all of these
agents can have adverse effects and interactions that need
to be carefully addressed when prescribing for anyone, but
especially for children, in whom less is known about these
effects than in adults. For example, salt restriction
increases ACE inhibitors antihypertensive effect.
546
Nifedipine and amlodipine are effective CCB for

children. The availability of long acting preparations
permits once or twice daily dosing. Sustained release
preparations of nifedipine should be swallowed whole,
and not crushed or chewed. Captopril, chiefly used in
young infants, requires dosing every 6-8 hr. Beyond
infancy, enalapril (1-2 daily doses) is preferred. Newer
ACEI (lisinopril, ramipril) require once daily dosing and
have fewer side effects. Angiotensin receptor blockers used
in children include losartan, valsartan and irbesartan.
Cardioselective -blockers (atenolol, metoprolol) are
effective agents, requiring once or twice daily dosing and
have few side effects. The use of propranolol is limited in
view of the need for multiple daily doses and side effects.
Labetalol, a - and -blocker, is useful in patients refractory
to other medications.
Specific Recommendations
Following are the recommendation by the expert committee
of IA P nephrology group on the management of
hypertension.
Essential hypertension: While there is no consensus on the
appropriate initial therapy, the choices are between CCB
and ACEI. Therapy with -blockers is recommended in
patients who cannot tolerate ACEI or CCB.
Acute glomerulonephritis: Hypertension in post-infectious
glomerulonephritis is of short duration and associated
with salt and water retention. Fluid and sodium restriction
and judicious use of loop diuretics are useful in patients
with circulatory congestion, hypertension and edema.
Severe hypertension with or without encephalopathy is
an emergency and usually responds to treatment with
CCB and furosemide. Occasionally treatment with a blocker or ACEI may be necessary.
Chronic kidney disease: The target blood pressure in these
patients is <90th percentile. For patients with chronic
kidney disease stage I-III (GFR >30 mL/min/1.73 m2)
therapy should be initiated with ACEI, since these agents
also reduce proteinuria and retard progression of renal
damage. Monitoring of serum potassium and creatinine
is necessary, initially at 7-14 days and then every 1-3
months. The dose of ACEI (or angiotensin receptor
blockers) is reduced if serum creatinine exceeds 30-35%
from the baseline or there is hyperkalemia. Treatment with
ACEI should be avoided in patients with advanced chronic
kidney disease (stage IV-V; GFR <30 mL/min/1.73 m2).
Therapy in these cases is initiated with either a CCB or blocker.
Renovascular disease: In patients with high probability or

confirmed renovascular disease, therapy should be
initiated with a CCB or/and a -blocker. Additional
agents include prazosin, labetalol, clonidine, hydralazine
and/or minoxidil. While therapy with ACEI or
angiotensin receptor blockers is avoided in patients with
suspected or confirmed bilateral renovascular disease,
these agents might be used cautiously in those with
unilateral renovascular hypertension.
ACEI are the preferred initial agents in subjects with
ventricular dysfunction. Additional therapy may be given
with loop or thiazide diuretics, blockers and aldosterone
antagonists. ACEI or angiotensin receptor blockers are
recommended for patients with associated proteinuria.
Blood pressure should be monitored every 3 months.
Screening for end organ damage and renal dysfunction
(proteinuria, serum creatinine) and surveillance for side
effects of drugs is required annually.
Drug Step-down
Step-down treatment is usually recommended in
overweight children with uncomplicated essential
hypertension, who successfully lose weight. This
approach attempts a gradual reduction of the medication
after 8-12 months of satisfactory blood pressure control.
Hypertensive Emergencies
Patients with stage 2 hypertension may present with acute,
life threatening target organ damage involving central
nervous system (encephalopathy, seizures), heart
(pulmonary edema) or kidneys (acute renal failure). These
patients need hospitalization for monitoring and
supportive care. Blood pressure levels are usually
5-15 mm above the 99th percentile, and should be reduced
to safe levels. Rapid reduction of blood pressure might,
however, compromise blood flow and result in ischemic
complications in the brain, retina, spinal cord and kidneys.
Blood pressure reduction, therefore, must be regulated in
order to prevent end organ damage to these organs.
The difference between the observed and desired (95th
percentile) blood pressure is estimated; 25-30% of the
desired reduction should occur in the first 3-4 hr, another
25-30% in the next 24 hr, and then to the desired level over
next 2 days. Agents of choice include short acting,
intravenous (IV) preparations that are titrated to response
(sodium nitroprusside, nitroglycerine, labetalol and
nicardipine) (Table 11.7.7). Therapy with enteral
antihypertensive drugs should be instituted within 6-12
hr of parenteral therapy, and the latter gradually
withdrawn over the next 12-24 hr. Sodium nitroprusside

is the agent with the longest track record, readily available
and the least expensive of all parenteral drugs. This agent
can be used in most hospital settings, provided there is
facility for monitoring of blood pressure. Initially infused
at a rate of 0.3-0.8 mg/kg per minute, the dose may be
increased in increments of 0.1-0.2 mg/kg per minute, every
15 minutes, if the desired reduction is not achieved. Blood
pressure is measured at least every 15 minutes; pupillary
reflexes, visual acuity and level of consciousness are also
monitored. Two IV lines should be maintained, one for
drug infusion and the other for saline infusion (if the blood
pressure were to fall precipitously). Loss of pupillary reflex
to light is an early indicator of retinal vascular ischemia,
requiring immediate infusion of normal saline. Patients
receiving nitroprusside at doses exceeding 2-3 mg/kg per
minute for longer than 48 hr are at risk of cyanide toxicity,
and even earlier if there is hepatic or renal dysfunction.
Nifedipine has been used safely and effectively, by
pediatricians, for hypertensive emergencies. The risks of
side effects due to sudden fall of blood pressure are limited,
particularly if the dose of nifedipine is between 0.1-0.25
mg/kg. Physicians should however be aware that the
response to short acting nifedipine might be inconsistent
and unpredictable (requiring more than one dose) or
uncontrolled (sudden fall of blood pressure).
Volume depletion is common in patients with severe
hypertension and IV administration of loop diuretic
together with a potent anti-hypertensive agent might lead
to a precipitous drop in blood pressure. Diuretics should
therefore be avoided unless specifically indicated for
volume overload as occurs in glomerulonephritis
coexisting pulmonary edema.
Hypertensive Urgencies
Hypertensive urgencies are not associated with acute
target organ damage. Patients have stage 2 hypertension
and less dramatic symptoms (e.g., headache and/or
vomiting), but are at risk for progression to hypertensive
emergencies. Controlled reduction of blood pressure,
using oral medications, over several hours is desirable.
Effective oral agents include nifedipine, clonidine and
labetalol. Despite overall efficacy of the above agents, a
predictable reduction of blood pressure is often not
possible. Patients with hypertensive urgencies should be
observed closely, since use of IV medications might be
required.
Neonatal Hypertension
Blood pressure in neonates is determined by birth weight
and gestational age. Renovascular (renal artery or venous
547
thrombosis) and renal parenchymal disorders are

important causes of hypertension. Newborns with severe
hyper-tension are managed with continuous IV infusion
of nitroprusside or labetalol. Effective oral agents include
CCB, hydralazine and minoxidil; ACEI should be
administered at lower doses.
Conclusions
Elevated blood pressure in children may be a sign of an
underlying disease or represent early onset essential
hypertension. Pediatricians should be aware of the
principles of early detection, evaluation and management
of such patients. Children with hypertension need long
term follow up, counseling and treatment, which should
be achieved by their primary pediatricians in collaboration with pediatric nephrologists.
BIBLIOGRAPHY
1. Birkenhager WH. Hypertension in the young: A
therapeutic perspective. J Hypertension 2003;21:5078.
2. Blumer JL, Vogt BA, Blowey DL, et al: Labeling
antihypertensive agents for children. Curr Ther Res
2001;62:279370.
3. Egger DW, Deming DD, Hamada N, Perkin RM, Sahney
S. Evaluation of safety of short acting nifedipine in children
with hypertension. Pdiatr Nephrol 2002;17:3540.
4. Houtman PN, Dillon MJ. Medical management of
hypertension in children . Child Nephrology, Urology
update. 1992;12:15461.
5. Indian Pediatric Nephrology Group, Indian Academy of
Pediatrics.Evaluation and Management of Hypertension.
Indian Pediatrics 2007; 44:103-121.
6. Joint National Committee on Detection, Evaluation and
Treatment of High Blood Pressure: The Sixth Report of
the Joint National Committee on Detection, Evaluation
and Treatment of High Blood Pressure (JNC VI). Arch
Intern Med 1997;157:241346.
7. Karen H: Practice Guidelines- Report on the Diagnosis,
Evaluation and Treatment of High Blood Pressure in Children
and Adolescents; American Family Physician 2005.
8. Moser M, Giles TD, Falkner B, et al. Hypertension in
children and adolescents. J Clin Hypertens (Greenwich).
2005;7:2430.
9. National High Blood Pressure Education Program
Working Group on Hypertension Control on Children
and Adolescents: Update on the 1987 Task Force Report
on High Blood Pressure in Children and Adolescents.
10. National High Blood Pressure Education Program
Working Group on High Blood Pressure in Children and
Adolescents. The fourth report on the diagnosis,
evaluation, and treatment of high blood pressure in
children and adolescents. Pediatrics 2004;114(2 suppl):
55576.
548
11.

Sider US, VonVigieve RO, Ceforzini C, et al. How good is
blood pressure control among treated hypertensive
children and adolescents. J Hypertension 2003;21(3):633-7.
12. The Seventh Report of the Joint National Committee on

Prevention, Detection, Evaluation and Treatment of High
Blood Pressure. JAMA 2003;289:256072.
11.8 Pericardial Diseases and Disorders

The heart is safely enclosed in a pericardial cavity, the
seromembranous visceral pericardium forming the outer
layer of the heart and the fibrous parietal pericardium
separating it from the lungs. It contains about 15-50 ml
of ultrafiltrate of plasma.
Congenital absence of pericardial sac, either totally
or partially, is a rare disorder. It is often asymptomatic.
Herniation of main pulmonary artery and left atrium
may occur through the partial defect, occurring more on
the left side. Congenital pericardial cysts and diverticula
are reported, but they are not large enough to pose clinical
problems but may cause diagnostic confusion.
ACUTE PERICARDITIS AND
PERICARDIAL EFFUSION
Pericardium gets involved in acute infective, inflammatory, neoplastic or traumatic processes. Pericardial
involvement is most often seen as one of the clinical
manifestations of a systemic disorder or a generalized
illness. Whenever pericardial involvement is detected
clinically, a thorough clinical examination to detect the
presence of generalized disease is essential. The clinical
and etiological classification is presented in the Table
11.8.1.
The symptom suggestive of acute pericarditis is chest
pain. The cardinal signs of effusion are pericardial rub,
and pulsus paradoxus.
Pathophysiology
Pericardial involvement, often as a result of infective or
inflammatory process, results in variable accumulation
of fluid within the pericardial sac, the degree of which
will determine the clinical picture. From a normal amount
of 15-50 ml of fluid, there can be massive amounts of fluid
accumulation. Mild effusion occurring in cardiac failure
or nephrotic syndrome as a transudate may go unnoticed.
Pyogenic infection will cause pyopericardium in which
even a small amount may be significant clinically. The
TABLE 11.8.1: Classification of pericarditis and

pericardial effusion
Clinical
a. Acute (< 6 weeks)
Fibrinous
Effusive
Serous
Purulent
Hemorrhagic
Chylous
Serofibrinous
b. Subacute (6 weeks to 6 months)
Effusive
Constrictive
Effusive-constrictive
c. Chronic (> 6 months)
Constrictive
Effusive
Adhesive
Etiological
I. Infectious
Viral: Coxsackie A and B, ECHO, adenovirus, Ebstein-Barr
virus, mumps, influenza, varicella zoster, vaccinia,
cytomegalovirus, rubella, herpes simplex, hepatitis and HIV
Bacteria: Staphylococci, Streptococci, Pneumococci,
Haemophilus influenzae, Meningococci, Legionella,
Salmonella, Mycobacterium tuberculosis, Mycoplasma,
Nocardiosis and Actinomycosis
Fungal: Histoplasmosis, Coccidioidomycosis, Candidiasis,
aspergillosis, blastomycosis
Protozoa: Amebiasis, Toxoplasmosis, Hydatidosis,
Rickettsial: Coxiella burnetii
II. Noninfectious, Inflammatory (Hypersensitivity/autoimmunity)
Rheumatic fever
Collagen vascular disorders: SLE, rheumatoid, arthritis,
scleroderma, Wegener's granulomatosis
Drug induced: Procainamide, hydralazine, minoxidil,
phenytoin, isoniazid, postcardiac injury, postpericardiotomy,
post-traumatic, postmyocardial infarct/ischemia
III. Noninfectious, Noninflammatory:
Uremia
Myxedema
Cholesterol
Chylopericardium
CHF, nephrotic syndrome, cirrhosis liver
Neoplasia: Primary and metastatic: Lymphoma, leukemia
Trauma: Aortic dissection, familial mediterranean fever,
cardiomyopathy, acute idiopathic
IV. Miscellaneous: Kawasaki, sarcoidosis, ulcerative colitis,
amyloidosis, bleeding disorders, radiotherapy.

symptoms and signs are due to severe cardiac
compression, impairment of ventricular diastolic filling,
increased systemic and pulmonary venous pressures and
eventually due to severly compromised cardiac output
and shock.
Clinical Features
The chest pain of acute pericarditis is dull, sharp and
stabbing precordial pain, radiating to the epigastrium,
neck, shoulder or left arm, increasing on lying down and
on deep inspiration, decreasing on sitting position with
forward leaning. Pericardial sac is devoid of nerve supply
and hence, the pain is due to adjacent diaphragmatic or
pleural irritation. Cough, fever and breathlessness of a
mild degree may be associated symptoms. The symptoms
of primary etiology may overshadow the mild secondary
symptoms.
In acute pericarditis without significant effusion, in
the early stages, the only clinical finding may be a
pericardial friction rub, heard best with the diaphragm
of the stethoscope kept firmly pressed on the left sternal
border and over the base of the heart. It resembles the
sound produced by the friction of sandpaper on wood
or creaking leather, better heard during expiration. It has
a to and fro component and is always in phase with the
heart sounds. The ECG shows generalized elevation of
the S-T segments (current of injury of the underlying
myocardium). After a week, the S-T segments return to
normal but there will be T wave flattening and inversion
in the same leads, which may persist for months after
resolution of the acute phase.
Pericardial Effusion
Within a short period of 48-72 hours, most cases will go
on to develop pericardial effusion. Pyogenic organisms,
still one of the most important causes of pericardial
involvement, cause pyopericardium and there is often
high fever, toxemia and other clinical evidences of
pyogenic infections like pneumonia, empyema or
pyoderma. Tuberculous effusion is the next most common cause of pericardial effusion in developing
countries. This is followed by viral infections.
Symptoms of chest pain with a feeling of compression over the chest in a child while lying down, elevation of jugular venous pulse, presence of pulsus paradoxus, enlarged area of cardiac dullness with a quite
precordium and diffuse apical impulse, well within the
549
outer border of cardiac dullness, shifting dullness, Ewart's

sign, muffled heart sounds with friction pericardial rub
and unexplained hepatomegaly all suggest pericardial
effusion with moderate collection.
Radiograph of the chest shows waterbottle type of
cardiomegaly with no increased lung shadows. Fluoroscopy shows diminished myocardial contractility.
ECG often shows diminished QRS voltages with
generalized S-T segment elevation. The diagnosis is easily
made with ultrasonography, and the area of collection
either posterior or anterior can be made out. Pericardiocentesis is done through the subxiphoid approach and
the fluid content is analyzed microscopically, biochemically and microbiologically. Gram staining and ZiehlNeelsen staining is done to identify the bacteria and the
mycobacteria. In hemorrhagic effusions, cytoanalysis for
malignant cells is also undertaken.
Acute Cardiac Tamponade
This term is applied to the state of acute heart failure
due to compression of the heart by massive, rapidly accumulating pericardial effusion or moderate degree of
effusion in an otherwise rigid, nondistensible pericardial sac. Significant rise in intrathroacic pressures and
ventricular end diastolic, atrial, systemic and pulmonary
venous pressures occur due to impaired ventricular
relaxation and filling, resulting in poor cardiac output.
The characteristic clinical symptoms are precordial
oppression, breathlessness, exercise intolerance, mild
facial puffiness and minimal pedal edema. The characteristic clinical signs of raised jugular venous pulse with
prominent X-descent, pulsus paradoxus, low volume
pulse, cold and clammy peripheral extremities, relatively
silent precordium, muffled heart sounds with hepatomegaly suggest cardiac tamponade. A positive
Kussmaul's sign of paradoxical rise in jugular venous
pulse is less characteristic of tamponade than of
constrictive pericarditis. Similarly, prominent X-descent
is present in tamponade whereas prominent, deep Ydescent is characteristic of constrictive pericarditis.
Low ECG-QRS voltages and electrical alternans may
be present in cardiac tamponade. Ultrasonogram shows
significant pericardial effusion, right atrial collapse and
right ventricular diastolic collapse with absent increased
early diastolic filling and mitral flow velocity.
The common causes of cardiac tamponade are
tuberculosis, neoplasms, trauma, uremia and idiopathic
pericardial effusion is an exclusion diagnostic state.
550
Diagnosis
A high index of suspicion of pericarditis and/or effusion
is essential in any child with fever, chest pain and
breathlessness, elevated jugular venous pressure, mild
pedal edema, unexplained hepatomegaly and a pulse of
low volume or of paradoxus which then needs confirmation by ultrasonography. Radiology and electrocardiography may be only suggestive of its presence
but is not absolutely diagnostic.
The diagnostic confirmation of pericarditis and/or
effusion invites a proper clinical and appropriate
laboratory evaluation to find out its cause, e.g. pyogenic,
tuberculous, viral, rheumatic, etc.
Myocarditis and cardiomyopathy are important
differential diagnoses which can be excluded by careful
history, physical examination, radiology, electrocardiogram amd ultrasonography.
The diagnosis of tamponade is mainly indicated by
the clinical signs of pulsus paradoxus, prominent Xdescent and absent Kussmaul's sign.
Pericardiocentesis
Removal of pericardial fluid by needle and syringe (20
gauge) aspiration for diagnostic and therapeutic purpose
is termed pericardiocentesis. The approach is through
subxiphoid region, with the needle advancement being
directed slowly towards the midthoracic spine at an angle
of about 20 degrees below the perpendicular to the body
surface. This can be done under electrocardiographic
monitoring, with the V lead attached to the advancing
needle and the other limb leads in position. Whenever
the needle touches the epicardium of the heart, marked
ST elevation will indicate the need to stop further
advancement of the needle.
The fluid collected is analyzed microscopically for the
cellular reaction, biochemicallytransudative or
exudative and microbiologically for the identification of
the offending organismpyogenic bacteria, mycobacteria, virus or fungus.
Management
In pyogenic pericardial effusion, the pus in the pericardial
sac is surgically drained after the institution of appropriate
antibiotics. This has resulted in improved survival, and
the mortality is now less than 15 percent with early
intervention. Constrictive pericarditis may occur and the
child must be on regular follow-up protocol.
Tuberculous effusion, diagnosed by history of contact,
unimmunized status or immunologically compromised
status, positive clinical, radiological, biochemical,

tuberculin hypersensitivity and microbiological studies
is treated with a minimum of 3 antituberculous drugs and
initial course of steroids. Chronic constrictive pericarditis,
a common complication, is treated surgically. It can be
prevented by early pericardiectomy. Pericardiocentesis is
done for diagnostic purpose, but if the collection is large
resulting in tamponade, therapeutic removal of significant
amount of fluid becomes essential.
Viral effusion needs only symptomatic treatment,
and it resolves spontaneously in 2 to 4 weeks. Other
conditions like collagen vascular diseases are treated
appropriately and the effusion resolves slowly with
steroids.
CHRONIC CONSTRICTIVE PERICARDITIS
Though less common in children, constrictive pericarditis
may follow tuberculous pericardial effusion or pyopericardium. Rarely, it may occur secondary to viral or
traumatic (hemorrhagic) pericarditis. It usually occurs
months or years after the treatment of primary condition.
The thick, fibrous and sometimes calcified pericardial
sac impairs diastolic ventricular filling, myocardial
contractility and effective cardiac function. These changes
gradually result in the development of the characteristic
clinical signs and symptoms of systemic venous congestion:
elevated jugular venous pulse with prominent y trough,
pulsus paradoxus, low volume pulse, low blood pressure,
quiet precardium, muffled or distant heart sounds, early
pericardial knock heard at the time of prominent y descent.
These signs must be carefully looked for in those children,
with gradually developing pedal edema, minimal puffiness
of face and swelling of eyelids, raised JVP and unexplained
hepatomegaly.
The differential diagnosis is chronic restrictive cardiomyopathy. Roentgenographic evidence of moderate
cardiomegaly is seen in only half of these cases. Calcification of pericardial surface may also be noted in similar
number of cases. Echocardiography may be helpful.
Radical pericardiectomy with decortication including
the sheathing over the great veins gives great relief in a
significant number of children. Postoperative cardiac failure
is managed by conventional decongestive measures.
BIBLIOGRAPHY
1. Chiappin E, Gall L, de Martino M, et al. Recurrent
pericarditis after Meningococcal infection. Pediatric
Infectious Disease Journal 2004;23:692-3.
2. Dupuis C, Gronnier P, Kachaner J, et al. Bacterial
pericarditis in infancy and childhood. Am J Cardiol
1994;74:807-9.

3. Feldman WE: Bacterial etiology and mortality of purulent
pericarditis in pediatric patients. Review of 162 cases.
Am J Dis Child 1979;133:641-4.
4. Jayashree M, Singhi SC, Singh RS, Singh M: Purulent
pericarditis: clinical profile and outcome following
surgical drainage and intensive care in children in
Chandigarh. Ann Trop Paediatr 1999;19:377-81.
551
5.
Morgan RJ, Stephenson LW, Woolf PK, Singh M: Surgical

treatment of purulent pericarditis in children. J Thorac
Cardiovasc Surg 1983;85:527-31.
6. Zahn EM, Houde C, Benson L, Freedom RM:
Percutaneous pericardial catheter drainage in childhood.
Am J Cardiol 1992;70:678-80.
11.9 Cardiac Arrhythmias in Children

The sinoatrial node (SA node) located at the junction of
superior vena cava and right atrium acts as an electrical
impulse generator or pacemaker with its own intrinsic
rate, controlled by the autonomic nervous system. The
impulse from SA node passes through atrioventricular
node (AV node), Bundle of His, to depolarize the atria
and ventricles in sequence determined by the slower
conductivity of AV node.
If the sinus rate slows down considerably, shift in
pacemaker activity occurs and the AV node (nodal
rhythm) or the ventricle (idioventricular rhythm) takes
over the function of impulse generation and propagation.
An arrhythmia is a disturbance in the electrical
activity of the heart, which may be episodic or continuous. When heart rate slows down to less than 60 per
minute, it is termed as bradycardia and when the same
is more than 120/min, it is called tachycardia.
On the standard surface ECG, P wave corresponds
to SA node depolarization, the P-R segment to the conduction time in the AV node and the Purkinje system
and the QRS complex to the ventricular depolarization
and the T wave to the ventricular repolarization.
The two basic mechanisms that initiate tachycardia
are: (i) increased automaticity resulting in ectopic
impulse formation and (ii) re-entry loop or closed circuit
propagation of ectopic impulse generated.
SINUS RHYTHMS
Sinus Bradycardia and Sinus Tachycardia
Sinus bradycardia (heart rate less than 60/min) occurs
in older children who are athletic. It occurs also following
therapy with drugs such as beta-blockers, digitalis,
verapamil; and conditions like hypothyroidism,
hypothermia, and raised intracranial pressure, etc.
Sinus tachycardia (heart rate > 120/min) occurs with

sympathetic stimulation after exercise, fever, anxiety,
anemia, heart failure, pregnancy, thyrotoxicosis, and
administration of drugs which stimulate sympathetics.
Sinus arrhythmia is a manifestation of normal automatic nervous activity with increase in sinus heart rate
during inspiration and a decrease during expiration. This
is seen in young children.
TACHYARRHYTHMIAS
Supraventricular Tachyarrhythmias
(SVT, Paroxysmal Atrial Tachycardia,
AV Nodal Re-entrant Tachycardia)
Supraventricular tachyarrhythmia is the most common of
the rapid rhythm abnormalities encountered in children,
the greatest frequency being recorded in infancy. It is
known to occur in fetus as early as in middle fetal life.
The mechanism of the supraventricular tachycardia
is commonly a re-entry of the electrical impulse back into
the conducting system either through an accessory
pathway (Wolff-Parkinson-White syndrome) or within the
atrioventricular node. It may originate in a localized focus
of enhanced automaticity in the atria or AV junction. In
the absence of the antegrade conduction by the bypass
accessory pathway, re-entry through the AV node or
through a concealed bypass tract, is responsible for more
than 90 percent of all SVTs.
AV nodal re-entrant tachycardia, being the most
common of all SVTs, has no specific predisposing factors.
It most often occurs in children who are otherwise normal.
In infancy, it is more common in children below 6 months
of age.
The heart rate is regular and often ranges between 200
and 320/minute and all impulses are conducted to the
552
ventricles. These children are often asymptomatic. In

infants, if it persists for more than 24 hours, symptoms
and signs of congestive heart failure (CHF) occur besides
pallor, fatigue and tachypnea. The onset of the paroxysm
is as sudden and abrupt as its termination. An older child
may sense palpitation with the sudden onset. Syncope
and hypotension may be the presenting symptoms. Acute
pulmonary edema can ensue. In the fetus, when the
arrhythmia is prolonged, heart failure and nonimmune
hydrops fetalis are known to occur. Polyuria may occur
due to release of atrial natriuric peptide during such
paroxysms.
ECG shows marked tachycardia (> 200/min) with
regular narrow QRS complexes and the P waves may be
absent, buried in the QRS complex or appear as distortions
at the terminal part of the QRS complexes. QRS complexes
become wider in presence of associated bundle branch
block.
Treatment
Drug treatment is not essential as simple vagal maneuvers like carotid sinus massage can effectively terminate
SVT in majority of cases. Adenosine with its short half-life
is the most preferred drug and verapamil is the next drug
of choice. Verapamil is not to be given in children below
one year of age. Beta-blockers, disopyramide and digitalis
are less preferred alternatives and digoxin is not helpful
in acute case.
Prevention of AV nodal re-entry is achieved by the use
of digitalis, beta-blockers or calcium channel blockers
which act primarily on the antegrade slow pathway. In
an emergency, DC cardioversion terminates the attack.
Temporary percutaneous venous, atrial or ventricular
pacing terminates the attack when drugs fail to do so or in
recurrent cases.
Catheter radiofrequency ablation of the re-entrant
circuit is frequently being resorted to in refractory cases.
In AV re-entrant tachycardia retrograde conduction
occurs from the ventricles back to the atrium by a concealed
bypass tract.
Wolff-Parkinson-White Syndrome
(Pre-excitation syndrome)
An abnormal band of specialized electrically conductible
atrial tissue acts as an accessory pathway bypassing the
junctional tissue. This occurs in association with some
congenital heart diseases and most commonly with
Ebstein's anomaly.
Wolff-Parkinson-White syndrome refers to antegrade

conduction by AV bypass tract resulting in a short P-R
interval, a slurred upstroke of the QRS complex termed
delta wave and a wide QRS complex. Differential
conducting speeds of accessory and normal pathways
with differing refractory periods cause re-entry phenomenon to occur resulting in paroxysmal SVT. Atrial flutter
and atrial fibrillation also occur commonly in this
condition. This in turn, may lead to very rapid ventricular
rates, even resulting in ventricular tachycardia and
fibrillation because of the lack of decremental conducting
properties in the bypass tract as in AV node.
SVT is treated as mentioned earlier. Class 1A drug
(quinidine, procainamide, disopyramide) or Class 1C
(flecainide) may be used to slow conduction and increase
refractoriness primarily in the bypass tract. Flecainide is
to be limited to be used in otherwise normal heart. Digitalis
and verapamil can precipitate ventricular fibrillation by
shortening the refractory period of the bypass tract.
Radiofrequency ablation of an accessory pathway is
another treatment option commonly used in patients with
re-entrant rhythm or atrial ectopic tachycardia.It is often
used electively in children and teenagers, as well as
patients who require multiple agents or find drug side
effects intolerable or for whom arrhythmia control is poor.
The overall initial success rate ranges from approximately
80-95 %,depending on the location of bypass tract. Surgical
ablation of bypass tract may also be successful in related
patients.
Flecainide is to be limited to be used in otherwise
normal heart.
ATRIAL TACHYARRHYTHMIAS
Atrial Ectopic Beats/Extrasystoles
Premature atrial beats are recognized by abnormally
shaped premature P waves followed by near normal P-R
interval with normal QRS complex. Rarely, QRS complex
may be aberrant. They may occur in normal newborns
and disappear with age and do not cause symptoms.
Multiple atrial premature beats may sometimes result in
transient atrial fibrillation.
Atrial flutter and Atrial fibrillation
These two types of atrial arrhythmias are less common in
children than in adults.

Atrial Flutter
In Atrial flutter, the characteristic features is a very rapid
atrial activity (250-400 beats per minute) with the ventricles responding to every second to fourth atrial beat
resulting in a regular or regularly irregular tachycardia.
Causes
Congenital heart diseases resulting in a grossly enlarged
atria, e.g. mitral or tricuspid insufficiency, tricuspid
atresia, Ebstein's anomaly, acquired rheumatic mitral
valvular heart disease, acute viral myocarditis, pericarditis and intra-atrial surgery.
Pathophysiology
An electrically active (irritable), abnormal focus in atria
produces abnormal impulse which gets repeatedly
propagated by a circus rhythm resulting in extremely rapid
atrial rate. All of these rapid atrial beats cannot get
transmitted through AV node. Varying degrees of
atrioventricular block results in, anywhere from, 2:1 to
8:1 atrial ventricular rate ratios.
Symptoms
They depend upon the ventricular rate. No symptoms
occur in atrial flutter with reasonable ventricular rate.
Prolonged episodes of atrial flutter with very rapid
ventricular rate precipitates congestive heart failure.
Electrocardiogram is characteristic showing the rapid
and regular atrial sawtoothed flutter F waves.
Treatment
Direct current cardioversion is the most effective
method of reverting back to sinus rhythm. If the clinical
status is stable, the ventricular rate is first slowed by
administration of AV node blocking drugs like betablockers, calcium channel antagonist (verapamil) or
digitalis. Once the ventricular rate is slowed, attempt is
made to convert the flutter into normal sinus rhythm by
the use of Class 1A drugs (quinidine, procainamide or
disopyramide), Class 1C drugs (flecainide) or amiodarone. The same drugs also prevent recurrences of atrial
flutter and fibrillation.
Atrial Fibrillation
Atrial fibrillation is characterized by totally distorted,
chaotic, rapid and ineffective atrial contractions with
irregular and erratic ventricular response resulting in the
553
diagnostic irregularly irregular radial arterial pulse

with pulse deficit. It may be paroxysmal or persistent.
The same causes mentioned above in atrial flutter, may
also result in atrial fibrillation. It may represent the
tachycardia phase of the sick sinus syndrome.
Symptoms
They occur with rapid ventricular ratefatigue, palpitation, giddiness or syncope, symptoms of heart failure
and symptoms of systemic embolization in children with
mitral valvular disease.
The electrocardiogram is characteristicno organized
discernible P waves, except for irregular, fibrillatory f
waves in the baseline with irregular but normal QRS
complexes.
Treatment
The therapeutic goal is to immediately slow down the
ventricular rate by using either beta-blockers (propranolol)
or calcium channel antagonists (verapamil). Quinidine
or other Class 1A drugs as mentioned above, or Class 1C
drugs like flecainide may then correct the condition to
sinus rhythm. If no response occurs within 24 hours,
electrical DC conversion is resorted to. The causative
factors have to be immediately attended to.
Anticoagulation 2 weeks prior to and 2 weeks after any
attempt at cardioversion, is indicated to prevent the
dreaded thromboembolic complications in situations
where atrial fibrillation has been persistent for more than
48-72 hours.
In exceptional circumstances of refractory atrial
fibrillation, surgical or transvenous catheter radiofrequency ablation may be resorted to deliberately induce
complete heart block with simultaneous permanent
VENTRICULAR TACHYARRHYTHMIAS
Ventricular Tachycardia (VT)
Ventricular tachycardia is defined as occurrence of at least
three or more ectopic ventricular beats in sequence.
Sustained ventricular tachycardia means a run of
ventricular premature contractions (VPCs) in succession
for a period of 30 seconds or more.
It is less common in children, and it indicates the
presence of a serious underlying structural or functional
cardiac problem. The prognosis is poor and carries a great
risk of mortality unless corrected immediately.
554
Cause
Myocarditis, ischemic damage, anomalous origin of the
coronary artery, cardiomyopathy, mitral valve prolapse,
prolonged Q-T interval (congenital or acquired), proarrhythmogenic drugs, Wolff-Parkinson-White syndrome, drug
abuse with cocaine or amphetamine, hypokalemia,
hypomagnesemia, hypoxia and severe acidosis are all
known predisposing factors. In a significant number of
children with SVT, an underlying cause may not be found.
Syncope, chest pain and dyspnea are the common
presenting symptoms.
It must be differentiated from SVT and all broad QRS
tachycardias should be considered as ventricular
tachycardia, until proved otherwise. The electrocardiographic features which are helpful in the diagnosis of VT
is the AV dissociation, capture fusion beats, extreme left
axis deviation, no response to carotid sinus massage or IV
administration of adenosine, besides the very broad QRS
complexes.
Treatment
Treatment is immediately initiated. DC conversion
(1-2 Watt/sec/kg) is the treatment of choice; if it is not
available or if VT is relatively well-tolerated, bolus dose of
lignocaine (1 mg/kg) is intravenously administered with
continuing IV infusion, at a rate of 10-50 mg/kg/min.
Bretylium is alternative drug in lignocaine refractory
cases. Mexilitine, flecainide, disopyramide and
amiodarone are suitable alternatives.
Phenytoin is effective in VT, especially when it occurs
following digitalis toxicity. The precipitating factors have
to be identified and immediately correc-tedhypokalemia, hypomagnesemia and others. Myocardial tumor,
anomalous origin of the coronary artery and similar
surgical problems are appropriately handled. Failure of
drug therapy necessitates alternative, treatment
strategiesimplantation of automatic cardioverter,
defibrillator or surgical resection of the diseased
myocardial area.
Ventricular Fibrillation (VF)
VF is a chaotic ventricular tachyarrhythmia with no
effective ventricular contraction. The ECG record shows a
wavy line without any discernible QRS complexes;
P waves may be discernible.
VF may be a preterminal event in many illnesses.
Hypokalemia, digitalis or quinidine toxicity, myocardial
inflammation or damage, catecholamines aminophylline,
anesthetic drugs and plant toxins may precipitate VF.
Uncontrolled VT or multifocal ventricular ectopic beats or

long Q-T interval syndrome may result in VF. If not
terminated instantaneously, death ensues.
A thump in the chest may restore sinus rhythm.
External cardiac massage with artificial ventilation and
DC defibrillation are immediate measures to be undertaken. The precipitating factors are corrected without
delay. After defibrillatory conversion, VT is treated with
drugs. Refractory cases are treated by implantable
automatic cardioverter-defibrillator.
Bradyarrhythmias
Sinus Arrest and Sinoatrial Block
Failure of impulse formation within the sinus node is
termed sinus arrest and blockade of the generated sinus
impulse from reaching the atrium is sinoatrial arrest.
Though rare in children, these disturbances may occur
secondary to digitalis toxicity and extensive atrial surgery.
Atrioventricular Block (AV Block)
AV Block occurs when interference occurs in normal
conduction of the electrical impulses from the atria to the
ventricles through the atrioventricular node.
First degree AV block P-R interval prolonged beyond what
is normal for that age and heart rate without blockage of the
conduction of any of the atrial impulses to the ventricles, is
defined as first degree heart block. No evidence of heart
disease is seen in majority of such cases. However, it may
be seen in children with congenital heart disease like atrial
septal defect, corrected transposition of great vessels.
Ebstein's anomaly, primary myocardial disease, rheumatic
carditis, diphtheria and in children receiving drugs like
digitalis and quinidine. Children with 1 degree block are
asymptomatic, and need no treatment except for the
treatment of primary cause.
Second degree AV block Some of the atrial impulses are
blocked and hence, not conducted to the ventricles.
In Mobitz type I (Wenckebach phenomenon) while PP interval remains constant, progressive increase in P-R
interval occurs with successive beats until an atrial
impulse seen as P wave is not conducted to the ventricle
(absent QRS complex). The P-R interval is again shorter in
the cycle following the dropped ventricular complex. It
will then progressively increase to result in another
blocked ventricular impulse.
In Mobitz type II, atrial conduction is blocked at
intervals without a change in P-R interval, once every
three, four or five beats.
555
Intravenous antiarrhythmic agents

Drug
Dosage
Comments
Monitoring
Verapamil
0.1-0.2 mg/kg
IV (5-10 mg max)
For hypotension
Propranolol
0.02 mg/kg IV
every 5 min to
max 0.1 mg/kg
Procainamide
10-15 mg/kg IV
over 30 min
1-2 mg/kg IV over
15 min
cont, infusion-3050 mcg/kg/min
0.05 mg/kg
through a central
line; double the
dose until effect is
seen to a max of
0.4 mg/kg
Contraindicated in
children < 12 months
of age
Contraindicated in
children with asthma,
congestive heart
failure. Not to be given with verapamil
Continuous monitoring
Lidocaine
Adenosine
Causes respiratory
depression, hypotension
Pulse, BP
Dizziness,
hypotension
BP
Caution in asthmatics,
contraindicated in pre-existing
type 2 and 3.
Atrioventricular block
without pacemaker
It is less often noticed in individuals with normal

hearts. The same predisposing factors mentioned in first
degree AV block also play a role. No treatment is
necessary. If Stokes-Adams syndrome occurs though rare,
pacemaker insertion is undertaken.
Congenital/acquired Complete
AV Heart Block
Autoimmune injury of the fetal conduction tissue by IgG
antibodies transferred from mother with active or inactive
systemic lupus erythematosus (SLE) is one of well-known
causes of this condition. Other autoimmune diseases such
as rheumatoid arthritis are reported to cause congenital
heart block. Myocarditis and postsurgical repair involving ventricles are other known causes of acquired complete heart block. In utero, it may result in hydrops fetalis. It
may also result in fetal wastage. In some children it may
occur at 3 to 6 months of age.
Older children are asymptomatic. Syncope, fatigue,
irritability, and night terrors may be some of the symptoms. Slow but bounding pulse less than 60 per minute
not increasing by more than 10 to 20 beats per minute
after exercise or atropine administration, cannon a waves,
varying intensity of the first heart sound are diagnostic.
The diagnosis is confirmed by electro-cardiogram. The
prognosis of this condition is usually good. In symptomatic children with Stokes-Adams syndrome, insertion
of artificial pacemaker is imperative to prevent sudden

death. All cardiac depressants should be avoided. Cardiac
pacing is recommended in neonates with low ventricular
rate (50/min), evidence of heart failure, wide complex
rhythms, or congenital heart disease. Isoproteronol ,
atropine or epinephrine may be used to try to increase the
heart rate temporarily until pacemaker placement can be
arranged. Transthoracic epicardial implants have
traditionally been used in infants. Transvenous placement
of pacemaker lead is available for young children.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
6.
Arrhythmias in infants and children: Current concepts in

diagnosis and management of atrial arrhythmias in
infants and children. 1998. Wolff G, Gelband H, Deal BJ
Futura Publishing Inc.
Campbell RM, Dick M, Rosenthal A. Cardiac arrhythmias in children. Annual Review of Medicine 1984;35:
397410.
Losek JD, Endom E, Dietrich A, et al. Adenosine and
pediatric supraventricular tachycardia in the emergency
department: multicenter study and review. Ann Emerg
Med 1999;33:18591.
Sacchetti A, Moyer V, Baricella R, et al. Primary cardiac
arrhythmias in children. Pediatr Emerg Care. 1999;15:957.
Walsh EP, Saul JP, Triedman JK (Eds). Cardiac arrhythmias in the pediatric patient. Lippincott Williams and
Wilkins 2001.
Ziegler, Gillette PC (Eds). Practical Management of Pediatric Cardiac Arrhythmias. Futura Publishing Inc. 2001.
12.1 Examination of the Respiratory System: YK Amdekar ........................................................................................................................ 558

12.2 Diagnostic Procedures and Investigations in Respiratory Diseases: Archana S Kher, Soumya Swaminathan, Milind S Tullu ......... 560
12.3 Flexible Fiberoptic Bronchoscopy: D Vijayasekaran ........................................................................................................................... 564
12.4 Respiratory Distress: MD Shah ............................................................................................................................................................. 567
12.5 Upper Respiratory Tract Infection: SK Kabra ...................................................................................................................................... 573
12.6 Infections of Larynx, Trachea and Bronchi: Keya R Lahiri, Roshani N Taori ..................................................................................... 576
12.7 Pneumonia in Children: A Balachandran, SO Shivbalan ...................................................................................................................... 578
12.8 Acute Bronchiolitis: Uday B Nadkarni ................................................................................................................................................... 583
12.9 Empyema: A Balachandran, Swati Y Bhave, S Thangavelu ................................................................................................................... 586
12.10 Bronchiectasis: A Balachandran, Swati Y Bhave, NC Gowrishankar ................................................................................................... 588
12.11 Lung Abscess: A Balachandran, Swati Y Bhave, T Thangavelu ........................................................................................................... 589
12.12 Hemoptysis: Vibha Mangal, Neeraj Jain, Vibhu Kwatra ......................................................................................................................... 591
12.13 Bronchial Asthma: H Paramesh, L Subramanyam, SO Shivbalan ....................................................................................................... 593
558
12.1 Examination of the Respiratory System

YK Amdekar
Clinical examination follows history taking and is
intended to arrive at the most probable diagnosis.
Following is the scheme of clinical examination of the
respiratory system, which will help in interpretation of
the signs.
General Examination
Respiratory rate more than 60/50/40 per min in
neonates, infants and children respectively indicates
tachypnea. This has to be correlated with body temperature and pulse rate for correct interpretation. Presence
of accessory muscles of respiration working such as
alaenasi or sternomastoid muscles often suggests
respiratory distress or dyspnea. Accompanying dyspnea
is often noisy breathing, which helps in localizing the
anatomy of the disease. Stridor indicates supratracheal
inspiratory obstruction and manifests as suprasternal
retraction. Grunting denotes nature's attempt to increase
end-expiratory pressure to improve oxygenation in lung
parenchymal disease as in pneumonia and often is
accompanying with chest retractions. Wheeze suggests
expiratory obstruction as seen in case of asthma. Marked
tachypnea without chest retraction is a feature of bronchial disease as in asthma or meconium aspiration in
newborn, while moderate tachypnea with chest retraction denotes parenchymal disease as in pneumonia or
hyaline membrane disease (HMD) in neonates. Most of
the children with tachypnea or dyspnea are irritable or
crying. However, if they are notsilent dyspneamay
indicate paralyzed respiratory muscles as in GB
syndrome. These children are not able to phonate and
often demonstrate paradoxical or seesaw respiration.
Such a situation exists also in case of respiratory failure
due to other causes. Marked tachypnea without
symptoms or signs of respiratory disease suggests
metabolic acidosis. Cyanosis is bluish discoloration of
mucous membranes or nails. Peripheral cyanosis is seen
only in fingertips or nails and is often accompanied with
cold extremities or pallor. Central cyanosis shows
discoloration of mucous membranes such as lips and
buccal mucosa and denotes extreme degree of oxygen
desaturation, an ominous sign in a respiratory disease.
Clubbing of nails indicates chronic hypoxia as seen in

case of bronchiectasis. Early clubbing manifests as
Schomroths signdiamond-shaped window seen on
opposition of two finger nails, while further changes are
seen as obliteration of angle between nail and nailbed
and subsequent swelling. Hence, clubbing is a sign of
chronic respiratory disease while cyanosis may be seen
in acute conditions also.
ENT Examination
This forms the part of respiratory system examination.
Ear should be examined through otoscope to diagnose
early signs of inflammation of the ear drum. Unilateral
nasal disease demands careful examination of the nasal
cavity through nasal speculum. Mouth breathing
suggests nasal obstruction and may result in typical
adenoid facies. Throat is generally examined last with
the help of a spatula or tongue depressor under a good
source of torchlight to assess tonsillar or pharyngeal
inflammation or any exudative membrane.
Chest Examination
Inspection
Shape of the chest may be asymmetrical with localized
flattening as in case of collapse or fibrosis or bulging as
in pneumothorax or pleural effusion. Chest deformity
may result from chronic lung disease. Anteroposterior
diameter of the chest may be increased in emphysema.
Movements of part of chest may be diminished with
underlying diseased lung. Chest retractions often indicate
underlying pneumonia or parenchymal disease. Marked
shift of trachea makes sternomastoid muscle belly
prominent on the same side and is referred to as trail
sign. Position of cardiac impulse is noted.
Palpation
Movements of chest are noted and inspection findings
confirmed. Inserting finger between sternomastoid belly
and trachea on either side assesses position of trachea.
Normally, trachea is central or slightly to the right.
Position of apex beat is also confirmed. Pathology in
Diseases of Respiratory System

upper part of lungs shifts the trachea while that in lower
part may shift only the apex beat. Collapse and fibrosis
cause shift on the same side, whereas pleural effusion
and pneumothorax result in shift on the opposite side.
Tactile vocal fremitus (TVF) is palpated by either placing
palm or medial border of hand on the chest while patient
is asked to phonate.
Symmetrical areas of the chest are compared. TVF is
increased in pneumonia and decreased in pneumothorax
or pleural effusion. Fluid being good conductor of sound,
large pleural effusion may result in increased TVF,
however, in most of the cases, presence of collapsed lung
underneath the fluid dampens the transmission of sound,
hence, TVF is generally decreased in pleural effusion.
Cavity may produce variable signs depending on
patency of bronchus and the contents of the cavity.
Occasionally tenderness may be elicited in empyema.
Percussion
Direct rib sternum, Cloride, Indirect finger
Chest is normally resonant with liver dullness in fifth or
sixth intercostal space in midclavicular line and cardiac
dullness coinciding with position of apex beat on the left
side and right border usually delineated to right sternal
border. Hyper-resonant note denotes either emphysema
or pneumothorax, while impaired note suggests collapse
or consolidation, stony dull note is characteristic of
pleural effusion. In case of suspected pathology on lower
side or right lung, in order to differentiate liver dullness
from a possible lung disease, percussion note is elicited
in normal breathing and on deep inspiration. This is
referred to as tidal percussion.
Auscultation
Normal breath sounds are equal on both sides and are
vesicular, like rustling of leaves. Bronchial breath sounds
are hollow with pause between inspiration and
expiration. High-pitched bronchial breath sounds are
559
referred to as tubular and are heard typically in

consolidation, while low-pitched cavernous breath
sounds are a feature of a cavity. Vocal resonance on
auscultation is commensurate with TVF on palpation.
Egophony, bronchophony and whispering pectoriloquy
represent merely the variability in the degree of increased
vocal resonance and are often heard in cavity. Posttussive suction refers to sudden rush of air during
inspiration following deep cough and is most pathognomonic of a cavity. Succussion splash is elicited in
hydropneumothorax. Crepitations are moist foreign
soundsfine crepitations suggest alveolar lesion while
coarse crepitations or rales denote bronchial pathology
such as bronchiectasis. Rhonchi are musical sounds as
heard in case of bronchospasm. Pleural rub is a localized
dry creaching sound heard at the end of inspiration and
beginning of expiration in pleuritis.
Interpretation of chest examination is often complicated by many variables in the pathology that accompany most of the respiratory disease. It is most important to differentiate the anatomical site of the disease. In
general, bronchial diseases are generalized and bilateral,
while parenchymal lesions are commonly localized.
Often pleural and parenchymal lesions are difficult to
distinguish as both the lesions may produce identical
signs. Most important difference between pleural and
parenchymal lesion is the distribution of signslobar
distribution related to the surface anatomy of lobes in
parenchymal lesion as against nonlobar distribution in
pleural lesion. It means that in upper lobe pneumonia,
clinical signs are noted anteriorly in upper half, middle
lobe represents anterior lower half, while lower lobe signs
are predominantly posterior. Clinical signs of pleural
lesions are not bound by lobar boundary and are noted
below a particular level on the chest both anteriorly and
posteriorly. When clinical signs do not follow any pattern,
it is likely to be due to a mediastinal pathology as in case
of a mediastinal tumor.
560
12.2 Diagnostic Procedures and

Investigations in Respiratory Diseases
Archana S Kher, Soumya Swaminathan, Milind S Tullu
A variety of respiratory disorders are encountered in
children. A scientific approach and accurate diagnosis
will enable proper treatment and outcome. This review
will discuss the investigations (simple and sophisticated)
and diagnostic procedures, which aid the diagnosis.
Table 12.2.1 gives a broad classification of the investigations and procedures that can be undertaken.
TABLE 12.2.1: Broad classification of
the investigations and procedures
Investigations
Procedures
Hematological
Hemogram
Blood gas analysis
Transillumination
Thoracocentesis
Serological
Antibody testing
IgE levels
Immunoglobulins, ECP,
RAST, PRIST
ELISA for HIV
alpha-1 levels (for alpha-1
antitrypsin deficiency)
Nasal biopsy (for

immotile cilia syndrome)
Lung puncture
Lung biopsy
Laryngoscopy
Bronchoscopy
Polygraphic monitoring
Microbiological
Sputum
Nasal, throat secretions
Ear fluid
Bronchoalveolar lavage
Radiographic
Plain X-rays
Sonography
CT, MRI
Radionuclide scan
Contrast studies
Invasive- Angiography
Molecular testing
MDRTB, CMV, other viruses
Cystic fibrosis
alpha-1 antitrypsin deficiency
Others
Skin tests
Sweat chloride test
Pulmonary function tests (PFT)
Important Investigations
Hematological
Complete hemogram is informative in infections where
there is leukocytosis; eosinophilia in allergic disorders,
and an elevated ESR is encountered in infections and
collagen vascular disorders.
Arterial blood gas (ABG) analysis is one of the most useful
tests of pulmonary function, as arterial levels of oxygen
and carbon dioxide reflect the result of ventilation,
perfusion and gas exchange. The samples can be drawn
from umbilical (in neonates), radial, brachial and
temporal arteries. Arterial capillary blood may be used
after local vasodilatation with nitroglycerin. Transcutaneous oxygen monitoring or ear oximetry can be used
continuously in critically ill patients. End tidal CO2
(capnography) monitoring correlates well with the
arterial PCO2. The normal arterial blood pH is 7.35 to
7.45, PCO2 is 35 to 45 mm Hg (venous PCO2 is 6 to 8 mm
Hg higher than arterial PCO2), and PO2 is above 90
mmHg.
Pulse Oximetry: The machine has light emitting diodes
and photodetector. Two wavelengths of light-red
(660 nm) and infrared (940 nm) are used which are
differentially absorbed by the oxy- and deoxy-hemoglobin and the difference between the two is used to
calculate SpO2 (oxygen saturation). It is accurate from
75-100 percent SaO 2 . It is commonly used in the
emergency room, casualty, ICUs and in operation
theaters to quickly check the oxygen saturation.
Serological
Immunoglobulins (G, A, M, D, E) can be measured in
suspected cases of immunodeficiency. Elevated IgE levels
help in the diagnosis of asthma and allergy. HyperIgE
syndrome or Jobs syndrome can present with recurrent
respiratory and skin infections. Recently, eosinophilic
cationic protein levels [ECP] have been found to be elevated
in asthma. This is a relatively costly test, but is a sensitive
test and elevated levels indicate active asthma and the

levels decrease during remission. Antibodies to
mycoplasma, cytomegalovirus, respiratory syncytial
virus and chlamydia can be detected with the use of
special kits. IgE levels can be estimated by using
Radioallergosorbent test (RAST) and paper radioimmunosorbent test (PRIST).
Microbiological Methods
Sputum examination: Large quantities of foul smelling
sputum are seen in lung abscess and bronchiectasis. The
consistency may be serous, purulent, hemorrhagic or
viscid (cystic fibrosis). The sputum sample is concentrated by the Petroffs method and a smear is made from
the deposit obtained after centrifugation. Gram stain and
Ziehl-Neelsens stain is done. Abnormal contents include
large number of epithelial cells, pus cells, malignant cells,
Curschmanns spirals, Charcot-Leyden crystals, fibrinous
casts and parasites. Special stains must be done for fungi
and Pneumocystis carinii.
Nasal cytology: It can be studied for eosinophil counts, in
cases of allergic rhinitis.
Tracheal secretions, throat cultures, bronchial aspiration after
lavage, sputum and ear discharge can be cultured to
detect bacterial growth and antibiotic sensitivity pattern.
Iron stains may reveal hemosiderin granules within
macrophages suggesting pulmonary hemosiderosis.
Viral pneumonia may be accompanied by intranuclear
or cytoplasmic inclusion bodies, as seen on Wrights
stained smears. Fungal forms can be identified by KOH
mount.
In younger children, sputum cannot be obtained. In
place of sputum, an early morning gastric aspirate is
suitable for smear culture for acid-fast bacilli (AFB) since
gastric motility and acidity are low in sleep. This is the
only specimen available for demonstrating AFB in young
children suffering from pulmonary tuberculosis.
561
information in patients with upper airway obstruction,

about the retropharyngeal, subglottic and supraglottic
space. Knowledge of the phase of respiration in which
the film is taken is necessary for interpretation.
The Waters projection is done to see the frontal and
maxillary sinus and the Caldwells view for frontal,
ethmoidal sinuses and nasal cavity and septal deviations. The frontal sinus develops after 5 years and
maxillary after 2 years of age. Lateral views are taken for
the sphenoid sinus. Schullers view is taken to detect
mastoiditis.
Fluoroscopic technique is useful in the evaluation of stridor
and abnormal movement of diaphragm and mediastinum. Ultrasonography is a simple noninvasive
technique and helps to detect fluid and intrathoracic
masses. Pleural aspirations and lung tap can also be
performed under ultrasonographic guidance.
Computed tomography is an accurate tool and aids
radiodiagnosis of mediastinal and pleural lesions, solid
and cystic parenchymal lesions, and to decide the extent
of parenchymal diseases (collapse/consolidation); while
a high-resolution CT is used for diagnosis of bronchiectasis. Intravenous contrast enhances vascular structures.
CT guided biopsy of mediastinal lymph nodes/suspicious masses can be done to obtain samples for
histopathology. Spiral CT provides a very fast study. CT
angiography aids the diagnosis of abnormalities like
vascular rings.
Magnetic resonance imaging (MRI) is very useful to
evaluate hilar structures, vascular abnormalities like
rings and chest masses. MRI is also being increasingly
used preoperatively in addition to color Doppler and 2Dechocardiography for complex congenital heart diseases.
Both CT and MRI need to be performed under short
general anesthesia in children.
Contrast Studies
Radiographic Techniques
An appropriate, properly performed and interpreted
posteroanterior and lateral views (upright and at full
inspiration), still remains a valuable diagnostic tool for
the pediatrician. Decubitus films are indicated, if there is
suspicion of pleural fluid. Oblique films help to evaluate
the hilum and area posterior to the heart, while the apices
are best seen in a lordotic view. A lateral neck film yields
A barium swallow is performed to rule out H shaped

tracheoesophageal fistula (thin barium study), where
barium is injected through a catheter, placed at several
locations in the esophagus. It is also used to evaluate
gastroesophageal reflux (which is mostly done with the
help of a radionuclide milk scan), to look for esophageal
indentation with vascular rings and to diagnose
esophageal strictures.
562
Mantoux Test
An injection of 5TU of PPD (2TU, R23 Tween 80) is given
intradermally on the forearm, using a tuberculin syringe.
Induration and erythema is checked after 48 to 72 hours.
The test is considered positive when the induration is
more than 10 mm in diameter.
The other skin tests used for diagnostic purpose are,
the Kveim test for sarcoidosis and Casonis test for
Echinococcus or hydatid disease.
Skin tests are also carried out to detect the presence
of atopic reagins (lgE) in skin. The skin bound reaginic
antibody reacts with the antigen, resulting in release of
mediators, which causes a wheal and a flare response at
the site of test within a period of 15 to 25 minutes. There
are three types of skin tests for allergies, i.e. scratch test,
prick test and intradermal test. A number of allergens
can be used for testing.
Sweat Chloride Test
The method used is pilocarpine iontophoresis, where a
3 mA current is used and a minimum of 50 mg of sweat
is collected on a filter paper. The chloride values are
elevated in cystic fibrosis and a value above 60 mEq/L
strongly suggests the diagnosis. Newer methods like
linkage analysis or DNA studies, using polymerase chain
reaction (PCR) are now used for molecular diagnosis of
cystic fibrosis. PCR can be set up to detect common
mutations.
Pulmonary Function Tests
Pulmonary function tests (PFTs) are an essential part of
the investigation of many respiratory diseases. Children
above the age of 6 years usually cooperate enough for
testing. PFTs are used for diagnostic (asthma, restrictive
disorders, etc.), monitoring (efficacy of treatment and
course of disease) and evaluation of disability (disease
severity). The lung volumes and lung capacities are
depicted in Figure 12.2.1. Spirometry is the most
important test of lung mechanics and measures the
volume of air exhaled from the lungs during a maximal
expiratory maneuver. The following parameters are
measured in spirometry:
i. Forced vital capacity (FVC)
ii. Forced expiratory volume in 1 second (FEV1)
iii. Ratio of FEV1 to FVC (normal > 80%, sensitive
indicator of obstructive airway disease)
Figure 12.2.1: Lung volumes as they appear on the spiro

graphic tracing. The four primary lung volumes and lung
capacities are shown. TV: tidal volume, IRV: inspiratory reserve
volume, ERC: expiratory reserve volume, RV: residual volume,
IC: inspiratory capacity, FRC: functional residual capacity, VC:
vital capacity, TLC: total lung capacity
iv. Maximal mid expiratory flow rate (MMEF or FEF

25 to 75%: indicator of small airways obstruction)
In obstructive airway diseases, the flow rates are
decreased while in restrictive diseases the lung volume
is reduced while the flow rates remain normal. The
configuration of the flow volume curve also provides
information regarding the disease class, in obstructive
diseases; the curve is convex towards the volume axis
while in restrictive diseases, it is normal in shape but
smaller (Fig. 12.2.2). Obstructive disorders are characterized by low FEV1/FVC ratio, low FEV1 and low or normal
FVC while restrictive disorders are characterized by low
FVC and normal FEV1/FVC ratio. Repeating the PFTs
after administration of aerosolized bronchodilator to the
patient and observing an increase in FEV1 of greater than
15 percent above the baseline can make the diagnosis of
reversible airway obstruction. Other pulmonary function
tests like exercise challenge, bronchial provocation,
polysomnography, ventilation-perfusion scans, etc. are
also rarely used.
The mini Wright peak flow meter is a simple, portable
and inexpensive device that measures peak expiratory
flow rate (PEFR) in L/min or L/sec. The test is effort
dependent and can be compared with standard norms
for age and sex and with the patients own values. Home
monitoring of PEFR is useful for early detection of an
impending asthma attack and for monitoring efficacy of
treatment. For recording the PEFR, the pointer (marker)
adjusted to zero. The subject should stand upright and
hold the device horizontally. Air is inhaled as much as
563
Figure 12.2.2: Flow volume curves for a normal child (A) and a child with moderate obstructive airway disease (B)
possible and the lips should be closed over mouthpiece.

Then the air should be blown as hard and as fast as
possible. The attempts are repeated three times at interval
of about 1 min. The best of the three blows is recorded as
the PEFR. The advantages of PEFR monitoring are:
objective measure of severity, correlates with FEV1,
small, simple, portable and convenient device, relatively
inexpensive, easy to maintain, used in children > 5 years
(especially poor perceivers of asthma symptoms) and
it can be used in clinics, hospitals and home. PEFR should
not be used for diagnosis of asthma but used only for
monitoring.
Measurement of lung volumes (FRC) is usually made
by either body plethysmography or gas dilution techniques.
Methacholine and histamine inhalation can be used for
bronchial provocation tests. Bronchial hyper-reactivity is
detected by a 20 percent fall in FEV1. Lung volumes and
flow rates vary with age, sex, height and ethnic group
and therefore it is important to have age and sex matched
reference values from the same population and
preferably the same laboratory.
Laryngoscopy
Inspection of the glottis is mandatory while evaluating
stridor and upper airway obstruction. Indirect (mirror)
laryngoscopy is not feasible in smaller children. Direct
laryngoscopy can be performed under sedation or
anesthesia, with a rigid or fiberoptic scope.
Bronchoscopy
Flexible bronchoscopy is performed under topical
anesthesia in children. Indications include recurrent/
persistent pneumonia, atelectasis, unexplained wheeze,
foreign body, hemoptysis, mass lesions, unexplained
interstitial disease/ pneumonia in immunocompromised
child, etc. Therapeutic procedures can also be carried out
including removal of mucus plug, granulation tissue,
foreign body and instillation of drugs. A rigid scope is
preferred for removal of mucous plugs and foreign body.
Fluid obtained with a bronchoalveolar lavage is
extremely useful for cytological and microbiological
diagnosis of certain lung diseases.
Thoracoscopy
Transillumination
Transillumination of the chest wall may yield positive
results in infants up to 6 months of age. A pneumothorax
can be diagnosed, because free air in the pleural space
often results in an unusually large halo of light in the
skin surrounding the fiberoptic light probe.
The pleural cavity can be examined through a thoracoscope, which is similar to a rigid bronchoscope. This
procedure is less invasive than an open thoracotomy.
Video-assisted thoracoscopic surgery (VATS) can now
be used for various diagnostic and therapeutic procedures (minimally invasive surgery).
564
Thoracocentesis
It is performed when X-ray or ultrasonography is suggestive of fluid in the pleural cavity. Please refer to the
chapter on Pediatric Procedures.
abdominal movements, arterial PCO 2 and SaO 2 are

monitored.
BIBLIOGRAPHY
1.
Lung Tap
A percutaneous tap with a needle and after instillation
of saline is the most direct method of obtaining specimens from the lung parenchyma.
2.
3.
4.
Lung Biopsy
This may be the only way to establish a diagnosis in
protracted noninfectious disease, e.g. interstitial disease.
An open biopsy or a transbronchial biopsy through an
endotracheal tube or a bronchoscope can be obtained.
This technique is most appropriate for diffuse lung
disease such as infection due to Pneumocystis carinii.
Polygraphic Monitoring
This is done during natural sleep, the number and
duration of obstructive apneas and upper airway obstructions are monitored. Heart rate, ECG, thoracic and
5.
6.
7.
8.
Balachandran A, Vijayasekaran D, Shivbalan S.

Bronchopist talks to you. Indian Journal of Pediatrics
2004;71(8):739-42.
Brand PLP, Roorda RJ. Usefulness of monitoring lung
function in asthma. Arch Dis Child 2003; 88: 1021-25.
Crapo RO. Pulmonary-function testing. New England
Journal of Medicine 1994;331(1):25-30.
Fletcher BD. Diagnostic imaging of the respiratory tract.
Chapter 8, Section 1. In: Chernick V, Boat TF, Kendig EL
(Eds): Disorders of the Respiratory Tract in Children (6th
ed). WB Saunders 1998;143-74.
Haddad GG, Palazzo RM. Diagnostic approach to respiratory disease, Chapter 359, Part XVIII. In: Behrman RE,
Kliegman RM, Jenson HB (Eds): Nelsons Textbook of
Pediatrics (17th ed), WB Saunders, 2004;1375-9.
Karkhanis V, Joshi JM. Pulmonary function testing in
pediatric practice. Pediatric Clinics of India 2003;41(2):
101-17.
Subramanyam L, Balachandran A, Somu N. Interpretation of Pulmonology function tests (PFT). Essentials of
Pediatric Pulmonology 1990;38:229-37.
Vijayasekaran D, Subramanyam L, Balachandran A,
Shivbalan S. Spirometry in clinical practice. Indian
Pediatrics 2003;40:626-32.
12.3 Flexible Fiberoptic Bronchoscopy (FFBS)

D Vijayasekaran
Flexible Fiberoptic Bronchoscopy (FFBS) has revolutionized the management of respiratory diseases because
of its extensive diagnostic and therapeutic applications.
It is an important tool added in the diagnostic work up
of respiratory medicine and without FFBS contribution
such work up may be incomplete in many instances.
Today a skilled bronchoscopist can sample from any
bronchopulmonary segment. Though pediatric scopy has
many advantages it is widely underutilized because of
lack of awareness, cost, and expertise training programs.
FFBS versus Rigid Scope

Both FFBS and rigid scope neither replace nor duplicate
the work of each other. The applications of rigid scope
in pediatric practice are mainly therapeutic, like removal
of foreign bodies and surgical intervention at tracheobronchial level, whereas flexible scope is largely used
for diagnostic work-up. Therapeutic applications of FFBS
is increasing day by day following the introduction of
newer slender scopes with larger working channel
(Table 12.12.1).
EVOLUTION OF SCOPY
The idea of bronchoscopy was started as early as
1928 by Jackson and Jackson, et al. The initial scopy
consisted of wide bore metal tube fitted with lamp and
lenses. The innovative idea of Japanese scientist, Shigeto
Ikedo, led to the invention of FFBS in early seventies.
Precautions
FFBS is made up of fiberoptic bundles and the diameter
of each glass fiber is around 10 microns. In FFBS, light
undergoes repeated internal reflection through fibreoptic
bundles and the image formed is due to conglomeration
565
TABLE 12.3.1: FFBS versus rigid scope in pediatric practice

FFBS
a. Done under local anesthesia
Rigid scopy
Done under general anesthesia
b. Meant for diagnostic applications
Meant for therapeutic applications
c. Bronchoscopic vision is possible up to the orifice

of fifth order bronchi
Can reach safely up to second order bronchi
d. Direct intraluminal evaluation of respiratory system

and broncho alveolar lavage are the
important procedures
Removal of foreign bodies and surgical intervention are the

important procedures
e. Distal end can be deflected above (180) and below

(100) and upper lobe bronchi can easily be inspected
Being a rigid tube bending and deflection is not possible
f. Since the bronchial lumen gets obstructed, the

procedure should be done quickly (within minutes)
and oxygen supplementation is necessary to
prevent hypoxemia
Jet ventilation through wide bore metal tube is advantageous

allowing the procedure fairly long time without any fear of
hypoxemia.
of thousands of points of light. The resolution of image

formed by FFBS is slightly inferior to that of rigid scope.
However, the added magnification gives better image.
Extreme delicacy and gentleness are important precautions to be observed throughout the procedure. At no
time acute bending should be done lest breakage of glass
fiber is imminent.
Since nosocomial infection is the potential hazard, the
scope should thoroughly be cleaned by immersing under
2 percent glutaraldehyde (Cidex) for twenty minutes
after each procedure if infection is suspected. The recent
scopes are so designed that they can safely be submerged
under cleaning tank filled with glutaraldehyde.
Indications
Children with atelectasis, persistent pneumonia, recurrent pneumonia, opportunistic pneumonia, bronchiectasis, unexplained hemoptysis, prolonged stridor or
cough, suspected congenital anomalies of the respiratory
tract (tracheomalacia, tracheal stenosis, tracheal web,
bronchial stenosis, bronchial web, hypoplasia or agenesis
of lung, vascular anomalies) endobronchial tuberculosis
and diffuse lung diseases can be benefitted with FFBS
evaluation.
If a child is deemed to be benefitted with FFBS
evaluation it should be done. However, if such information could be possible with any other noninvasive
procedures, FFBS can preferably be avoided. Removal
of mucus plug may result in normal expansion of
atelectatic lung especially in young children forms the
useful therapeutic indication. Fragmented or dissolved

foreign body placed beyond the bronchoscopic vision of
rigid scope can be sucked out at times with FFBS. This
forms another therapeutic indication of FFBS.
Newer indications of FFBS are expanding, which
include laser therapy, selective bronchogram, regional
lung function studies, intrapulmonary stent and bronchoscopic ultrasonogram. However, these are not practised with pediatric FFBS because of narrow working
channel.
Preparation
Motivation and explaining the harmlessness about the
procedure both to parents and older children gains their
confidence, alleviates their unnecessary fear and increases their cooperation. Six hours fasting is advisable with
prior xylocaine sensitivity. In children with cardiac
problems atropine premedication (0.01 ml/kg) may
prevent complications of vagal stimulation (arrhythmias). Some centers do administer midazolam and
ketamine to sedate. Though such things may be required
initially, once mastery of technique is achieved they are
rarely required.
Pep talk and a friendly atmosphere is all that is
required for constant success.
Topical anesthesia of upper respiratory tract can be
achieved with xylocaine instillation supplemented with
a small amount of xylocaine jelly applied over the
selected nostril. Though spray while you go technique
is the traditional way of topical anesthetisation few
566
centers claim xylocaine nebulization is useful especially

if noncooperation is anticipated.
Procedure
After lubricating the patients nostril with 2 percent
xylocaine jelly, the distal end of FFBS should carefully
be inserted through the floor of the nostril closer to
inferior turbinate bone for better negotiation and
minimum discomfort. On reaching the nasopharynx, the
epiglottis is visualized. The scope has to be pushed
downwards to look for vocal cords at a distance. At this
location we should wait for at least a minute to study
the anatomy of vocal cords. If the child is not fully
cooperative instillation of a small dose of xylocaine over
the vocal cords results in thorough anesthetization and
ensures full cooperation. Negotiating the glottic opening
is an art that needs repeated training under the expert
supervision. The total dose of xylocaine should not
exceed 6 mg/kg of body weight. Once FFBS enters
trachea, the remaining procedure is relatively easy. The
normal side has to be inspected first to prevent contamination from side of lesion. In trained hands inspection
of intraluminal tree hardly takes more than a minute and
prolonging the maneuver is not necessary as it may lead
to hypoxemia. If intraluminal evaluation needs longer
time, the scope can be reinserted after adequate
oxygenation rather than continuing the procedure for a
long time at a single stretch. Two trained assistants are
required to monitor vital signs and to assist in sampling
techniques during flexible scopy. Childs head and hands
should be held otherwise the agitated child may pull out
the scope resulting scope damage. Young children may
be allowed to cry and older children are allowed to talk
as both these acts may encourage the scopist to do the
procedure easily. Monitoring with pulse oximeter is the
objective evidence of oxygenation status and SaO2 should
be maintained between 92 to 95 percent throughout the
procedure to prevent hypoxemia related complications.
Moreover pulse oximeter monitoring will increase the
confidence of the scopist while he engages in evaluating
the intraluminal tree.
Intraluminal Evaluation
Basic knowledge about the anatomy of the nasopharynx,
epiglottis, vocal cords, trachea and bronchial tree is
mandatory to identify abnormal anatomical features. The
art of visualizing intraluminal aspect of bronchial tree
should be learned before venturing interventions with

scope. During intraluminal evaluation one should look
for mucosal lesions, endobronchial granulations, mucus
plugs, missed foreign bodies, adenomas, bronchial
distortion due to external compression and abnormal
airway anatomy.
Sampling Techniques
Apart from intrabronchial evaluation, the following
sampling techniques can be done with presently
available pediatric scope: (a) bronchial aspiration with
polythene tube, (b) catheter brush biopsy with double
catheter system, (c) bronchoalveolar lavage (BAL).
While doing catheter brush biopsy, double catheter
system is preferred to prevent contamination from upper
respiratory flora. The telescopic (inner) catheter carrying
the brush is protruded out only when it reaches the target
site and after sampling, the inner catheter should be
drawn back into the outer catheter to prevent contamination. Disposable catheters are available whose distal
end can be cut and sent for various bacteriological
investigations after the procedure.
Bronchoalveolar Lavage (BAL)
BAL can rightly be called as Liquid Biopsy of the Lung
comparable to urine analysis which is designated as
Liquid Biopsy of the Kidney. BAL collects the lining
fluid of bronchial epithelium containing cells and soluble solutes rich in immunoglobulins and biochemical
contents. During BAL the distal end of the scope is
wedged into the desired bronchoscopic segment (affected
segment in localized disease and right middle lobe or
lingular segment in diffuse lung disease). Calculated
amount of normal saline (2 ml/kg) is instilled in three
aliquots to retrieve the maximum lavage fluid. Though
the retrieval after the first aliquot will be hardly anything
as the major quantity of fluid will trickle down to deeper
parts of lung, fair collection will be obtained from other
two aliquots. Usually, the BAL collected will be around
50 to 70 percent of instilled fluid which can be subjected
for cytological, biochemical, immunological and bacteriological investigations.
BAL plays a major role in identification of causative
etiological agents in opportunistic pneumonia (immunosuppressive states including HIV) persistent/recurrent
pneumonia, pulmonary hemosiderosis, sarcoidosis,
alveolar proteinosis and other interstitial lung diseases.

Complication
The inherent complications of FFBS are hypoxemia,
subglottic edema, vagal stimulation which can safely be
avoided if the said precautions are meticulously
followed. Minor complications like nasal bleed, blood
tinged sputum, fever can settle without any treatment.
SUMMARY
FFBS is one of the useful gadgets in the diagnostic
armamentarium of respiratory medicine but not widely
applied in pediatric practice. It is the right time that
young doctors interested in the respiratory medicine
should come forward to take up this interesting field.
Methodical training under competent trainer with
expertise in this technique is all that is required. Though
it appears to be a costlier affair initially, considering
enormous benefits obtained in a short time it is definitely
a cost-effective procedure. In trained hands the
procedure is cent percent free of complications and its
risk benefit ratio is highly favorable. Many poor children
with chronic lung disease can immensely be benefitted
with FFBS and the technique is totally radiation free.
BIBLIOGRAPHY
1.
Abadco DL, Steiner P. Gastric lavage is better than

bronchoalveolar lavage for isolation of mycobacterium
tuberculosis in childhood pulmonary tuberculosis.
Pediatr Infect Dis J 1992;11:7358.
2. De blick J, Azevedo I, Burren CP, Le Bourgeois M,
Lallelund D: Scheinmann. The value of flexible bronchoscopy in childhood tuberculosis. Chest 1991;100(3)
68892.
3. Gibson NA, Coutts JA, Pator J. Flexible bronchoscopy
under 10 kg. Respiratory Medicine 1994;88(2):131-4.
567
4. Godfreys, Avital A, Maayan C, Rotschild M, Springer C.

Yield from flexible bronchoscopy in children. Pediatr
Pulmon 1997;23(4)261-9.
5. Monnden Y, Morimoto, Taniki T, Uyama T, Kiard S.
Flexible bronchoscopy for foreign body in airway.
Tokushima J Exper Med 1989;36(1-2):35-9.
6. Phillips E2, Libsekal K. Flexible bronchoscopy in the
management of congenital lobar emphysema in the
neonate. Canad Respir 1998;5(3):21921.
7. Raine J, Warner JO. Fiberoptic bronchoscopy without
general anaesthetic: Arch Dis Child 1991;66:481-4.
8. Rebort A, Goldstein, Prastiant K, et al. Clinical role of
bronchoalveolar lavage in adults with pulmonary
disease. Am Rev Resp Dis 1990;142:481-6.
9. Rennard SI. Future directions for bronchoalveolar lavage.
Lung 1990;10506.
10. Reynolds HY. State of the art: bronchoalveolar lavage.
Am Rev Respir Dis 1987;135:250-63.
11. Schellahase DE, Fawcett DD, Schutze GE, Lensing SY,
Tryka AF. Clinical utility of flexible bronchoscopy and
bronchoalveolar lavage in young children with recurrent
wheezing. Pediatric 1998;132(2):312-8.
12. Schellhase DE, Graham LM, Fix EJ, Sparks LM, Fan LL.
Diagnosis of tracheal injury in mechanically ventilated
premature infants by flexible bronchoscopy a Pilot study.
Chest 1990;98(5):1219-25.
13. Somu N, Swaminathan S, Paramasivam CN, et al. Value
of bronchoalveolar lavage and gastric lavage in the
diagnosis of pulmonary tuberculosis in children.
Tubercle and Lung Disease 1995;295-9.
14. Su YY, Niu CK, Liang CD, Herang CB, Ko SF. Usefulness
of pediatric flexible bronchoscopy in the early diagnosis
and postoperation evaluation of vascular rings: report
of three cases: Chang-Keny 1 Hshn Tsa chih, 1999;(22)4:
627-32.
15. YU HR, Nu CK Su. YT. Huang CB. Flexiable bronchoscopic diagnosis of airway injuries after intubation in
children. J Formosan Med Assoc 2000;99(8):618-22.
12.4 Respiratory Distress

MD Shah
Acute respiratory distress is one of the most common
pediatric emergencies. Respiratory distress signifies
potential respiratory failure. Any infant or child who is
having difficulty in breathing, characterized by excessive
work of the muscles of respiration, is said to be in
respiratory distress. It is equivalent to the symptom of
dyspnea in an older child who is able to communicate
this subjective symptom which is defined as abnormally

uncomfortable awareness of breathing. However,
dyspnea and respiratory distress are not exactly
synonymous as in some metabolic causes of respiratory
distress such as metabolic acidosis and in cyanotic
congenital heart disease, there may not be dyspnea even
though child is in respiratory distress. Respiratory
568
distress may be acute or chronic. Acute respiratory

distress is more easily recognized by the clinician
whereas chronic respiratory distress is often overlooked.
However, it is important to recognize the later as it is an
important cause of disability in a child.
ETIOLOGY
Most of the conditions producing respiratory distress
involve airway obstructions which may be extrathoracic
and intrathoracic (extrapulmonary or intrapulmonary).
Parenchymal lung diseases and nonpulmonary conditions can also cause respiratory distress. Based on these
considerations, the causes of respiratory distress can be
classified into following major groups.
Extrathoracic Airway Obstructions
Tumors in anterior mediastinum pressing on

intrathoracic trachea, e.g. lymphoma, lymphangioma,
hemangioma, thymoma, congenital goiter
Tracheal stenosis, tracheomalacia, bronchial stenosis,
T-0 fistula
Chondrodystrophies e.g., Ellis-van Creveld
syndrome
Diphragmatic hernia.
Intrapulmonary
Bronchial asthma
Foreign bodies
Congenital bronchial stenosis
Bronchiolitis
Endobronchial tuberculosis
Congenital lobar emphysema.
Causes in the Newborn
Bilateral or unilateral choanal atresia

Stuffy nose syndrome (turbinate hypertrophy)
Nasopharyngeal encephalocele, dermoid, chordoma
Macroglossia (primary or secondary)
Internal thyroglossal duct cyst
Laryngomalacia
Bilateral vocal cord paralysis
Congenital subglottic stenosis or hemangioma .
Laryngeal web
Trauma caused by endotracheal intubation.
Causes in Infants and Children
Foreign body in nose

Acute or chronic adenoiditis and tonsillitis
Hypopharyngeal foreign body
Croup syndrome caused by
Acute L TB/Acute epiglottitis
Spasmodic laryngitis/Laryngeal angioedema
Laryngeal diphtheria/Laryngeal abscess
Bacterial tracheitis/Retropharyngeal abscess
External trauma to neck
Burns of upper airways
Postendotracheal intubation and instrumentation.
Intrathoracic Airways Obstructions
Extrapulmonary
Vascular anomalies: Double aortic arch, right sided
aortic arch with aberrant left subclavian artery,
pulmonary arterial sling
Parenchymal Lung Diseases

Pneumonias, bronchopneumonias, aspiration
syndromes
Respiratory distress syndrome in newborns
Pediatric acute respiratory distress syndrome (ARDS)
Air leak syndromes: Pneumothorax, interstitial
emphysema, pneumomediastinum, pneumopericardium
Pulmonary hemorrhage
Bronchopulmonary dysplasia
Wilson-Mikity syndrome
Chronic pulmonary insufficiency of prematurity
Pulmonary hypoplasia or agenesis
Pleural effusions, empyema, chylothorax.
Nonpulmonary Causes of Respiratory Distress
Congestive cardiac failure
Metabolic causes: Acidosis, ketoacidosis, hypoglycemia
Persistent pulmonary hypertension of newborn
Birth asphyxia and other CNS disorders.
Pathophysiology
Pathophysiology varies with the etiological cause and is
described elsewhere. Hence, here only pathophysiology
of pediatric ARDS is described.
Pediatric acute respiratory distress syndrome (ARDS),
formally known as adult respiratory distress syndrome,
has now been recognized as an important cause of
respiratory distress in children and forms 1 to 4% of PICU

admissions in western countries. It may arise as a result
of a direct pulmonary disease or secondary to systemic
disease elsewhere in the body. Common pulmonary
diseases that may cause ARDS are aspiration, smoke
inhalation, bacterial and fungal infections. Systemic
disorders which may cause ARDS include sepsis, trauma,
near drowning, burns, massive transfusions and drug
overdosage. The hallmark of ARDS is the destruction of
the capillary-alveolar unit which sets in motion all the
pathophysiological changes of ARDS which are characterized by three stages namely the exudative, fibroproliferative and fibrotic.
Exudative stage: Injury to lung endothelial cells and
alveolar epithelial cells (type I and II) resulting in protein
rich exudate filling the alveoli and interspaces and
development of microvascular thrombi in capillaries.
Fibroproliferative stage: This stage occurs between
the first and third week after the initial insult and is
characterized by cellular infiltration and proliferation of
type II pneumocytes, firoblasts and myofibroblasts.
Fibrotic stage: This stage occurs 3 weeks after the
initial injury and is characterized by fibrosis, healing and
remodelling of the lungs.
There is release and accumulation of cytokines in
alveolar spaces in early ARDS. It is the migration of these
cytokines into the systemic circulation which contributes
to the development of multiorgan failure (MOF), which
is a serious and often fatal complication of ARDS.
Clinical Features
A child with respiratory distress needs a thorough clinical
evaluation for diagnosis, assessment of severity and
determining the etiology and for this following clinical
features should be carefully evaluated.
Respiratory Rate and Depth
The respiratory rate, when properly measured, is
invaluable to determine both initially and longitudinally
the severity of respiratory dysfunction. It should be
measured for a full 2 minutes, and the total number of
breaths then divided by two. In patients with airway
obstructions, the respiratory rate is either slow or fast
but the excursions are deep. In patient with metabolic
acidosis, the respirations are deep, rapid and sighing
(Kussmaul breathing). In patients with decreased lung
compliance as in pneumonia or pulmonary edema, the
respirations are rapid and shallow. In patients with
encephalitis, the respirations are usually rapid and deep,
569
but can be rapid and shallow. Orthopnea should also be

noted as its presence is indicative of severe respiratory
distress.
Respiratory Rhythm
Cheyne-stokes breathing is characterized by cycles of
increasing and decreasing tidal volumes separated by
apnea. It may occur normally in prematures and in fullterm newborns during sleep but in older children, it is
seen with CCF and increased intracranial pressure. Biots
breathing may be seen in children with meningitis or
severe brain damage. Biots breathing consists of
irregular cycles of respiration at variable tidal volumes
interrupted by apnea and is an ominous finding in
patients with severe brain damage.
Inspiratory Retractions
The increased negative intrathoracic pressure generated
to move a desired tidal volume past obstructed airways
or into poorly compliant lung, leads to intercostals,
supraclavicular, suprasternal, substernal and subcostal
retractions. Retractions result from an abnormal pressure
relationship between the pleural space pressure and the
atmospheric pressure. Increased effort of breathing results
in increased negative pressure in the pleural space creating
an increased pressure gradient between atmospheric
pressure and pleural space resulting in sinking in of soft
tissues. This is observed clinically as retractions. These are
especially striking in extrathoracic airway obstructions,
as the large negative pressure below the site of obstruction
during inspiration produces collapse of extrathoracic
airways. In premature infants and in patients with frail
chest, marked retractions may occur, even with slightly
increased negative inspiratory pressures. Suprasternal
retractions are particularly marked in cases of upper
airway obstructions. Inspiratory indrawing of the lateral
chest is known as Hoovers sign and is observed in patients
with obstructive airway disease.
Intercostal Bulging
This is seen in severe asthma, during expiration as the
pleural pressure becomes greatly positive to force the
expiration against increased airway resistance.
Head Bobbing
In head bobbing the head bobs forward in synchrony
with each inspiration. This is observed in infants in whom
570
accessory muscles of respiration are active. Contraction

of the sternocleidomastoid muscles during inspiration
leads to forward bending of neck. The relatively weak
cervical spinal muscles of infants are unable to resist the
strong pull exerted by sternocleidomastoid muscles.
Stridor
Stridor refers to a musical sound of single pitch that is
produced by oscillations of critically narrowed extrathoracic airways. Initially, it is inspiratory but when the
obstruction becomes more severe, it is both inspiratory
and expiratory. When stridor is higher pitched, the child
is in more distress. As the patient improves with the
resolution of the primary disease, the stridor becomes
lower in pitch. The pitch of the stridor can be used to
assess improvement or worsening of the condition in
relation to the therapy.
Wheezing
Expiratory wheezing is heard in any condition where
there is intrathoracic airway obstruction, e.g. brochial
asthma, vascular ring, bronchial stenosis, bronchogenic
cyst, etc. Widespread narrowing of airways in asthma
leads to various pitches and so wheezing is polyphonic,
whereas a fixed obstruction in larger airways produces
monophonic wheezing. Wheezing may not be heard in
very severe airway obstruction.
Grunting
It is a low-pitched sound, which is produced by expiration against a partially closed glottis. It is an attempt to
maintain a positive end expiratory pressure (PEEP) as
long as possible, so as to prevent alveolar collapse at end
of expiration. This is most beneficial in small airway
obstruction and in alveolar diseases that produce
widespread loss of functional residual capacity such as
pulmonary edema, diffuse pneumonia, and hyaline
membrane disease (HMD). It is a prominent feature of
RDS in newborn.
Flaring of the Alae Nasi
It is a sensitive sign of respiratory distress. By enlarging
the anterior nasal passages, it reduces upper and total
airway resistance and helps in stabilizing the upper
airway by preventing large negative pharyngeal pressure
during inspiration.
Paradoxical Breathing
Inward motion of the chest during inspiration is called
paradoxical breathing. It is seen when there is paralysis
of intercostals muscles or a very compliant rib cage (e.g.
in premature infants). The development of paradoxical
breathing in an awake, nonparalyzed patient beyond the
newborn period indicates respiratory muscle fatigue and
impending respiratory failure.
Plusus Paradoxus
The widening of systolic blood pressure difference
between inspiratory and expiratory phase of respiration
is known as pulsus paradoxus. A drop of greater than
10 mmHg during inspiration is taken as clinically
significant and indicates increased airway resistance.
Pulsus paradoxus is useful in assessing the severity of
bronchial asthma. It may be as high as 40 mmHg in very
severe asthma. Pulsus paraldoxus can be qualitatively
assessed by palpation of a peripheral pulse during the
respiratory cycle and it can be quantitatively measured
by the difference in systolic pressure with inspiration and
expiration.
Cyanosis
Central cyanosis is frequently associated with significant
respiratory distress. Clinically pediatric ARDS is
characterized by four phases: First phase is of acute lung
injury caused by initial insult and is followed by second
phase of silent latent period of 24-72 hours. Third phase
is of progressive tachypnea, leading to dyspnea and
respiratory failure. This may be followed by fourth phase
of severe respiratory failure and MOF.
Assessment of Respiratory Distress in Newborns
Newborns develop respiratory distress due to several
causes of which the most important is the hyaline
membrane disease (HMD). It is important to diagnose it
early and assess the severity from the point of view of
management. Silverman has designed a scoring system
that takes multiple factors into account to quantify the
severity of respiratory distress into three grades (0, 1,
and 2). The clinical signs observed are movement of
upper chest in relation to abdomen, retractions in lower
chest, xiphoid retractions, dilatation of anterior nares and
expiratory grunt.

Grade 0: Synchronized movements of upper chest and
abdomen, no retraction of lower chest and xiphoid, no
dilatation of nares and no expiratory grunt.
Grade 1: Lag of upper chest on inspiration in relation to
abdomen, mild retractions of lower chest and xiphoid,
minimal dilatation of nares and expiratory grunt heard
with stethoscope only.
Grade 2: See-saw movement of upper chest and abdomen,
marked retractions of lower chest and xiphoid, marked
dilatation of nares and expiratory grunt heard with naked
ear.
INVESTIGATIONS
The following four basic investigations are required in
almost all cases of respiratory distress.
1. CBC
2. Mantoux test
3. X-ray of chest, frontal and lateral views
4. Arterial blood gases.
The correct interpretation of arterial blood gas values
is very valuable in localizing the site of diseases, in
estimating the severity of disease and in diagnosing
presence or absence of respiratory failure (Table 12.4.1).
The following special investigations may be required
only in selected cases: X-ray of soft tissues of neck:
Anteroposterior and lateral views:
CT Scan/MRI of chest
Bronchoscopy, laryngoscopy, rhinoscopy
ECG
Sonography of chest
Pulmonary function tests
TABLE 12.4.1: Interpreting blood gas values in
respiratory distress
A. Extrathoracic and central intrathoracic (above the carina)
airway obstruction
PaCO2, PaO2
Response to supplementary oxygen is good
B. Intrathoracic intrapulmonary airway obstruction.
Mild: PaCO2, PaO2
Moderate: Normal PaCO2, PaO2
Severe: PaCO2, PaO2
Response to supplementary oxygen is good to fair
C. Alveolar or parenchymal pathology
PaO2 decreased depending on severity
PaCO2 variable, may be increased when exhaustion or
respiratory muscles fatigue supervenes.
Response to supplementary oxygen is fair
571
Pleural tapping
Lung biopsy
Sputum examination: smear and culture
Ventilation and perfusion scan of lung sleep study
Aortogram, pulmonary angiorgram
Esophagoscopy and esophagogram
Bronchoalveolar lavage fluid examination
In pediatric ARDS examination of BAL fluid for the
levels of inflammatory mediators like TNF-L, IL-1, IL-6
and IL- 8 as they correlate with severity of respiratory
failure and association of MOF. Increased serum levels
of IL-6 correlate with presence of MOF.
DIAGNOSIS
Diagnosis of respiratory distress is easy when the above
described clinical features are present. However, it is
important to determine the site of the problem and in
this regard, Table 12.4.2 which correlates the clinical
features with site of the problem is very helpful.
Next step is to determine the cause of respiratory
distress. Respiratory distress can be caused by airway
obstructive diseases, parenchymal lung diseases or nonpulmonary causes are ruled out, Tables 12.4.1 and 12.4.2.
are of much help in narrowing down the likely causes.
In pediatric ARDS X-ray chest and CT scan are useful
in diagnosis. X-ray chest shows diffuse bilateral infiltrates
and chest CT scan demonstrates areas of relatively
normal lung interspersed with atelactatic and consolidated regions in the dependent zones.
The diagnosis of ARDS has now become more
uniform and rational since the proper diagnostic criteria
formulated by the 1994 American-European consensus
conference on ARDS. The consensus committee gave the
following diagnostic criteria for ARDS and acute lung
injury (ALl):
1. Acute onset
2. Diffuse bilateral infiltrates on chest radiograph.
3. A pulmonary artery wedge pressure less than or
equal to 18 mm Hg or no clinical evidence of left atrial
hypertension.
4. A ratio of partial pressure of oxygen in arterial blood
to fraction of inspired oxygen (PaO2/FiO2) of less than
or equal to 300 in ALT and 200 in ARDS regardless of
levels of PEEP.
Postnatal diagnosis of RDS in a newborn should be
suspected in a premature baby who develops shortly
after birth tachypnea, retractions, flaring of alae nasi,
572

TABLE 12.4.2: Correlation of clinical features with the site of problem
Clinical features
Airway obstruction
Extrathoracic
Extrapulmonary
Parenchymal lung disease

Intrathoracic
Intrapulmonary
Tachypnea
++
++++
Retraction
++++
++
++
++
Stridor
++++
++
Grunting
++
++++
Wheezing
+++
++++
grunting and cyanosis with X-ray of chest showing

diffuse reticulogranular pattern and air bronchogram.
MANAGEMENT
This will depend upon the etiological conditions causing
the respiratory distress and is described elsewhere under
the individual conditions. Hence, here only the management of pediatric ARDS is briefly described. Mechanical
ventilation is the key supportive therapy for ARDS and
the most revolutionary change in the ventilation strategy
is the adoption of lung protective strategy in which lower
tidal volume (Vt < 6 ml/kg), lower peak inspiratory
pressure (PIP< 30 cm H2O) and higher PEEP are used as
compared to conventional ventilation. This strategy
prevents or reduces the ventilator induced lung injury
(Volutrauma and barotrauma). Adoption of this strategy
has led to improved oxygenation and survival of the
child. Another lung protective strategy like high
frequency oscillatory ventilation (HFOV) is also used in
selected cases of ARDS. Other adjunctive therapies which
are being evaluated are nitric oxide inhalation, prone
positioning, surfactant administration, use of steroids,
extracorporeal membrane oxygenation (ECMO) and
anticoagulation therapy. Of these prone positioning,
surfactant therapy and steroid therapy appear promising
whereas others are still of questionable benefit. Prone
positioning is safe and simple to apply and it improves
oxygenation and should be considered for all patients
with ARDS. Steroid therapy helps by reducing the
overaggressive inflammatory response and end stage
fibrosis. They should be given for 4 to 6 weeks. It should
be tried in cases which are not improving. Surfactant
therapy improves oxygenation but does not benefit over
all mortality and hence should be tried only in selected
cases which are resistant to treatment. ECMO is
recommended only when there is severe respiratory

failure that would otherwise be fatal. Its use is restricted
because of its serious complications like intracranial
bleeding, sepsis from canula and cerebral injury related
to carotid cannulation. The anticoagulation therapy with
activated protein C, found useful in adults, is still not
evaluated in children. It may be useful in cases of sepsis.
All these recent advances in management of ARDS have
considerably reduced the mortality and morbidity of
ARDS.
FOLLOW-UP
Any newborn, infant or child who has suffered from
respiratory distress should be followed up over a long
period of time by clinical examination, X-ray and PFT in
order to detect long-term sequel and pulmonary
morbidity.
ACKNOWLEDGEMENT
I sincerely thank Dr. Snehal Shah Sharma, ex-lecturer,
BJ Wadia Children Hospital Mumbai, for her valuable
assistance in preparing this manuscript.
BIBLIOGRAPHY
1. Ackerman NB, Hendon BL. Assessment of the Neonate.
In: Barnhart SL, Czervinske MP (Eds): Perinatal and
Pediatric Respiratory Care. (1st edn) WB Saunders
Company 1995;23-44.
2. Anderson MR. Update in pediatric acute respiratory
distress syndrome. Respiratory care, 2003;48(3):261-78.
3. Andrew HN, Christopher JL. Acute respiratory distress
syndrome in the pediatric patient. In: Chernick Victor
EL (Eds): Kendigs Disorders of the Respiratory Tract in
Children. (7th edn) Saunders Elsevier 2006;639-52
4. Bhakta KY. Respiratory Distress Syndrome. In: Cloherty
JP, Eichenwald EC, Stark AR (Eds): Manual of Neonatal
Care. (6th edn) Wolters Kluwer (India) pvt Ltd, New
Delhi 2008;323-30.

5. Pasterkamp H. The history and physical examination:
In: Chernick Victor EL (Ed): Kendigs disorders of the
respiratory tract in children. (7th edn). Saunders Elsevier
2006;75-93.
6. Ronald HI, Eugene B. Dyspnea and pulmonary edema:
In Harrisons principles of internal medidine (13th edn),
McGraw-Hill, New Delhi 1994;74-8.
573
7. Sarnaik AP, Vernon DO, Mary Leih-Lai. Respiratory

emergencies in children. In: Vidyasagar O, Sarnaik AP (Eds):
Neonatal and Pediatric Intensive Care, Jaypee Brothers
Medical Publishers (P) Ltd, New Delhi, 1991;40-58.
8. Somu N, Devaki V, Thangavelu S. Dyspnea: In Somu N and
Subramanyam L (Eds): Essentials of Pediatric Pulmonology.
(2nd eds) M/s Siva and Co. Chennai 1996; 22-7.
12.5 Upper Respiratory Tract Infection

SK Kabra
INTRODUCTION
Acute respiratory infections are a major cause of
morbidity and mortality in children and of particular
significance in developing countries like India. Outpatient attendance attributed to acute respiratory
infections is as high as 20-40 percent of all outpatients
and 12-35 percent of in-patients. The overall incidence
of acute respiratory infection in the under-fives may be
between 3-8 episodes/child/year. Of this majority are
upper respiratory tract infection (URTI).
Upper respiaratory tract infection (URTI) is a loose
term which includes, infection of nasal cavity, throat,
nasopharynx, ears and sinuses. URTIs are common
causes of morbidity in children.
ACUTE NASOPHARYNGITIS
Infection of nasopharynx is also called common cold. It
is probably the most common infection in children. In
young children 5 to 8 episodes of common cold may occur
in one year.
Etiology
Acute nasopharyngitis is caused by viruses. The common
viruses include rhinovirus, and corona viruses. The other
viruses include adenoviruses, influenza, parainfluenza
or respiratory syncytial viruses. These are spread by
droplet infection. Predisposing factors include chilling,
sudden exposure to cold air, and overcrowding. Rhinitis
could also be due to allergy.
Clinical Features
Clinical features of common cold are due to congestion,
swelling and increased secretion of nasopharyngeal
mucosa. Clinical manifestations are more distressing in

infants and young children. The common manifestation
include nasal discharge, initially watery than thick white
to yellowish, nasal block, cough and conjunctival
congestion. Nasal block causes difficulty in feeding,
irritability, excessive crying and breathing from mouth.
Occasionally may be complicated by secondary bacterial
sinusitis and otitis media. Otitis media should be
suspected in a child with no relief in crying, even after
treatment for nasal block. If a course of common cold is
prolonged beyond 7-10 days, then sinusitis should be
considered in a school going child.
Treatment
Acute nasopharyngitis is caused by virus and selflimiting requires no specific treatment. For fever
paracetamol can be given 4 to 6 hourly. For nasal block
normal saline can be instilled in nostrils every 4 to 6
hourly and specially, before giving feeds. Child may be
given warm drinks with plenty of liquids. There is no
role of antibiotics, antihistaminics, local decongestive
drops or steroids. Home remedies for cough and cold
such as tulsi, ginger or honey may be beneficial in
common cold. However, mother should be told to bring
the child to hospital immediately, if there is rapid
respiration, lower chest indrawing or poor feeding.
ACUTE PHARYNGITIS
Acute pharyngitis includes infection of pharynx and
tonsils. This is also called acute tonsillopharyngitis. Most
of the times, it is associated with rhinitis, sinusitis and
occasionally laryngitis.
574
Etiology
Commonly caused by viruses such as rhino, corona,
influenza, parainfluenza and adenoviruses. 10 to 20
percent of sore throats are caused by bacteria. The
important bacterial pathogen is Group A beta hemolytic
streptococcus.
Clinical Features
Children with acute pharyngitis may have fever, sore
throat, pain during deglutition, nasal discharge,
conjunctival congestion and discomfort in throat. There
may be enlargement of tonsils and palate, enlarged
tonsils are soreness in throat may cause blockade of
oropharynx, leading to poor intake by children and
occasionally, may present with drooling of saliva.
Cervical lymph nodes may be enlarged and tender.
Viral pharyngitis is self-limiting and recovers in 5 to
7 days. Pharyngitis caused by group A beta hemolytic
streptococcus, may lead to suppurative complication
such as retropharyngeal and peritonsillar abscess.
Presence of these complications may be indicated by
high-grade fever severe dysphagia and bulge in the
posterior wall of pharynx or around tonsils. The nonsuppurative complications due to streptococcal pharyngitis include acute rheumatic fever and acute glomerulonephritis. These complications can be prevented by
administration of antibiotics. It is very difficult to
differentiate viral from bacterial pharyngitis. Presence
of exudates on pharynx with enlarged tender cervical
nodes and absence of nasal discharge, suggests bacterial
pharyngitis and may be used to start antibiotics.
Diagnosis
Acute pharyngitis is a clinical diagnosis. At times, it is
very difficult to differentiate nasopharyngitis from
pharyngitis. Diagnosis of streptococcal pharyngitis can
be made with presence of exudates, enlarged tonsils and
absence of nasal discharge. The diagnosis can be
confirmed by throat swab culture. Now, a rapid
diagnostic test based on latex agglutination is also
available for diagnosis of streptococcal pharyngitis and
can be carried out in office practice.
Treatment
The major consideration in treatment of acute pharyngitis
is to prevent acute rheumatic fever. If a clinical diagnosis
of streptococcal pharyngitis is made, a throat swab

should be taken or rapid diagnostic test performed to
demonstrate streptococci and penicillin should be
administered.
Penicillin can be given orally or by intramuscular
route. The duration of oral penicillin is for 10-14 days. If
compliance is a problem, single injection of Benzathine
penicillin can be given. The other alternative antibiotics
are ampicillin, amoxicillin or oral cephalosporins. If an
individual is sensitive to penicillin, he or she may be
treated with erythromycin. The newer macrolide
antibiotics such as roxithromycin, clarithromycin and
azythromycin are alternative to erythromycin.
ACUTE SUPPURATIVE OTITIS MEDIA (ASOM)
Acute suppurative otitis media (ASOM) is a common
cause of morbidity in children. It is defined as inflammation of mucoperiosteal lining of the middle ear. If the
duration of illness is more than 2 weeks, it is termed as
chronic suppurative otitis media. Children are more
prone for ASOM because, the eustachian tubes communicating throat with ears are straight and short. ASOM
may be one of the complications of other respiratory
infections.
Etiology
ASOM in children is commonly caused by Streptococcus
pneumoniae, Haemophilus influenzae, and Moraxella
catarrhails. Very rarely, it may be caused due to
Staphylococcus and gram-negative organisms. The later
is more common in immunocompromized hosts.
Clinical Features
ASOM presents with fever, ear pain, ear discharge and
restlessness. In young children, this is common cause of
excessive crying. Once the tympanic membrane perforates, the child may get relief in pain but could develop
pus discharge from ear. ASOM may cause infection of
mastoids in older children. The intracranial extension
may be in form of pyogenic brain abscess. Sometimes,
ASOM may cause lower motor neurone facial palsy.
Children may develop middle ear effusion even after
treatment with antibiotics, it is self limiting and resolve
in majority in 12 weeks time. If it persist, these children
should be sent to otolaryngologists for consideration of
grommet insertion. Chronic middle ear effusion may lead
to hearing impairment.

Diagnosis
In a setting of URTI if a child crying excessively, his ears
should be examined by otoscope. The eardrum may be
inflamed, and bulging with loss of normal anatomy with
fluid in middle ear. Otoscopic examination should be part
of routine examination in young children, presenting
with fever with localization.
Treatment
ASOM is a bacterial infection and should be treated with
antibiotics. The antibacterial useful in ASOM include
ampicillin, amoxicillin, oral cephalosporins or macrolides. Children below 2 years of age may be treated with
antibiotics from the time of diagnosis. However, in
children above 2 years of age with mild disease one can
wait for 2-3 days for improvement in clinical symptoms
without antibiotics. In severe disease as indicated by
presence of high fever (explosive onset, sever otalgia and
toxic appearance and high grade fever >102 F) and
children with mild disease in beginning but deterioration
in 48-72 hours one should consider starting antibiotics.
The antibiotic of choice is amoxycillin. The antibiotic is
continued for 10 days to prevent recurrence and development of chronicity. If the child is not improving by 3-4
days, an alternative medicine should be started and the
child should be referred to an otolaryngologist.
Alternative medicines may be amoxycillin clavulinic acid
or cephalosporins. In severe cases injectable third
generation cephalosporin (Cefotaxime or ceftrioxone)
may be started.
For relief of pain, paracetamol or one of the
nonsteroidal anti-inflammatory, i.e. ibuprofen may be
given, round the clock. Occasionally, tympanocentesis
may be required to relieve pain. There is no role of local
antibiotic drugs in ASOM.
For treatment of chronic otitis media (COM), it is
recommended to keep the ears dry by cotton wick. One
course of oral antibiotics sometimes may be useful.
may be invaded by bacterial pathogens. The common

bacterial pathogens include Streptococcus pneumoniae, H.
infuenzae and Moraxella catarrhalis. Gram-negative
bacteria and fungi may invade paranasal sinuses in
immunocompromised patients.
Clinical Features
Common presentation of sinusitis include non-resolving
rhinitis or common cold even after 7 days, thick purulent
nasal discharge, fever and tenderness over sinuses. In
young infants there may be swelling around eyes. There
may be headache-unilateral, bilateral, temporal or
occipital depending on sinus involvement.
Diagnosis
Usually prolonged course of nasopharyngitis in form of
persistence of fever and nasal discharge could be due to
sinusitis. If tenderness over sinuses can be demonstrated
or periorbital puffiness is present in young children, a
clinical diagnosis of sinusitis can be made. It can be
confirmed by demonstrating opacity or mucosal
thickening or fluid level in paranasal sinuses on X-ray
films. Other imaging such as CT or MRI scan of sinuses
may be done in immunocompromised host or complicated cases.
Treatment
The clinical significance of sinusitis is due to bacterial
invasion. A course of amoxicillin, ampicillin or oral
cephalosporin should be given to the child. The supportive care includes normal saline in nostrils and paracetamol for fever and pain relief. There is no role of routine
administration of antihistamines.
BIBLIOGRAPHY
1.
2.
ACUTE SINUSITIS
In children, ethmoid and maxillary sinuses are present
in infancy. Sphenoid sinuses are well-developed by 3 to
5 years and frontal sinus develop between 6 and 11 years
of age. Infection of sinuses is common and associated
with nasopharyngitis and pharyngitis.
3.
4.
Etiology
Commonly, the viruses causing pharyngitis and nasopharyngitis, are responsible for sinusitis. Sometimes, they
575
5.
Aroll B. Antibiotics for upper respiratory tract infections:

an overview of Cochrane reviews. Respir Med 2005;99:
255-61.
Casey JR, Pichichero ME. Meta-analysis of short course
antibiotic treatment for group a streptococcal tonsillopharyngitis. Pediatr Infect Dis J 2005;24:909-17.
Kabra SK, Lodha R. Acute respiratory mortality. In Child
Survival and Development: Recommendations of
National Consultation Meeting on Child Survival and
Development 20-21 Nov 2004, Held at All India Institute
of Medical Sciences, New Delhi. Indian Academy of
Pediatrics 2004;19-29.
Mirza A, Wludyka P, Chiu TT, Rathore MH. Throat
culture is necessary after negative rapid antigen detection
tests. Clin Pediatr (Phila) 2007;46:241-6.
Simasek M, Blandino DA. Treatment of the common cold.
Am Fam Physician 2007;75:515-20.
576
12.6 Infections of Larynx,

Trachea and Bronchi
Acute infections of larynx, trachea and bronchi are of great

importance in infants and small children. The airway
resistance is inversely proportional to the 4th power of
radius and hence any mucosal edema or inflammation of
the respiratory tract in children, especially involving the
small airways, leads to significant increase in the work of
breathing. These infections produce a dry, hacking cough,
hoarseness of voice and inspiratory stridor, giving them
the common name, croup. Stridor, produced by turbulent
airflow, is a harsh high-pitched respiratory sound, which
is usually inspiratory in nature but can be biphasic. There
are four clinically distinct syndromes which produce
common clinical features. These include laryngitis,
laryngotracheobronchitis (LTB), spasmodic croup and
acute epiglottitis.
Infections of the larynx, trachea and bronchi must be
differentiated from one another and from the following
diseases.
Diphtheritic/ measles croup
Foreign body aspiration
Retropharyngeal or peritonsillar abscess
Extrinsic airway compression or laryngeal web
Intraluminal obstruction
Laryngotracheomalacia
Etiology
Viral agents are more commonly implicated. The
parainfluenza virus type 1, 2 and 3 are the most common
etiologies. Other viruses associated with croup are
influenza A and B, adenovirus, respiratory syncytial
virus (RSV) and measles. Diphtheria and Mycoplasma
pneumoniae are the bacterias implicated in the etiology.
Clinical Features
For the initial 2-3 days, there may be signs of upper
respiratory tract infection characterized by rhinorrhea,
pharyngitis, mild cough, and low grade fever. The child
then develops the characteristic barking cough, hoarseness and stridor. Symptoms are characteristically worse
at night and resolve completely within a week. They are
aggravated by crying and agitation and reduced in
upright position. On examination, there is a hoarse voice,
normal to moderately inflamed pharynx and variable
degree of respiratory distress. As it is a disease of upper
airways and the gas exchange in the alveoli is normal,
hypoxia is seen only when complete airway obstruction
is impending. X-ray of the neck soft tissues show typical
subglottic narrowing called as the steeple sign (Fig.
12.6.1). Croup is essentially a clinical diagnosis and
routine radiographs are not indicated. They should be
considered only after airway stabilization.
CROUP (LARYNGOTRACHEOBRONCHITIS)
Complications
Epidemiology
Children are affected between 3 months to 5 years of age
with a peak during second year of life. The incidence is
higher in males and can occur throughout the year with
peaks in winter and late fall. There may be an associated
family history.
Occur in 15 percent of patients.

Extension of the infectious process to other regions
of the respiratory tract, e.g. middle ear or pulmonary
parenchyma.
Bacterial tracheitis (bacterial superinfection of viral
croup).
577
Etiology
The etiology for acute epiglottitis is bacterial and is
mainly caused by Hemophilus influenzae. However, in
countries with high coverage of Hib vaccine, the
organisms are Streptococcus pyogenes, Pneumococcus and
Staphylococcus aureus.
Clinical Features
Figure 12.6.1: Steeple sign (white arrow)
Treatment
Laryngotracheobronchitis needs a supportive care
including intravenous fluids to maintain hydration and
oxygen inhalation to relieve hypoxia. The mainstay of
treatment is airway management. Options available are
cool, mist, nebulized epinephrine (racemic prepararion
preferable) or single dose dexamethasone 0.6 mg/kg/
dose. Inhalation of epinephrine may decrease the
symptoms of stridor and respiratory distress immediately. A single dose of dexamethasone may decrease
the severity and duration of illness. A beneficial effect of
inhalation of budesonide has been shown in some
studies. However, it needs more research before it is
recommended for routine use. Antibiotics are usually not
indicated. Hospitalization is needed if there are any
danger signs like progressive stridor, severe stridor at
rest, respiratoy distress, hypoxia, apnea or altered
sensorium.
If the child with croup is comfortable and stridor is
audible only on stethoscope, the child may be managed
on ambulatory basis. If the stridor is audible without a
stethoscope, he should be kept in the hospital under
observation at least for a period of 24-48 hours.
It is characterized by an acute potentially fulminating

course of high fever, sore throat, dyspnea, drooling of
saliva and rapidly progressing respiratory obstruction.
The degree of respiratory distress at presentation is
variable. Child looks toxic and may assume the tripod
position sitting upright and leaning forward with the
chin up and mouth open while bracing arms. Stridor is a
late finding and suggests a near complete airway
obstruction. It may be difficult to examine the epiglottis
in an irritable, hypoxic child and it should be done
carefully in an emergency room equipped with measures
for resuscitation. On direct larnygoscopy, the inflamed
epiglottis is large, swollen and cherry red. A lateral
X-ray film of the neck shows an enlarged epiglottis, also
known as thumb sign.
Complications
Include pneumonia, cervical lymphadenitis, otitis media
or rarely, meningitis or septic arthritis due to local and
systemic spread of infection.
Treatment
ACUTE EPIGLOTTITIS
Acute epiglottitis is a medical emergency in children. On

suspicion of acute epiglottitis, the child should be
immediately admitted. Antibiotics recommended for use
include chloramphenicol or third generation cephalosporins like ceftriaxone, cefotaxime administered by
intravenous/intramuscular route. Supportive care
including oxygen and hydration should be provided. The
patient may be nursed in the mothers lap to decrease
the agitation and irritability. Avoid use of sedatives,
however, if unavoidable trichlorofos or chloral hydrate
may be used. Fever can be controlled with antipyretics.
Rifampicin prophylaxis for unimmunized siblings less
than 2 years should be considered.
Epidemiology
ACUTE INFECTIOUS LARYNGITIS
The typical age group for acute epiglottitis is children

between 2-4 years of age. It is not very common in India.
It is most commonly caused by viruses, except diphtheria.

It is generally a mild illness, onset of which is charac-
578
terized by upper respiratory tract infection consisting of

sore throat, cough and hoarseness. Respiratory distress
is unusual. Physical examination is usually unremarkable. However, mild pharyngeal inflammation may be
evident. Treatment is symptomatic.
SPASMODIC CROUP
It is commonly seen in 1-3 years of age. The etiology of
spasmodic croup is controversial and both viral and
allergic mechanisms have been postulated. It occurs most
frequently in the evening or night-time, and maybe
preceded by mild to moderate coryza and hoarseness.
Patient is usually afebrile. The child awakens with
characteristic barking, metallic cough and respiratory
distress. Symptoms diminish within several hours and

such episodes often recur several times.
BIBLIOGRAPHY
1. Bjornson CL, Klassen TP, Williamson J, et al. A randomized trial of a single dose of oral dexamethasone for
mild croup. N Engl J Med 2004;351:1306-13.
2. Knutson D, Aring A. Viral Croup. Am Fam Physician
2004; 69:535-40, 541-2.
3. Kristjansson S, Berg-Kelly K, Winso E. Inhalation of
racemic adrenaline in the treatment of mild and
moderately severe croup: clinical symptom score
and oxygen saturation measurements for evaluation
of treatment effects. Acta Paediatr 1994;88:1156.
4. Roni Grad: Acute infections producing upper airway
obstruction. In Kendigs disorders of the respiratory tract
in children. WB Saunders Company, 1998.
12.7 Pneumonia in Children

Pneumonia in children is a major cause of concern in the
developing countries, because one-third of hospital
outpatients comprise acute respiratory infections and
nearly 30 percent of them are being admitted to the
hospitals for pneumonia. Pneumonia is the leading cause
of death in under-five, in developing countries. In any
hospital about 90 percent of death in respiratory illnesses
are due to pneumonia and its complications. Most often,
the exact etiological diagnosis is difficult to establish.
Definition
Pneumonia: It is an inflammatory process, involving the
lung parenchyma.
usually manifest with or after the onset of measles.

Radiologically, it is seen as peribronchial thickening,
usually bilateral and often extensive.
Interstitial pneumonia: It is characterized pathologically
by massive proliferation and desquamation of alveolar
cells and thickening of alveolar walls. Chest skiagram
may reveal a diffuse, hazy, ground glass appearance,
usually at the lung bases, with poorly defined hilar
densities.
Persistent pneumonia: It is defined as persistence of
symptoms and roentgenographic abnormalities of more
than one month.
Bronchopneumonia: It is primarily a spreading inflammation of the terminal bronchioles and their related
alveoli.
Recurrent pneumonia: It is defined as two episodes of

pneumonia in one year, or more than three episodes at
any time with radiographic clearance between two
episodes of illness.
Lobar pneumonia (consolidation): It is a pathological state

of the lung, where the alveolar air has been replaced by
cellular exudate and transudate.
Etiology
Pneumonitis: It is a localized inflammation of the lung

parenchyma due to noninfectious causes.
Postmeasles bronchopneumonia: It is a mixed pneumonia
involving the alveoli, supportive tissue and bronchioles,
The cause of pneumonia depends on age, immune status,

presence of underlying chronic lung disease, exposure
history and the clinical setting. Certain infectious agents
are more common at a particular age. The causative
agents of pneumonia in children according to age are

TABLE 12.7.1: Pneumoniapathogens in various
age groups
Age
Bacteria
Viruses
Neonate
Group B
CMV, Herpes
streptococci,
E. coli, Klebsiella sp.
Listeria M, S. aureus
Chlamydia
13 months
S. pneumoniae,
S. aureus,
H. influenzae
Chlamydia
4 months
5 years
S. pneumoniae, RSV,
S. aureus,
Adenovirus,
H. influenzae,
Influenza
Group A
Streptococcus,
Klebsiella,
Pseudomonas sp/
M. tuberculosis
Over 5 years S. pneumoniae,

S. aureus,
H. influenzae,
M. tuberculosis
CMV, RSV,
Influenza,
Parainfluenza
Influenza,
Varicella
Others
Mycoplasma
579
of the lungs. There will be gross alteration in the properties

of the normal lung secretions. They also inhibit the
phagocytosis by the alveolar macrophages. The normal
bacterial flora in the respiratory tract is modified, which
disrupts the normal epithelial layer of the respiratory tract.
Thus, the bacteria and other organisms invade the
respiratory tract and produce pneumonic process.
Microorganisms gain access to the lung by hematogenous
dissemination or local spread descending through the
respiratory bronchial tree. Lobar pneumonia occurs when
there is a reduction in the defense mechanisms or due to
the pathogenicity of the microorganism like S. pneumoniae,
Klebsiella and Staphylococcus.
Clinical Features
Mycoplasma,
Legionella sp.
M. catarrhalis
S. pneumoniae, H. influenzae and Staphylococcus are the

pyogenic bacteria that most commonly cause pneumonia
in children. Mycoplasma pneumoniae and Chlamydia
pneumoniae are the most common causes of atypical
pneumonia in children. Atypical pneumonia is also called
as walking pneumonia. In contrast to children with
pyogenic bacterial pneumonia, children with pneumonia
caused by these organisms are often older than 5 years
of age and the disease onset is gradual. The salient
differentiating features between typical and atypical
pneumonia are depicted in Table 12.7.2.
Presence of rapid respiration has acceptable sensitivity

for clinical diagnosis of pneumonia. The rapid respiration for diagnosis of pneumonia is defined as respiratory
rate of more than 60 breaths/minute in children below
2 months of age, more than 50 breaths/minute in children
between 2 months and 12 months of age, and more than
40 breaths/minute in children between 1 to 5 years of
age. For diagnosis of pneumonia in the community,
presence of rapid respiration is sufficient. Radiograph
of chest is not required, unless specifically indicated, such
as sick child rapid deterioration, poor response to initial
therapy, suspicion of effusion or pneumothorax or
presence of high-risk factors for pneumonia (Table
12.7.3). Chest indrawing, cyanosis, difficulty in feeding,
indicates the increasing severity of pneumonia.
TABLE 12.7.3: High-risk factors for pneumonia
Congenital anatomical defects:

Airwaycleft palate, tracheoesophageal fistula,
bronchial stenosis.
Upper Gl tractCricopharyngeal incoordination,
gastroesophageal reflux.
Pathogenesis
In children, the pneumonia is invariably preceded by viral
infection. Viral infections disturb the defense mechanism
TABLE 12.7.2: Differentiating features of typical and
atypical pneumonia
Newborn, preterm and small-for-date babies and infants

< 2 months.
Children with immunodeficiency
Cystic fibrosis
Congenital bronchiectasis/ciliary dyskinesia
Iatrogenic factors
Features
Typical
Atypical
Onset
Sudden
Gradual
Gross nutritional disorders, e.g. Grade III and IV undernutrition
Fever
+++
+/
Congestive cardiac failure and nephrosis
Cough
Productive
Dry
Poor muscle tonee.g. poliomyelitis
Symptoms
Pulmonary
Systemic
Chest X-ray
Localized
Diffuse
Chronically ill children in prolonged bed-ridden state,

nosocomial infections.
Trauma, anesthesia and aspiration
580
Neonatal pneumonia is often difficult to diagnose,

since there are some peculiarities which are highlighted
in Table 12.7.4.
Bacterial and viral pneumonia cannot be differentiated without microbiological study. The typical clinical patterns of viral and bacterial pneumonias usually
differ, although the distinction is not always clear for a
given patient. Table 12.7.5 is helpful to identify bacterial
and viral pneumonia.
TABLE 12.7.6: A guide to radiological

diagnosis of pneumonia*
Acute lobar pneumoniaconsider pneumococcal pneumonia

(Fig. 12.7.1)
Right upper lobe pneumoniasuspect aspiration, especially

in neonates and infants
Upper lobe pneumonia with cavitationtuberculosis

(Fig. 12.7.2)
Recurrent right middle lobe pneumonitisconsider partial

bronchial obstruction due to glands and others
Diagnosis
Lower lobe pneumonitischemical pneumonitis
In a previously normal child, presence of cough with

rapid respiration is sufficient to make diagnosis of
pneumonia. The following investigations if available,
may provide more information or clue towards to the
severity of illness.
CBC (complete blood count) to look for evidence of
sepsis.
Multiple small abscessesstaphylococcal/Klebsiella pneumoniae (Fig. 12.7.3)
Severe bilateral interstitial pneumoniavirus (Fig. 12.7.4)
Bilateral interstitial pneumonia with malignancyPneumocystis

carinii
TABLE 12.7.4: Peculiarities of pneumonia in newborn
Absence of cough or fever

Apneic spells and increased incidence of periodic breathing
Grunting is a common feature in neonates
Rapid clinical deterioration, often galloping in nature
Cyanosis
Progressive air hunger

Associated septicemia with progressive abdominal distention,
altered sensorium, and bleeding tendency
Bronchopneumonia is more common than lobar pneumonia
High mortality rate in spite of therapy
TABLE 12.7.5: Clinical differentiation of pneumonia

Feature
Bacterial
Viral
Onset
Epidemic pattern
Course
Temperature
Toxemia
Associated URTI
Auscultation
Crackles
Wheeze
Radiological
Abrupt
Progressive
+++
+++
++
Gradual
+
Self-limiting
+ /
+ (Infants)
+
++
+/
Confluent infiltrates
(Consolidation)
+/
++
Diffuse infiltrates in
perihilar areas
+ (RSV
Infection)
Hyperinflation
+/
Pleural involvement
Pneumatocele
+
+
*The X-ray changes often lag behind clinical findings, both at the
onset of pneumonia and at the time of resolution
WBC count of more than 15,000 cells/mm3 with

polymorpholeukocytosis or count less than 5000/
mm3 or febrile neutopenia (absolute neutrophil count
< 500/mm3) are bad prognostic indicators.
Nasopharyngeal aspirate for viral antigene.g. CMV,
Adenovirus, etc.
M. pneumoniae may be suspected if cold agglutinins
are present in peripheral blood and confirmed by
detecting presence of Mycoplasmaspecific IgG or
IgM in serum.
The diagnosis of M. tuberculosis may be considered
with tuberculin skin test, smear and culture of sputum
or gastric juice for tuberculosis.
Roentgenographic picture (Table 12.7.6).
Invasive procedures, such as bronchoscopy and
bronchoalveolar lavage, lung aspiration, or lung biopsy,
may be necessary to obtain culture specimens. These
invasive procedures are not used in typical pneumonias,
but they may be employed in special instances, such as
pneumonia in the immunocompromised host or when
the clinical picture is unusual.
Infants
Bronchiolitis
Wheeze associated lower respiratory tract infection
(WALRTI)
Congestive heart failure
581
Figure 12.7.1: Lobar consolidation right upper lobe

Figure 12.7.4: Interstitial pneumonia
Figure 12.7.2: Cavitatory tuberculosis
In older children
Acute exacerbation of bronchiectasis
Endobronchial TB and secondary bacterial pneumonia
Lower lobe pneumonia may present as acute
abdomen
Accompanying ileus with absent bowel sounds, may
mimic acute appendicitis
Upper lobe pneumonia can present as meningismus
(can be differentiated from meningitis by lumbar
puncture).
Treatment of Pneumonia
It is important to decide if the child can be managed as
outpatient or to be hospitalized. Indication for hospitalization are listed in Table 12.7.7.
Antimicrobials in Pneumonia
Figure 12.7.3: Multiple lung cysts
Aspiration of foreign body

Sequestered lobe
Atelectasis
Pulmonary abscess
Choice of antimicrobials depends on causative organisms. In clinical practice often causative organisms are
presumed based on the following:
i. Age of the child and epidemiology
ii. Clinical and radiological features
iii. Extrapulmonary manifestations
iv. Prevailing drug sensitivity pattern in the community/hospital.
Outpatient Management
If the child is not sick and is suggestive of viral etiology
withhold antibiotics, give only supportive care and
follow-up the child. If clinical features are suggestive of
582

TABLE 12.7.7: Indication for hospitalization
Features of Hypoxia (Restlessness, anxiety, cyanosis,

Inability to sleep, talk, walk, unconsciousness, seizures)
Reduced urine output/dehydrated
Vomiting/poor intake
No improvement/Progressive deterioration when on

treatment as outpatient
Presence of high-risk factors
atypical pneumonia start the child on macrolides. In

other children with suspected pneumonia they can be
either started with oral cotrimoxazole or amoxycillin or
cephalexin. Normal oral diet is to be advised.
Warning signs need to be explained to the parents.
The child should be reassessed after 48 hours or any time
in between if there is deterioration in the condition of
the child.
On follow-up after 48 hours, if there is sense of wellbeing and improvement in clinical status of the child
continue with the same management. If the condition
remains same or had deteriorated, reassess the child,
revise your diagnosis and look for associated complications. Then consider introducing/changing antibiotics,
if need be, hospitalize the child for further management.
Inpatient Management
Consists of specific and supportive care (Table 12.7.8).
In infants below 2 months of age consider and treat
them as sepsis. The antibiotics of choice would be
ampicillin or 3rd generation cephalosporins with
aminoglycoside. If there is a suspicion of meningitis start
on meningitic dose of antibiotics.
In children more than 2 months of age treat with
parental amoxicillin/cefuroxime/third generation cephalosporins with or without aminoglycoside. These
children should be assessed at least twice a day and if
there is rapid deterioration a chest X-ray should be done
to look for evidence of staphylococcal infection

(pneumatoceles), if present, the antibiotics should be
changed to cloxacillin.
If there are indication of specific etiological agents
like chlamydia or mycoplasma infection, then macrolides
such as erythromycin or clarithromycin may be given.
Supportive care include treatment of fever with
paracetamol (1015 mg/kg/dose) every 4 to 6 hourly.
In presence of tachypnea, cyanosis or chest
indrawing, oxygen should be administered by nasal
catheter, nasopharyngeal catheter, oxygen hood or
oxygen mask.
Intravenous fluids should be administered if child is
not drinking milk/water or is dehydrated. Oral feeds
should be started as soon as tachypnea and chest
retractions are under control. Duration of antibiotic
therapy depends on the causative organism and clinical
condition of the patient as depicted in Table 12.7.9.
TABLE 12.7.9: Duration of treatment
Pneumonia (OP)
Pneumonia (IP)
Atypical organisms
Staphalococcal pneumonia
57 days
1014 days
10 days
34 weeks
Complications of pneumonia are empyema, lung

abscess, pyopneumothorax, osteomyelitis, pericardial
effusion, and sepsis. Early recognition, prompt therapy
and a good follow-up would decrease the incidence of
complications.
The prognosis of pneumonia in children is based on
the following factors. Younger the age higher the
mortality. Poor nutritional status likePEM Grade III
and IV, extensive bilateral bronchopneumonia, associated diseases and conditions like cystic fibrosis and
immunodeficiency state, malignancy and associated
complications such as respiratory failure and congestive
cardiac failure act as poor prognostic factor.
BIBLIOGRAPHY
TABLE 12.7.8: Inpatient management pneumonia

Specific
Supportive
Antimicrobial therapy
Hydration
Nutrition
Oxygen
Antipyretics
Physiotherapy
Adjuvants
1. Charles G Prober. Pneumonia. In Richard EB, Cictor

(Eds): Nelson Textbook of Pediatrics (15th edn). WB
Saunders Co., 1996.
2. Edwin LK , Chernick V. Disorders of the respiratory tract
in children (5th edn). WB Saunder Co., 1994.
3. Ellen R Wald. Recurrent and nonresolving pneumonia
in children. Seminars in Respiratory infections 1993;8:46
58.
4. Govan A, Macfarlane PS, Callander R (Eds): Pathology
Illustrated (2nd edn) Churchill Livingstone, 1986.

5. Howard E, James JL, Homrighausen J. Recurrent
pneumonias in children and its relationship to bronchial
hyperreactivity. Pediatrics 1982;70:698707.
6. Hugh L Moffet. Pneumonia syndromes: Pediatr infec dis
102 JB Lippincott Co, 1975.
7. Kercsmar CM. The respiratory system. In Richard EB,
Kliegman RM (Eds): Nelson Essentials of Pediatrics (3rd
edn). WB Saunders Co., 1998.
583
8. Ralph JW, Starkey DD, George C Ray, Cincent CK,

Vincent CK. Infection in Children, Harper and Row
Publishers, 1982.
9. Robbin SL, Cotran RS, Kumar V. Pathologic Basis of
Disease (3rd edn). WB Saunders, 1983;706-8.
10. Schreiner A, SoIVerg C. Lower Respiratory Infections.
Schering Corporation USA, 1982.
11. Shohet FL, Lieberman JM. Bacterial pneumonia in children, Seminars in Ped. Infectious diseases 1998;9:191-8.
12.8 Acute Bronchiolitis

Uday B Nadkarni
INTRODUCTION
Bronchiolitis is an acute infection of small airways.
Although many pathogens can cause bronchiolitis, more
than 50 percent cases are due to respiratory syncytial
virus (RSV). Two subtypes ( A and B) of this virus exist
subtype A is the more common cause of bronchiolitis
and is associated with more severe disease. It has been
estimated that about 600000 infants and young children
die from RSV annually, and if bacterial coinfections are
included this number may approach 1,000,000 deaths
annually. Thus in developing countries where RSV is the
main cause of lower respiratory tract infections in the
community, its prevention may result in significant
reductions in RSV related morbidity and mortality.
Definition
Bronchiolitis can be defined as first episode of expiratory
wheeze of acute onset in a child less than 2 years of age
who has signs of viral respiratory illness like coryza, otitis
media or fever with or without indications of respiratory
distresses, pneumonia and atopy. It occurs in both
epidemic as well as sporadic forms.
Factors that increase the visit of severe or fatal RSV
infection are:
1. Complicated congenital heart disease (including
pulmonary hypertension)
2. Age < 6 weeks
3. Concomitant pulmonary disease (e.g. BPD)
4. Prematurity
5. Immunodeficiency states.
Epidemiology
In our country, epidemics occur in winter and monsoon
and may last for 1 to 5 months. They have also been
reported in newborn nurseries. Parental smoking
increases the risk of bronchiolitis. Peak incidence of the
disease occurs before 6 months of age in 70 to 80 percent
of the cases, peaking between 3 to 4 months. Both sexes
are equally affected and severe cases may require
hospitalization.
Etiology
Respiratory syncytial virus (RSV) is the causative agent
in 50 to 60 percent of the cases, other viruses responsible
are Parainfluenza I, II and III, Adenoviruses, Influenza
virus and Rhinovirus. At times, Mycoplasma and
Chlamydia have also been implicated.
Pathology
Acute bronchiolitis is characterized by bronchiolar
obstruction due to edema and accumulation of mucus
and cellular debris and by invasion of the smaller
bronchiolar radicles by virus. There is necrosis of the
respiratory epithelium in the bronchioles and is
associated with peribronchiolar lymphocytic infiltrations.
Submucosa may be edematous but collagen and elastic
tissues in bronchioles are usually preserved. In most of
the cases, the alveoli escape damage however, occasionally, an increased cellularity of subepithelial tissues
of the bronchus extend to the alveoli also.
Resistance in the small air passages is increased
during the inspiratory and expiratory phases. However,
584

Investigations
WBC count is usually normal. Neutrophilic leukocytosis
may indicate secondary bacterial invasion. Blood gases
reveal hypoxia and hypercarbia. Serum electrolyte
estimation may show hyponatremia. X-ray of the chest,
AP and lateral view may show marked generalized
emphysema, patchy consolidation, atelectasis and
abnormal linear shadows, due to thickening of the
bronchioles. Virus may be demonstrated in nasopharyngeal secretions by antigen detection (by ELISA or PCR)
or by culture.
Figure 12.8.1: Pathophysiology
since the radius of an airway is smaller during expiration,

the resultant ball valve respiratory obstruction leads to
air trapping and over inflation. Atelectasis may occur if
obstruction becomes complete and trapped air is
absorbed. Impaired ventilation/perfusion leads to
hypoxia (Fig. 12.8.1).
Asthma: This condition presents with repeated episodes

of sudden onset wheezing with or without preceding
infection and family history of atopy or asthma.
Postbronchodilator reversibility of an attack confirms the
diagnosis.
Other entities are foreign body, congestive cardiac failure,
pertussis, cystic fibrosis and bacterial pneumonias.
Management
Clinical Features
Most affected infants present with a history of exposure
to older children or adults with minor respiratory
diseases within a week, preceding the onset of illness. It
starts with mild upper respiratory tract infection with
serous nasal discharge, cough and sneezing, accompanied by diminished feeding and fever of 38.5 to 39C.
There is a gradual increase in respiratory distress,
accompanied by paroxysmal wheezy cough, dyspnea
and irritability. Feeding is also affected due to rapid
respiratory rate. Apnea early in illness with cyanosis is
seen in 10 to 20 percent of cases.
Examination reveals a tachypneic infant often in
extreme distress. Respiratory rate ranges between 60 to
80 per minute, severe air hunger and cyanosis may occur.
The alae nasi flare and use of accessory muscles of
respiration result in intercostals and subcostal retractions,
which are shallow because of persistent distention of the
lungs by the trapped air. Liver and spleen, are palpable
below the costal margin due to overinflated lungs. Fine
crackles may be heard in early expiration. Wheezes are
usually audible in most severe cases, and breath sounds
are barely audible when bronchiolar obstruction is almost
complete.
An initial assessment of the disease severity is critical.

Hospitalize babies with moderate to severe bronchiolitis
having retractions, apnea, poor feeding, cyanosis, toxic
appearance, SaO2 < 91 percent and PR > 70/minute.
Monitoring of pulse oximetry is the best predictor of
severity.
General Measures
Treatment of bronchiolitis is mainly supportive with
close observation and minimal handling. Infants with
bronchiolitis are mildly dehydrated due to decreased
fluid intake and increased losses because of fever and
tachypnea. Intravenous fluids are given as two-thirds of
maintenance requirement.
Oxygen
It should be warm and humidified having concentration
of 30 to 40 percent. It is delivered by head box, tent, nasal
prongs, nasopharyngeal catheter or facemask taking care
that SaO2 is maintained at 95 percent. As RSV is shed in
respiratory secretions and cross-infection occurs in 15 to
30 percent cases, cohorting and handwashing by health
professionals and parents is of paramount importance.

Bronchodilators
Wheezing and rhonchi are usually present and it is
difficult to differentiate first episode of asthma from
bronchiolitis. Hence, a trial of bronchodilator salbutamol with or without ipratropium should be given. If there
is improvement, bronchodilators may be continued
round the clock, otherwise they should be stopped. Some
studies have shown modest clinical improvement as an
improvement in pulmonary function with beta agonist
therapy especially with high dose salbutamol 0.5 mg/
kg. Some researchers evaluated efficacy of nebulised
epinephrine versus salbutamol. They found that
nebulised epinephrine superior to salbutamol as regards
improvement in clinical symptoms and length of hospital
stay. Possible explanation is mucosal edema in bronchiolitis may be diminished by alpha-receptor stimulation
causing construction of precapillary arterioles reducing
microvascular leakage.
Steroids
Use of steroids is not beneficial. In critically ill, hypoxic
and apneic babies, role of steroids is controversial and
should not be used. Even combination therapy of
salbutamol and systemic steroids did not show significant improvement in clinical course.
585
b. Infants hospitalized with RSV and lower respiratory

tract disease who are severely ill.
c. Infants hospitalized with lower respiratory tract
disease that is not initially severe but may be at
increased risk of progressing to complicated course.
d. Mechanically ventilated infants may be benefited.
Palivizumab
A humanized anti-RSV monoclonal antibody (palivizumab) has been developed, which is 95 percent human
and 5 percent mouse in composition. It is directed at an
epitope on the F protein, which is expressed on the
surface of the virus envelope. This monoclonal antibody
is estimated to be 50 to 100 times more potent against
RSV than the polyclonal RSV-IGIV allowing the dose to
be reduced 50-fold.
A large multi-center trial was conducted in 139
centers in North America and UK to test the efficacy of
palivizumab when 15 mg/kg dose was administered IM
monthly for 5 months. There was 55 percent reduction
in hospitalization rate for RSV-related illness. The
decrease was most pronounced in infants with a history
of prematurity without CLD. There was also a substantial
decrease in number of hospital days, the number of days
that supplemental oxygen was required and in the
number of admissions to the intensive care unit.
Antibiotics
Follow-up
Though acute bronchiolitis is viral in origin, dual

infections can coexist. In the presence of fever, clinical
deterioration, high WBC count, raised CRP and
infiltrations on chest X-ray, antibiotics are indicated.
It is essential to follow-up patients of bronchiolitis for

hyper-reactive airway disease/asthma. Approximately,
33 to 50 percent of all patients with bronchiolitis, develop
bronchial asthma and the incidence is higher, if there is
family history of asthma or other atopic disorders. The
common disease of infancy still merits our close attention
and prompt treatment, as this would go a long way in
preventing hyper-reactive airway disease in later life.
Ribavirin
Studies have shown effective in reducing severity of the
disease and shortening the hospital stay, provided they
are given early in the course of the disease. It should be
given to patients with assisted ventilation. It is very useful
in infants < 2 months and babies with congenital heart
disease, pulmonary hypertension, hyaline membrane
disease and bronchopulmonary dysplasia. It is administered as a mist for 12 to 20 hours for 3 to 5 days with a
small particle aerosol generator (SPAG).
The American Academy of Pediatrics (AAP) recommends the use of Ribavirin suggesting that it will be
reserved for:
a. Infants at high-risk for severe or complicated RSV
infection.
BIBLIOGRAPHY
1.
Behram RE, Kliegman RM, Arvin AM, Orenstein DM.

Acute bronchiolitis. In: Nelsons Textbook of Pediatrics
(15th edn). WB Saunders:Philadelphia 1996;12113.
2. Bertrand P, Arinabar et al. Efficacy of nebulized
epinephrine versus salbutamol in hospitalized infants
with bronchiolitis. Pediatr Pulmonol 2001;31(4):2848.
3. Canny GJ. Acute Bronchiolitis: Recent advances in
treatment. Indian J Pediatr 1996;634551.
4. First Annula Saul Krugman symposium on pediatric viral
infection: Viral respiratory diseases in children.
Hemming V (Ed). J Pediatr 1994;124:2934.
586
5. Groothius JR, Simoes EAF et al. Prophylactic administration of respiratory syncytial virus immune globulin
to high-risk infants and younger children. N Engl J Med
1993;329:152430.
6. Impact-RSV study group. Palivizumab, a humanized
respiratory syncytial virus monoclonal antibody, reduces
hospitalization from respiratory syncytial virus infection
in high-risk infants. Pediatrics 1998;102:5317.
7. Johnson S, Oliver C et al. Development of a humanized
monoclonal antibody (MEDI-493) with potent in vitro and
in vivo activity against respiratory syncytial virus. J Infect
Dis 1997;176:121524.
8.
Kending EL, Chernick V, Wohl ME. Acute bronchiolitis:

In Disorders of Respiratory Tract in Children, (5th edn).
WB Saunders: Philadelphia 1990;36070.
9. La via WV, Marks M, Stutman H. Respiratory Syncytial
Virus Puzzle: Clinical features, Pathophysiology,
Treatment and Prevention. J Pediatr 1992;121:50310.
10. MsConnochie KM: BronchiolitisWhat is the name. Am
J Dis Child 1983;137:113.
11. Wang EEL, Milner R, Allen V. Treatment of Mild Bronchiolitis: Afactorial randomized trial. Arch Dis Child
1992;67:289-93.
12.9 Empyema
have toxemia, grunting, reduced respiratory movements
with stony dullness and absence of breath sounds on one
side of chest. Urgent chest radiograph will confirm the
diagnosis.
Empyema is the serious complication of bacterial

pneumonia commonly observed in infancy and preschool
age group. Empyema is the term used for the collection of
purulent fluid in the pleural cavity. This has to be
differentiated from hydrothorax, which is a noninflammatory fluid collection occurring in conditions such
as nephrotic syndrome and other hypoalbuminemic states.
Tuberculous pleural effusion is the other condition which
needs differentiation, but generally in a preschool child
with fever and respiratory distress pleural fluid indicates
empyema unless proved otherwise.
Stages of Empyema Thoracis: Exudative phase, i.e. stage of

parapneumonic effusion is usually present for 1 to 3 days,
followed by fibrinopurulent phase, i.e. stage of empyema
thoracis, which may last for 4 to 14 days. The organizing
phase may occur beyond 14 days, which is commonly
termed as trapped lung, a complication of empyema
thoracis.
Etiology
Investigations
Empyema is a complication of pnemonia caused by

staphylococci and less commonly with pneumococci and
H. influenzae. Empyema secondary to trauma or
mediastinitis is very rare.
Uniformly dense opacity with obliteration of costopherenic angle on one side of chest is the usual radiological sign (Fig. 12.9.1). Mediastinal shift may or may
not be present. Some times pneumatocele may be present.
Often pneumothorax may be associated and the density
will be an intermediate one between air and fluid. In
pneumonia varying degrees of density with ill-defined
borders are seen with preservation of costophrenic
angles. Radiology cannot differentiate the nature of fluid
and hence needle aspiration is mandatory to ascertain
the nature of fluid. Needle thoracentesis done at the level
of seventh intercostal space in the midaxillary line.
Aspiration of pus confirms the diagnosis of empyema,
which necessitates intercostal tube drainage. In case of
tubeculous effusion needle aspiration of fluid as much
as possible is enough. Sometimes macroscopic appearance does not contribute to probable diagnosis where
other laboratory tests to analyse the pleural fluid will be
useful (Table 12.9.1). Gram staining and AFB staining
are simple and useful bedside investigations to prove
the etiology and to decide about the choice of antibiotics.
Pathology
There are three stages in the evolution of empyema. In
the exudative stage, fluid with relatively low cell amount
and viscosity collects in the pleural space. This fluid is
simple parapneumonic effusion and has a normal pH
and glucose. In the fibrinopurulent stage, neutrophils and
fibrin accumulates, effusion becomes purulent and
viscous, pleural fluid pH and glucose falls and LDH rises.
The term empyema is used at this stage. During the
organizing stage fibroblast activity on both pleural
surfaces produces thickened pleura.
Clinical Features
Clinical diagnosis of empyema is entertained in any child
who presents with high grade fever, tachypnea and
severe respiratory distress. On examination child will
587
is a common complication observed during treatment.

If the pus is not drained immediately, it may cause
adhesion to form a thick envelope restricting lung
expansion.
Treatment
Figure 12.9.1: Empyema right lunglarge collection of pleural

fluid on the right hemithorax with shift of mediastinum towards
left
Blood counts and cultures of blood and pleural fluid are

very useful.
Complications
Empyema may be associated with other septic complications such as septicemia, meningitis or osteomyelitis.
Untreated empyema may dissect through chest wall
resulting in empyema necessitans. Bronchopleural fistula
1. Empyema is a medical emergency. Initial treatment

includes oxygen, IV fluid and antipyretics.
2. Intercostal tube drainage (closed tube throw) should
be done as soon as the child is hospitalized without
any undue delay, as this is the single most important
step that will bring relief. Tube with largest possible
size should be used and connected to under water
seal drainage.
3. Choice of antibiotics is based on suspected microorganisms. If staphylococcal infection is suspected,
Cloxacillin, Vancomycin are effective drugs. Pneumococcal infection responds well to penicillin or
ceftriaxone and H. influenzae responds to cefuroxime,
ceftriaxone or cefotaxime. When organism is not
identifiable Ampicillin with Cloxacillin or Cloxacillin
with third generation cephalosporin is the right
combination. When anaerobic organisms are suspected metronidazole should be added. Systemic
antibiotic therapy is required for at least two to three
weeks.
TABLE 12.9.1: Pleural fluid analysis

Test
Transudate
(Hydrothorax)
Exudate
(TB effusion)
Exudate
(Empyema)
Physical appearance
Clear
Straw colored
Turbicf yellow
Microscopy
No cells
Lymphocytes
Pus cells
Pleural F Protein
< 3 gm/dl
> 3 gm/dl
> 3 gm/dl
Pleural F Protein/Serum Protein
< 0.5
> 0.5
> 0.5
Pleural FLDH/Serum LDH
< 0.6
> 0.6
> 0.6
Pleural F pH
> 7.2
< 7.3
< 7.2
Pleural F Glucose
> 40 mg/dl
< 40 mg/dl
< 40 mg/dl
Pleural F-Pleural Fluid
TABLE 12.9.2: Modified light classification

Class I Parapneumonic Effusion
a. CXRLateral decubitus view < 10 mm fluid
b. CXRLateral decubitus view > 10 mm fluid
pH > 7.2, glucose > 40, Gram stain-negative
pH < 7.2, glucose < 40, Gram stain-positive
Class II Empyema (frank pus)
a. Loculation
b. Multiple Loculation/Pleural peel
Antibiotics only
Antibiotics + Thoracentesis
Antibiotics + Tube thoracostomy
Antibiotics
+ Tube thoracostomy
+ Thrombolytics (intrapleural) or
Debridement (VATS) or decortication
588
4. Nutrition and physiotherapy are useful adjuncts.

Surgical management (decortications) is needed
when fibrinous envelope restricts expansion of
lung.
5. Video assisted thoracoscpic (VATS) adhesiolysis and
pleural debridement is nowadays recommended for
empyema that does not resolve with closed tube

thoracostomy.
6. Modified light classification is a method by which
various stages of empyema are identified. This will help
to make appropriate therapeutic choices such as needle
thoracentesis or tube thoracostomy (Table 12.9.2).
12.10 Bronchiectasis
A Balachandran, Swati Y Bhave, NC Gowrishankar
Bronchiectasis is the third common chronic respiratory
disease next only to asthma and tuberculosis. It is an
important cause for chronic cough in children, but often
present with complications such as pneumonia. It is a
disease characterized by permanent dilation of the
bronchi caused by previous illness with accumulation of
exudative material resulting in chronic cough with foul
smelling sputum production.
Etiology
Causes of bronchiectasis are traditionally classified as
congenital or acquired. More often it is due to wide range
of acquired condition causing obstruction, infection or
both.
Despite multiple causes bacterial and viral pneumonia
are the common causes. Other causes are preventable
infections like measles, pertussis, undetected or untreated
foreign body aspiration, chronic atelectasis due to various
causes, aspirative pathology such as gastroesophageal
reflux and immunodeficiency syndromes including HIV
infection. Due to various reasons, sinusitis is a common
association. Though cystic fibrosis is the leading cause of
bronchiectasis in the west, it is not that common in our
country.
Congenital causes are rare, which includes Kartageners syndrome (triad of bronchiectasis, sinusitis and situs
inversus) and William Campbell syndrome (absence of
bronchial cartilage and ring).
Pathology
Except in cystic fibrosis, bronchiectasis due to other causes
generally follows segmental distribution, commonly
involved segments in the order of frequency are left lower
lobe segment, right middle lobe and lingular segment of
the left upper lobe. Right lower lobe is commonly
involved in foreign body aspiration.
Morphologically two types are described, cylindrical

and secular. It is labeled as cylindrical when dilatation is
reversible.
Clinical Features
Common presentation is chronic cough is with large
quantity of foul smelling sputum production more in the
morning hours. Recurrent pneumonia, hemoptysis,
wheezing episodes, clubbing and failure to thrive are
other features. Systemic examination may show coarse
crepitations over the affected areas. When sputum is
collected in a conical flask it forms three layer: thin and
frothy syperficial layer, thick and mucopurulent intermediate layer, opaque and purulent layer with Dietrichs
plugs at the bottom. Presence of foul smelling sputum,
hallitosis, clubbing and failure to thrive differentiate this
from asthma. However, this diagnosis must be confirmed
through imaging studies. X-ray chest, high resolution CT
scan and bronchography are more useful. Fiberoptic
bronchoscopy is also useful for visualizing the airway
directly and to collect the secretions from individual lobes.
Investigations
X-ray chest: It is not diagnostic, but following features are
suggestive.
1. Increased bronchovascular markings
2. Loss of lung volume indicated by crowding of vascular
marking (Fig. 12.10.1)
3. Honeycomb pattern
4. Linear streaks (rail road tracks)
5. Cystic lesions with air fluid level.
CT scan: High resolution CT scan has almost replaced
bronchography. Following are the findings diagnostic of
bronchiectasis
1. Air fluid level in the distorted bronchi
Figure 12.10.1: X-ray chest showing bilateral bronchiectasis
2. Linear airway or cluster of cysts

3. Distended bronchi in the periphery of lung
4. Bronchial wall thickening due to peribronchial
fibrosis.
Bronchography: Though a gold standard test, it is less often
performed now because of the risk involved. But it is still
used in selected patients where surgical option is
contemplated and there is a plan to spare few segments
inside an affected lobe. To identify the underlying cause,
other investigations such as mantoux test, sweat chloride
estimation, immunoglobulin assay, screening for HIV and
skin test for aspergillosis are useful.
Management
Following are the aims of management:
1. To provide the patient symptom-free days and good
quality of life. Chronic cough, foul smelling sputum
and hallitosis adversely affect the social life.
2. To reduce further damage to lung and to prevent
complications.
3. To identify whether surgical option will be useful.
589
Primary treatment of bronchiectasis is medical.

Removal of excessive secretions by chest physiotherapy,
treatment of intercurrent infection and good nutrition are
important components of medical management.
Antibiotic therapy is definitely indicated only for acute
infection which is evident by worsening of cough, yellow
sputum production, fever and malaise. Antibiotics should
be directed against organisms such as H. influenzae, S.
pneumoniae, S. aureus, Pseudomonas aeruginosa and Proteus
vulgaris.
Chest percussions and postural drainage are effective
in facilitating clearance of secretions. Postural drainage is
a method by which the mucociliary escalator is enhanced
by gravity, by placing the patient in various positions
where the diseased segment is kept in a higher level. Chest
physiotherapy is done 3 to 4 times a day, each session
lasting for 10 minutes and the duration not exceeding 30
minutes in total.
Surgical Management: Full extent of the disease is carefully
assessed before proceeding with a surgical option. Nature
of surgery is segmental or lobar resection and less
commonly pneumonectomy. Indication for surgical
treatment are:
1. Impairment of normal social life in patient with
localized bronchiectasis despite medical treatment.
2. Localized disease associated with growth delay.
3. Presence of life-threatening hemorrhage from a
demonstrable source.
4. Obstruction with suppurative lesion where the foreign
body eludes bronchoscopic removal.
5. Demonstrable site of recurrent pneumonia.
Contraindication for surgery are extensive bilateral
lesion associated diffuse bronchitis, emphysema or
pulmonary or cardiac insufficiency.
To conclude bronchiectasis is the end result of many
disease processes affecting the lung parenchyma. Majority
of them can lead normal lives, if they are put on a
treatment plan to avoid progressive pulmonary deterioration. If the plan fails, surgical treatment should be
considered.
12.11 Lung Abscess

Lung abscess is a subacute suppurative disease of lung
resulting in the formation of cavity containing purulent
material.
Etiology
Usually occurs in the setting of chronic and persistent
aspiration. Most common predisposing conditions are
590
seizure disorder, unconscious state, poor oral hygiene,

dental procedures and intubation. It can be a complication of poorly managed pneumonia. Staph. aureus, H.
influenzae, S. viridans and S. pneumoniae commonly affect
the previously normal host and anaerobic organisms and
Klebsiella are considered in immune compromised.
Posterior segment of the upper lobes and superior
segments of the lower lobes are affected during
aspiration, in recumbent position.
When aspiration occurs in erect position, basilar
segments of the lower lobes are affected.
Clinical Features
Onset is often insidious with high-grade fever with
cough, chest pain, dyspnea, sputum production fetid
breath and hemoptysis. Copius amount of foul smelling,
blood stained purulent sputum is characteristic.
However, lack of putrid sputum does not exclude the
diagnosis. A careful history will often reveal an episode
of aspiration. Sometimes, aspiration of a foreign body
goes unnoticed until after removal of foreign body.
Physical examination may show dullness of percussion,
decreased breath sounds and egophony.
Laboratory Findings
Total WBC count may be elevated with neutrophilic
predominance. Chest radiograph may show one or more
thick walled cavities (Fig. 12.11.1). Air fluid level may
be present. Hydatid cyst, congenital cyst and loculated
empyema may show similar picture in the radiography.
CT scan is useful for localization and for differentiation
from other pulmonary masses. Bronchoscopy is helpful
in assessing bronchial obstruction caused up by a foreign
body and also for aspiration of pus. Gram staining and
microscopy of the sputum may reveal the presence of
numerous polymorphs with microorganism and culture
will identify the organism.
Treatment
Broad spectrum parenteral antibiotics covering Staph.
aureus, H. influenzae and anaerobes are used for a period
of 3 to 4 weeks. Along with antibiotics, nutritional
supplements and postural drainage with physiotherapy
are very useful. Penicillin G, Chloramphenicol,
Amoxicillin-Clavulanate, Metronidazole, TicarcillinClavulanate, 3rd or 4th generation Cephalosporin and
Carbapenam are antibiotics that are used in combination.
Drainage procedure includes percussion and positioning
Figure 12.11.1: Lung abscess right upper lobe
to increase drainage through airway. Lung abscess often

will rupture spontaneously into the airway. Some
advocate catheter drainage of abscess. Rarely open
drainage is performed with resection.
Prevention
This involves prevention or minimizing aspiration in the
presence of predisposing factors.
BIBLIOGRAPHY
1. Balachandran A, Shivbalan S, Thangavelu S,
Vijayasekaran D, Subramanyam L. Empyema thoracis. Indian J Pediatr 2003;70:803-6.
2. David M Orenstein. Diseases of the pleura. In Richard E
Behrmann, Robert M Leigman, Hal B Jenson (Eds):
Nelsons Textbook of Pediatrics (16th edn). Philadelphia,
WB Saunders 1999.
3. DeLuca A, Kurland G. Empyema in children: Epidemiology, diagnosis and management. Seminars in
Pediatric Infectious Diseases 1995;9:205-11.
4. Fisher MC. Lung abscess and other anaerobic pulmonary
infections. In: Feign RD (Ed): Seminar on Ped. Infectious
diseases 1998;9(3):199-204.
5. Robert C Stern. Bronchiectasis and lung abscess. In
Richard E Behrmann, Robert M Kleigman, Hal B Jenson
(Eds): Nelsons Textbook of Pediatrics (16th edn).
Philadelphia. WB Saunders, 1999;1308-10.
6. Thangavelu S, Vijayasekaran D, Somu N. Bronchiectasis
A respiratory orphan, Essentials of Pediatric Pulmonology, M/s. Siva and Co, II Edn, Chennai 1996.
7. Vijayasekaran D, Subramanyam L. Anaerobic lung
infection. Pediatric Pulmonology update, official bulletin
of Respiratory Chapter of Indian Academy of Pediatrics,
1999;11(3):43-51.
8. Wallace W, Neblett III, Walter M, Morgan III, Tomitta S.
Surgical management of complications of pulmonary
infection. Seminars in Pediatric Infectious Diseases
1995;6:188-200.
591
12.12 Hemoptysis
Vibha Mangal, Neeraj Jain, Vibhu Kwatra
Definition
Hemoptysis is defined as the spitting of blood derived
from the lungs or bronchi as a result of pulmonary or
bronchial hemorrhage. The lungs receive blood from both
the pulmonary and bronchial arterial systems. The lowpressure pulmonary system tends to produce smallvolume hemoptysis, whereas bleeding from the
bronchial system, which is at systemic pressure, tends
to be profuse.
Types of Hemoptysis
Hemoptysis may be frank or spurious.
1. Frank hemoptysis: Expectoration of blood only
2. Spurious hemoptysis: Hemoptysis is present secondary
to upper respiratory tract infection, above the level
of larynx.
3. Pseudohemoptysis: It is due to pigment prodigiosin
produced by the gram-negative organism, Serratia
marcescens.
4. Endemic hemoptysis: Present in infection with
Paragonimus westermani.
The first task is to confirm the presence of blood
followed by differentitation between hemoptysis and
hematemesis (vomitting of blood). Some important clues
for this are given in Table 12.12.1.
Etiology
The common causes of hemoptysis in children are listed
in Table 12.12.2.
DIAGNOSIS
History
History helps to differentiate hemoptysis from hematemesis and pseudohemoptysis, identify the anatomic
site of bleeding, and narrow the differential disgnosis.
Factors such as age, nutrition status, and comorbid
conditions can assist in the diagnosis and management
of hemoptysis. Some of these are listed in Table 12.12.3.
Details of previous episodes of hemoptysis and
diagnostic assessments are helpful.
TABLE 12.12.1: Differentiating features of hemoptysis

and hematemesis
Hemoptysis
Hematemesis
History
Absence of nausea and
vomiting
Lung disease
Asphyxia possible
Presence of nausea and

vomiting
Gastric or hepatic disease
Asphyxia unusual
Sputum examination
Frothy
Liquid or clotted
appearance
Bright red or pink
Laboratory
Alkaline pH
Mixed with macrophages
and neutrophils
Rarely frothy
Coffee ground appearance
Brown to black
Acidic pH
Mixed with food particles
TABLE 12.12.2: Etiology of hemoptysis

1. Infection:
Tracheobronchitis
Pneumonia
Bacterial: Mycobacterium tuberculosis, Staphylococcus aureus, Pseudomonas aeruginosa
Fungal: Aspergillosis
Influenza
Parasitic: Echinococcosis
2. Tracheostomy-related
3. Bronchiectasis
4. Cystic fibrosis
5. Ciliary dyskinesia
6. Trauma
7. Foreign body
8. Congenital heart disease (mainly with pulmonary vascular
obstructive diseases)
9. Pulmonary A V malformations
10. Pulmonary thromboembolism
11. Alveolar hemorrhage syndromes
12. Immunodeficiency
13. Connective tissue disease vasculitis: Goodpastures
syndrome, Wegener granulomatosis
14. Primary pulmonary hemosiderosis: Heiner syndrome
15. Tumors: Bronchial adenoma, metastatic
592

TABLE 12.12.3: Diagnostic clues in hemoptysis: History
Clinical clues
Suggested diagnosis
Anticoagulant use
Mdication effect, coagulation disorder
Dyspnea on exertion, fatigue, orthopnea, paroxysmal

nocturnal dyspnea, frothy pink sputum
Congestive heart failure, left ventricular dysfunction,

mitral valve stenosis
Fever, productive cough
Upper respiratory infection, acute sinus acute bronchitis,

pneumonia, lung abscess
History of chronic lung disease, recurrent lower respiratory

tract infection, cough with copious purulent sputum
Bronchiectasis, lung abscess
HIV, immunosuppression
Neoplasia, tuberculosis
Pleuritic chest pain, calf tenderness
Pulmonary embolism or infarction
Travel history to endemic regions
Tuberculosis, parasites (paragonimiasis, schistosomiasis,

amebiasis, leptospirosis), biologic agents (plague, tularemia,
T2 mycotoxin)
Blood from the lower bronchial tree typically induces

cough, whereas a history of epistaxis or expectoration
without cough would be consistent with an upper
respiratory source but does not exclude a lower tract site.
Try to determine the volume and rate of blood loss. This
can be done by observing as the patient coughs or by the
use of a graduated container. Blood-streaked sputum
deserves the same diagnostic consideration as blood
alone.
A good history will narrow the differential diagnosis and
help focus the physical examination. Examination of the
expectoration may helping to localize the source of
bleeding. The physician should record vital signs,
including pulse oximetry, and document fever, tachycardia, tachypnea, weight changes, and hypoxia.
Constitutional signs such as cachexia and level of patient
distress should be noted. The skin and mucous membranes should be inspected for cyanosis, pallor,
ecchymoses, telangiectasia, gingivitis, and evidence of
bleeding from the oral or nasal mucosa. Lymph nodes
should be examined in the neck, supraclavicular region,
and axilla. The cardiovascular examination includes an
evaluation for jugular venous distension, abnormal heart
sounds, and edema. The physician should check the chest
and lungs for signs of consolidation, wheezing, rales and
trauma. The abdominal examination should focus on
signs of hepatic congestion or masses, with an inspection
of the extremities for signs of edema, cyanosis and

tenderness. Clubbing is present in bronchiectasis, lung
abscess and severe chronic lung diseases. Cachexia,
clubbing, hoarseness of voice, hyperpigmentation and
Horners syndrome may suggest a primary lung cancer.
Diagnostic Evaluation
After a careful history and examination, a chest radiograph should be obtained. Some of the common
TABLE 12.12.4: Diagnostic clues in hemoptysis:
chest radiograph
Chest radiograph finding
Possible diagnosis
Cardiomegaly, increased
pulmonary vascular
distribution
Chronic heart failure, mitral valve

stenosis, pulmonary edema
Cavitary lesions
Lung abscess, tuberculosis
Diffuse alveolar infiltrates
Chronic heart failure, pulmonary

edema, aspiration, toxic injury.
Lobar or segmental
infiltrates
Pneumonia, thromboembolism
Patchy alveolar infiltrates
Bleeding disorders, idiopathic

pulmonary hemosiderosis,
Goodpasture syndrome
Hilar adenopathy or mass
Infectious process, sarcoidosis,

malignancy
Mass lesion, nodules,

granulomas
Wegener granulomatosis, septic

embolism vasculitides
Normal or no change from

baseline
Upper respiratory infection,

sinusitis, pulmonary embolism

TABLE 12.12.5: Diagnostic clues in hemoptysis:
Laboratory tests
Test
Diagnostic findings
White blood cell counts

and differential counts
Elevated cell count and differential

shifts may be present in upper and
lower respiratory tract infections
Hemoglobin, hematocrit
Decreased in anemia
Platelet count
Decreased in thrombocytopenia
Prothrombin time,
International Normalized
Ration (INR) partial
thromboplastin time
Increased in anticoagulant use,

disorders of coagulation
Arterial blood gases
Hypoxia, hypercarbia
d-dimer
Elevated in pulmonary embolism
Sputum:Gram stain,
culture, acid-fast bacillus
smear and culture
Pneumonia, lung abscess,

tuberculosis
Tuberculin (PPD) skin test
Positive test increases risk for

tuberculosis
HIV test
Positive test increases risk for

tuberculosis, Kaposis sarcoma
Erythrocyte sedimentation
rate (ESR)
Elevated in infection, autoimmune

disorders (Wegener granulomatosis, SLE, sarcoidosis, Goodpasture
syndrome)
593
radiologic findings and possible diagnosis are listed in

Table 12.12.4. If the diagnosis remains unclear, further
imaging with chest computed tomography (CT) or direct
visualization with bronchoscopy is indicated.
Fiberoptic bronchoscopy is used mainly for diagnostic
purpose as it permits tissue biopsy, bronchial lavage or
brushings for pathologic diagnosis. It can provide direct
therapy in cases of continued bleeding. Rigid bronchoscopy is the preferred in cases of massive bleeding
because of its greater suctioning and airway maintenance
capabilities.
Patient with recurrent or unexplained hemoptysis
may need additional laboratory evaluation to establish
a diagnosis (Table 12.12.5.)
BIBLIOGRAPHY
1. Cahill BC, Ingbar DH. Massive hemoptysis. Assessment
and management. Clin Chest Med 1994;15:147-67.
2. Corder R. Hemoptysis. Emerg Med Clin North Am
2003;21:421-35.
3. Harrison TR, Braunwald E. Hemoptysis. In:Harrisons
Principles of Internal Medicine.15th edition. New
York:McGraw-Hill, 2001:203-6.
4. Pianosi P, Al-Sadoon H. Hemoptysis in children, pediatr
Rev 1996;17:344-8.
5. Soni PN, Reddy I, Rauff S. Pneumonia and severe
haemptysis. Lancet 1998;352:198.
6. Taskar AD, Flower CD. Imaging the airways. Hemoptysis, bronchiectasis, and small airways disease. Clin
Chest MEd 1999;20:761-73
12.13 Bronchial Asthma

H Paramesh, L Subramanyam, SO Shivbalan
INTRODUCTION
Asthma is a chronic lung disease with airway obstruction,
airway inflammation and airway hyper-reactivity to
various stimuli, often reversible with bronchodilators
and anti-inflammatory drugs. If not treated properly
some of persistent asthmatics end up in irreversible state
due to airway remodelling.
Asthma is a major health concern globally and
causes a great burden on the family and society and
accounts for a large number of lost school days and
interfere with academic achievement and social
interaction, in addition places a strain on health visits

to physician and hospital.
EPIDEMIOLOGY
There is substantial evidence that the prevalence of
asthma is increasing worldwide and the likely causes
for the increase or for the variations in prevalence
among countries differ. However, there is general
agreement that the environmental factors, including
increasing exposure to air pollution, tobacco smoke,
allergens, western life style, of living, deviating from
594
traditional food habits and rearing the child in

extremely hygienic atmosphere, that is devoid of even
protective germs.
The study in Papua New Guinea showed that introduction of mites in the indoor environment by using
blankets had caused increase prevalence of asthma.
Synergic actions of air pollution, tobacco smoke have
been implicated for increase prevalence along with
western life style of living and insulation of houses as an
important cause. Polluted cities in Sweden have shown
increased prevalence of allergy. Similar observations
have been made in Chile, where school children living
in heavily polluted areas present with asthma more than
those living in less polluted areas.
TABLE 12.13.2: Asthma prevalence in schools/density of

traffic/affluence
Group
No. of studied
% of asthma
I. School in heavy traffic

region, children from affluent
families
3722
19.34
II. School in heavy traffic with

children of low socioeconomic
groups (less affluent)
273
31.14
III. School in low traffic region,

children from affluent family
groups
2565
11.15
P. Value 1: II < 0.001, II: III < 0.001, 1: III < 0.001
PREVALENCE OF ASTHMA IN BANGALORE, INDIA

Based on international guidelines, a two decade study
conducted by a pediatric pulmonologist in a pediatric
OPD children < 18 years of age in a metropolitan cities
revealed asthma prevalence rates every five years since
1979 as follows as shown 9 percent, 1984-10.5 percent,
1989-24 percent, 1989-29.5 percent. The steady rise in
prevalence correlated with demographic changes in the
city like - increase in numbers of industries, increased
density of population from migration of rural population
in search of jobs and increased number of automobiles
to commute, leading to air pollution.
In continuation of the study we undertook further
study in 12 schools on 5570 urban children and 990 of
rural children in the age group of 6 to 15 years, the
prevalence of asthma in this age group is shown in
Table 12.13.1.
TABLE 12.13.1: Asthma prevalence Urban /
rural. age 6-15 years
Urban Children
5570
Rural Children
990
16.635 %
5.7%
Further we categorized the urban children into three

groups depending upon the geographical situation of the
schools in relation to vehicular traffic and affluence of
the family and the results are shown in Table 12.13.2.
Is the Magnitude of Asthma Going to
Rise Incessantly?
Recent Studies in Australia, Hong Kong, Mexico and Italy
show that there is a decreasing trend in asthma
Figure 12.13.1: Prevalence of asthma (1979-2004) (P<0.05)
prevalence and emergency visits and hospitalization after

a steady increase over past two and half decade.
Our hospital-based study on 6677 children under the
age of 18 years in the year 2004, in comparison to earlier
studies shows a decrease in the prevalence of asthma as
in Figure 12.13.1. This decrease in prevalence can be due
to saturation of genetically predisposed population.
However, further analysis revealed that the persistent
asthma is increased from 20 to 36.3 percent in 10 years
from 1994 to 2004 shown in Figure 12.13.2. It is the
persistent asthma causes great economic burden to the
society.
The point prevalence of asthma in 800 adolescents in
the age group of 16-19 years of age is 10.3 percent.
The admission rate to the hospital from acute severe
asthma is reduced from 24.5 percent/year in 1995-97 to
12.34 percent/year in 1997 to 2003.
The emergency room visits of asthma decreased from
21.35/year to 11.92/year in 3 years. This reflects the good
595
and atopy. The Adam 33 gene is involved in airway

remodelling and airway hyper reactivity. Often there is
a history of asthma in the close family members. The
monozygotic twins suffer more than dizygotic twins.
Etiology and Triggering Factors
Figure 12.13.2: Prevalence of persistent asthma

(1994-2004) (P<0.0058)
impact of hands on education of patients and parents in

the outpatients about compliance and technique of
inhalation.
Age of Onset
Asthma may have its onset at any age; 26.3 percent of
patients are symptomatic by one year of age, 51.4 percent
by 1-5 years and 22.3 percent after five years of age. It
was observed that 77.7 percent of asthma cases are in
the age group of less than 5 years.
Distribution of Sex
The male to female ratio is 1.8:1 on par with various other
studies. Contrary to the well-established facts, the recent
observation by the another rural study by the auther on
119 children of agricultural farm workers, in the age
group of 6-15 years of age, who live 6 km away from the
main road has shown that the ratio of male to female is
1:2.3. This change in gender ratio is mainly due to the
fact that girls living in ill ventilated huts, helping the
mother to cook and inhalation of smoke from dirty fuel
(cow dung cakes and agricultural waste) lead to airway
inflammation and asthma.
Genetics
Asthma is a complex genetics disorder influenced by
environment. The current knowledge is, it is inherited
as an autosomal dominant trait. The abnormal loci is on
chromosome 11, and for total IgE (Atopy) it is on
chromosome 5 for specific IgE, it is on chromosome 7.
There are over 51 genes loci are implicated in asthma
In children the most common trigger for asthma is viral

infections almost 40 percent of the time.
Seasonal variation occurs more in monsoons and
winter but less in summer months. Aeroallergens like
pollens and fungi are present in 7.5 percent of the time.
Indoor allergens are the most common cause for
persistent asthma and include dust mites, cockroaches,
fungi and animal, saliva danders, urine in the bedrooms.
Irritants like cigarette smoke, cologne sprays,
burning of mosquito coils and cooking smell can trigger
asthma. Food as a triggering factor is observed in 19.75
percent by the parental history only. The most blamed
offenders are grapes, banana, guavas, citrus fruits, ice
creams, fried foods and tomato in that order.
Air pollution is both outdoor and indoor. Nitrogen
oxide, sulfur dioxide, ozone and suspended particulate
matters from combustion of fossil fuels sensitize airway
to inflammation and trigger asthma attacks. Polluted
pollens are 50 times more allergenic.
Pets ownership is 5.12 percent in urban locale and
42.3 percent in rural agrifarm workers.It is observed that
where the pet ownership is more the prevalence of
asthma is less. If at all any asthma in children due to pets
it is from their saliva and urine predominantly from cats.
Pathophysiology
Various stimuli can initiate asthmatic symptoms. These
include immunologic IgE mediated type I hypersensitivity reaction to allergens (dust mites, pollens, fungi and
cockroach) and non-immunologic stimuli (viral infections, physical or chemical stimuli) which acts by
increasing the exposure of airway to cool dry air and
activates the cells and stimulates autonomic nervous
system which releases bronchoactive and vasoactive
mediators like histamine, eosinophilic chemotactic factor
of anaphylaxis (ECF-A), neutrophil chemotactic factor
(NCF-A) and platelet activating factor (PAF). In
individuals with nasal polyps salicylate and nonsteroidal anti-inflammatory drugs (NSAIDs) can trigger
asthma by inhibiting prostaglandins and increasing
leukotriens production via blockage of the cyclo-
596

Flow chart 12.13.1: Pathways of physiology
oxygenase pathways. Gastroesophageal reflux (GER)

triggers asthma possibly by cholinergic mechanisms or
as a direct result of aspiration.
Three major pathologic events contribute to airway
obstruction:
1. Spasm of airway smooth muscles.
2. Edema of mucus membrane.
3. Excess mucus production. This airway obstruction
interferes with mucociliary escalator clearance. The
proposed pathways of pathophysiology are shown
in Flow chart 12.13.1.
Clinical Features
It is a common statement that all that wheezes is not
asthma, however, all asthmatics do not present with
wheeze. Cough is a predominant symptom for asthma
in 90 percent of the time. The cough which persists after
an episode of upper respiratory infection lasting more
than 10 days should be considered as cough variant
asthma unless proved otherwise. The cough has a special
feature like it is more at night or early morning; crying,
running and loud laughing increases cough and patting
on the back of the child produces cough from vibration
TABLE 12.13.3: Asthma signs in abnormal physiology

1. Increase airway
resistance
Retraction with increasing

severity
Over working abdominal muscle
Subcostal retractions
Intercostal retractions
Suprasternal retractions
Head bobbing anterior flexion of
head during inspiration in infants
Flaring of nostrils
2. Airway obstruction
Muscle spasm
Mucosal edema
Excess trapping of
air
Prolonged expiration
Wheeze
Ronchi
Elevated shoulder
Hunchback position
Increase anteroposterior
diameter of chest
3. Excess mucus
secretion
Wet sounds (crackles) more

often predominant in infants
4. Hypoxia
Irritability, confusion, refusal to

feed, semi coma, coma
5. Hypercarbia
Bounding pulses, warm hands,

dilated retinal vessels.
of the chest. Wheezing is noticed in 74 percent, vomiting

in 5 percent (precede by cough), abdominal pain in
3 percent (due to over-activity of abdominal muscles
during expirations) and chest pain in 1 percent of
children.
The signs are related to increased airflow resistance
during expiration, airway obstruction and excessive
mucus production, hypoxia and hypercarbia as shown
in Table 12.13.3.
Diagnosis
The diagnosis of asthma in children under 5 years is
predominantly by clinical features of persistent cough
over one week duration after a bout of cold having more
and wheeze than three episodes per year prolonged
expiration and other signs of airway obstruction. Having
other features of atopy like eczema and allergic rhinitics,
family history of asthma and improvement with
therapeutic trial of bronchodilators is often helpful.
Peripheral blood smear show eosinophilia, total IgE is
elevated in atopic children. In children above 3 years of
age one can measure peak expiratory flow rate (PEF)
before and after inhalation of bronchodilators. If there is
15 percent improvement of peak expiratory flow after

therapy, it is highly suggestive of asthma. In bigger
children spirometric study is beneficial where the ratio
of forced expiratory flow at one second (FEF1) to forced
vital capacity (FVC) ratio is less than 0.8, or less than 80
percent of normal. Forced expiratory flow rates (FEF2575) is an effort independent measure and is low in small
airway obstruction. Chest X-ray is not diagnostic of
asthma. It may show only air trapping, but it is needed
if any complication of asthma or any other diagnosis is
suspected. Radio allergosorbent test (RAST), enzyme
linked immunosorbent assay (ELISA) and skin testing
to confirm the specific allergenic causes are not needed
routinely.
Anyone of the inflammatory or congenital abnormalities
of upper respiratory tract like rhinitis, croup syndrome,
tonsillitis, retropharyngeal abscess, laryngomalacia and
vascular ring and supraglottitis can be mistaken for
asthma. All these upper airway diseases have the
following features in common: (a) inspiratory difficulty,
(b) stridor. Depending on the pitch of the sound one can
make the location of upper airway pathology.
In the lower respiratory tract bronchiolitis is the most
common condition to be differentiated from asthma.
Bronchiolitis is diagnosed clinically if associated with
fever. One can ascertain about bronchiolitis by bronchial
biopsy and decrease in breath nitric oxide, unlike in
asthma (these measures are of academic interest only).
Foreign body aspiration should be suspected in sudden
onset cough and wheeze during play hours in a healthy
child. Non-opaque foreign body aspiration can be
suspected when uneven ventilation of lung is present
and confirmed by inspiratory and expiratory chest
X-rays. Cystic fibrosis, a genetic disease is not uncommon
in our country and is diagnosed by increase in sweat
chloride.
Parenchymal diseases like pneumonias can be
diagnosed by tachypnea, flaring of nostrils and grunting
during expiration. X-ray will be diagnostic.
Complications
The usual complication of asthma is atelectasis observed
more in children under 5 years of age due to lack of
collaterals in that age group which is often mistaken for
recurrent pneumonia and treated with antibiotics.
Pneumonia, middle ear infection, sinusitis, occasionally
597
pneumomediastinum and subcutaneous emphysema

may occur.
Management
While managing the children with asthma, a special
interest to be focussed on children under five years of
age because, the under diagnosis, under treatment are
a major factors. The aims of management of the asthma
in children are: (a) relieve the symptoms, (b) prevent
the relapse of attacks to prevent school absenteeism,
encourage to participate in sports and attain good growth
and development, (c) education of the patients, parents,
grandparents about the disease, need to use the medicine
and proper use of technique of inhalation therapy, (d)
good pharmacological therapy and (e) environment
control.
And in adolescentsthe poor compliance is quite
common because they fail to recognize the danger of
poorly controlled asthma, not able to accept the chronicity
of the illness and they feel the therapy will infringe on
their emerging independence. They also fear the stigma
of asthma on their future life style in society and sports.
Especially the adolescent girls try to avoid inhalation
treatment for fear of marriage and mother-in-laws.
Pharmacological Therapy
There are two groups of drugs in the management of
asthma:
1. Quick relieversBronchodilators like beta 2 agonists,
salbutamol, and terbutaline are similar in their
efficacy, actions, kinetics and adverse effects. While
inhalation is the method of choice, oral alternative
may be justified in children whose symptoms are mild
and less frequent. Long acting beta 2 agonists like
(salmeterol, formeterol) are not recommended in
acute attacks. Amino-phylline is the second choice
as bronchodilator. In recent days their usage has come
down since better and safer bronchodilators are
available. However, they still find some place in
managing acute severe asthma episodes in ICU
setting as an additive drug for their mild effect of
improved diaphragm contractility, mucociliary
clearance and mild anti-inflammatory effects.
However, caution is exercised while using the
medicine. In addition it has some role to play in
nocturnal asthma as a prophylactic.
598
2. Preventors or anti-inflammatory drugs (mast cell stabilizers):

Cromolyn glycate has mild anti-inflammatory effect;
but 4 times daily regime is difficult to implement.
Leukotriene inhibitors: These drugs block the
synthesis of leukotrienes at various levels.
Montelukast has been shown to be beneficial for
exercise-induced asthma, add-on therapy in
persistent asthma in reducing the steroid dosage
and in nocturnal asthma.
Steroids: They are the best anti-inflammatory
drugs available now. Inhaled steroids are the best
mode of therapy where adverse steroid effects are
negligible. The available inhaled steroids include
beclomethasone, budesonide, and fluticasone.
Fluticasone is the most potent and least bioavailable to produce adverse reactions. Combining with long acting beta-2 agonists will
enhance the effect of steroids (seroflo, combitide,
seretide).
Treatment of Acute Attack of Asthma
The first line of management of an acute attack of asthma
in the emergency room is to administer beta-2 agonists
through a nebulizer or give epinephrine (1: 1000 dilution)
0.1 to 0.3 ml subcutaneously depending on the age. The
dose may be repeated two times at 15 minutes intervals
if needed. If there is good response discharge the patient
on oral bronchodilators. If there is no response, the child
should be admitted and treated as a case of acute severe
asthma as per guidelines given in Table 12.13.4.
TABLE 12.13.4: Management of acute severe

asthma rule of six Ms
1. Metabolic correction
Humidified warm oxygen, use of

sodium bicarbonate in some
cases as per base excess
2. Muscle spasm to be
relieved
Beta-2 agonists inhalation Methyl

Xanthines intravenously
3. Mucosal edema
Steroids to be used at the earliest
4. Mucus secretions in
excess
Hydration. Stacchato type of

coughing
5. Monitor for infections
Antibiotics if the mucus is yellow

or green or evidence of pneumonia
6. Mechanical breathing
Ventilators. When ventilator

failure is established
during mild exacerbations. Persistent asthma should be

suspected in children who require bronchodilator
therapy more than 2 times a week and trial of antiinflammatory drugs can be given.
After assessing the severity of asthma, signs and
symptoms can be controlled by the use of preventor
drugs suitable to a grade higher than the patients grade
of severity (step down method). This is preferred as it
helps to get quick control of symptoms and gain the
confidence of patients and parents, and adherence to the
regime of treatment as in Table 12.13.6.
Children with intermittent asthma but have severe
exacerbations should be treated as having moderate
persistent asthma.
Treatment of Chronic Asthma
Selection of Spacers
Chronic asthma is graded as intermittent and persistent

asthma. Persistent asthma is further graded as mild,
moderate and severe based on clinical features and PEF
values as in Table 12.13.5. Children with intermittent
asthma require only inhaled/or oral bronchodilator
therapy to relieve the symptoms and bronchospasm
The inhalation therapy is the better method in delivering

the medications, and spacer devices are always
necessary, in small children who are unable to cooperate,
a facemask can be attached to the mouthpiece of the
spacer. The proper selection of the inhalation devices for
inhalation is shown in Table 12.13.7.
TABLE 12.13.5: Persistent asthma in childrenGrading

Grade
Frequency
Night symptoms with

disturbed sleep
Peak expiratory flow (PEF)
Intermittent
Less than twice a week

Brief exacerbation
Less than twice a month
> 80% of personal best

< 20% diurnal variation
Mild persistent
More than once a week but

less than once a day
More than twice a month
> 80% personal best

20 to 30% diurnal variation
Moderate persistent
Once a day
Once a week
> 60% < 80 percent of personal best

> 30% diurnal variation
Severe persistent
Continuous
Frequent
< 60% of personal best

> 30% of diurnal variation

TABLE 12.13.6: Selecting the optimal preventer regime
Severe persistent
Inhaled high dose steroids

+
LA beta 2 agonists
Moderate persistent
Inhaled low dose steroids + LA beta

2 agonists
Or
Inhaled medium dose steroids
Mild persistent
Inhaled steroids low dose

Or
Leukotriene inhibitors
Or
Inhaled cromoglycate
Note: Low dose = < 400 ug/day

Medium dose = 400 to 800 ug/day
High dose = > 800 ug/day of beclomethasone or budesonide.The
corresponding doses of fluticasone is half of the dose.
SA = Short acting, LA = Long acting
TABLE 12.13.7: Selection of whatever devices
Nebulizer
Suitable for all ages
Metered dose inhaler

(MDI)
Children over 10 years.

However, a spacer is still
recommended.
MDI with Spacer
Suitable for all ages
MDI with Spacer and mask
Children less than 3 years
Dry Power Inhaler (DPI)
Above 6 years
Please note whatever be the device a spacer is a must in all

cases.
Environment Control
Seventy-five to eighty-five percent of asthma patients
have positive skin tests for common inhalants existing
inside the house. Avoid big crowds to prevent respiratory
viral infection. Encase the pillow and mattress, sundry
the bedding weekly, avoid carpets, upholstered
furnishing, tobacco smoke, mosquito burning coils, wood
burning smoke, strong odors, and cologne sprays; and
avoid air pollution (oxides of nitrogen, ozone, sulfur
dioxide, suspended particulate matters). Cockroach
control measures and avoiding the wet humid and moldy
places. Stay indoor especially during mid-day and
afternoon when pollen and mould counts are high. Wet
mopping of floors is better. A good cross-ventilation and
good sunlight inside the house is always better in our
country. Avoid suspected food, which increases the
symptoms during the asthma episodes. Traditional food
habits are always better.
599
Immunotherapy
Specific immunotherapy is directed at treating the
underlying allergy when avoidance of aeroallergens is
not possible and drug therapy is not successful.
Sublingual immunotheraphy (SLIT) is promising in
children.
Prognosis
Although asthma can be a fatal disease, the long-term
prognosis is good in children. Most of the children with
viral infection triggered asthma will be free of symptoms
by 5 years of age. By 8 years of age some more will be
symptoms free when airway caliber reaches adult size.
By adolescent age almost 90 percent of asthmatics will
be free from symptoms. The risk factors for persistent
asthma are: (a) atopic child (b) family history of asthma,
(c) maternal smoking, (d) over-crowded houses with
poor indoor air quality (e) poor adherence of medication.
In patients who are on long-term steroids one has to
observe for cushingoid features, linear growth failure,
cataracts, osteoporosis and acne.
BIBLIOGRAPHY
1. Consensus guidelines on management of childhood
asthma in India. Indian Pediatrics 1990;157-65.
2. Consensus statement on the diagnosis and management
of asthma in children. Asthma by Consensus - National
Guidelines IAP Respiratory chapter.Update Dec 2003.
3. GWK Wong, et al. Declining asthma prevalence in Hong
Kong Chinese School Children. Cli Exp allergy 2004;
34:1550-5.
4. Mario H Varges, Guiltermo S Daz Mejsa, Maria EY
Furuya, Jorge Sales, Alejandro Lugo.
5. Paramesh H. Asthma and the Environment .Indian
Journal of Pediatrs 2006;73:S51-55.
6. Paramesh H. Asthma in children: Seasonal variation.
Paper read Vienna. Austria in International Conference
on Environment and Child Health; June 2007.
7. Paramesh H. Epidemiology of asthma in India. Indian
Journal of Pediatrics 2002;300-12.
8. Paramesh H. Indoor Air Pollution and Child Health. In
Anupam Sachdeva, (ed).Pediatric and Adolescent
environment Health,Indian Academy of Pediatrics
Presidential Action Plan 2004;1:76-8.
9. Paramesh H. Peak flow values in urban and rural
children, Indian Journal of Pediatrics 2003;70:375-7.
10. Paramesh H, Cherian E. Pediatric allergies. Epidemiology and management principles and practice of
tropical allergy and asthma In: Wiqar A Shaikh (Ed):
Vikas Medical Publishers, Mubai 2006;603-14.
13.1 Diarrheal Diseases: Ashok K Patwari .................................................................................................................................................... 602

13.2 Persistent and Chronic and Protracted Diarrhea in Children: Gadadhar Sarangi, Jnanindra Nath Behera ................................... 609
13.3 Parenteral Nutrition in Children: Anand N Pandit, Ashish R Bavdekar .............................................................................................. 613
13.4 Parasitic Bowel Diseases: BD Gupta ................................................................................................................................................... 616
13.5 Vomiting in Infants and Children: S Nagabhushana .......................................................................................................................... 620
13.6 Gastroesophageal Reflux in Infants and Children: Neeraj Jain, Vibha Jain, Deepak Seth .............................................................. 622
13.7 Gastrointestinal Bleeding in Infants and Children : Saroj Mehta, Rajiv Chandra Mathur ................................................................ 624
13.8 Constipation: VR Ravikumar ................................................................................................................................................................. 627
13.9 Abdominal Pain: S Srinivas ................................................................................................................................................................... 629
13.9.1 Acute Abdominal Pain in Children ........................................................................................................................................ 629
13.9.2 Chronic Abdominal Pain in Children ..................................................................................................................................... 632
13.10 Helicobacter Pylori Infection in Children: Neeraj K Jain, Vibha Mangal ........................................................................................... 637
13.11 Cystic Fibrosis: Sushil K Kabra, Madhulika Kabra ............................................................................................................................... 639
13.12 Juvenile Tropical Pancreatitis: A Riyaz ............................................................................................................................................... 644
13.13 Liver and Biliary System: B Bhaskar Raju, B Sumathi ........................................................................................................................ 646
13.14 Hepatosplenomegaly: A Practical Diagnositic Approach: Sheila Bhave, Ashish Bavdekar ............................................................ 650
13.15 Differential Diagnosis of Jaundice in Infancy: MK Jain, Sunil Karande ............................................................................................ 653
13.16 Viral Hepatitis: Malathi Sathiyasekaran, Ramaswamy Ganesh ............................................................................................................ 655
13.17 Chronic Hepatitis in Children: BR Thapa ............................................................................................................................................ 667
13.18 Chronic Liver Disorders in Children: VS Sankaranarayanan, S Srinivas .......................................................................................... 672
13.19 Cirrhosis of Liver: VS Sankaranarayanan, S Srinivas .......................................................................................................................... 675
13.20 Neonatal Cholestasis Syndrome: BR Thapa ....................................................................................................................................... 682
13.21 Fulminant Hepatic Failure: Rajiv Chandra Mathur ............................................................................................................................... 692
13.22 Ascites: Balvir S Tomar, Anurag Tomar ................................................................................................................................................ 695
602
13.1 Diarrheal Diseases

Ashok K Patwari
Diarrheal diseases constitute a leading cause of morbidity
and mortality among children under five years of age in
developing countries. On an average 3.3. episodes of
diarrhea are experienced per child per year but in some
areas the average exceeds 9 episodes per year. More than
2 million deaths are estimated to result each year as a
consequence of diarrheal disease in under fives. 80% of
these deaths occur in the first 2 years of life, main causes
being dehydration, complications associated with
dysentery, malnutrition and serious infection such as
pneumonia.
Diarrhea is usually defined as passage of 3 or more
loose or watery stools in a 24 hour period, a loose stool
being one that would take the shape of a container.
However, for practical purposes, it is the recent change
in consistency and character of stool and its water content
rather than the number of stools that is important. Infants
who are exclusively breast fed normally pass several soft
or semi-liquid stools each day; for them, it is practical to
define diarrhea as an increase in stool frequency or
liquidity that is considered abnormal by mother.
Types of Diarrhea
Three clinical syndromes of diarrhea have been defined,
each reflecting a different pathogenesis and requiring
different approach to treatment.
Acute Watery Diarrhea
It refers to diarrhea that begins acutely, lasts for less than
14 days, with passage of frequent loose or watery stools
without visible blood. Vomiting may occur and fever may
be present. Loss of large volume of water and electrolytes
can result in dehydration and dyselectrolytemia.
Dysentery
It is the term used for diarrhea with visible blood and
mucus. Dysentery is often associated with fever and
tenesmus. Common clinical features of dysentery include
anorexia, rapid weight loss and complications like renal
failure and encephalopathy.
Persistent Diarrhea
It represents diarrhea, presumed to be caused by
infectious agents, that begins acutely but is of usually
long duration ( more than 14 days). The episode may
begin either as acute watery diarrhea or as dysentery.
Marked weight loss is common. Diarrheal stool volume
may also be great, with a risk of dehydration. Persistent
diarrhea should not be confused with chronic diarrhea
which is recurrent or long lasting diarrhea due to noninfectious causes such as sensitivity to gluten or inherited
metabolic disorder (See section 13.2).
Risk Factors
Most of the diarrheal episodes occur during the first 2
years of life (incidence is highest in 6-11 months), low
socio-economic status, in non breastfed infants, and in
association with measles, severe malnutrition, and
immunodeficiency.
Etiology
In developing countries, the organisms most frequently
associated with acute watery diarrhea include enterotoxigenic Escherichia coli (ETEC), enteropathogenic Escherichia
coli (EPEC), Shigella and Campylobacter jejuni. Rota virus
is a common cause of severe diarrhea, vomiting and fever
leading to rapid dehydration. Vibrio cholera is an
important organism in endemic areas and during
epidemics. Non-typhoidal salmonella is a common
organism in areas where commercially processed foods
are widely used and in hospital outbreaks. Most of these
organisms produce watery diarrhea. The main cause of
acute dysentery are Shigella, Campylobacter jejuni and
infrequently enteroinvasive Escherichia coli (EIEC) or
salmonella. Epidemics of dysentery are usually caused
by S. dysentery type 1. Entamoeba histolytica can cause
dysentery in adults but is a less common cause in young
children.
Diarrhea may also be caused by a number of
antibacterial agents like ampicillin, cotrimoxazole,
chloramphenicol, amoxicillin, clindamycin, etc. Pseudo-
Diseases of Gastrointestinal System and Liver

membranous colitis is the most severe form of antibiotic
associated diarrhea.
603
place in the gastrointestinal tract. Three clinical types of

diarrhea have been defined, each reflecting a different
mechanism.
Pathophysiology of Infectious Diarrhea

Various mechanisms which have been suggested include:
(i) increased secretion of fluid and electrolytes,
(ii) decreased digestion and absorption of nutrients, and
(iii) abnormal transit due to aberrations of intestinal
motility.
Increased Secretion
Increased secretion of fluid and electrolytes may occur
due to the effect of enterotoxins liberated by microorganisms which mediate through cyclic AMP or cyclic
GMP thereby disturbing the sodium pump and leading
to (a) increased secretion from crypt cells, (b) poor
absorption of water and electrolytes from the villi and
(c) increased passive flow of water and electrolytes from
ECF to small bowel lumen through intercellular channels.
Decreased Digestion and Absorption
Decreased digestion and absorption of nutrients particularly carbohydrates can take place as a consequence
of: (a) disorganized epithelial cell renewal i.e. villus
atrophy and crypt hyperplasia with failure of normal
enterocyte maturation during migration from the crypt
to villus or (b) damage to absorptive surface as a result
of brush border damage, cytotoxin production resulting
in severe epithelial damage and epithelial invasion
leading to patchy micro abscess formation, decreased
mucosal disaccharidase activity and impaired
absorption.
Disordered Transit
Abnormal intestinal myoelectrical activity initiated by
non-invasive organisms and their enterotoxins as well
as by invasive enteropathogens can result in disordered
transit not only as a secondary response to disordered
mucosal transport but may also occur independently as
a primary pathophysiological mechanism.
Clinical Features
Most enteropathogens can cause diarrhea by more than
one mechanism. Hence the clinical presentation depends
upon the underlying pathophysiological changes taking
Secretory Diarrhea
It is characterized by acute watery diarrhea with
profound losses of water and electrolytes due to sodium
pump failure as a result of the action of identified toxins.
This group is at risk for rapid development of dehydration and electrolyte imbalance. Common causes are ETEC
and V. cholerae.
Invasive Diarrhea (Dysentery)
Intestinal mucosal cells are actually invaded by the
microorganisms which set up an inflammatory reaction
clinically presenting with blood and mucus in the stools.
This group is prone to develop other complications like
intestinal perforation, toxic megacolon, rectal prolapse,
convulsions, septicemia and hemolytic uremic syndrome.
Osmotic Diarrhea
Injury to enterocytes may result in brush border damage
and epithelial destruction leading to decreased mucosal
disaccharidase activity. Clinical presentation is characterized by passage of large, frothy, explosive and acidic
stools. High osmolar solutions given orally (e.g.
carbonated soft drinks and ORS with high sugar content)
can also result in osmotic diarrhea. Besides worsening
the hydration status of the child there is a serious danger
of developing hypernatremia.
Consequences of Diarrhea
Dehydration
Dehydration is the commonest and life threatening
consequence of diarrhea. Young children are more
susceptible to develop dehydration due to limited
urinary concentration capacity of the kidneys, more
insensible losses of water through skin and lungs owing
to large surface area and rapid breathing, and their
dependence on adults to replace their fluid losses. Loss
of water and electrolytes in the diarrheal stool results in
depletion of the ECF volume, electrolyte imbalance and
clinical manifestation of dehydration. The first symptom
of dehydration appears after fluid loss of 5% of body
weight. When fluid loss reaches 10% , shock often sets
in, and the cascade of events that follows can culminate
in death unless there is immediate intervention to
rehydrate.
604

TABLE 13.1.1: Assessment of hydration status in a patient with diarrhea
Clinical signs
General condition
Eyes
Thirst*
Skin pinch
Well, alert
Normal
Drinks normally,
not thirsty
Goes back quickly
Restless, irritable
Sunken
Drinks eagerly,
thirsty
Goes back slowly
Lethargic or unconscious
Sunken
Drinks poorly,
not able to drink
Goes back very slowly
The patient has

no signs of
dehydration
If the patient has

two or more signs,
there is some
dehydration
If the patient has

two or more signs,
there is severe
dehydration
Plan A
Plan B
Plan C
Decide hydration status
Treatment Plan
* In a young infant less than 2 months of age, thirst is not assessed and decision regarding some or severe dehydration is made
if two of the three signs are present
Malnutrition
Oral Rehydration Therapy
Diarrhea is a major cause of malnutrition in children,

owing to low food intake during the illness (poor
appetite, vomiting, oral thrush/stomatitis, diluting/
withholding of food, etc.), reduced nutrient absorption
in the intestines, and increased requirements as a result
of infection. Repeated and prolonged episodes of
diarrhea have even more deleterious effects and may
eventually result in growth failure, intercurrent infections
and problems associated with severe malnutrition and
even death.
Concept of Oral Rehydration Therapy (ORT) has

revolutionized the management of diarrhea with the
discovery of coupled active transport of glucose and
sodium in the small bowel, resulting in the pas-sive
absorption of water and other electrolytes even during
copious diarrhea. Oral Rehydration Therapy (ORT)
includes:(a) ORS solution of recommended composition,
(b) solution made from sugar and salt (if prepared
correctly), (c) food based solutions with appropriate
concentration of salt, like lentil soup, rice, kanji, butter
milk, etc. and (d) plain water given along with continued
feeding.
Management of a Child with Diarrhea

Principles of Treatment
General assessment of the child
Assessment of hydration status. A number of clinical
signs and symptoms can help in detecting dehydration. However, a simple assessment chart can be
referred for quick assessment of dehydration (Table
13.1.1) and administration of appropriate fluids for
prevention and treatment of dehydration
Correction of electrolyte and acid base imbalance
Proper feeding to provide normal nutritional
requirements
Zinc supplementation
Treatment of associated problems like dysentery and
persistent diarrhea
Nutritional rehabilitation
Health education for prevention of diarrhea
Oral Rehydration Salts (ORS) solution: Optimum

absorption of glucose takes place from the intestines
between a glucose concentration of 111-165 mmol/l and
the sodium: glucose ratio between 1:1 to 1:1.4. Therefore,
the standard WHO/UNICEF formula (Table 13.1.2) has
been recommended for rapid rehydration of dehydrated
patients. ORS with this formulation can also be used for
maintenance therapy after correcting dehydration, when
given with equal amounts of plain water or breastfeeding.
Low Osmolarity ORS: The standard WHO-ORS, used for
over three decades, has saved millions of lives but did
not decrease diarrheal duration or stool output.
Additionally, there was a concern among pediatricians
that there was a risk of hypernatremia with standard
WHO-ORS when given to children with non-cholera

TABLE 13.1.2: Composition and concentration of WHO/
UNICEF recommended oral rehydration salts (ORS)
Ingredients
Composition Ingredients
(grams/l)
Concentration
(mmol/l)
Sodium chloride
3.5
Sodium
90
Potassium chloride
1.5
Potassium
80
Trisodium citrate
2.9
Citrate
10
20
Glucose
111
Osmolarity
311
(anhydrous)
Glucose (anhydrous)
TABLE 13.1.3: Low osmolarity ORS formulation

recommended by WHO/UNICEF
mmol/liter
Reduced osmolarity grams/litre

ORS
Reduced
osmolarity ORS
Sodium chloride
Glucose, anhydrous
Potassium chloride
Trisodium citrate
Sodium
75
Chloride
65
Glucose, anhydrous 75
Potassium
20
Citrate
10
Total osmolarity
245
2.6
13.5
1.5
2.9
diarrhea. Reduced osmolarity of ORS achieved by

reducing the glucose and salt concentrations of the
solution, to avoid possible adverse effects of hypertonicity on net fluid absorption, has been found to be
safe and efficacious in treating children with diarrhea.
Because of the improved effectiveness of reduced
osmolarity ORS solution, WHO and Indian Academy of
Pediatrics now recommend use of low osmolarity ORS
(Table 13.1.3) as the universal solution for treatment and
prevention of dehydration for all causes of diarrhea and
at all ages.
Prevention and Treatment of Dehydration
Management of No Dehydration
The objective of treatment is prevention of dehydration
and malnutrition (Plan A). The management can be
successfully carried out at home, by the mother/
caretaker who is advised to: (i) give more fluids than
normal (Table 13.1.4), (ii) continue feeding, and (iii) bring
the child back after 2 days, or earlier if he has any of the
danger signs (thirsty, irritable/restless, fever, high purge
rate, repeated vomiting, blood in the stool, eating or
drinking poorly, lethargic).
605
TABLE 13.1.4: Guidelines for replacement of fluid and

electrolytes in children with No Dehydration (Plan A)
Age
< 6 months
7 months2 years
25 years
Older children
After each loose stool, offer*:

Quarter glass or cup (50 ml)
Quarter to half glass or cup (50 ml100 ml)
Half to one glass or cup (100200 ml)
As much as the child can take
* Fluids which can be offered include ORS, lemon water, butter

milk, rice kanji, lentil soup, light tea, etc.
Management of Some Dehydration

The objective of treatment is to treat dehydration and
electrolyte imbalance, and to continue feeding. These
children should be rehydrated with ORS under supervision in a health facility (Plan B).
Correction of Dehydration
For correction of fluid and electrolyte deficit on
account of dehydration, administer 50-100 ml/kg
body weight (75 ml/kg) of ORS, over a period of 4
hours. If the child wants more, give more ORS.
Breastfeeding should be continued.
For infants less than 6 months who are fed on artificial
milk, and are rehydrated with standard WHO-ORS,
100- 200 ml of plain water should be given in addition
to ORS
Older children should have free access to plain water.
Acceptance of ORS, purge rate and vomiting should
be closely monitored.
Reassess after 4 hours
If still dehydrated, repeat deficit therapy and also
offer milk/food.
If rehydrated, treat as no dehydration with
maintenance therapy with ORS as in Plan A.
If ORT is not successful, treat as severe dehydration
with intravenous fluids as in Plan C.
Management of Severe Dehydration
The primary objective is to quickly rehydrate the child
in a hospital with facilities for IV fluid therapy. Ringers
lactate is the preferred solution for rehydration given as
100 ml/kg over 6 hours in infants < 1 year and over 3
hours in older children (Table 13.1.5). If Ringers lactate
606

TABLE 13.1.5: Deficit fluid therapy for Severe
Dehydration (Plan C)
Volume of
Ringers
lactate
Monitoring
Infants (<1 year)
Older child (>1 year)
30 ml/kg body wt.

within first 1 hour,
followed by
70 ml/kg body
weight over next
5 hours
30 ml/kg body
weight within
hour, followed by
70 ml/kg body
weight over next
2 hours
Assess for improvement every 1-2 hours:

If not improving, give IV infusion
more rapidly
Encourage oral feeding by giving
ORS 5 ml/kg/hour, along with IV
fluids, as soon as the child is able to
drink
Reassess hydration status:
After 6 hours (infants) and 3 hours
(Older children) assess hydration
status and choose appropriate plan
for hydration (Plan A, B or C)
is not available, other alternatives like normal saline may

be used.
TABLE 13.1.6: Feeding during diarrhea

Stage of hydration
Recommended schedule of feeding
During rehydration phase

Breastfed infants
Non-breastfed infants
Severely malnourished
children
After rehydration phase

Breastfed infants
Non-breastfed infants
Infants 612 months
For older children
Rehydration of Severely Malnourished Children

Rehydration of severely malnourished children deserves
special attention owing to certain pathophysiological
changes in water and electrolyte balance peculiar to
protein energy malnutrition (PEM). Dehydration may
be over or under estimated in the presence of marasmus
or edema. These children are at risk to develop
hypoglycemia and electrolyte imbalance. Rehydration
with ORS solution should be preferred because IV fluids
can easily cause overhydration and heart failure.
Therefore, it is recommended that severely malnourished
children are slowly rehydrated, carefully monitored and
feeding started early.
Feeding During Acute Diarrhea and Dysentery
Nutritional management of acute diarrhea and dysentery
takes optimal advantage of intestinal absorption capacity,
which is affected to some extent during diarrhea, by
feeding small, frequent, energy dense food taking in to
consideration the age, pre-illness feeding pattern and
state of hydration of the child (Table 13.1.6). Feeding is
continued in children with no dehydration, and resumed
as early as possible in some dehydration.
Continue breastfeeding
Should be preferably given
only ORS till they are
rehydrated
Animal milk/food should
be offered, if rehydration
takes longer than 4 hours
Offer some food as soon as
possible
Breastfeed more frequently
Offer undiluted milk as
before
Give easily digestible energy
rich complementary foods in
addition to breast/animal milk
Encourage to eat at least
3 times a day in breastfed
infants and 5 times in nonbreastfed infants
Give thick preparation of
staple food with extra
vegetable oil or animal fats,
rich in potassium (legumes,
banana), carotene (dark
green leafy vegetables, red
palm oil, carrot, pumpkin)
Encourage to eat at least
6 times a day
Zinc Supplementation for Treatment of Diarrhea

Zinc deficiency is common in children from developing
countries because of intake of predominant vegetarian
diets and the high content of dietary phytates. Increased
fecal losses during many episodes of diarrhea aggravate
pre-existing zinc deficiency. WHO and Indian Academy
of Pediatrics recommends zinc supplementation as an
adjunct to ORS in the treatment of diarrhea. The National
IAP Task Force recommended that all children older than
6 months suffering from diarrhea should receive a
uniform dose of 20 mg of elemental zinc as soon as
diarrhea starts and continued for a total period of 14 days.
Children aged 2 to 6 months should be advised 10 mg
per day of elemental zinc for a total period of 14 days.
Use of Antimicrobial Agents
Antibiotic therapy should be reserved only for cases of
dysentery and suspected cholera (Table 13.1.7). Every
607
TABLE 13.1.7: Antimicrobials used to treat specific causes of diarrhea in children

Causes
Drugs of choice
Doses
Cholera
Doxycycline
or
Furazolidone
or
Trimethoprim
(TMP)-sulfamethoxazole (SMX)
Single dose of 5 mg/kg (Maximum 200 mg)
Dysentery*
Trimethoprim
(TMP)-sulfamethoxazole (SMX)
or
Nalidixic acid
58 mg/kg/day in 4 divided doses 3 days

TMP 10 mg/kg and SMS 50 mg/kg in 2 divided
doses 3 days
TMP 10 mg/kg and SMX 50 mg/kg in 2 divided
doses 5 days
Amebic dysentery
Metronidazole
Acute giardiasis
Metronidazole
or
Tinidazole
In view of wide spread resistance to trimethoprim-sulfamethoxazole (TMP-SMX) and reported resistance to nalidixic acid, Indian
Academy of Pediatrics Task Force recommends ciprofloxacin as first line drug in areas where resistance rates to TMP-SMX
exceeds 30%
case of diarrhea needs to be carefully evaluated for the

presence of blood in the stools which indicates dysentery
and to identify cases of suspected cholera (high purge rate
with severe dehydration in a child above 2 years in an
area where cholera is known to be present). Associated
non-gastrointestinal infections like pneumonia, meningitis, urinary tract infection, etc. should also be carefully
looked for and appropriately treated. In severe malnutrition, the usual signs of infection such as fever are often
absent, yet multiple infections are common in these
children. Therefore, it is assumed that all severely
malnourished children may have an underlying infection
which should be treated with broad spectrum parenteral
antibiotics.
Management of Persistent Diarrhea
Management of persistent diarrhea involves a broad
based therapeutic approach to take care of some of the
problems associated with prolonged episodes which
include: (i) impaired absorption of nutrients, particularly
lactose and other disaccharides; (ii) persistent gut
infection, and (iii) presence of associated non-gastrointestinal infections. Broad principles of management of
persistent diarrhea include the following :
Assess hydration status and manage dehydration as
discussed
Investigate stool (pH, reducing substances, ova or

cyst, RBC)
Continue breastfeeding. Offer low lactose diet for non
breastfed babies
Treat dysentery, if visible blood in stool
Treat amebiasis or giardiasis, if cysts or trophozoites
of these parasites are detected in the stool.
Hospitalization
Age less than 6 months, dehydration, severe malnutrition, associated infections and severe lactose malabsorption are indications for hospitalization. Approach to
management of persistent diarrhea in the hospital is
based on following guidelines:
Investigate and treat for associated infections (ARI,
UTI, Septicemia, etc.)
Treat persistent infection due to enteropathogens , if
diagnosed
Dietary manipulations: Offer low lactose diet (kheer,
dalia, phirni, yoghurt, khichri with yoghurt, etc.) if there
is evidence of lactose malabsorption. If there is no
improvement in 2-3 days change over to lactose free
diet (lactose free commercial formula in artificially
fed young infants less than 6 months of age and kichri
with egg in older children). If there is no response to
lactose free diet, change over to disaccharide free
feeding (chicken glucose puree).
608
Nutritional Rehabilitation
Nutritional support to a child following an episode of
acute or persistent diarrhea is of immense importance in
view of the known adverse impact of diarrheal diseases
on the nutrition of a young child. The need for proper
feeding after an episode of diarrhea has even greater
importance particularly because the efforts made by the
mother/caretaker to feed during convalescence are more
rewarding when these children tend to have better
appetite. Therefore, one extra meal at least for 2 weeks
after an episode of acute diarrhea and for at least one
month after persistent diarrhea, stressing the need for
catch up growth, is likely to help in nutritional
rehabilitation of these children.
Diarrhea Training and Training Units and
ORT Corners
Diarrhea case management is very simple and can be
easily carried out at the community level by a health
worker. In fact, the success of the diarrhea case
management lies with the important role played by the
mothers/caretakers who can manage children with
diarrhea at home. However, hospital based referral
facilities are essential for the management of more severe
and complicated cases. Therefore, establishment of
Diarrhea Training and Training Units (DTTUs) in
medical colleges and large referral hospitals will help to:
(i) practice and promote standard case management of
diarrhea (SCMD) on routine basis, (ii) train faculty
members and other health personnel, (iii) train medical
students in SCMD, and (iv) encourage and educate
mothers/caretakers about home management of
diarrhea by providing information and demonstration.
SCMD is an essential component of Integrated Management of Neonatal and Childhood Illness (IMNCI)
strategy.
In order to improve case management of diarrhea at
all levels of health care system, treatment areas need to
be identified within the facility to manage patients with
diarrhea. These identified areas serve to shorten the

waiting time of the patients, screen patients with diarrhea
who need to be referred/hospitalized, provide ORS,
practice SCMD on routine basis and educate mothers/
caretakers about home management. Depending upon
the patient load, available space and other facilities, this
identified area may function as a Mini DTTU (one room
multi-purpose assessment and treatment area for
mothers and children with all sorts of problems) as in a
District Hospital or ORT Corners (extension of
outpatient department with facilities of providing ORS,
rehydration under observation and educating mothers)
as in a Primary Health Centre.
Prevention of Diarrhea
Diarrheal diseases can be prevented to a great extent by
improving infant feeding practices and personal and
domestic hygiene. Some of the interventions which are
feasible and costeffective include: (i) promotion of
exclusive breastfeeding up to 6 months of age;
(ii) improved complementary feeding practices; (iii) use
of clean drinking water and sufficient water for personal
hygiene; (iv) hand washing; (v) use of sanitary toilets;
(vi) safe disposal of the stool of young children and (vii)
measles vaccination.
Rota Virus Vaccines
Recent studies have demonstrated safety and efficacy of
2 new live, oral, attenuated rota virus vaccines (RVV) in
middle and high income countries thereby suggesting a
combined preventive and treatment strategy (vaccine,
low osmolarity ORS and zinc supplementation) to significantly reduce child mortality. However, the diversity
of rotavirus strains and high prevalence of mixed
infections are unique features of rota virus epidemiology
in India. Therefore there is a need for uniform,
widespread surveillance for rotaviruses before the
initiation and during the implementation of RVV
immunization programs.
609
13.2 Persistent and

Chronic Diarrhea in Children
Gadadhar Sarangi, Jnanindra Nath Behera
PERSISTENT DIARRHEA
Definition
Prolongation of acute diarrhea or dysentery for more than
14 days generally with associated weight loss is termed
persistent diarrhea (PD).
When the age of onset is before 3 months, it is often
termed intractable diarrhea of infancy. Persistent
diarrhea with weight loss and extreme malnutrition is
noted as protracted diarrhea or malnourishing diarrhea.
2. Moderate form is characterized by several motions/

day with marginal weight loss, without dehydration
and non-tolerance to milk and milk products.
3. Severe form of persistent diarrhea is heralded by
dehydration, weight loss and non-tolerance to milk
and cereals. Secondary infection often coexists with
this category (Figs 13.2.1A and B).
Causes of Persistent Diarrhea

The most important causes are:
Persistent infection with one or more enteric
pathogens.
Secondary malabsorption of carbohydrates and fat.
Intestinal parasitosis.
Infrequently dietary protein allergy/intolerance.
Pathology
Prolonged cell mediated immune form of damage to the
small intestinal mucosa is probably the final common
pathway by which a variety of noxious influences nutritional, infective and possibly allergic perpetuate the
syndrome of persistent diarrhea in children in
developing countries. There is impairment and considerable delay in the repair of the damaged epithelium of
the gut. Carbohydrate, fat and protein malabsorption
ensues as a result of the damage to the upper small
intestinal mucosal absorptive surface. The loss of brush
border enzymes and direct absorption of macromolecular
foreign proteins result in food intolerance and allergy
(Cows milk or wheat protein allergy). Overgrowth of
bacteria in small bowel and altered intestinal flora are
also marked as a consequence.
Three clinical types of persistent diarrhea are recognized:
1. Mild form is characterized by several motions/day
without significant weight loss and dehydration.
Figures 13.2.1A and B: Persistent diarrhea with marasmic

kwashiorkor, a resultant of infection and malnutrition
610

TABLE 13.2.1: Management guidelines for persistent diarrhea
MILD PERISTENT DIARRHEA

Try low milk formula feeds (Rice, milk, sugar and oil - diet of plan A)
MODERATE PERSISTENT DIARRHEA
Do not try milk. Permit cereal based feeds.
(Rice / wheat / bengal gram/ragi, sugar, oil-diet of plan B)
SEVERE PERSISTENT DIARRHEA
Phase - I
Resuscitation<24hours.
Phase - II
Partial control of diarrhea, sustained maintenance of vital signs. Electrolyte, metabolic and hemodynamic
balance by partial parenteral nutrition (PPN), intravenous fluids, colloids, parenteral antimicrobials (1-4 days)
Phase - III
5 days onwards (Nutritional rehabilitation)

Monitor weight
Hypo-osmolar, hypoallergenic, home available caloridense nonoffending (lactose free) feeds (plan B) in gradual
increments depending upon tolerance. If it fails - diet of plan - C (chicken / egg white, glucose and oil) along
with PPN to be given. If no response - total parenteral nutrition (TPN)
Criteria for Changing Over from Plan A to B to C

Purge volume and rate >7 stools/day at the end of 7 days
Tendency for dehydration. No weight gain/weight loss despite oral intake of 100 cal /kg/day x 3 days.
Indication for antimicrobials
1. Presence of gross blood in the stool or >10 pus cells/ HPF.
2. Resistant shigella/salmonella in the stool culture.
3. Associated systemic infections.
4. Severe malnutrition.
Antiprotozoals
For giardia or Entamoeba histolytica trophozoites in the stool.
Indications for TPN in PD

1. Protracted diarrhea with recurrent dehydration.
2. Intolerance to plan C treatment.
3. Weight loss or no weight gain even after plan C treatment.
Supplemental vitamins and minerals
About twice recommended daily allowance (RDA) of supplemental multivitamins and minerals are to be given
for at least two to four weeks. (Special attention to be given for vit A and zinc).
In severely malnourished infants
Magnesium sulphate IM and oral postassium in recommended doses to be given.
Prevention
Promotion of breastfeeding, active and prompt management of acute dirrhea, and appropriate dietatic
management during diarrhea with judicious administration of drugs will prevent dirrhea of infancy.
Diagnosis
CHRONIC DIARRHEA
The emergency risk factors arising out of dehydration,

malnutrition and infection should be assessed. Stool
examination for culture and reducing sugar with pH will
help in management. The effect of previous treatment
modalities and diet regimen should be evaluated. The
attitude and cooperation of the parents remains the
cornerstone in therapy.
Definition
Management
Pathophysiology
The management of persistent diarrhea is given in Tables

13.2.1 and 13.2.2.
Chronic diarrhea results from brakedown of intraluminal

factors responsible for digestion and mucosal factors
Chronic diarrhea is defined as diarrhea of at least 2 weeks

duration or 3 attacks of diarrhea during the last 3 months,
usually with specific conditions like celiac disease,
tropical sprue, cystic fibrosis, congenital, biochemical or
metabolic disorders.
611
TABLE 13.2.2: Diets for persistent diarrhea

Plan -A (Milk rice diet for persistent
diarrhea)
Plan -B (Egg based milk free diet for

persistent diarrhea)
Plan -C (Chicken based diet for

persistent diarrhea)
Ingredient
Amount (g)
Ingredient
Amount (g)
Ingredient
Amount / Liter
Puffed rice
Milk
Sugar
Oil
12.5
40.0
2.25
2.0
Puffed rice
Egg
Sugar/Glucose
Oil
13.5
11.0
3.5
3.5
Water to make
100.0
Water to make
100.0
Chicken
Glucose
Coconut Oil
KCL (15 %)
NaHCO3 (7.5%)
100 g
20 to 40 g
40 to 50 g
7.5 ml
20 to30 ml
Total
1000 ml
The above will yield following.

Energy density
96 Kcal/100 g
Protein
10.0%
Carbohydrate
55.87%
Lactose
1.73%
Fat
33.9%
Amino acid score
1.0%
Note: Puffed rice is ground and appropriate quantities are mixed with sugar and
oil. Boiled water is then added to make a
thick gruel. This feed has a shelf life of
around 3 hours.
The above will yield following.

Energy density
92.2 Kcal/100 g
Protein
9.5%
Carbohydrate
56.9%
Fat
33.29%
Amino acid score
1.0%
Note: Egg white is added to the mixture
of weighed rice, sugar and oil. Boiled
water is added to make a thick gruel
weighing 100 gm
The above will yield energy 720 Kcal and

Protein 26 g
Note: (i) It is prepared by grinding the
precooked boneless chicken stuff in a
mixie. Glucose, oil and some water are
added to it and the feed is brought to a
boil. Additional water is added to make a
final volume of 1 liter. Finally KCL and
NaHCO3 are added to safe guard against
spoilage it is stored in a refrigerator.
(ii) Glucose is initially added in 2%
concentration and then built up to 4% by
increasing 1% every alternate day. To
reduce osmolar load a mixture of Glucose
and sugar may be employed.
(iii) Any vegetable oil may be employed in
place of coconut oil.
responsible for digestion as well as secretion. The

mechanism of diarrhea with the involved intestinal sites
are as follows:
1. Osmotic diarrhea in which the undigested nutrients
get fragmented to short chain fatty acids and increase
the intraluminal osmotic load in colon. It shows good
response to fasting.
2. Secretory diarrhea is one in which due to noxious
agents or exotoxins threre is increase of intracellular
adenosine monophosphate (AMP) or guanosine
monophosphate (GMP) which results in sodium and
fluid secretion.
3. Mutation in apical membrane transport protein like
chlorde bicarbonate exchange transporter which
results in chronic diarrhea from neonatal period with
failure to thrive.
4. Reduction in anatomic surface area of the gut due
to extensive resection in necrotizing enterocolitis,
midgut volvulus or intestinal atresia results in loss of
fluid, electrolyte and nutrients from the gut.
5.
Alteration in intestinal motility as in malnutrition

and diabetes mellitus, causes secretory diarrhea.
6. Inflammatory process like regional enteritis and
ulcerative colitis involving a signficant portion of the
gut causes chronic diarrhea.
Causes
The common causes of chronic diarrhea is given in Table
13.2.3.
Evaluation
The evalution should be done in a stepwise manner in
order to avoid confusion in diagnosis (Table 13.2.4).
Treatment
Treatment depennds upon the cause.
Restriction of carbonated drinks or excess fruit juice
will reduce stool frequency in chronic nonspecific
diarrhea. In diarrhea due to secondary carbohydrate
612

TABLE 13.2.3: Common causes of chronic diarrhea
Infancy
TABLE 13.2.4: Evaluation of patients with chronic diarrhea

PHASE- I
Clinical history including specific amounts of fluids

ingested per day. Physical examination including
nutritional assessment. Stool exam (pH, reducing
substances, smear for white blood cell count, fat,
ova, and parasites)
Stool culture
Stool for Clostridium difficile toxin
Blood studies (complete blood cell count,
erythrocyte sedimentation rate, electrolytes, blood
urea nitrogen, creatinine)
PHASE- II
Sweat chloride
72- hr stool collection for fat determination
Stool electrolytes, osmolality
Stool for phenolphthalein, magnesium sulfate,
phosphate, Breath H2 test
PHASE- III
Endoscopic studies
Small bowel biopsy
Sigmoidoscopy or colonoscopy with biopsies
Barium studies.
PHASE- IV
Hormonal studies - vasoactive intestinal polypeptide, gastrin, secretin, 5-hydroxyindoleacetic

assays.
Post-gastroenteritis malabsorption syndrome

Protein - energy malnutrition
Cows milk / soy protein intolerance
Secondary / primary disaccharidase deficiencies
Cystic fibrosis
Childhood
Excessive consumption of carbonated fluids (Chronic

nonspecific diarrhea)
Secondary disaccharide deficiency
Intestinal parasites - Giardia, E. histolytica, Cryptosporidia.
Post-gastroenteritis malabsorption syndrome
Celiac disease
Cystic fibrosis
Intestinal infection - Enteropathogens, M. tuberculosis
Tropical sprue
Adolescence
Irritable bowel syndrome

Inflammatory bowel disease - Crohns disease, ulcerative
colitis
Giardiasis
Lactose intolerance
intolerance reduction of lactose or sucrose in the diet will

help. Lactase can be used to aid in digestion of lactose. If
diarrhea persists, elimination of lactose/sucrose
depending upon the situation is indicated.
If stool examination revelas more fat, malabsorption
syndrome remains a distinct possibility. Postgastroenteritis malabsorption syndrome needs predigested formula
to which a great proportion responds favorably.
Infants presenting with secretory diarrhea in the 1st
month of life need nutritional support as the likely cause
is congenital defect in transport proteins.
In instances where chronic diarrhea is a minfestation
of a disease, the etiology should be established and
specific treatment instituted.
Nitazoxanide therapy can be instituted where giardia
lamblia or cryptosporidium parvum are suspected or
found.
BIBLIOGRAPHY
1. Bhan MK (Ed). Guidlines for Managment of Diarrhoea
in childen. Task force on diarrhoeal disease.
2. Bhave SY, et al. Common problems faced in diarrhea in
pediatrics. J Gen Med 1993,5:16-24.
3. Branski D, Lerner A, Lebenthal E. Chronic diarrhea and

malabsorption. Pediatr Clin North Am 1996;43:307.
4. Donowitz M, Kokke FT, Saidi R. Evaluation of patients
with chronic diarrhea. N Engl J Med 1995;332:725.
5. Fayez K. Ghisshan diarrhea. In: Beharman RE, Kliegman
RM, Jenson HB (Eds): Nelson Textbook of Pediatrics, 18th
edn, 1621-6.
6. Gupte S, Anderson RA. Persistent diarrhea and Chronic
diarrhea, In: Gupte S (Ed): The short text book of
pediatrics, 10th edn, 2004;382-7.
7. IAP Guidelines for management of diarrhea in children,
1994.
8. Kneepkens CM, Hoekstra JH. Chronic nonspecific
diarrhea of childhood: Pathophysiology and Management Pediatr Clin North Am 1996;43:375.
9. National child survival and safe motherhood programme, integrated clincial skills course for physicians.
Diarrheal disease, module, MCH division, Dept. of
Family Welfare, Ministry of Health and Family Welfare,
Govt. of India, 23-4.
10. Sullivan PB, Marsh MN. Small intestinal mucosal
histology in the syndrome of persistent diarrhoea and
malnutrition: a review. Acta pediatrica 1992;81(s383):
72-7.
11. World Health Organization; Diarrhea managment
training course manual; Guidelines for conducting
clinical training couses at health centers and small
hospital, 1990.
613
13.3 Parenteral Nutrition in Children

Anand N Pandit, Ashish R Bavdekar
Nutritional therapy is now increasingly recognized as
an important component of pediatric intensive care. In a
number of illnesses (both surgical and medical), the
nutritional demands of the child cannot be met
adequately through the enteral route for prolonged
periods. Nutritional support however, is critical not only
to minimize negative nitrogen balance but also to
promote growth and development, which, during early
childhood is at its peak velocity. The concept of providing
all the required nutrients like proteins, carbohydrates,
fats and vitamins via the intravenous route, is called
parenteral nutrition (PN).
The advent of successful parenteral nutrition (PN) has
indeed reversed the prognosis of many such illnesses,
which were hitherto fatal. The popularity of PN is now
fast growing in our country too, despite the constraints
of cost and infrastructure. Although widespread
availability is very much desired, it is important that the
technique is developed with considerable expertise and
used judiciously with full knowledge of its indications,
limits, danger and benefits.
INDICATIONS
PN is required in any situation in which the baby should
not be fed, will not feed, or cannot be fed adequately for
prolonged periods. The range of indications of PN has
grown considerably in recent years. It is usually indicated
when oral intake has been or is likely to be inadequate
for more than 5 to 10 days. Other deciding factors are
age, underlying malnutrition, nature of concurrent
therapeutic measures (e.g. ventilation) and the expected
outcome of the disease. In our setup, social and monetary
background also are important considerations. Some
common indications are discussed below.
Surgical Conditions
PN has dramatically changed the outcome in extensive
resections of the small intestine, entero-cutaneous fistulae
and proximal enterostomies (short gut syndrome). At our
center too, the most gratifying results with PN were in
surgical neonates with successful corrections, e.g.
tracheoesophageal fistula, duodenal atresia, omphalo-
cele, and Hirschsprungs disease. The need for PN in such

conditions can be predicted early and therapy can be
started immediately after corrective surgery.
Low Birth Weight Infants (LBWS)
The numerous feeding difficulties, the poor intestinal
function, and the greatly increased requirements make
PN a logical choice in very LBWs. Though routine
supplementation of VLBWs with PN is controversial,
its critical role in conditions such as necrotizing enterocolitis, and surgical anomalies is undoubted.
Malabsorption Syndrome
One of the commonest indications for PN has been severe
protracted diarrhea in children irrespective of the
etiology: infectious diarrheas, milk protein or lactose
intolerance, or immune deficiency. The recent use of
special enteral diets have definitely reduced the need of
PN in these cases. However, a few with severe small
intestinal mucosal pathology like intractable diarrhea
often require long-term PN as gastrointestinal losses of
fluids, electrolytes and proteins continue even after
stopping all enteral feedings. A judicious combination
of enteral and parenteral nutrition will obviously allow
restoration of normal nutritional status while
maintaining gastrointestinal function.
Non-gastrointestinal Indications
An increasingly common indication of PN today is in
management of children with malignant diseases, as
chemotherapy and radiation may impair intestinal
mucosa, damage circulatory vessels and lymphocytes and
interfere in gastrointestinal motility. PN is also increasingly
used in a host of other conditions such as end stage liver
disease (waiting for liver transplants), renal failure (with
appropriate amino acids) and multiple trauma or extensive
burns (to combat excessive nitrogen losses).
NUTRIENT SOURCES
The basic solutions comprise a protein source, a lipid
source, and a carbohydrate source to be mixed with
614
electrolytes, vitamins and trace metals, all appropriate

to the age, body weight and energy requirements of the
child.
Proteins
These solutions are mixtures of crystalline amino acids
(AA), at least 40 percent of which are essential amino
acids. Neonates and young infants are particularly
sensitive to imbalance in amino acids solutions. The
amino acids of particular concern are methionine,
phenylalanine and glycine, which are not fully metabolized by infants. Caution should, therefore, be exercised
while using AA solutions primarily designed for adults.
Lipids
Parenteral lipid emulsions are available in 10 percent or
20 percent strengths. They are calorie dense, rich in
essential fatty acids and have a protein sparing effect.
Being isotonic and low in osmotic activity, lipids can be
given through peripheral veins for prolonged periods.
Tolerance to lipids is, however, reduced in VLBWs and
should therefore, be introduced cautiously.
Carbohydrates
Glucose is the carbohydrate of choice, as it is an energy
substitute with ubiquitous utilization by all tissues of the
body. Glucose substitutes such as sorbitol, fructose, and
xylitol, have also been tried although they are
metabolized only in the liver and tend to cause osmotic
diuresis.
Electrolytes, Vitamins,
Minerals and Trace Elements
Daily estimated requirements of electrolytes, vitamins
and minerals (Na, K, Ca, P and Mg) must be added to
PN. Intravenous preparation for phosphorus is not easily
available in India and has to be supplied orally.
PN ASSEMBLY AND REGIMENS
PN is introduced gradually over a period of 2 to
4 days depending on size and age of child. The calculated
quantities of amino acids, dextrose and electrolytes are
mixed in the same bottle under laminar air flow. This
mixture and the lipid emulsion are administered by
separate IV sets and the two lines coupled by a Y
connector just before entry into the vein. Both the
solutions should be regulated by infusion pumps to
Figure 13.3.1: Parenteral infusion: assembly
TABLE 13.3.1. Guidelines for parenteral nutrition doses

Nutrient
Starting
dose
Advance by Goal
Maximum
% of total
cals
Proteins
1 gm/kg/
day
1 gm/kg/
day
3 gm/kg/
day
15
Lipids
1 gm/kg/
day
1 gm/kg/
day
3 gm/kg/
day
3050
Carbo-
57 mg/
24 mg/
1012 mg/
5060
hydrates
kg/min
kg/min
kg/min
provide accurate steady flow rates (Fig. 13.3.1).

Progressive build up regimens for neonates, infants and
older children have been described (Table 13.3.1).
Proteins/fat/dextrose should not be decreased until
enteral feeds exceed 50 ml/kg/day. However, do not
exceed total (enteral + parenteral) proteins 3.5 g/kg/day
and fat 5 g/kg/day. Stop PN when three-fourth of daily
enteral intake has been achieved. Parenteral nutrition is
to be given preferentially by peripheral veins. Central
catheters should be used as sparingly as possible because
of high rate of complications.

COMPLICATIONS
The provision of parenteral nutrition is associated with
significant and sometimes life-threatening complications.
These need to be considered before starting PN to any
child. These complications can be classified as:
Technical
Complications of peripheral access are thrombosis,
perforation of vein, with necrosis of tissue, and
thrombophlebitis. Central venous access has potential
for more serious complications, pneumothorax, arterial
hemorrhage, air embolism and cardiac arrhythmias.
Infections
Sepsis associated with PN is life-threatening. Sources are
multiple and include entry site of catheter, connections,
PN fluids, etc. The common organisms are Staph.
epidermidis, Staph. aureus and occasionally gram negative
and fungal sepsis. Therapy is determined by the organism
involved and antibiotic sensitivity. Most catheters can be
preserved using appropriate antibiotics with heparin or
urokinase. Prevention of catheter related sepsis is of
paramount importance and strict asepsis during catheter
insertion, preparation and administration of PN, use of
laminar flow system and training of staff dealing with PN
will go a long way in reduction of sepsis.
Metabolic
i. Complications of protein metabolism: The use of
crystalline amino acids has significantly reduced
the risk of hyperammonemia. Amino acid infusion
may have to be reduced till ammonia levels
normalize. Metabolic acidosis is more frequent
when a large infusion of amino acids is given to
preterm infants.
ii. Complications of carbohydrate metabolism: Hyperglycemia is usually a problem in central venous
administration when dextrose is delivered directly
into the central venous flow. Other causes to be
considered are hypokalemia, sepsis are steroid use.
Hyperglycemia could lead to glycosuria, osmotic
diuresis and dehydration.
iii. Complications of fat metabolism: Hypertriglyceridemia and high free fatty acid levels are
associated with PN. These can be prevented by
either using mixed solution of MCT and LCT or
regular monitoring of serum triglyceride levels.
615
iv. Complications related to electrolytes and minerals:

Hyponatremia, hypo/hyperkalemia hypocalcemia,
hypomagnesemia and hypophosphatemia are
commonly associated with PN. These are often
iatrogenic and preventable by monitoring. Trace
element and vitamin deficiencies are common on
long-term PN. They need to be supplemented
especially in LBW infants.
Hepatobiliary Complications
These include steatosis, cholestasis, fibrosis, cirrhosis or
cholelithiasis. Abnormal LFT is seen in quite a few
children on PN for more than two weeks. In most
patients, these liver enzymes improve with initiation of
partial enteral feeds. Fatty infiltration of the liver occur
due to excess carbohydrate calories or inappropriate nonprotein calorie nitrogen ratio. This is readily reversible
by reducing the carbohydrate infusion.
The fear of PN related complications has always been
a deterrent in the institution of this potentially life-saving
technique. However, the complication rates have shown
a marked decline with experience and expertise the
world over. Specially designed, locally manufactured
intravenous sets, use of a laminar flow workstation for
compounding and other such adaptations have
contributed further.
MONITORING
Meticulous monitoring is necessary not only to detect
complications, but to document clinical benefit. Most
septic and metabolic complications can be prevented or
detected before they cause serious consequences, if the
biochemical monitoring protocol is followed rigidly.
Monitoring should be more frequent in the initial stages
of PN and perhaps, less frequent once PN is well
established. The monitoring protocol at our hospital is
given in Table 13.3.2. It is mandatory to develop micromethod systems for biochemical monitoring in newborns
and young infants. In absence of these, blood sampling
volumes should be carefully recorded and replenished
when indicated. Adjustments in daily electrolytes,
nutrients and fluid orders are based on biochemical
monitoring.
COST ANALYSES
Cost saving may be achieved by (i) reducing wastage by
sharing solutions and preventing over prescription; (ii)
616

TABLE 13.3.2. Suggested monitoring protocol for
parenteral nutrition
Serum electrolytes
3 times/week initially, then weekly
Serum urea nitrogen
3 times/week initially, then weekly
Calcium, magnesium,
phosphorus
3 times/week initially, then

weekly
Glucose
2 times/day
Serum proteins
Weekly
Weekly
Hematocrit
Weekly
Urine glucose
Daily
Serum triglycerides
4 hours after a dose increase of

lipids initially, then weekly
decreasing complications by using peripheral lines,

preventing metabolic complications, and strict asepsis
and (iii) indigenization of equipment.
A reduction in cost should not be attempted by

(i) repeated use of solutions; (ii) compromise on biochemical monitoring; (iii) compromise on disposables;
(iv) compromise on infusion pumps; and (iv) substituting
hypertonic glucose for lipids.
BIBLIOGRAPHY
1. Arnold WC. Parenteral nutrition, and fluid and electrolyte therapy. Pediatr Clin North Am 1990;37:45961.
2. Arthur CD. Fundamentals of Parenteral Nutrition, 2nd
edn. London, Smith and Smith, 1985.
3. Ball PA, Booth IW, Puntis JWL. Pediatric Parenteral
Nutrition. Bourne End. Kabi Vitrium 1989;1619.
4. Bhave SA, Bavdekar AR. Pediatric parenteral nutrition
in India. Indian J Pediatr 1999;66(1 Suppl):S1419.
5. Cochran EB, Phelps SI, Helms RA. Parenteral nutrition
in pediatric patients. Clin Pharmacy 1988;7:35165.
6. Zlotkin SHM, Stallings VA, Pencharz MB. Total
parenteral nutrition in children. PCNA 1985;32:381400.
13.4 Parasitic Bowel Diseases

BD Gupta
Parasitic bowel diseases. are group of infectious diseases
due to protozoa and helminths, and are a major cause of
morbidity in infants and children in many parts of the
world.
Parasitic bowel diseases may be classified according
to their etiological agents as under:
I. Protozoal diseases: Entameba histolyica, Giardia
lamblia, Balantidium coli, Cryptosporidium parvum.
Blastocystis, Isospora belli, Cyclospora cayetanensis and
Microsporidia.
II. Helminthic diseases:
A. Nematodes: Ascaris lumbricoides, Enterobius
verrmicularis, Hookworms, i.e. Ankylostoma
duodenale and Necator americanus, Trichinella spiral
is, and Trichuris trichura.
B. Trematodes: Fasciolopsis buski, Nanophyetus
salmincola, and Heterophyes heterophyes.
C. Cestodes: Taenia solium, Taenia saginata,
Diphyllobothrium laturn, Hymenolepis nana, and
Echinococcus granulosus.
ETIOPATHOGENESIS
Parasitic bowel diseases are endemic in areas of world
with poor sanitation and low socioeconomic standards.
Two distinct modes of transmission are known, namely
faeco-oral route and cutaneous route.
1. Protozoa like E. histolytica, G. lamblia and B. coli infect
humans by ingestion of cysts while nematodes like
A lumbricoides, T. trichura, E. vermicularis and
cestodes like T. saginata, T. solium and D. latum spread
by ingestion of contaminated food and water with
eggs of respective parasites.
2. Hookworms like A. duodenale and N. americanus alter
the human body through skin penetration by their
larvae. These larvae undergo extraintestinal
migration through the venous circulation and lungs
before they are swallowed to reach intestine.
Various parasites localize themselves at various sites
in small as well as large intestine as per their suitable
environment, e.g. E. histolytica dwell in colon, G. lamblia
colonize in the lumen of duodenum and proximal

jejunum, B. coli infests the large intestine, A. lumbricoides
in small intestine, T. trichura in caecum and ascending
colon, and E. vermicularis typically inhabits caecum,
appendix and adjacent areas of ileum and ascending
colon.
Various parasites cause symptoms due to invasion
(E. histolytica), obstruction (A. lumbricoides), reduced
absorptive surface (G.lamblia) and blood sucking
(Hookworms).
CLINICAL FEATURES
Parasitic bowel disease is associated with wide variety
of clinical manifestations ranging from asymptomatic
carrier stage to various intestinal and extraintestinal
manifestations. The clinical features depend largely on
the parasite, site of involvement, mechanical factors and
interference with hosts nutrition.
General Symptoms
Most of parasites present with diarrhea which can be
acute, chronic or recurrent; bloody or nonbloody;
associated or not associated with tenesmus, abdominal
cramps, bloating, flatulence etc. Other symptoms include
nausea, vomiting, anorexia, weight loss, fever, abdominal distension, malaise, myalgia, headache, etc.
Various other clinical features caused by different

parasites are summarized in Table 13.4.1.
LABORATORY DIAGNOSIS
Parasitic bowel diseases can be diagnosed by examination
of stool samples by direct microscopy. Repeated fresh
samples may be required to reach the diagnosis of
clinically suspected organisms. The stool examination may
be supported by blood examination for evidence of
eosinophilia and various serological tests specifically
designed for the organism under consideration. Stool
examination along with endoscopically obtained smears
and tissue biopsy helps a lot in diagnosis of parasites.
Ideally fresh stools should be examined within 30 minutes
of passage for evidence of trophozoites/cysts in case of E.
histolytica or G. lamblia. Stool samples preserved in
polyvinyl alcohol (PVA) helps in diagnosis of these
organisms. Serological tests like Indirect hemagglutination
are available for E. histolytica. Enterotest on duodenal fluid
for giardiasis is another alternative.
Stool examination and demonstration of oocysts helps
in diagnosis of spore forming intestinal protozoa like
Cryptosporidium, Isospora, Cyclospora etc. Other tests for
parasites are enzyme immunoassay, indirect immunofluorescence and PCR.
TABLE 13.4.1: Clinical manifestations

Clinical manifestation
Parasitic bowel disease(s)
Nutritional Deficiency
(Vitamin A deficiency)
Ascariasis, giardiasis, and infection by intestinal flukes
Anemia
Iron deficiency
B12 or folic acid deficiency
Hookworm disease
D. latum (Diphyllobothriasis), Trichuriasis
Malabsorption Syndrome
Giardiasis, ascariasis, hookworm diseases and infection by intestinal flukes
Weight loss
Giardiasis, hookworm disease, diphyllobothriasis and spore forming protozoa like

cryptosporidiasis, isosporiasis and cyclosporiasis
Intestinal obstruction
Ascariasis, taeniasis
Rectal prolapse
Giardiasis, trichuriasis
Extraintestinal involvement:
Liver
Muscles
Skin
Brain
Lungs
Amebiasis, intestinal flukes

Trichinosis, flukes, spore forming protozoa, e.g microsporidia
Cutaneous larva migrans-hookworm, Strongyloides stercoralis
Amebiasis, trichinosis, microsporidiasis, taeniasis-neurocysticercosis
Amebiasis, ascariasis, hookworm disease Strongyloides stercoralis
Immunodeficiency states
617
Associated parasites-Cryptosporidium parvum, Isospora belli, Cyclospora

cayetaeniasis, Microsporidium (AIDS), Giardiasis, Amebiasis
618

TABLE 13.4.2: Common parasitic infections and their treatment
Etiological agent
Major clinical features
Treatment
Alternative Drug (s)
Entamoeba
histolytica
Diarrhea
Dysentry
Liver abscess
Metronidazole 30-50 mg/kg/day orally

in 3 doses for 10 days
Diloxanide furoate 20 mg/kg/day
orally in 3 doses for 10 days
Dehydroemetine 1 mg/kg/day sc or im daily
for 7-10 days
Omidazole 30-50 mg/kg/day orally

in 2 dose
Nitazoxanide 7.5 mg/kg twice daily
for 3 days
Giardia lamblia
Diarrhea
Malabsorption
Metronidazole 5-10 mg/kg tid orally for

5 days
Furazolidone 6 mg/kg/day q 6 hrs.
for 10 days
Nitazoxanide 7.5 mg/kg twice daily for 3 days
Quinacrine 2 mg/kg tid orally for

5 days
Albendazole 400 mg OD for 5 days
Tinidazole 50 mg/kg once
Balantidium coli
Diarrhea/dysentery,
pain abdomen
Metronidazole 45 mg/kg/day q 8 hrs.

orally for 5 days
Tetracycline 40 mg/kg q 6 hrs.

for 10 days (>=8 yrs)
Iodoquinol 40 mg/kg/day q 8hrs
PO (10 days)
Crytosporidium
Severe diarrhea with

malabsorption in
AIDS patients
Nitazoxanide 100 mg bid orally for

3 days
Paromomycin 1 gm bid orally +

azithromycin 600 mg/day orally
for 4 week followed by paromomycin
1 gm bid oral 8 weeks
Isospora belli
As above
Trimethoprim 5 mg/kg/dose +
sulphamethoxazole 25 mg/kg/
dose 8 hourly for 10 days
then bid for 3 weeks
Ciprofloxacin or pyrimethamine +/folinic acid in sulpha-intolerant patients
Cyclospora
As above
Trimethoprim 5 mg/kg/dose +
sulphamethoxazole 25 mg/
kg/dose bid orally for 7 days
Ciprofloxacin
Microsporidium
As above
Albendazole 400 mg bid for

3 weeks
Nitazoxanide 7.5 mg/kg

bid for 3 days
Atovaquone
Albendazole 400 mg orally

once Mebendazole 100 mg
bid orally for 3 days or 500
mg once Pyrantel pamoate
11 mg/kg once
Piperazine citrate 150

mg/kg orally initially
followed by 65 mg/kg/
dose 12 hourly for 6 doses
Ascaris lumbricoides Abdonimal pain, cough,

nausea
Ivermectin 200 mcg/kg

day od orally for 1-2 days
Strongyloides
stercoralis
Loeffler like syndrome

abdominal pain,
diarrhea malabsorption
Enterobius
vermicularis
Pruritus ani,
sleeplessness
Trichuris trichiura
Ivermectin 200 mcg/kg/day

once orally for 1-2 days
Pyrantel pamoate 11 mg/kg

once Mebendazole 100 mg bid
PO for 3 days Albendazole
400 mg/kg once (Therapy to
be repeated after 2 weeks)
Chronic dysentery
Mebendazole 100 mg bid
Rectal prolapse, anemia orally for 3 days or 500 mg
once
Thiabendazole 50 mg/kg
bid orally for 2 days
Albendazole 400 mg
once for 2 days
Ivermectin 200 mcg/kg/day
orally for 1-2 days
Albendazole 400 mg once
Contd...
619
Contd...
Etiological agent
Major clinical features
Hookworm infection
(A.duodenale,
N.americanus)
Abdominal pain, loss of Albendazole 400 mg/day

appetite, diarrhea,
orally once Mebendazole
anemia, hypoalbuminemia 100 mg bid for 3 days
Pyrantel pamoate 11 mg/kg/day

once for 3 days
Hymenolepis nana
Abdonimal pain,
discomfort
Praziquantel 25 mg/kg orally once

(if available)
Nitazoxanide 7.5 mg/kg bid orally for 3 days
Albendazole 400 mg/day for 3 days
Trichinella spiralis
Diarrhea, fever,
periorbital edema,
myalgia
Megaloblastic anemia,
leukopenia,
thrombocytopenia
Mebendazole 200-400 mg tid orally for

3 days then 400-500 mg tid for 10 days
Albendazole 400 mg bid orally for

8-14 days
Praziquantel 5-10 mg/kg orally once
Niclosamde 50 mg/kg once
Diphyllobothrium
latum
Treatment
Demonstration of eggs of helminths in stool is the

mainstay of diagnosis of most of the parasites. For
ascariasis, Katos thick smear examination of stool is easy
and sensitive method. Fertilized eggs signify infection
with both male and female worms while unfertilized
eggs show infection with female worm only. Enterobiasis
can be diagnosed by examining cellophane tape imprint
from perianal area. For trichinosis serologic tests like
Bentonite flocculation test, muscle biopsy levels of muscle
enzymes like creatine kinase and LDH help in diagnosis.
PREVENTION AND CONTROL
Parasitic bowel diseases essentially are much more
prevalent in areas of poor sanitation and environmental
conditions. Hence, these diseases can be prevented by
following measures viz. safe disposal of human excreta
safe water supply, proper food hygiene, personal and
community hygiene, health education, and early
diagnosis and treatment of symptomatic and asymptomatic cases.
Treatment
Treatment for various parasitic diseases is outlined in
Table 13.4.2.
Alternative Drug (s)
BIBLIOGRAPHY
1. Chen X M, Keithly JS, Paya CV, et al. Cryptosporidiasis.
N Engl J Med 2002;346:1723-31.
2. Chandler AC. Indian J Med Res 1927;15:695-743.
3. Chowdhary AB, Sehad GA, Am J Trop Med and hyg
1972; 21: 300-301.
4. Conteas CN, Berlin OG, Ash LR, Pruthi JS. Therapy for
human gastrointestinal microsporidiasis. Am J Trop Med
Hyg 2000;63:121-7.
5. Franzen C, Muller A. Cryptosporidia and microsporidiawaterborne diseases in the immunocompromised host. Diagn Microbiol Infect Dis 1999; 34:245-62.
6. Gardener TB, Hill DR. Treatment of giardiasis. J Clin
Microbiol 1997;35:1526-29.
7. Kliegman RM, BehrnIan RE, Jenson HB and Stanton BF
(Eds). lnfectious diseases. In: Nelson Textbook of
Pediatrics. 18th atition. New Delhi, Saunders Elsevier
Indian Edition 2008;1448-1519.
8. Park K. Intestinal infections. In: Parks text book of
Peventive and Social Medicine. 17th edition. Ed Park K.
Jabalpur, Banarsidas Bhanot 2002;166-70.
9. Park K. Intestinal infections. In: Parks textbook of
Peventive and Social Medicine. 19th edition. Ed Park K.
Jabalpur, Banarsidas Bhanot 2007;167-205.
10. Patel SS, Kazura JW. Helminthic diseases. In: Nelson Text
book of Pediatrics. 17 th edition. Eds Behrman RE,
Kliegman RM, Jenson HB. Saunders, Philadelphia 2004;
1155-73.
11. Tripathi KD. Antiamoebic and other antiprotozoal drugs
and anthelmintic drugs. In: Essentials of medical
pharmacology. 6th edition. Ed Tripathi KD. New Delhi,
Jaypee Brothers Medical Publishers (P) Ltd 2008;797-816.
12. WHO. Tech Rep Ser 1969:421.
620
13.5 Vomiting in Infants and Children

S Nagabushana
Vomiting is a coordinated motor response of the
gastrointestinal and respiratory tracts that results in
increased salivation followed by forceful expulsion of the
stomach contents. It occurs in three phases, i.e (a)
nausea,(b) retching and (c) emesis. In very young
children and in those with raised intracranial pressure,
vomiting is induced without nausea.
Regurgitation (Possetting), on the other hand is a
nonforceful, effortless expulsion of gastric contents
through the mouth, It is common in neonates and infants,
is often a developmental process and does not need
therapy; the symptoms resolve with age and the child
thrives well. In contrast, Gastroesophageal reflux disease
(GERD) is abnormal as in addition to vomiting it is
usually associated with complications like aspiration,
pneumonia and esophagitis and the child may not thrive
well. It therefore needs early recognition and prompt
therapy.
Pathophysiology
The causative mechanisms can be depicted as in the Flow
Chart 13.5.1.
The common causes of vomiting in different age
groups are as illustrated in Table 13.5.1
Approach to Management
Enquire about the duration, frequency, presence of blood
or bile in the vomitus. Ask about associated abdominal
pain, recent changes in feeding pattern, changes in
urinary color, drug consumption and presence of
associated fever or sensorial alteration. Look out for
symptoms and signs attributable to the respiratory,
gastrointestinal, urinary and central nervous system in
that order. Assess the child for signs of dehydration.
Remember that parental perception of how sick their
child is in between episodes of vomiting helps us to
determine the seriousness of the illness and the measures
to be adopted. In neonates and infants with acute
vomiting the possibility of serious infections like sepsis,
meningitis or urinary tract infection needs to be
considered and ruled out, i.e. the Cause of vomiting may
be outside the gastrointestinal tract. Further, vomiting
due to benign non-organic causes does not lead to
significant dehydration or weight loss.
Flow Chart 13.5.1: Mechanism of vomiting in children
The clinical features that indicate common organic

causes of vomiting are given in Table 13.5.2.
Investigations
The history of the child and the clinical features on
presentation most often guide the diagnosis.
a. Urine for evidence of infection (pus cells, granular
casts, bacteria, Gram stain, culture and sensitivity),
proteinuria and abnormal metabolites.
b. Blood for evidence of systemic infection (leucocytosis,
toxic granules, band forms, C reactive protein,
appropriate cultures, etc.)
c. Liver function tests
d. Renal function tests, electrolyte studies and metabolic
screening tests (e.g. Lactate, Organic acids, Ammonia,
etc.)
e. Stool for blood, pus cells, evidence of parasitic
infestations
f. Radiological studies: Plain and Contrast X-rays of
abdomen, ultrasound or endoscopy.
g. Lumbar puncture and CSF analysis in children with
clinically suspected intracranial infection.
h. CT or MRI Scan of skull or abdomen or sinuses as
and when indicated.

TABLE 13.5.1: Common causes of vomiting by age of
presentation
Newborn
Infant and child
Infections
Sepsis
Meningitis
Gastroenteritis
Meningitis
Respiratory
infections
Anatomic
Atresias and webs

Duplications
Malrotation/
volvulus
Pyloric stenosis
Intussusception
Gastrointestinal
Overfeeding/
Possetting
Gastroesophageal
reflux
Gastritisswallowed
meconium
Gastroesophageal
reflux
Gastritis
Hepatitis
Appendicitis
Renal
Urinary tract
infection
Urinary tract
infection
Neurologic
Birth trauma
Subdural
hematoma
Increased intracranial tension
Migraine
Metabolic
Uremia
Endocrine
Congenital
adrenal
hyperplasia
Diabetes mellitus
Acute intermittent
porphyria
Others
Cyclical vomiting
Toxin ingestion
TABLE 13.5.2: Features indicating organic causes
I. Persistent forceful vomiting

II. Abdominal distension
III. Palpable mass/abdomen or visible peristalsis
IV. Failure to gain weight/loss of weight
V. Altered sensorium/ failure to accept/demand feeds
VI. Bulging fontanelle/persistent headache
VII. Sudden onset in a well child/vomiting in an ill child
with fever.
VIII. Persistent irritability in an infant with vomiting
IX. Persistent copious bilious vomiting
621
Management
The principles of management include recognition and
treatment of the primary causes of vomiting in addition
to symptomatic therapy and correction of dehydration.
Steps of symptomatic treatment include stomach wash
in neonates and infants, with holding oral fluids for a
few hours and gradually restarting in sips. If a child
has persistent vomiting, dehydrated or electrolyte
imbalances, IV fluids are necessary. The preferred fluid
is normal saline or 5 percent dextrose saline.
Persistent vomiting due to simple gastroenteritis is
relieved by a single dose of antiemetic. If vomiting is not
relieved, look out for other causes like intestinal
obstruction, raised ICT, infection, etc. It is always prudent
to remember that organic causes of vomiting do not
satisfactorily respond despite adequate doses of
antimetics. In clinical practice, hasty use of an antiemetic
without definite diagnosis of the cause has to be avoided.
Antiemetics like Metaclopromide or Domperidone
hasten stomach emptying and are useful if used
judiciously. Ondonsetron, a serotonin antagonist is
effective in the treatment of chemotherapy induced and
refreactony causes of vomiting.
Cyclic vomiting is a syndrome of recurrent vomiting
(about 9 episodes per month) with onset in children aged
3 to 5 years. It occurs periodically, lasts 3 to 4 days, with
four or more episodes per hour it is usually due to a
combination of psychogenic factors (excitement and
stress) and a liability to Ketone formation. Abdominal
migraine may present as idiopathic cyclic vomiting.
Treatment consistes of rest, IV rehydration with dextrose
saline administration and Ondonsetron. Preventive
treatment with drugs like Amitryptaline or Cyproheptidine is possible.
Recurrent vomiting (> 3 episodes in 3 months) needs
prompt investigations to identify the cause.
BIBLIOGRAPHY
1.
Approach to a child with acute, chronic or cyclic

vomiting. Rudolph AM, Hoffmann JIE, Rodolph CD
(Eds): Rudolphs Pediatrics, 20th end. 1991>Prentice hall
International Inc. USA, 2;303:1523-24.
2. Behrman, Kliegmenn, Jensonand Stanton (Eds): Nelson
Textbook of pediatrics 18th edn. Elsevier Saunders
2004;1199-1200.
622
3.
Flake ZA, Sca1ley RD, Bailey AG. Practical selection of

antiemetics. Am Fam Physician 2004;69:1169-74,1176.
4. Illingworth RS (Ed). Common symptoms of disease in
children. Oxford University press (9th edn) 69-82.
5. John W Graef (Ed). Manual of Pediatric therapeutics.4th
edn. Little Brown company: Boston l988;33-34.
6. Judith M Sondheimer (Ed). Current Pediatric diagnosis

and treatment. 16th edn 1919;614-15.
7. MK Bhan, et al. Consensus statement of IAP taskforce:
Report on management of Acute Diarrhea. Indian
Pediatrics 2004;41:335-48.
13.6 Gastroesophageal Reflux in

Infants and Children
Neeraj Jain, Vibha Jain, Deepak Seth
The term gastroesophageal reflux (GER) implies a
functional or physiologic process in a healthy infant with
no underlying systemic abnormalities. GER is a common
condition involving regurgitation, or spitting up,
which is the passive return of gastric contents retrograde
into the esophagus.
The prevalence of GER peaks between 1 to 4 months
of age and usually resolves by 6 to 12 months of age. No
gender predilection or definite peak age of onset beyond
infancy has been established. Regurgitation has been
reported in 40 to 65% of healthy infants, but decreases to
1 % by one year of age.
Gastroesophageal reflux disease (GERD) is a pathologic
process in infants manifested by poor weight gain, signs
of esophagitis, persistent respiratory symptoms, and
changes in neurobehavior. Abnormal signs and symptoms that warrant a diagnosis of GERD occur in
approximately 1 in 300 infants. A higher prevalence of
GERD is present in children who have the following: a
history of esophageal atresia with repair; neurologic
impairment and delay; hiatal hernia; bronchopulmonary
dysplasia; asthma; and chronic cough. GERD is also
associated with pulmonary aspiration, chronic bronchitis,
and bronchiectasis. All infants with GERD, therefore, do
not visibly regurgitate, and the majority of infants who
regurgitate do not have GERD.
Infants with GER regurgitate without any secondary
signs or symptoms of inadequate growth, esophagitis,
or respiratory disease. Infants with GER are thriving and
represent the majority of infants who present to the
physician with this condition.
Patients with GERD may manifest persistent

regurgitation with secondary poor weight gain and
failure to thrive. Failure to thrive occurs when caloric
intake is less than ongoing losses. Infants may manifest
signs of esophagitis, including persistent irritability, pain,
feeding problems, and iron deficiency anemia. A subset
of infants may demonstrate significant reflux by
esophageal pH monitoring but will not have symptoms
of regurgitation, known as silent GERD.
A variety of respiratory symptoms occur in infants.
Apnea and cyanotic episodes may arise secondary to
upper airway stimulation by pharyngeal regurgitation.
Instead of a pure obstructive apnea pattern, a mixed
pattern of both obstructive and central types generally
predominates. Symptoms include belching, refusal to eat,
abdominal pain, vomiting, hiccups, gagging, choking,
frequent cough, coughing fits at night, wheezing and
frequent upper respiratory infections. However, each
child may experience symptoms differently.
After infancy, more classic symptoms of esophagitis
predominate, including lower chest pain, heartburn
(pyrosis), odynophagia, dysphagia, and signs of anemia
and esophageal obstruction from stricture formation.
With the exception of apnea, older children experience
respiratory symptoms similar to infants. Complications
of reflux esophagitis may be seen, including signs of
peptic stricture and Barretts esophagus, which is the
progressive replacement of distal eroded squamous
mucosa with metaplastic gastric epithelium. Barretts
esophagus may increase the risk of esophageal adenocarcinoma in adulthood, but the risk is much lower in
children.

Differential Diagnosis of GERD
Management
Other gastrointestinal and systemic disorders must first

be excluded before considering GERD as the main cause
of an infants or childs symptoms of silent or visible
regurgitation or vomiting (Table 13.6.1).
Conservative
Diagnostic Evaluation
Diagnostic procedures for evaluation ofGERD include
chest x-ray, barium swallow with fluoroscopy of the
upper gastrointestinal tract, radio-nuclear (technetium)
scan, endoscopy, esophageal manometry, esophageal pH
studies and gastric emptying studies. In most cases of
GER, no invasive diagnostic studies are required.
TABLE 13.6.1: Differential diagnosis of GERD

Gastrointestinal tract
Pyloric stenosis
Malrotation
Cows milk allergy
Peptic ulcer disease
Hepatitis
Viral gastroenteritis
Urinary tract
Infection
Obstruction
Central nervous system
Hydrocephalus
Meningitis
Metabolic disorders
Urea cycle defects
Hypocalcemia
Drugs/toxins
Respiratory disorders
Functional rumination
623
1. Thickened feedings and positional changes in infants,

and dietary modification in children.
2. Avoidance of foods and behaviors that decrease lower
esophageal sphincter tone: This includes excessive
intake of caffeinated, acidic, and alcoholic beverages
in children and cigarette smoking in adolescents.
3. Completely upright and prone positioning is
beneficial in infants with GERD.
4. Weight reduction.
5. H2receptor antagonist: Ranitidine 1-2 mg/kg/dose.
6. Prokinetic agents: Metoclopramide 0.1 mg/kg/dose or
lisapride 0.2mg/kg/dose. Cisapride is not used
because of bradycardia and nodal dysrhythmias
associated with its use.
7. Proton pump inhibitors: Omeprazole 1.0-3.3 mg/kg/
day; lansoprazole 0.8-4 mg/kg/day; rabeprazole 1020 mg/kg/day and pantoprazole 20- 40 mg /kg/day.
Surgery
In severe cases of reflux, a surgical procedure called
fundoplication may be performed. This procedure is
usually done laparoscopically.
BIBLIOGRAPHY
1.
Glassman M, George D, Grill B. Gastroesophageal reflux

in children: clinical manifestation, diagnosis, and
therapy. Gastroenterol Clin North Am 1995;24:71-98.
2. Hill SL, Evangelista JK, Pizzi AM, Mobassaleh M, Fulton
DR, Berul CI. Proarrhythmia associated with cisapride
in children. Pediatrics 1998;101:1053-6.
3. Khoshoo V, Edell D, Clarke R. Effect of cisapride on the
QT interval in infants with gastroesophageal reflux.
Pediatrics 2000;105:E24.
624
13.7 Gastrointestinal Bleeding in

Saroj Mehta, RC Mathur
UPPER GASTROINTESTINAL BLEEDING
Upper Bleeding denotes bleeding from any site in the
gastrointestinal tract proximal to the ligament of Treitz.
It can present as hematemesis (coffee ground vomitus)
and/or Malena (tarry black stools). Massive upper
gastrointestinal bleeds can present as hematochezia
(frank bleeding per rectum), however occult bleeding is
a rare presentation of upper gastrointestinal bleeding.
Etiology
The common of upper gastrointestinal bleeding are given
in Table 13.7.1.
Clinical Features
Acute gastrointestinal bleed leads to hypovolemia and
shock whereas, chronic gastrointestinal bleed usually
produces severe anemia. Hematemesis (or acute
hematochezia or melena with positive NG aspirate for
blood) may result from swallowed blood, upper GI
mucosal lesions, variceal bleeding, or rarely, hemobilia
(hemorrhage into the biliary tract). Swallowed blood may
be seen in conjunction with epistaxis, sore throat, or
breast feeding or may follow dental work or
TABLE 13.7.1: Common causes of upper
gastrointestinal bleeding
Newborn:
Swallowed blood
Hemorrhagic disease of the new born
Septicemia and DIC
Reflux esophagitis
Reactive gastritis
Stress ulcers
Necrotizing Enterocolitis
Variceal bleedesophageal, gastric varices
Drug inducederosive gastritis
Viral hemorrhagic fever
Reflux esophagitis with hiatus hernia
Mallory Weiss esophageal tear
Gastric, Duodenal ulcers.
tonsillectomy. Mucosal lesions include esophagitis,

Mallory Weiss tear, reactive gastritis, stress ulcer and
peptic ulcer. A history of chronic heart burn, chest pain,
vomiting, oral regurgitation, or dysphagia suggests reflux
esophagitis or ulcer disease.
A Mallory Weiss tear is an acute mucosal laceration
of gastric cardia or gastroesophageal junction. The classic
presentation is hematemesis following repeated forceful
retching, vomiting, or coughing. Abdominal pain is
uncommon and if present more likely to be musculoskeletal in origin due to forceful emesis. Such vomiting
episodes usually are linked to a concurrent viral illness.
Reactive gastritis may be diffuse or localized in the
stomach. Significant hemorrhage may be seen with
diffuse hemorrhagic stress gastritis associated with
trauma, surgery, burns or severe medical problems
requiring hospitalization in an intensive care unit.
Associated coagulopathy is not uncommon. Localized
reactive gastritis is more common and may be associated
with non-steroidal anti-inflammatory drugs (NSAID
gastropathy), ingestion of caustic substances, Helicobacter pylori infection, viral infection, Crohns disease,
vasculitis (Henoch Schonlein purpura) radiation
exposure, bile reflux, bezoars, hiatus hernia, prolapse of
the gastroesophagial junction, or congestive gastropathy
(associated with portal hypertension). Reactive gastritis
may coexist with duodenal erosive lesions. Bleeding from
localized gastritis usually manifests as coffee ground
emesis. Peptic ulcer is rare in children. A more common
cause of gastric mucosal erosion is due to stress and
trauma from tips of NG tubes.
Upper gastrointestinal bleeding may be the initial
presentation of esophageal varices. Variceal bleeding
caused by portal hypertension should be considered in
any child who has hepatomegaly, spenomegaly, ascites,
and jaundice.
Vital signs should be evaluated first in every child. Most
previously well children who present with hematemesis

are hemodynamicaly stable and describe hematemesis
as a coffee ground like or bright red tinged vomitus,
indicating a low rate of bleeding. Bleeding from mucosal
lesions usually stops spontaneously. The initial laboratory evaluation should be a hematocrit, MCV, platelet
count, coagulation profile, liver function tests, blood
grouping.
Upper GI endoscopy is the test of choice for
evaluating upper GI bleeds. The goal is to identify the
site of bleeding, diagnose the specific cause and initiate
therapeutic interventions when indicated. Push enteroscopy has shown to have a higher diagnostic yield as the
scope goes beyond jejunum. Wireless capsule endoscopy
is also useful for diagnosis.
Epigastric pain and tenderness are seen in gastric
mucosal lesions.
Management of a Massive Upper
Gastrointestinal Bleed
1. Vital signs to be assessed and look for signs of
hypovolemia (Tachycardia, hypotension/postural
hypotension). There is intravascular and extravascular volume reduction resulting in shock.
Resuscitation should be done with intravenous
normal saline/ringer lactate or blood transfusions.
2. Nasogastric intubation, aspiration for diagnostic
purposes.
3. Parenteral somatostatin or its analogue octreotide to
arrest the bleed.
4. Upper GI endoscopy (within 12 hr) for diagnosis and
treatment.
5. Further management depends on the cause and is
discussed under three categories:
a. Variceal bleed
b. Reflux esophagitis, hiatus hernia, Mallory Weiss
tear
c. Acid peptic disease, stress ulcers, erosive gastritis.
Variceal Bleed
i. Emergency endoscopic sclerotherapy(EST) or band
ligation.
ii. Parentral somatostatin or its analogue for three more
days to prevent early rebleeds. If early rebleeds
persist IV vasopressin or esophageal balloon
tamponade with Sengstaken Blackmore or Linton
tubes.
iii. Management of late rebleeds (bleeding after 2 weeks
of therapy)
625
a. Periodic EST or banding

b. TIPS (Transjugular intrahepatic portasystemic
shunt) in older children
c. Surgery (shunt surgery and non-shunt)
d. Prevention of bleeds: acid suppression by proton
pump inhibitors, sucralfate, beta blockers.
Gastro-esophageal Reflux Disease (GERD)
i. Head up position after meals and low fat diet.
ii. H2 receptor antagonist, proton pump inhibitors and
pro kinetics constitute the medical line of management.
iii. SurgeryFundoplication.
Acid Peptic Disease
i. Screen for H. pylori. If positive, treat with metronidazole + amoxicillin/clindamycin + proton pump
inhibitors.
ii. If negative treat with either antacids H2 antagonists,
proton pump inhibitors or sucralfate.
iii. Laser photocoagulation for immediate control of
ulcer bleed.
LOWER GASTROINTESTINAL BLEEDING
Lower gastrointestinal bleeding is defined as bleeding
distal to the ligament of Treitz. Bloody diarrhea and
bright red blood mixed or coated normal stool are classic
presentations of lower GI bleed.
Etiology
The common causes of lower gastrointestinal bleed are
Clinical Features
Swallowed maternal blood either from the vagina or
breast is confirmed by a positive Apts test. Hemorrhagic
disease of the newborn responds well to vitamin K
therapy. NEC occurs in premature/low birth weight
babies and presents as rectal bleeding, abdominal
distension and sepsis.
Acute hematochezia in an ill appearing child who
has acute abdominal pain and tenderness suggests
intestinal ischemia as a complication of intussusception,
mid gut volvulus, incarcerated hernia or mesenteric
thrombosis. The sudden onset of colicky abdominal pain
and vomiting in the setting of an antecedent viral illness
626

TABLE 13.7.2: Common causes of lower
gastrointestinal bleed
Newborn
Swallowed maternal blood
Hemorrhagic disease of newborn
Anal fissure
Necrotizing Enterocolitis(NEC)
Malrotation and midgut volvulus
Infants and older children
Anal fissure
Intussusception, gangrenous bowel due to volvulus
Polyp and polypoid disease
Gastroenteritis-Salmonella, Shilgella, Yersinia, Campylobacter,
Ehe. coli, Ete. coli, Clostridium difficile, CMV, Entamoeba
histolytica, Trichuris trichuria
Colitis
Meckels diverticulum
Inflammatory bowel disease
AV malformations
followed by passage of currant jelly stool is indicative of

an intussusception.
Painless passage of blood per rectum suggests
Meckels diverticulum, polyp, intestinal duplication or
A V malformation. Anal fissure occurs in constipated
children and presents as painful passage of streaks of
blood in stool.
Clinical Assessment
Stools in children with bloody diarrhea should be
examined for polymorphonuclear leukocytes and
cultures should be done to identify the organism. All
infants who experience acute hematochezia should
undergo abdominal flat plate/upright or cross table
lateral radiography to screen for intestinal obstruction
or pneumotosis intestinalis (gas in bowel wall seen in

NEC). Intussusception can be diagnosed by barium
enema study (shows coiled spring appearance) and this
can also be therapeutic. Ultrasound and CT scan of the
abdomen can also be used. Meckels diverticulum can
be diagnosed by Meckels scan (99Tc -pertectenate
nuclear can).
Anal fissure can be seen by direct anorectal examination. Polyps are most commonly found in the recto
sigmoid region and can be identified by direct rectal
examination or colonoscopy. AV malformations are
diagnosed by radioisotope tagged RBC scans using
technetium 99m sulfur colloid if there is bleeding or by
colonoscopy/capsule endoscopy.
Management
Lower GI bleeding is rarely life threatening. Anal fissure
should be treated with stool softeners, sitz bath and rectal
dilatation. Nonoperative management has a high
recovery rate in NEC. Malrotation with midgut volvulus
should be treated by exploratory laprotomy and Ladd
procedure. If enema reduction is unsuccessful or the child
is very sick operative manual reduction or resection of
the intussusception should be done. Colonoscopy can be
used to treat polyps, telangiectasias and small hemangiomas. Meckels diverticulum should be surgically
resected.
BIBLIOGRAPHY
1. Gastrointestinal bleeding in infants and children. Boyle
JT. Pediatr Rev 2008;29(2):39-52.
2. Lower gastrointestinal bleeding in children. Leung AK,
Wong AL. Pediatr Emerg. Care 2002;18(4):319-23.
3. Upper gastrointestinal bleeding in children. Chawla S,
Seth D, Mahajan P, Kamat D. Clin Pediatr 2007;46(1):
16-21.
627
13.8 Constipation
VR Ravikumar
Constipation is passage of firm or hard pellet like stools
at infrequent and long intervals with difficulty to expel.
Frequency of stooling varies in different age groups and
only the hard consistency is the important factor.
Obstipation refers to the absence of passage of both
feces and flatus. Encopresis is fecal soiling in the presence
of functional constipation due to fecal retention and
overflow, whereas fecal incontinence is due to anatomic
or organic cause.
The common causes of constipation are given in Table
13.8.1.
Other rare causes of constipation are neuronal
intestinal dysplasia, Chagas disease, small left colon
syndrome, neurofibromatosis, and intrinsic myopathy
leading on to pseudo-obstruction.
Functional Constipation (Habitual constipation)
It is the most common cause of constipation in children
beyond 4 years. However, it can happen in younger age
period during weaning, or more commonly during toilet
training or at the time of joining a school.
Many present with chronic recurrent abdominal pain.
Enuresis may be the presenting feature.
Unlike Hirschsprungs disease the abdomen is only
mildly distended with hard stool felt in the left lower
quadrant of the abdomen. Rectal examination reveals a
TABLE 13.8.1: Common causes of constipation

Newborn
1. Preterm infant underfeeding
2. Hypothyroidism
3. Hirschsprungs disease
4. Anorectal anomalies
5. Spinal abnormalities
6. Meconium plug
syndrome
7. Anterior perineal anus,

anal stenosis, presacral
masses
Infants and children

Bad dietary habits and lack
of fiber in the diet
Hypothyroidism
Hirschsprungs disease
Functional or psychogenic
Cerebral palsy
Drugs: Antispasmodics,
antimotility drugs,
phenothiazines, codeine
containing cough mixtures,
vincristine and vinblastine
dilated rectum filled with hard fecal masses. Children

adopt peculiar postures during defecation and many
children cross their legs and push back the fecal mass. A
vicious cycle follows and there is fecal retention and
impaction. The child starts soiling the under clothes due
to the seepage of liquid fecal material around the
impacted mass.
In chronic constipation a cycle of events take place.
Fecal retention rectal distension decreased
sensory perception hard stool fissure in ano
pain and with holding evacuation impaction
fecaloma formation.
HIRSCHSPRUNGS DISEASE
The common differential diagnosis of habitual constipation in older children is with Hirschsprungs disease,
which is due to aganglionosis of rectum and colon. It
usually involves the rectum and distal sigmoid but the
aganglionosis may extend to variable length. Total
colonic aganglionosis is less common and rarely the small
intestines may be affected. The diagnosis is usually made
by barium enema, which will show the dilated rectum,
transition zone and the narrow portion. Rectal biopsy
either full thickness or the suction biopsy of the mucous
membrane of rectum will show absence of ganglion cells,
hypertrophy of nerve bundles and increased acetylcholinesterase staining in hypertrophy of nerve bundles
in Hirschsprungs disease. Anal manometry is valuable
especially for ultra short segment of Hirschsprungs
disease.
This disease presents with progressive abdominal
distension, constipation and vomiting not responding to
laxatives.
Ultra short Hirschsprungs disease is where internal
sphincter achalasia is difficult to differentiate from
chronic constipation (Table 13.8.2). The rectal biopsy is
not helpful. Anal manometry will be diagnostic. A
posterior myomectomy is usually curative (Figs 13.8.1
and 13.8.2).
Treatment
Treatment of constipation depends on the cause. Anal
stenosis and incomplete covered anus get corrected by
628
TABLE 13.8.2 Difference between habitual constipation and

Clinical features Habitual constipation Hirschsprungs
disease
Age of onset
Meconium
history
Rectal
examination
Perineal soiling
Nutrition
Barium enema
Manometry
Rectal biopsy
2 to 3 years
Normal
Birth onwards
Delayed passage
Loaded rectum
Empty rectum
Perineal soiling
present
Thriving well
Dilated rectum
without transition
zone
Internal sphincter
relaxation present
Ganglion cells are
present
Perineal soiling is
absent
Failure to thrive
Dilated segment
with narrow
aganglionic rectum
Internal sphincter
relaxation absent
Ganglion cells are
absent
Figure 13.8.2: Classical Hirschsprungs disease
Figure 13.8.1: Short segment HIrschsprungs disease
anoplasty. Acute fissures in ano respond to local

application of local anesthetic agents and stool softeners.
Hirschsprungs disease needs surgical removal of
aganglionic colon and bringing the ganglionated colon
to the anal region by different techniques. Ultra short
segment can be corrected by posterior myomectomy. A

small percentage of children with history of meconium
plug syndrome may develop constipation and need
investigation to exclude Hirschsprungs disease.
A separate group of children have idiopathic mega
rectum and do not respond to conservative measures and
need excision of the redundant rectum.
Constipation due to hypothyroidism responds to
thyroxine replacement. Drug induced constipation needs
identifying the drug and withdrawal of the offending
drug.
Treatment of functional constipation is difficult and
needs patience and perseverance and include the
following:
1. Proper toilet training.
2. Avoidance of precipitating factors.
3. Diet rich in residue and fiber like bran, pop corn,
fruits, green vegetables and reduced milk intake.
The parents need to be educated on the long-term
safety of laxatives and the need for prolonged treatment.
The change in dietary habits is stressed upon. The rectum
need to be emptied regularly with stool softeners, enemas

and laxatives. The idea is to promote regular evacuation
at fixed timings so that the distended rectum slowly
regains its normal tone and sensory perception. The
treatment may be prolonged upto six months to one year
and may relapse if there is interruption in the training.
The common drugs that promote softening the stool
and promote evacuation are:
1. Milk of magnesia at doses of 0.5 ml per kg per day in
children less than two years and 5 to 15 ml in children
between 2 to 5 years and 15 to 30 ml above 6 years.
2. Biscodyl can be used as a suppository 5 mg or
10 mg.
3. Liquid paraffin is not generally used in children less
than 3 years of age. 10 to 30 ml can be given at bed
time in toddlers. However it seeps by the side of the
fecal bolus and stains the undergarments, but it is
one of the effective stool softeners.
4. Lactulose is a syrupy solution: 2.5 ml to 10 ml per
day for infants can be given in divided doses.
5. Senna preparations are stimulant laxatives and can
be given for a short period of time at 10 to 20 mg per
kg at bedtime.
629
6. Dietary fiber increases the bulk and increases the

amount of water in the stool and is a natural stool
laxative. Various commercial preparations are
available.
7. Prokinetic agents like cisapride has also been used
but carries the danger of inducing cardiac arrhythmias and hence not routinely recommended now in
children.
8. Biofeed techniques to condition to relax the external
anal sphincter has been tried with success.
The ultimate goal is to achieve normal bowel
movements without the need for laxatives. This will need
proper training to evacuate at fixed timings daily with
judicious use of stool softeners and other non-punitive
measures.
Children with intractable constipation especially
those with neurological weakness of the sphincters and
following surgery for anorectal anomalies and mega
rectum are most difficult to treat and may benefit by
antegrade continent enema procedures using either the
appendicular stump or a Montis tube connected to colon.
13.9 Abdominal Pain

S Srinivas
Abdominal pain is a very common symptom in
childhood. It can be present in acute and chronic or
recurrent manner. In acute abdominal pain, it is
important to distinguish between medical and surgical
causes of abdominal pain. On the other hand, in children
with recurrent abdominal pain, the distinction has to be
made between organic and nonorganic (or psychogenic)
pain abdomen.
Numerous disorders can cause abdominal pain (Table

13.9.1.1) and it must be remembered that causes of
chronic abdominal pain can have an initial acute
presentation. The most common medical causes are
gastroenteritis and constipation, and the most common
surgical cause is appendicitis.
In most instances, abdominal pain can be diagnosed
through the history and physical examination
HISTORY
13.9.1 ACUTE ABDOMINAL PAIN IN

CHILDREN
Abdominal pain is one of the most common reasons for
a parent to bring his or her child to medical attention.
The evaluation of a tummy ache can challenge both
parents and the physician.
Age is a key factor in evaluating the cause; the incidence

and symptoms of different conditions vary greatly over
the pediatric age spectrum. Infantile colic occurs in
infants. It is not important to inspect genitalia and not
miss an incarcerated hernia in a crying and irritable
infant. Intussuception and volvulus tend to occur in
infants and younger children below five years of age.
630

TABLE 13.9.1.1: Causes of acute abdominal pain in children
Gastrointestinal causes
Reflux esophagitis
Gastritis/ Gastroenteritis
Food poisoning
Constipation
Peptic ulcer
Mesenteric lymphadenitis
Lactose intolerance
Irritable bowel syndrome
Liver, spleen, and biliary tract

disorders
Hepatitis
Liver abscess
Cholecystitis
Cholelithiasis
Splenic infarction
Rupture of the spleen
Pancreatitis
Genitourinary causes
Urinary calculi
Perinephric abscess
Ovarian/ testicular torsion
Dysmenorrhea
Mittelschmerz
Pelvic inflammatory disease
Hematocolpos
Ectopic pregnancy
Surgical causes
Appendicitis
Abdominal trauma
Intussusception
Peritonitis
Metabolic disorders
Diabetic ketoacidosis
Acute intermittent porphyria
Hematologic disorders
Henoch Schnlein purpura
Sickle cell crisis
Miscellaneous
Infantile colic, Functional pain, Worm colic, Lead poisoning, Venoms
Pharyngotonsillitis, Basal pneumonia, Familial Mediterranean fever,
Vascular causes like mesenteric ischemia or dissecting aneurysm of abdominal aorta
Pharyngotonsillitis and Henoch Schonlein purpura are

more common in preschoolers and children below 12 yr
of age whereas dysmenorrhea, ectopic pregnancy,
inflammatory bowel disease and irritable bowel
syndrome are more common in adolescents.
Pain history Pain from foregut structures (e.g., lower
esophagus, stomach) generally is felt in the epigastrium.
Midgut structures (e.g., small intestine) cause periumbilical pain, and hindgut structures (e.g., large
intestine) cause lower abdominal pain. Pain in the right
hypochondrium may either be due to acute stretching of
the capsule of the liver as in acute viral hepatitis,
cholecystitis or rarely peptic ulcer disease. Pain in
pancreatitis is epigastric or central and may be referred
to the back. Pain in cystitis or dysmenorrhea is usually
suprapubic in location. Appendicitis classically is
described to start with periumbilical pain and vomiting;
then slowly gets localized to the right iliac fossa. In
infants, appendicitis progresses quickly to perforation
and peritonitis because of the lack of an adequate omental
barrier to limit peritoneal spread.
Younger children who do not verbalize and older
children may have a poor sense of onset or location of
pain. Thus, inquiry into the location, timing of onset,

character, severity, duration, and radiation of pain are
all important points but must be viewed in the context
of the childs age.
Recent trauma: A history of recent blunt abdominal
trauma might suggest pain due to parietal wall injury or
internal organ injury to bowel or pancreas causing
pancreatitis.
Precipitating or relieving factors: Parietal pain is aggravated
by movement. Relief of pain after a bowel movement
suggests a colonic source, and relief after vomiting
suggests a source in the more proximal bowel.
Associated symptoms: In the acute surgical abdomen, pain
generally precedes vomiting, and the reverse is true in
medical conditions. Any child presenting with bilious
vomiting should be presumed to have a bowel obstruction. Diarrhea often is associated with gastroenteritis or
food poisoning but may be associated with other
conditions including retrocaecal appendicitis. Bloody
diarrhea is much more suggestive of inflammatory bowel
disease or infectious enterocolitis. The typical red currant
jelly stool is seen in intussusception. Failure to pass flatus
or faeces may suggest intestinal obstruction.

Urinary frequency, dysuria, urgency, and malodorous urine suggest a urinary tract infection. Cough,
shortness of breath, and chest pain point to a thoracic
source. Polyuria and polydipsia suggest diabetes
mellitus. Joint pain and skin rash suggest HenochSchnlein purpura.
Gynecologic history: In adolescent girls, a thorough
gynecologic history is essential.
Past health: All previous hospitalizations or significant
illnesses such as sickle cell anemia and porphyria should
be noted. Previous surgery can increase the risk of
intestinal obstruction from adhesions. Nephrotic
syndrome predisposes to bacterial peritonitis. A
Mediterranean background along with fever and
abdominal pain could suggest Familial Mediterranean
Fever.
General appearance: In general, children with visceral pain
tend to writhe during waves of peristalsis, while children
with peritonitis remain quite still and resist movement.
The hydration status of the child should be assessed.
Vital signs: Fever indicates an underlying infection or
inflammation. Tachycardia and hypotension suggest
hypovolemia. If a postmenarcheal girl is in shock, ectopic
pregnancy should be suspected. Hypertension may be
associated with Henoch-Schnlein purpura or hemolytic
uremic syndrome. Kussmauls respiration indicates
diabetic ketoacidosis.
Abdominal examination: The breathing pattern should be
observed, and the patient should be asked to distend the
abdomen and then flatten it. After the child is asked to
indicate, with one finger, the area of maximal tenderness,
the abdomen should be gently palpated, moving toward
(but not palpating) that area. The physician should
examine for Rovsings sign (when pressure on the left
lower quadrant distends the column of colonic gas,
causing pain in the right lower quadrant at the site of
appendiceal inflammation), then gently assess muscle
rigidity. Gentle percussion best elicits rebound tenderness. Deeper palpation is necessary to discover masses
and organomegaly. It is important to include examination
of genitalia and hernial orifices. A rectal examination may
provide useful information about tenderness that might
suggest pelvic appendicitis or pelvic abscess and the
presence of masses/stool/blood.
631
Associated signs: Pallor and jaundice point to sickle cell

crisis. A positive iliopsoas test (passive extension of the
right hip and flexion of the right thigh against resistance)
or obturator test (rotation of the right flexed hip) suggests
an inflamed retrocaecal appendix, a ruptured appendix,
or an iliopsoas abscess. A positive Murphys sign
(interruption of deep inspiration by pain when the
physicians fingers are pressed beneath the right costal
margin) suggests acute cholecystitis. Cullens sign (bluish
umbilicus) and Grey Turners sign (discoloration in the
flank) are unusual signs of internal hemorrhage. Palpable
purpura and arthritis suggest Henoch-Schnlein
purpura.
LABORATORY STUDIES
Laboratory studies should be tailored to the patients
symptoms and clinical findings. Initial tests may include
a complete blood cell count, urinalysis, liver function
tests, and serum amylase. A low hemoglobin level
suggests blood loss or underlying hematologic abnormalities, such as sickle cell disease. However, a normal
hemoglobin level does not exclude an acute massive
hemorrhage for which the body has not yet compensated.
Leukocytosis, especially in the presence of a shift to the
left and toxic granulations in the peripheral smear,
indicates an infection. Urinalysis can help identify
urinary tract pathology, such as infection or stones. A
pregnancy test should be considered in postmenarcheal
girls.
Plain-film abdominal radiographs are most useful
when one suspects intestinal obstruction or perforation.
It may however occasionally detect ascariasis or reveal a
loaded colon as the cause of abdominal pain. Chest
radiographs may help rule out pneumonia. Ultrasonography is a very useful investigation and aids in the
diagnosis of intussusception, gallstones, renal stones,
appendiceal pathology and gynecologic pathology such
as ovarian cysts with torsion or hemorrhage. CT involves
significant radiation exposure and may require the use
of contrast agents.
MANAGEMENT
Treatment should be directed at the underlying cause.
The indications for surgical referral are listed below in
Table 13.9.1.2.
632

TABLE 13.9.1.2: Indications for surgical referral
Bile-stained or feculent vomitus

Involuntary abdominal guarding/rigidity
Rebound abdominal tenderness
Marked abdominal distension with diffuse tympany
Signs of acute fluid or blood loss into the abdomen
Significant abdominal trauma
Suspected surgical cause for the pain
In many patients, the key to diagnosis is repeated

physical examination by the same physician over an
extended time after judicious use of analgesics, which
may enhance diagnostic accuracy by permitting detailed
examination of a more cooperative patient.
BIBLIOGRAPHY
1. Davenport M. Acute abdominal pain in children. BMJ
1996;312:498-501.
2. Leung AK, Sigalet DL. Acute abdominal pain in children.
Am Fam Physician 2003;67:2321-6.
13.9.2 CHRONIC ABDOMINAL PAIN IN

CHILDREN
The traditional definition of recurrent abdominal pain
used over the last 50 years has used Apley and Naishs
criteria of at least three pain episodes over a three month
period interfering with daily function. This has been

replaced by the term chronic abdominal pain which
refers to pain present continuously or occurring on a
weekly basis for a minimum period of 2 months. It is a
description and not a diagnosis, and can be due to organic
disease or functional causes.
A child with chronic abdominal pain poses a
formidable challenge as the parents may be terribly
worried; child may be distressed and the practitioner
may be concerned about ordering multiple tests to avoid
missing occult disease. Yet only in a small number of
children is the pain caused by organic disease and in the
majority the pain is functional i.e. without demonstrable evidence of a pathologic condition.
The differential diagnosis of abdominal pain in
children varies with age, sex, genetic and environmental
factors. Besides organic and functional components are
not mutually exclusive, since psychological complications of organic disease are common in children. Hence
the diagnostic approach to abdominal pain in children
relies heavily on the history provided by the parent and
child to direct a step-wise approach to investigation
rather than multiple exclusionary investigations.
ETIOLOGY
Table 13.9.2.1 lists the common causes of chronic
abdominal pain in children.
TABLE 13.9.2.1: Causes of chronic abdominal pain in children

Functional disorders (as classified by Rome III criteria)
1. Functional dyspepsia
2. Irritable bowel syndrome
3. Abdominal migraine
4. Childhood functional abdominal pain
5. Childhood functional abdominal pain syndrome
Gastrointestinal causes
Reflux esophagitis
Helicobacter pylori gastritis
Peptic ulcer
Lactose intolerance
Giardiasis
Liver, spleen, and biliary tract

disorders
Hepatitis
Liver abscess
Cholelithiasis
Recurrent or chronic pancreatitis
Genitourinary causes
Urinary calculi
Hydronephrosis
Dysmenorrhea
Pelvic inflammatory disease
Surgical causes
Malrotation with intermittent volvulus
Chronic appendicitis
Miscellaneous
Infantile colic, lead poisoning, familial mediterranean fever,
Vasculitis, angioneurotic edema, acute intermittent porphyria

HISTORY
The location of the pain is important and the child may
indicate the location of the pain by pointing with one
finger or with the whole hand. Apleys observation that
the further the pain from the umbilicus, the greater the
likelihood of organic disease has held up reasonably
well and most children with functional abdominal pain
present with pain around the region of the umbilicus.
Night pain or pain on awakening suggests a peptic
origin, while pain that occurs in the evening or during
dinner is a feature of constipation. Children often deny
heartburn, but other features of peptic disease include
early satiety, nausea and the complications of gastrooesophageal reflux.
A diary that lists diet, symptoms and associated
features for three to seven days is invaluable since it will
indicate potential causes of the symptoms, such as
exposure to lactose or the failure to have a normal bowel
movement.
A history of abdominal distension, involuntary
weight loss, deceleration of linear growth, prolonged
fever, bile stained or persistent vomiting, chronic
diarrhea, dysphagia, nocturnal symptoms, family history
of inflammatory bowel disease and pain persistently
located away from the central abdominal area are the
red flag symptoms and should trigger a search for
organic disease.
History of recent medications is important as
antibiotics may predispose the patient to intestinal
bacterial overgrowth; acne medications may induce
esophagitis and tricyclic antidepressants may cause
constipation.
Family history of peptic disease, irritable or inflammatory bowel disease, pancreatitis, biliary disease or
migraine should be determined.
The influence of pain on the childs daily activity is
assessed through questions about school attendance,
athletic endeavours and peer relationships. Whenever
possible, a few minutes should be taken alone with
adolescents to address concerns in the absence of parents
and to elicit honest answers about sexual issues,
psychological fears and the disruptions to lifestyle caused
by the parents interventions.
EXAMINATION
Anthropometric data of weight, height and growth
velocity are documented. Blood pressure is recorded and
the weight-for-height is plotted to assess malnutrition
633
or obesity. The physician should percuss the liver span,

document the spleen and kidney size and determine the
influence of leg motion (psoas sign). Examination for pain
should be performed with gentle and deep pressure as
well as with rebound.
Abdominal and rectal examinations will identify
constipation, perianal inflammatory lesions of Crohns
disease, abdominal tumors such as neuroblastoma or
Wilms tumor and the presence of umbilical or abdominal
wall hernias. The pelvic examination may suggest
gynecologic problems, such as endometriosis, ectopic
pregnancy or ovarian cysts or torsion.
The red flag signs of organic disease include
localized tenderness in right upper or lower quadrants,
localized fullness or palpable mass, hepatomegaly,
splenomegaly, costo-vertebral angle tenderness or
perianal abnormalities.
LABORATORY TESTING
The routine screening laboratory evaluation of abdominal pain in children includes the complete blood cell
count with differential and erythrocyte sedimentation
rate to evaluate for anemia, leukocytosis and chronicity.
Platelet counts and CRP are frequently elevated in
inflammatory diseases. Urinalysis and routine urine
culture are indicated. A sample to check the stool for
blood is obtained during the rectal examination and the
result is often confirmed with three additional outpatient
samples. Additional laboratory investigations are chosen
on the basis of the history and physical examination.
These investigations include stool culture, stool testing
for parasites or Giardia antigen, a chemistry profile to
evaluate liver enzymes, serum amylase, lipase and
serology testing for coeliac disease and Helicobacter pylori.
Carbohydrate breath testing for lactose intolerance is
indicated if empiric dietary interventions are inconclusive.
Imaging Investigations
Sonography of the abdomen and pelvis is usually
performed first to exclude non-intestinal origins of the
pain which include gallstones and renal stones. Pelvic
sonography is indicated because of its sensitivity for free
fluid, the frequency of retroperitoneal disease and the
visualization of the ileum for Crohns disease, lymphadenopathy and chronic features of abscess from fistulas
or Meckels diverticulum. It also provides information
about possible pelvic/ovarian disease in adolescent girls.
634
Barium swallow is not a sensitive test for gastroesophageal reflux disease. A barium contrast of the upper
gastrointestinal tract may be useful to rule out malrotation especially if episodes of colicky abdominal pain
are associated with vomiting. Barium enema is indicated
primarily in the context of obstruction or chronic
intussusception. Abdominal computed tomographic
(CT) scan with contrast allows evaluation of the pancreas,
extraintestinal mass lesions, abscess and retroperitoneal
disease.
Endoscopy
Upper endoscopy is rarely indicated as a first-line
investigation. The yield is maximal in patients with
epigastric pain, symptoms of gastrooesophageal reflux
or positive coeliac screen. Biopsies of the esophagus,
gastric antrum and duodenum may be indicated even
in the absence of macroscopic disease to identify
microscopic diagnostic features of reflux esophagitis, H.
pylori, eosinophilic gastritis, granuloma of Crohns
disease and villous injury with enteropathy. Colonoscopy
has replaced barium enema in the evaluation of pain with
chronic diarrhea or bleeding.
MANAGEMENT
Empiric Intervention
The childs response to empiric intervention is also part
of the diagnostic evaluation. This may include:
Addition of a fiber supplement to rule out constipation
A trial of H 2 blocker in children with gastroesophageal reflux disease or peptic ulcer disease prior
to confirmatory investigations or
A trial of lactose elimination
Empiric trials of antispasmodic, anxiolytic or
antidepressant medications are not indicated.
SOME SPECIFIC DISEASE STATES
Functional Abdominal Pain
Functional abdominal pain is the most common cause
of chronic abdominal pain. It was previously referred to
as recurrent abdominal pain syndrome and has
traditionally remained a diagnosis of exclusion. This
trend is changing and a positive diagnosis of functional
abdominal pain can be made in most circumstances
without the need for extensive investigations when there

are no alarm symptoms or signs, physical examination
is normal and stool sample is negative for occult blood.
Tests are sometimes performed to reassure the patient,
parent or physician especially when pain diminishes
quality of life.
Functional abdominal pain is uncommon under
5 years of age. The typical presentation is a child aged
5-10 years of age with vague, peri-umbilical pain which
can be quite severe, interrupt normal activities and be
associated with nausea, pallor and headache. Epigastric
pain is also described. The pain occurs during daytime
and is unrelated to food intake, activity levels or stool
pattern. The episodes resolve spontaneously and the
child functions normally in between bouts of pain. The
physical examination is striking for its normality, and
the screening laboratory investigations are by definition
normal. The family history is often positive for functional
bowel disease such as irritable bowel syndrome.
Although there is a high rate of spontaneous remission
(30-70%) of chronic abdominal pain in children there is
also evidence that some children with chronic abdominal
pain can progress to have irritable bowel syndrome as
in adults.
The pathophysiology of functional abdominal pain
is thought to involve abnormalities in the enteric nervous
system. The enteric nervous system is also referred to as
the little brain in the gut and has bi-directional
interaction with the central nervous system. It is now
believed that adults and children with functional bowel
disorders may have abnormal reactivity to physiologic
stimuli (meal, gut distension), stressful stimuli (inflammatory or psychological). There is also growing
evidence of association of functional bowel disorders
with visceral hyperalgesia.
The management of functional abdominal pain
begins with the acknowledgement that the pain is real,
that extensive investigations are not warranted.
Education of the family in simple understandable
language is an important part of treating a child with
functional abdominal pain - likening the abdominal pain
to a headache and giving examples of hyperalgesia like
a healing scar. The primary goal of therapy is not
eradication of pain but resumption of a normal lifestyle
with regular school attendance, extracurricular activities
and a normal sleep pattern. Parents must be discouraged
from reinforcing the symptoms by allowing the child to
miss school and paying too much positive attention to
the pain.

It is important to identify, clarify and reverse possible
physical and psychological stress factors that may
exacerbate or maintain pain.
Dietary interventions that have been tried with
variable benefit include increasing dietary fibre intake.
Psychological approaches including cognitive
behavioural therapy and gut-directed hypnotherapy are
increasingly being used with success in children with
functional abdominal pain.
Drug therapy for pain related FGIDs has generally
been directed at symptoms alleviation rather than at
precise pathophysiological abnormalities. However with
increased understanding on the etiology of visceral
hypersensitivity and dysmotility, newer strategies are
being developed which include 5 HT3 antagonists.
Since pain related FGIDs tend to be chronic, waxing
and waning - a quick cure is unlikely. As they have a
high rate of spontaneous remission - a stepwise approach
is necessary with the initial step being education,
alleviation of stress factors and diet modifications.
True irritable bowel syndrome occurs infrequently
before late adolescence. It is best characterized as an
intestinal dysmotility with intervals of nuisance diarrhea
or constipation. The pain is dull, crampy and located in
the left lower quadrant or periumbilical region.
Autonomic symptoms may be associated. Stress is
implicated in the flare-up of symptoms, and a positive
family history is common. Management includes dietary
factors such as exclusion of contributory lactose
intolerance and the addition of fiber to the diet and stress
management techniques.
Cyclic Vomiting Syndrome (CVS)
Gees original description of a syndrome with fits of
vomiting.... with disease-free intervals in 1882 has held
up well in the clinical definition of periodic syndrome,
which is now called cyclic vomiting syndrome. CVS is a
severe form of functional vomiting syndrome - considered to be a brain-gut disorder. The typical patient is a
5-8 year old girl, who has repeated episodes of severe
vomiting (median 6 emeses per hour and 15 emeses per
episode) typically beginning during the night or early
morning hours and lasting from six to 48 hours, with
intervening intervals of 2-4 weeks with no symptoms or
findings at all. The episodes are stereotypic within
individuals as related to time of onset, duration and
symptomatology including pallor, listlessness, nausea,
retching and abdominal pain. Typical migraine symp-
635
toms of headache and photophobia affect 30-40%. More

than half require intravenous hydration. The diagnosis
remains clinical and a positive response to anti-migraine
therapy supports the diagnosis. Treatment is empiric and
includes lifestyle changes (e.g. regimenting sleep,
avoiding triggers). In the acute phase early use of nasal
anti-migraine medication like sumatriptan may abort the
episode in progress. Other supportive therapies include
nursing the child in a dark and quiet environment,
intravenous rehydration, anti-emetics, sedation and
analgesia for pain relief. NASPGHAN guidelines
recommend prophylactic anti-migraine medications
(cyproheptadine, amitriptyline, and propranolol) for
frequent or prolonged episodes.
Constipation
Constipation is a major cause of chronic abdominal pain
in children from toddler age to the preteen years. The
etiology of constipation in most children is a combination
of improper toilet training and a diet low in fiber
producing a dilated lower colon, painful defecation,
erratic stool patterns and frequent encopresis. The
parents usually do not understand what is causing the
childs discomfort. The child avoids passing the hard
stool. Aside from complicating encopresis and bleeding
from rectal fissures, symptoms include crampy pain that
occurs during large meals, reduction in appetite and
distention of the abdomen (from stool and gas) that
occurs in the evening.
The management goal is complete evacuation of the
lower colon on a nearly daily basis. This is achieved by
using stool softeners like lactulose until muscle tone can
be restored over two to six months. These are combined
with motivation to go, which can be achieved in some
children with behavior-modification sticker charts but
usually requires stimulant laxatives. The child is
encouraged to establish the habit of toilet use especially
after a meal to make use of the gastro-colic reflex, the
use of a daily calendar, rewards for attempting defecation
and rewards for absence of encopresis. Dietary efforts
begin with reducing intake of constipating foods and
eventually including increased fiber.
If there is fecal impaction, the initial management
may require use of an enema or suppository. Manual
disimpaction is rarely needed. Both softening and
stimulant medications are then initiated and adjusted to
the response of averaging two soft stools a day for six to
eight weeks. At that point, most children can tolerate a
636
transition to increased dietary fiber and habitual toilet

use.
Peptic Disorders
The peptic disorders causing chronic abdominal pain
include reflux esophagitis, antral gastritis, gastric and
duodenal ulcer, and H. pylori infection.
The signs and symptoms of peptic disease include
early morning pain, early satiety, night arousal and a
positive family history. The pain may be epigastric or
periumbilical and is remarkably consistent in character.
Occult bleeding is frequent with ulceration and less
common in gastritis.
Gastro-esophageal reflux disease can present with epigastric
or retro-sternal pain of a burning nature with associated
symptoms of sour eructations or water brash. These
symptoms are more common in older children and
younger children often present with vomiting and
irritability as the predominant symptom. Some children
may have associated minor upper GI bleeding secondary
to oesophagitis.
Stress ulcers usually present with acute, relatively
painless, dramatic upper gastrointestinal bleeding,
features shared with gastric ulceration resulting from use
of nonsteroidal anti-inflammatory drugs (NSAIDs).
Antral gastritis following a viral infection is not
uncommon in children. Children present with chronic
epigastric pain, early satiety with nausea, modest weight
loss and a low frequency of family history of peptic
disease. Gastric emptying is impaired, and reflux
symptoms may be prominent.
Helicobacter pylori gastritis In 1984, Marshall and Warren
demonstrated the role of a gram-negative aerophilic
bacterium, H. pylori, in chronic gastritis and peptic ulcer
disease in adults. This bacterium produces a cytotoxin,
urease, mucinase and superoxide dysmutase, which act
in concert to produce gastric and/or duodenal injury.
Recognizing the limitations of a positive serology result
and the research status of the C-13 -urease breath test,
the diagnosis in children has been dependent on
documentation of the bacterium in endoscopic biopsies
of the stomach and duodenum. Most children receive
triple therapy with continued acid suppression combined
with a two week course of amoxicillin and clarithromycin
or metronidazole. Children who fail to eradicate H. pylori
and remain symptomatic would need quadruple therapy

with addition of bismuth subsalicylate. Antibiotic
resistance is an increasing concern, so empiric treatment
for possible Helicobacter infection is discouraged.
Endoscopic confirmation of healing is indicated with
recurrent or persistent symptoms.
Inflammatory Bowel Disease
Abdominal pain is frequently reported in children with
ulcerative colitis and Crohns disease. The pain, which
typically occurs in the lower abdomen, is cramping in
nature and increases after meals or activity. The pain is
reduced by eating smaller meals, which contributes to
the anorexia and growth impairment that occur in
children with inflammatory bowel disease. The diagnosis
is relatively easy when the child has bloody diarrhoea,
the need to defecate during the night, perianal disease
or an ileal mass on abdominal examination. More subtle
features include delayed puberty, anemia that is
unresponsive to iron therapy, recurring oral aphthous
ulcers, chronic liver disease, or large joint synovitis or
arthritis. The diagnosis is established by small bowel
barium contrast x-ray and colonoscopy with biopsies.
Once the etiology of chronic abdominal pain is
established, the process of patient and family education
has just begun. Careful follow-up is necessary to monitor
compliance with treatment, restoration of normal
activities and appropriate family interventions.
BIBLIOGRAPHY
1. American Academy of Pediatrics and North American
Society of Pediatric Gastroenterology, Hepatology, and
Nutrition Subcommittee on Chronic Abdominal Pain.
Chronic abdominal pain in children. Pediatrics 2005;
115:812-15.
2. Arine M Vlieger, Marc A Benninga. Chronic Abdominal
Pain including Functional Abdominal Pain, Irritable
Bowel Syndrome, and Abdominal Migraine. In:
Kleinman G, Mieli-Vergani S, Sherman S, eds. Walkers
Pediatric Gastrointestinal Disease, Volm 1,5th edition.
BC Decker Inc, Hamilton. 2008;715-26.
3. Chronic abdominal pain in children: a clinical report of
the American Academy of Pediatrics and the North
American Society for Pediatric Gastroenterology.
Hepatology and Nutrition. J Pediatr Gastroenterol Nutr
2005;40:245-48.
4. Lake A. Chronic abdominal pain in childhood: diagnosis
and management. Am Fam Physician 1999;59:1823-30.
5. Rasquin A, Di Lorenzo C, Forbes D, et al. Childhood
functional gastrointestinal disorders: child/ adolescent.
Gastroenterology 2006;130:1527-37.
637
13.10 Helicobacter Pylori Infection in Children

Neeraj K Jain, Vibha Mangal
INTRODUCTION
Helicobacter pylori, first cultured and identified as
Campylobacter pylori in 1982 by Warren and Marshall, is
a spiral gram-negative bacillus, which produces urease,
catalase and oxidase and is associated closely with antral
gastritis and duodenal ulcers in adults and children. It is
highly motile with multiple unipolar flagella. It inhabits
the muscus adjacent to the gastric mucosa and can live
in the stomach and in the duodenum for long.
Epidemiology
Worldwide, H. pylori prevalence in children ranges from
10 to 80%. At least half of the worlds population is
infected by H. pylori. However, most infected people
(>70%) are asymptomatic. Man is the only known
reservoir of H. pylori. The infection is transmitted mainly
through feco-oral route in developing countries and poor
water supply are major risk factors. Thus prevalence of
infection is higher in developing countries than
developed nations. Up to 50% of children living in poor
socio-economic conditions are infected. Around 80% of
children under the age of 10 years are infected in
developing countries. Prevalence of infection in India is
about 22%, 56% and 87% in 0-4, 5-0 and 10-19 years age
groups respectively. Re-infection rate after treatment of
H. pylori is higher in under five-age group of children.
Pathogenesis
H. pylori is almost always acquired in childhood, and if
untreated infection is usually lifelong. Colonization of
H. pylori depends on virulence factors of the organism,
host factors and environmental factors. H. pylori produces
disease-inducing factors including urease, vacuolating
cytotoxin, catalase, and lipopolysaccharide (LPS). Urease,
a potent antigen, induces increased IgG and IgA
production. Vacuolating cytotoxin induces inflammatory
cytokines leading to more pronounced inflammation.
Catalase helps H. pylori to survive in the host by
preventing the formation of oxygen metabolites from
hydrogen peroxide in neutrophils. The LPS outer
membrane of H. pylori is a less potent inducer of the host
complement cascade and enhances the ability of H.pylori

is a less potent inducer of the host complement cascade
and enhances the ability of H.pylori to colonize the
stomach.
The microbial virulence factors identified so far
include the H. pylori cytotoxin associated gene A (cagA),
its related pathogenicity island (cag PAI), vacuolating
toxin A (vacA) and factors involved in adherence of H.
pylori to gastric epithelial cells. The immunoreactive 120145 KDa protein cagA is encoded by cagA of H. pylori.
Some of the gene in the cagPAI region encode a type IV
bacterial secertion apparatus, which can translocate cagA
into host target cells. Phosphorylation of cagA may
activate host signaling pathways and subsequently
influence host cellular functions, including proliferation,
apoptosis, cytokine release, and cell motility. VacA
expression is determined by variations in the signal
sequence and mid-region of the vacA gene.
Host genetic factors might affect H. pylori colonization
and development of diseases. Genetic polymorphism of
the cytokines and other related ligands, receptors and
enzymes might influence H. pylori infection. Interleukin
1-B is a pro-inflammatory cytokine and a powerful
inhibitor of gastric acid secretion. Host genetic factors
that affect IL-1 B may determine why some individuals
infected with H. pylori develop gastric cancer or ulcers
while others do not.
Interactions between host, environment and H. pylori
in the development of peptic ulcer diseases have been
proposed. A two-way interaction might exist between H
pylori and gastric acid that determines pattern of gastritis
and hence clinical outcome. Infection in infancy leads to
pangastritis (low acid secretion status), whereas in latter
childhood it may lead to a predominantly antral gastritis
(high acid load). Environmental factors (smoking,
malnutrition, high salt intake and vitamin deficiency)
and host factors associated with low acid secretion status
favor the colonization of H. pylori with intense inflammation and further reduction in acid secretion. The
resultant hypochlorhydria promotes H. pylori colonization, more intense inflammation leading to gastric
atrophy, gastric ulcer and cancer.
638
H. pylori associated duodenal ulcers are seldom seen in
children below 10 years of age. The spectrum of clinical
manifestations infection in children is not well defined.
Primary infection appears to be mainly asymptomatic.
Histologic changes of gastric inflammation generally
occur after several years and signs of gastric injury are
more frequently found in older children. Infection with
H. pylori in childhood apparently does not last a lifetime
but is often spontaneously cleared, although children
frequently become re-infected.
In symptomatic H. pylori infection in children, one of
the most frequent clinical symptoms is chronic, recurrent
abdominal pain; however, most recurrent abdominal pain
in children is not associated with H pylori infection. The
infection in young infants can present as an acute illness
characterized by protracted vomiting that can be
confused with upper gastrointestinal tract obstructive
disorders. Three clinical entities have been associated
with H. pylori infection: asymptomatic gastritis; acute
active gastritis; and chronic gastritis, duodenitis, and
peptic ulcer.
Asymptomatic gastritis: The frequency of asymptomatic
gastritis is not known, but according to seroepidemiologic
studies in general population, it is not a rare event,
particularly in older children. The reason for absence of
symptoms is not known.
Acute active gastritis: Symptoms may begin with epigastric
pain, nausea, and vomiting that may last for a few days.
Patients may improve rapidly and remain asymptomatic.
The pH of gastric juice usually is neutral or alkaline as a
result of a decrease in gastric acid output. This
hypochlorhydria may persist for several weeks and may
present with halitosis and mild gastrointestinal tract
disturbances.
Chronic gastritis, duodenitis, and duodenal ulcer: The triad
of antral gastritis, duodenitis, and duodenal or gastric
ulcer seen by endoscopy is associated with chronic and
more severe gastrointestinal tract symptoms. Children
may present with severe chronic and recurrent abdominal pain, anorexia, and failure to thrive or with
persistent vomiting. Occasionally, hematemesis may be
the first symptom. If H. pylori infection is associated with
chronic gastritis alone, the only symptom may be
recurrent abdominal pain or symptoms of non-ulcerative
dyspeptic syndrome and occasionally, chronic diarrhea.
No pediatric cases with H pylori-associated gastric

cancer have been reported so far. However, precancerous
lesions including mucosal atrophy can develop in the
infected children. Infected persons also have a 2 to 6fold increased risk of developing mucosa-associated
lymphoid tissue (MALT) lymphoma, and gastric cancer
compared with uninfected counterparts. The extraintestinal manifestations of H. pylori infection in children
include iron deficiency anemia, growth retardation and
migraine.
Diagnosis
1. Endoscopy: The histology test is the gold standard of
diagnosis of H. pylori infection can be performed on
the tissue sample taken from the lining of the stomach.
The culture is however performed in very few
laboratories and is helpful in the choice of antibiotics.
2. Urea breath test (UBT): This is a rapid diagnostic test
for H. pylori infection. Infection can be detected in
the exhaled breath. This test is positive only if the
person has a current infection. Sensitivity and
specificity of this test ranges from 94 to 98%.
3. Serologic test (IgG antibody): Detection of antibodies
to H. pylori denotes past infection as it remains
positive for years after infection and also for several
months after H. pylori has been successfully treated.
It has limited clinical value.
4. H. pylori antigens in feces: Recently, a test that detects
H. pylori antigens in feces has been proposed as a
pretreatment diagnostic tool and, especially, as posttreatment control. It is still awaiting full confirmation
before the test is recommended widely.
Treatment
Since H. pylori is colonizes a large number of people who
are asymptomatic, there is a debate whether patients
need treatment. It is recommended in those with peptic
ulcer disease. Eradication of H. pylori is difficult as the
lining of the stomach protects them from antibiotics.
Several therapeutic regimens have been shown to be
effective. In general, the use of single agents has been
found to be ineffective for curing infection in the majority
of patients. Two or three drugs for 14 to 21 days are
recommended for treatment. At least two effective
antibiotics along with either an acid-lowering agent
(proton-pump inhibitor or histamine H2 receptor blocker)

or bismuth subsalicylate are prescribed. The following
combination therapies are currently in use:
1. Amoxicillin 50 mg/kg/day twice daily for 14 days +
clarithromycin 15 mg/kg/day twice daily for 14 days
+ one proton pump inhibitor for 1 month.
2. Amoxicillin 50 mg/kg day twice daily for 14 days +
metronidazole 20 mg/kg day twice daily for 14 days
+ one Proton pump inhibitor for 1 month.
3. Metronidazole 20 mg/kg/day twice daily for 14 days
+ clarithromycin 15 mg/kg/day twice daily for 14
days + one proton pump inhibitor for 1 month.
Proton pump inhibitors commonly use are:
1. Omeprazole 1.0-3.3 mg/kg/day
2. Lansoprazole 0.8-4 mg/kg/day
3. Rabeprazole 10- 20 mg/kg /day
4. Pantoprazole 20- 40 mg /kg/day.
Those who relapse are treated with a repeat course
and metronidazole for 4 weeks. Compliance with such
regimens is a problem and shorter treatment courses that
are equally effective in children have been tried. There
may be a need for whole family eradication therapy for
removal of the intrafamilial reservoir of H. pylori infection
in cases with relapse after treatment.
639
BIBLIOGRAPHY
1.
2.
3.
4.
5.
6.
7.
Chan FKL, Leung WK. Peptic ulcer disease. Lancet

2002;360:933-941.
Das JC, Nazir MFH. Helicobacter pylori infection in
children: Diagnosis and treatment -A Review.
Bangladesh. J Child Health 2005;29:22-30.
Hocker M, Hohenberger P. Helicobacter pylori virulence
factors -one part of a big picture. Lancet 2003;362:
1231-3.
Malaty HM. Helicobacter pylori infection and eradication
in paediatric patients. Paediatr Drugs 2000;2:357-65.
Obata Y, Kikuchi S, Miwa H, Yagyu K, Lin Y, Ogihara
A. Diagnostic accuracy of serological kits for Helicobacter
pylori infection with the same assay system but different
antigens in a Japanese patient population. J Med
MicrobioI 2003;52:889-92.
Siberry GK, Iannone R, Eds: Formulary: drug doses. In:
The Harriet Lane Handbook. 15th edition. Mosby-Year
Book; 2000;622,630,645-6,674-5,772-3,795,837.
Sotudehmanesh R, Malekzadeh R, Fazel A, Massarrat S,
Ziad-Alizadeh B, Eshraghian MR. A randomized
controlled comparison of three quadruple therapy
regimens in a population with low Helicobacter pylori
eradication rates. J Gastroenterol Hepatol. 2001;16:
264-8.
13.11 Cystic Fibrosis

Sushil K Kabra, Madhulika Kabra
Cystic fibrosis (CF) is the most common life limiting
recessive genetic disorder in Caucasians with an
incidence of approximately 1 in 2500 children born in
the United Kingdom. It is less common in African
Americans (1 in 15000) and in Asian Americans (1:31000).
It also affects other ethnic groups such as black
population with an incidence of 1 in 17,000 and the native
American population with an approxi-mate incidence of
1 in 80,000.
CF was thought to be extremely rare in India.
However recent review of CF in Indian children suggests
that CF does occur in Indian children and frequency is
unknown. The incidence in migrant Indian populations
in the UK and USA has been estimated to be 1 in 1000 to
1 in 40000. The precise incidence of CF among Indians is
unknown. As a result of the widespread belief that CF
does not occur in Indians, the disease is rarely suspected
and even if it is suspected the diagnosis is not confirmed
due to the poor availability of facilities for diagnosis.
Molecular Genetics of Cystic Fibrosis

The basic defect in CF is a mutation in the gene for
chloride conductance channel i.e. cystic fibrosis
transmembrane conductance regulator (CFTR). The
failure of chloride conductance by epithelial cells leads
to dehydration of secretions that are too viscid and
difficult to clear.
Till now more than 1400 mutations in the gene have
been recognized. The commonest mutation is delta F 508
which constitutes about 70% of the total cases. The
frequency of this mutation in Indian children has been
reported between 19 to 44%.
Pathogenesis
Due to mutations in CFTR there is defective chloride
channel leading to thick and viscid secretions. This leads
to impaired airway clearance. Airways get colonized with
bacterial agents. Over a period of time it airways gets
colonized with pseudomonas spp. After colonization
640
there may be release of proteolytic enzymes leading to

progressive destruction of airways resulting ultimately
in bronchiectasis. Similarly due to blockade of pancreatic
ducts enzyme do not reach to intestine and cause
destruction of remaining pancreatic tissue resulting in
steatorrhoea and failure to thrive.
The clinical features of CF are variable. The clinical
features depend on age of diagnosis, supportive care
received and treatment. The common clinical presentation includes meconium ileus in neonatal period,
recurrent bronchiolitis in infancy and early childhood,
recurrent lower respiratory tract infections, chronic lung
disease, bronchiectasis, steatorrhoea and with increasing
age, pancreatitis, and azoospermia. Pancreatic insufficiency is present in > 85% of CF patients (Table 13.11.1).
Diagnosis
The diagnosis of CF should be suspected by the presence
of a typical phenotype or family history and confirmed
by the demonstration of a high sweat chloride (> 60 mEq/
L) on repeated measurements and/or by identifying two
CF causing mutations. Nasal potential difference
measurements can be used as an adjunct to sweat test
but is not widely available.
In the absence of sweat chloride estimation and
mutation analysis at most centers in India, CF may be
suspected by supportive investigations. An algorithm
based on clinical features and laboratory investigations
is given in Figure 13.11.1 for making a diagnosis of
suspected CF.
TABLE 13.11.1: Common clinical features of cystic fibrosis

0-2 years
Meconium ileus
Obstructive jaundice
Hypoproteinemia/anemia
Bleeding diathesis
Heat prostration /hyponatremia
FTT
Steatorrhoea
Rectal prolapse
Bronchitis/Bronchiolitis
Staphylococcal pneumonia
2-12 years
Malabsorption
Recurrent pneumonia
Nasal polyposis
Intussusception
>13 years
Chronic Pulmonary disease
Clubbing
Abnormal GTT
DM
Chronic intestinal obstruction
Focal biliary cirrhosis
Portal hypertension
Gall stones
Azoospermia
10-15
85
20
85
60
6-36
1-05
70
20-30
7
10-20
25
4-14
98%
the number of infecting organisms and suppressing the

inflammatory process and hyperreactivity of airways.
The principle components of care used to achieve this
includes airway clearance techniques, antibiotics and anti
inflammatory agents
Airway Clearance Techniques
Management
The treatment of cystic fibrosis in children includes
respiratory management, nutritional care, anticipation
and early diagnosis of liver disease, diabetes and other
organ dysfunction.
Respiratory Management
Respiratory manifestations are important cause of
morbidity during childhood in children with CF. In
majority respiratory illness is main cause of mortality.
Lung damage in cystic fibrosis is caused by excessive
poorly effective inflammatory processes in response to
bacterial infection of normally sterile airways. Respiratory therapy aims to limit lung damage by decreasing
The airway secretions are very viscid in CF. They are

very difficult to clear and lead to secondary infections
and damage to respiratory tract. Airways can be kept
clear by adequate hydration, chest physiotherapy,
judicious use of antibiotics and mucolytic agents. To keep
the secretions less viscid it is important to maintain good
hydration by ensuring intake of plenty of liquids and
extra salt.
Chest Physiotherapy
Chest physiotherapy techniques for keeping airways
clean includes following methods:
1. Postural drainage and chest clapping
2. Active cycles of breathing
641
Figure 13.11.1: Suggested algorithm for diagnosis and management of cystic fibrosis in resource limited setting
3.
4.
5.
6.
7.
Positive expiratory pressures (PEP)

High pressure PEP
Flutter therapy
Autogenic drainage
High frequency chest wall oscillation (HFCWO)
The method can be selected for an individual on the
basis of age of patient, clinical status, experience of
physiotherapist, personal preference of patients, social
issues including level of support etc. They can be used
under supervision of physiotherapist.
Mucolytic Agents
Various mucolytic agents have been used by oral as well
as in-halation route. N-acetyl cystein breaks the
sulphydryl bonds of the mucous glyco-protein thereby
reducing the viscosity of airway secretions. Because of
its offensive odor and propensity to cause bronchospasm,
hemorrhagic tracheitis and impaired ciliary clearance, it
is not used. Recombinant human DNase (rhDNase): In CF
patients, there is inordinately high concentration of DNA
642
in respiratory secretions that is released by disintegrating

inflammatory cells. DNAse, given as aerosol, increases
mucociliary clearance and reduces incidence of
respiratory infections; it also decreases rate of
hospitalization, number of days missed from work or
school and the frequency of CF related symptoms.
Hypertonic saline (7% saline) inhalation is relatively
inexpensive and may be used in place of DNAse which
is very expensive.
Nutritional Management of CF
The main aim of nutrition management is to achieve
normal growth and development of children. Nutritional
management of CF can be discussed as follows:
i. Increasing caloric intake
ii. Supplement fat soluble vitamins
iii. Replace pancreatic enzymes.
Increase Caloric Intake
Antibiotic Therapy
The commonly encountered microbial agents causing
pulmonary exacerbation in children with CF include
Staphylococcus aureus, Haemophilus influenzae b, Pseudomonas spp, Burkholderia cepacia etc. Different viruses,
mycoplasma, Mycobacterium spp, and aspergillus are
other important pathogens responsible for pulmonary
exacerbation. It is important to select an antibiotic on
basis of organisms isolated from respiratory secretions.
The organisms can be isolated by obtaining cough swab,
sputum or deep throat swabs after physiotherapy
(DTSP). Periodic cough swab cultures may help in
empirical treatment of acute exacerbation.
The treatment of acute exacerbation of infection if the
patient is known to be colonized with Pseudomonas
include ceftazidime, or cefoperazone or piperacillin or
imipenam or meropenam in combination with an
aminoglycoside. If the colonization status is not known
then a combination of drugs effective against Pseudomonas and Staphylococcus are used empirically. These
drugs may be started early and given for 2-3 weeks.
Aerosolised antibiotics: The airways of CF patients get
colonized with Pseudomonas spp. and may be responsible
for frequent exacerbation. Use of prolonged use of
aerosolised antibacterials by nebulizer has shown to
improve pulmonary function and decrease pulmonary
exacerbation. The drugs commonly used are tobramicin
or colistin.
Bronchodilator and Inhalation Steroid Therapy
Bronchial hyper-responsiveness occurs in 25-50% patient
particularly during intercurrent infections and in those
with poor baseline lung function. Some patient may have
atopic asthma as well as cystic fibrosis. These patients
should be treated for asthma on usual guidelines.
The caloric need increases in situations with persistent

chest infection or frequent pulmonary exacerbations.
Caloric demand may increase up to 50% during acute
pulmonary exacerbation. Caloric intake can be increased
by encouraging the child to eat energy rich food
throughout day e.g. full fat dairy products and fried
food. Parents should be told not to restrict fat in the childs
diet.
Oral Caloric Supplements
In addition to caloric needs, supplementary feeds by
using commercial preparations or home made feeds can
be used. It should be kept in mind that the caloric
supplements are given in addition to the regular meals.
Nasogastric and Gastrostomy Feeding
In some patients short term/long term nasogastric or
gastrostomy feeding is required. Indications for
nasogastric feeding are (1) no weight gain for 6 months
even with adequate caloric intake, (2) acute pulmonary
exacerbation with poor oral intake, (3) consistently poor
appetite and inability to maintain caloric intake, (4) before
major surgical procedures, (5) during periods of
increased caloric requirement e.g. puberty and pregnancy.
Supplementation of Fat-Soluble Vitamins and Minerals
Children with pancreatic insufficiency are at risk of
developing deficiency of fat-soluble vitamins. Children
should receive 2 times the daily recommended doses of
vitamin A, D and E. Vitamin K is given in presence of
clinical manifestation of deficiency and those having liver
disease.

Increased sweating in hot weather may result in
clinical manifestations of hyponatremia. Sodium
supplement is recommended in hot climate. They may
be allowed to take extra salt in their meals during hot
and humid climates.
Pancreatic Enzyme Supplement
Regular enzyme supplement in form of enteric-coated
spherules has improved nutritional management
significantly. The enzyme preparation is given with
meals. The pancreatic supplements can be given in form
of capsules or the spherules can be sprinkled over small
amount of food and given before meals in infants and
young children who are not able to swallow capsules.
Doses can be adjusted by observing stool consistency and
weight gain in the child.
Management of other GIT Manifestations
The common GI manifestations in CF include pain
abdomen, abdominal distention, meconium ileus
equivalent, intussusception, meconium peritonitis and
liver disease.
Pain abdomen in CF may be due to pancreatic
insufficiency, rectal prolapse, gastroesophageal reflux,
or intestinal obstruction. Pain and abdominal distention,
rectal prolapse due to pancreatic insufficiency respond
after increasing doses of enzymes.
For gastroesophageal reflux prokinetic agents along
with H-2 receptor antagonist are required. Pain abdomen
secondary to constipation can be treated with oral
lactulose in doses of 1 ml/kg/day in 2 divided doses.
Management of Liver Disease in CF
With improved survival, liver involvement in CF is
recognized more frequently. Early administration of
ursodeoxycholic acid (UDCA) may improve outcome
of liver disease in children with CF. It is speculated that
ursodeoxycholic acid may prove to affect the natural
history of cystic fibrosis-related liver disease.
Assessment and Monitoring
CF is chronic illness and require regular follow-up at
centers that have experience in managing these patients.
They should visit CF clinics every 2-3 months for clinical
assessment. The assessment includes clinical monitoring,
643
spirometry and anthropometry. All children need a detail

clinical and lab assessment annually.
Gene Therapy
CF is caused by mutations of the cystic fibrosis
transmembrane conductance regulator (CFTR) gene.
Consequent to mutations in parental genes; airway
epithelial cells have insufficient CFTR function. Because
this can be corrected in vitro by transfer of the normal
CFTR gene into airway epithelial cells, it is reasonable to
hypothesize that the respiratory manifestations of CF
could be prevented by transfer of the normal CFTR cDNA
to airway epithelium in vivo. Studies with experimental
animals demonstrated that inhalation of gene with a
vector in the airways, CFTR cDNA could be transferred
to the airways epithelium, with expression of the human
CFTR cDNA for at least 6 weeks. This is still experimental
and details of ongoing trial are awaited eagerly. Till now
no major success has been reported.
Prognosis
The median life expectancy for cystic fibrosis is now over
30 years, and it is projected that in newborn infants it
will become more than 40 years. With the identification
of the cystic fibrosis gene and its product, cystic fibrosis
transmembrane conductance regulator (CFTR), it has
been possible to discover the wide-spectrum of the
disease from the classical case of the infant with cystic
fibrosis to the elderly childless man with unexplained
bronchiectasis. There is increasing evidence of the
advantages of newborn screening for cystic fibrosis and
subsequent specialist care. Management concentrates on
optimizing nutritional status and preventing lung
infection and inflammation. Survival analysis of Indian
children with CF suggest that early mortality was
associated with early onset (below 2 months) of
symptoms, severe malnutrition at the time of diagnosis,
more than four episodes of pulmonary exacerbations in
a year and colonization with pseudomonas.
Prenatal Diagnosis
As of today there is no cure for CF. It is an autosomal
recessive disease there are 25% chances of affected child
644
in each pregnancy. With the identification of genetic

mutations in a child and parents, now it is possible to
make a prenatal diagnosis by chorionic villous (CV)
biopsy around 10-12 weeks or amniotic fluid cell culture
at 15-16 weeks of gestation in future pregnancies, in
addition pre implantation diagnosis that is also possible.
BIBLIOGRAPHY
1. Kabra SK, Kabra M, Lodha R, Shastri S. Cystic fibrosis in
India. Pediatric Pulmonology 2007;42:1087-94.
2. Kabra SK, Kabra M, Shastri S, Lodha R. Diagnosing and

managing cystic fibrosis in the developing world.
Paediatr Respir Rev 2006;7 Suppl 1:S147-50.
3. Kabra SK, Kabra M. Cystic fibrosis in India. Natl Med J
India 2003;16:291-93.
4. Kabra SK, Kabra M, Lodha R, Shastri S, Ghosh M, Pandey
RM, Kapil A, Aggarwal G, Kapoor V. Clinical profile and
frequency of delta f508 mutation in Indian children with
cystic fibrosis. Indian Pediatr 2003;40:612-19.
5. Taccetti G, Campana S, Neri AS, Boni V, Festini F.
Antibiotic therapy against Pseudomonas aeruginosa in
cystic fibrosis. J Chemother 2008;20:166-69.
13.12 Juvenile Tropical Pancreatitis

A Riyaz
Juvenile tropical pancreatitis (JTP) is a form of chronic
calcific non-alcoholic pancreatitis. It is the commonest
cause of pancreatitis in children in the tropical countries.
Some of its synonyms are nutrititional pancreatitis,
tropical pancreatitis, Afro-Asian pancreatitis and
fibrocalculous pancreatic diabetes.
Epidemiology
JTP was first reported by Zuidema from Indonesia in
1955. Subsequently it was reported from other Asian
countries like India, Bangladesh, Sri Lanka, Malaysia and
Thailand, and African countries like Uganda, Nigeria,
Congo, Zambia and Ghana. A few cases have been
reported from Brazil also.
In India, the highest incidence is in the south eastern
part of Kerala, the prevalence being 125/100000
population. A few cases have been reported from the
other southern states like Tamil Nadu, Karnataka and
Andhra Pradesh and also from the eastern state of Orissa.
It is very rare in the northern and western parts of India.
As it is restricted to a belt between latitudes 30 degrees
north and south of the equator, the term tropical
pancreatitis is appropriate.
Etiopathogenesis
The exact pathogenesis is not known, but the following
factors may predispose to it:
PEM and Free Radicals

JTP is almost exclusively seen in the poor children of
developing countries with severe PEM. PEM also leads
to increased production of free radicals, which also may
cause pancreatic damage. The deficiency of free radical
scavengers like vitamin C, E, beta-carotene, zinc,
selenium etc in PEM also contributes to pancreatitis.
However, the incidence of JTP is very low in some
poor countries with a high incidence of PEM like
Ethiopia. Besides, kwashiorkor is not associated with
pancreatitis and pancreatic stones are not seen even in
advanced stages of kwashiorkor. PEM thus very well
could be the effect rather than the cause of the disease.
Cassava Toxicity (Cyanogen Toxicity)
Cassava (tapioca, Manihot esculenta) is a tuber rich in
carbohydrates but very poor in proteins (0.4 g%)
especially methionine and cysteine. It is the staple food
of about 400 million people in the developing countries,
where JTP is common. It is very popular in the south
eastern belt of Kerala, from where most of the cases of
JTP are reported.
It contains toxic cyanogenic glycosides like linamarin
and methyl linamarin (Iotaustralin). These react with
gastric hydrochloric acid to form the toxic hydrocyanic
acid. The enzyme rhodanase detoxifies hydrocyanic acid
to thiocyanate in a reaction requiring sulphur containing
amino acids like methionine and cysteine. As these amino

acids are essential for the proper functioning of pancreas,
pancreatitis results. Besides, these toxins can also injure
the pancreas directly. Sorghum, which is the staple diet
of the people of the rural belt of Karnataka, is also rich in
cyanogenic glycosides. This may be responsible for JTP
in this state.
However, the cassava hypothesis lacks experimental
support.
Familial Aggregation
JTP sometimes affects several members of the same
family. This suggests, but does not necessarily prove a
hereditary etiology for JTP, since several members of a
family could be exposed to the same toxic or other
environmental factors.
Genetic Factors
SPINK 1 is a potent protease inhibitor which is a major
protective mechanism preventing inappropriate
activation of pancreatic enzyme cascade by inhibiting up
to 20% of trypsin activity. The absence of SPINK 1 gene
may predispose to chronic pancreatitis in general and
JTP in particular.
Pathology
The pancreas is markedly atrophied and may be as small
as the little finger in advanced stages of the disease. There
is extensive intralobular and interlobular fibrosis.
Immunohistochemistry has shown paucity of alpha cells
and beta cells. There are advanced fibrosis and calculi of
varying shapes and sizes. They are composed of 95.5%
calcium carbonate and small amounts of calcium
phosphate and traces of magnesium, urate and oxalate.
645
severe pain that disturbs his sleep. The pain is increased

by food and hence he refuses to eat. This aggravates PEM.
Thus, a vicious cycle is produced causing persistent
damage to the pancreas. As the disease progresses, the
severity of pain tends to decrease and it usually
disappears with the onset of exocrine pancreatic
insufficiency
Unfortunately, abdominal pain is usually passed off
as functional pain by the parents and doctors, and hence
the diagnosis is very much delayed.
Diabetes Mellitus
Diabetes is an inevitable consequence of JTP and occurs
one or two decades after the first episode of abdominal
pain. It is referred to as fibrocalculous pancreatic diabetes
(FCPD). It is brittle with episodes of hypo and hyperglycemia, with or without insulin therapy.
One of the characteristic features of FCPD is that
despite requiring insulin for control, ketosis is rare unlike
type I diabetes. .However, microvascular complications
do occur.
Exocrine Pancreatic Insufficiency
Steatorrhoea is seen in only 20% of patients with JTP.
This is only because these children consume very little
fat due to the poor appetite. If a high fat diet is given
most of them will develop steatorrhea.
Diagnosis
The association of diabetes mellitus and recurrent
abdominal pain in a young patient suggests the diagnosis
of JTP. Extreme emaciation, a peculiar cyanotic hue of
the lips, bilateral painless parotid gland enlargement,
retarded growth and development, potbelly and
hepatomegaly are seen in most of the patients.
Clinical Features
Complications
The clinical features of JTP can be aptly summarized as

recurrent abdominal pain in childhood, diabetes mellitus
and pancreatic calculi by adolescence and death in the
prime of life, due to severe malnutrition, complications
of uncontrolled diabetes and carcinoma of pancreas.
1. Severe malnutrition.
2. Both microvascular and macrovascular complications
may occur in FCPD. However, macrovascular
complications are relatively rare as the patients are
young, lean and have lower lipid levels.
3. Complications due to chronic pancreatitis like
pseudocysts, pancreatic abscess and ascites may
rarely occur.
4. Carcinoma of pancreas is the most sinister complication of JTP. The risk factors for cancer remain
unknown.
Abdominal Pain
Recurrent severe abdominal pain that radiates to the back
is the chief complaint. It may be associated with vomiting.
The child may get up in the middle of the night with
646
Investigations
Endoscopic and Surgical Treatment
1. Plain radiograph of the abdomen shows pancreatic

calculi, usually to the right of L 1 and L2 vertebrae.
They are most numerous in the head of the pancreas.
2. Ultrasound and CT scan detect smaller pancreatic
calcifications not evident on radiographs and also
complications like carcinoma of pancreas.
3. Endoscopic retrograde cholangiopancreatography
shows a dilated main pancreatic duct with radio
opaque and lucent calculi.
4. Endoscopic ultrasonography is an exciting new tool
for the diagnosis of chronic pancreatitis.
Exploration of the pancreatic duct and removal of stones

or endoscopic papillotomy and removal of stones are
useful procedures. Severe pain is an indication for
surgical treatment
Puestow-Gillesby operation: Ductal decompression and side
to side pancreaticojejunostomy.
Duvals procedure: here, distal pancreaticojejunostomy is
done.
Ablative procedures like partial or subtotal pancreatectomy are done in those with intractable pain.
BIBLIOGRAPHY
Management
Medical
Therapy is directed towards repletion of nutritional
deficits and the management of chronic pain. Diabetes
is managed with insulin or at times with oral hypoglycemic agents. Pancreatic enzymes may be given if the
child has steatorrhoea. It may also decrease abdominal
pain because suppression of pancreatic secretion reduces
intraductal pain. Antioxidant supplementation may also
help to decrease pain.
1. Barman KK, Premalatha G, Mohan V. Tropical chronic

pancreatitis. Postgrad Med J 2003;79:606-15.
2. Narendranathan M. Chronic calcific pancreatitis of the
tropics. Trop Gastroenterol 1981;2:40-45.
3. Pitchumoni CS. Juvenile tropical pancreatitis. Walker
WA, Durie PR, Hamilton RJ, Smith JAW, Watkins JB
(Eds). Paediatric gastrointestinal disease pathophysiology, diagnosis and Management. 2nd edn. Mosby
St. Louis: Missouri 1996;1502-10.
4. Schneider A, Suman A, Rossi L, et al. SPINK 1/PSTI1
mutations are associated with tropical pancreatitis and
type 2 diabetes in Bangladesh. Gastroenterology
2002;123:1026-30.
13.13 Liver and Biliary System

B Bhaskar Raju, B Sumathi
EMBRYOLOGY
The hepatobiliary system consists of the liver, gallbladder
and bile ducts. It develops from an endodermal
outgrowth that arises from the ventral aspect of the gut
at the junction between foregut and midgut called the
hepatic diverticulum during fourth week of embryogenesis. The hepatic diverticulum divides into two parts:
pars hepatica (larger cranial part, the primordium of the
liver) and pars cystica (smaller ventral invagination, the
primordium of gallbladder) (Fig. 13.13.1). The endodermal cells of the hepatic diverticulam form the hepatic
parenchyma and bile capillaries. The mesenchyme of
septum transversum forms the capsule, fibrous tissue of
the liver and Kupffer cells. Umbilical and vitelline veins
are broken up to form the sinusoids of the liver and they
Figure 13.13.1: Embryology

are also formed from the mesenchyme of the septum
transversum. The pars cystica of the hepatic bud forms
the gallbladder, the cystic duct and extra-hepatic bile
ducts.
ANATOMY
Liver is the largest organ in the body and is relatively
larger in infancy comprising oneeighteenth of the birth
weight. It is apparently divided into right and left lobes
by the falciform ligament. Right lobe contains the caudate
and quadrate lobes. Actually, the principle plane which
divides the liver into functional lobes passes through the
bed of the gallbladder. Anatomical variations include
accessory lobes, Riedls lobe (downward tongue like
projection of the right lobe of the liver, occasionally
palpable per abdomen, more common in girls). The
biliary system comprises of biliary canaliculi which
combine to form bile ductules, bile ducts, right and left
hepatic ducts which unite to form the common bile duct
(CBD) at porta hepatis. The common bile duct enters the
second part of duodenum, along with the main
pancreatic duct at the ampulla of Vater. The distal end
of the common bile duct contains the sphincter of Oddi
which prevents bile flow during fasting (Fig. 13.13.2).
Blood Supply
The liver has a dual blood supply. 75% of the blood
supply to the liver is from the portal vein which carries
nutrient rich but oxygen-poor venous blood to the liver
from the intestines and spleen. The hepatic artery (a
branch of the celiac axis) carries well-oxygenated arterial
blood to the liver (50 to 80% of the livers oxygen supply)
and accounts for the remaining 25% of the blood supply.
Figure 13.13.2: Hepatobiliary system
647
The venous drainage is by three main hepatic veins

which drain directly into the inferior vena cava(IVC)
except the caudate lobe which has independent drainage
to IVC. The cystic artery and vein, perfuse the gallbladder
and biliary apparatus.
Lymphatic Drainage
Lymphatics from both lobes drain into the nodes at the
porta hepatis, celiac axis, mediastinal nodes and those
along the intra thoracic portion of IVC. Lymphatics of
the gallbladder drain into the cystic node, nodes along
the CBD and head of pancreas.
Morphology
The hepatic lobules form the basic liver architecture. The
lobules are separated from the portal tract by limiting
plates (Lamina Limitans) (Fig. 13.13.3).
At the center of each lobule run the tributaries of the
hepatic veins carrying back venous blood from the
liver.
At the junction of three hepatic lobules run the portal
tracts, consisting of the branches of the portal vein,
hepatic artery, and the bile duct.
Columns of liver cells and sinusoids extend between
these two systems. The microscopic spaces between the
hepatocytes and the bordering sinusoidsare the Spaces
of Disse and they contain tissue fluid, flowing into the
hepatic lymphatics.
FUNCTIONS OF THE LIVER
Production of bile that excretes bilirubin, the end
product of hemoglobin metabolism and Copper. Bile
Figure 13.13.3: Structure of the liver lobule
648
is also rich in phospholipids (predominantly

phosphatidylcholine) that form mixed vesicles and
micelles with bile salts and thereby provide a means
for the disposal of highly lipophilic endogenous and
exogenous compounds, such as cholesterol, from the
body.
Production of plasma proteins (Albumin, Globulin,
Fibrinogen); transport proteins; coagulation factors
(fibrinogen, prothrombin, V, VII, IX, X, XIII) and
components of the complement system.
Production of cholesterol and special proteins which
help to carry lipids throughout the body.
Conversion of excess glucose into glycogen for storage
(This glycogen can later be converted back to glucose
for energy).
Regulation of blood levels of amino acids, which form
the building blocks of proteins.
Processing of hemoglobin for use of its iron content
(The liver stores iron).
Conversion of poisonous ammonia to urea (Urea is
one of the end products of protein metabolism that is
excreted in the urine).
Storage of vitamins A, D, E, K, B12, Iron and Copper.
Detoxification of drugs and other poisonous substances.
Resisting infections by producing immune factors and
removing bacteria from the portal blood stream.
SIGNS AND SYMPTOMS OF LIVER DISEASE

Jaundice, nausea, dark urine, light-colored stools, pain
in the upper right part quadrant of abdomen, pruritus,
varicose veins in the esophagus, fatigue, hypoglycemia,
low grade fever, muscle aches and pains, unusual weight
loss or weight gain, vomiting, diarrhea, loss of sex drive
in adolescents, depression, malaise, or a vague feeling of
illness, loss of appetite, fluid retention, neuropsychiatric
symptoms and hepatomegaly are some of the important
signs and symptoms of liver disease.
Liver span: It is the distance between upper and lower
borders of the liver, estimated by percussion in the right
mid-clavicular line. The liver span increases linearly with
body weight and age in both sexes. Normal values in
infants are about 5-7 cm, in 5 yrs old it is 7-8 cm and in
10-12 yrs old it is 9-10 cm. A decreased liver span is seen
in cirrhosis (shrunken liver). Acute hepatocellular
necrosis also shows rapid reduction in liver span. If a
rapid increase in liver span is seen, we should exclude a

space occupying lesion.
1. Jaundice (icterus) is yellowish discoloration of skin
and mucus membranes- especially, elastin rich
tissues like sclera due to hyperbilirubinemia. It is
clinically detectable when serum bilirubin is >2.5
mg/dl. Hyperbilirubenemia may be due to (1)
Excess production of bilirubin, e.g. hemolytic
anemia, (2) Decreased uptake of bilirubin into
hepatic cells, (3) Disturbance in conjugation, (4)
Obstruction to bile flow.
2. Pruritus or itching is due to deposition of bile salt
or similar pruritogenic factor/factors produced in
the liver in the skin and is seen in cholestatic
jaundice.
3. Abdominal pain in the epigastrium/right hypochondrium is due to distended liver causing
capsular stretch, caused by viral hepatitis, congestive hepatomegaly, liver abscess, perihepatitis
and or cholangitis.
4. Pale or clay colored stools seen in cholestatic
conditions indicates the absence of bile in the
intestines due to obstruction to flow and usually
leads to fat malabsorption.
5. Dark colored urine is seen in all types of jaundice
except hemolytic jaundice (acholuric jaundice) due
to excretion of conjugated bilirubin in the urine.
6. Symptoms due to vitamin deficiencies include night
blindness (vitamin A); bone deformities (vitamin D);
bleeding tendencies (vitamin K and clotting factors)
7. Fluid retention. The presence of ascites, pedal edema
and bilateral hydrothorax suggests hypoalbuminemia. Fluid retention due to Portal hypertension
is usually localised to the abdomen.
8. Abdominal distension in liver disease may be due
to ascites and or hepato/hepatosplenomegaly.
9. Neuropsychiatrist symptoms like confusion,
drowsiness, altered sleep rhythm, may be due to
hepatic encephalopathy.
10. Symptoms like anorexia, nausea, vomiting, malaise
constitute the usual prodrome in acute hepatitis.
SYMPTOMS OF LIVER FAILURE
An enlarged and tender liver which rapidly shrinks,
altered sensorium, coagulopathy, encephalopathy,
ascites and aplastic anemia may be evidence of acute liver
cell failure.
AIM OF THE INVESTIGATIONS

A single liver function test is of little value in screening
for liver disease as some serious liver diseases may be
associated with normal levels of individual tests.
Selective combination of tests may be required to identify
liver disease and diagnose the etiology. Tests of liver
function and disease are done for:
a. To detect hepatic abnormality
b. Measure severity of liver damage
c. Identify the specific cause of the liver disease
d. Investigations to diagnose possible complications
INVESTIGATIONS FOR LIVER DISEASE
1. Baseline investigations: Complete hemogram, ESR,
smear study.
2. Serum bilirubin (normal< 1 mg/d1. 80% unconjugated). If the conjugated fraction is >20% of total
bilirubin, it may suggest cholestasis.
3. Serum aspartate transaminase (AST) or (SGOT):
Normal-5-35 IU/L. Serum alanine transaminase
(ALT) or (SGPT) normal-5-35 IU/L. Elevated levels
indicate hepatocyte injury. AST (SGOT) is sensitive
but ALT (SGPT) is more specific for liver disease.
(SGOT is also present in heart, skeletal muscle and
kidney).
4. Serum alkaline phosphatase (ALP) (Normal 3-13 KA
units/dl or 21-100 IU/L) is raised in liver disease
and cholestasis.
5. Gamma glutamyl transpeptidase (GGTP) (Normal
7-30 IU/L) is also raised in cholestasis. Its activity is
induced by drugs like phenobarbitone, rifampicin
and also by alcohol and they may elevate its blood
levels.
6. Serum proteins: Albumin (normal 4.5-5.5 g/dl). Low
levels indicate poor synthetic function. Low albumin
suggests poor prognosis in fulminant hepatic failure.
It is usually low in decompensated chronic liver
disease (<3 g/dl). Globulin (Normal 1.5 g/dl) may
be raised in cirrhosis. Reversal of albumin/globulin
ratio occurs when raised gamma globulins are
accompanied by fall in serum albumin levels. That
occurs in cirrhosis and similar inflammatory chronic
liver diseases
7. Prothrombin time (PT): (Normal 10-14 sec).
Prolonged PT indicates severe liver damage or poor
absorption of Vit K. If uncorrected by parenteral Vit
K, it indicates poor prognosis in liver disease
649
8. Activated partial thromboplastin time (PTTa):

Prolonged PTTa suggests coagulopathy. It is usually
accompanied by prolonged Prothrombin time
9. Antimitochondrial antibody (AMA); Elevated levels
are seen in primary biliary cirrhosis and autoimmune chronic active hepatitis.
10. Viral markers for Hepatotrophic viruses A to E.
11. PCR (Polymerase chain reaction) can be used to
confirm viral etiology.
12. Ultrasonogram of abdomen to assess the liver
echotexture, splenoportal axis, collaterals in portal
hypertension, presence of ascites, space occupying
lesions.
13. CT scan of abdomen.
14. Liver biopsy is used to confirm the tissue diagnosis.
It is also useful in follow up of chronic liver disease
and for the assessment of effect of therapy.
15. Hepatobiliary radioisotope scan is used to asses the
excretory capacity of the liver and delineate the
extrahepatic biliary passages.
16. Splenoportovenogram is no longer preferred for
diagnosis. Some hepatologists however still consider
it as the gold standard test for delineating portal
anatomy, but it has been mostly replaced by non
invasive imaging techniques now.
17. Procollagen III: Serum concentration of procollagen
III peptide is used as surrogate marker for hepatic
fibrosis. It may also be raised in chronic inflammation in the liver. It is useful in follow up of
chronic liver disease.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
6.
BR. Thapa and Anuj Walia, Liver Function Tests and their
Interpretation. Indian Journal of Pediatrics 2007;74.
Daniel S, Pratt, Marshall M. Kaplan. Evaluation of liver
function; Harrisons Principles of internal medicine; 16th
edition; McGraw Hill Medical publishing division
2005;2:1813-16
Inderbir Singh, GP Pal. Human embryology, Chapter 14
Liver, Pancreas, Spleen; Respiratory system; Body
cavities, Seventh edition 2001;187-88.
Sheila Sherlock, James Dooley. Disease of the Liver and
biliary system, Eleventh Edition 2002; Blackwell Science
publications, 1-17.
Sleisenger, Gastrointestinal and Liver Disease; Pathophysiology/Diagnosis/Management 7th Edition,
Saunders Publications 2002;2.
William F.Ganong, Review of medical physiology,
Regulation of Gastrointestinal Function Chapter 26;
Twenty second edition. International edition 2005;
500-503.
650
13.14 Hepatosplenomegaly: A Practical

Diagnostic Approach
Sheila Bhave, Ashish Bavdekar
Hepatomegaly is a common clinical problem in infants
and children. Many disease processes, which may or may
not be primarily hepatic, cause liver enlargement. The
pathophysiological mechanisms causing hepatomegaly
are:
Infection, inflammation (hepatitis, fibrosis)
Kupffer cell hyperplasia
Venous congestion
Storage of glycogen, fat and other metabolites (inborn
errors)
Infiltrations
Tumors, neoplasia.
Figure 13.14.1: Assessment of hepatosplenomegaly
CLINICAL EVALUATION
Practical Clues
Is the Liver Really Enlarged?
In infancy and early childhood, the liver may be felt
normally upto 3 cm below the costal margin. In chest
diseases, such as pneumothorax, bronchiolitis and
emphysema and in chest deformities such as in rickets,
the liver may be pushed down giving an apparent
hepatomegaly. Hence, percussion for the upper border
of the liver is important in the assessment of hepatomegaly.
Size, Margin, Contour, and Consistency of Liver
Size of the liver is better assessed by liver span, i.e.
height of the liver in right mid clavicular line (superior
border by percussion and inferior border by palpation
Fig. 13.14.1).
Epigastrium should always be palpated for the left
lobe. Firm to hard consistency with sharp margin, usually
implies cirrhosis or fibrosis. Soft, enlarged and tender
livers occur in inflammatory and congestive processes
such as viral hepatitis and congestive heart failure (CHF).
An isolated mass felt in an otherwise normal liver or an
asymmetric enlargement may suggest tumor or cyst.
Is it a Primary Liver Disorder or a Part of

Generalized Disease?
Common pediatric conditions such as protein energy
malnutrition, anemia and tuberculosis can cause
significant hepatomegaly. History and general clinical
examination can give important clues to these diseases.
Primary liver disorders usually present with signs of liver
cell failure (e.g. jaundice, ascites) and abnormal liver
function tests (See chapter 13.13 Liver and biliary system).
Age of the Child
The age of onset is an important clue to the etiology of
pediatric liver disease (Table 13.14.1). Neonatal
cholestasis syndrome presents in early infancy; Indian
childhood cirrhosis occurs typically in preschool children
whereas Wilsons disease affects older children and
adolescents.
Other Clues in History and
General Physical Examination
Helpful clues are:
Onset: acute (viral hepatitis) or chronic (as in cirrhosis,
chronic hepatitis)
651
TABLE 13.14.1: Common causes of hepatosplenomegaly according to age

Neonates and infants
Children and adolescents
Intrauterine infections (TORCH)

Neonatal cholestasis syndrome (NCS)
Biliary atresia
Neonatal hepatitis
Erythroblastosis (Rh, ABO incompatibility)
Congestive heart failure (CHF)
Sepsis, systemic viral infections
Metabolic liver disease
Galactosemia
Tyrosinemia, Alpha 1 AT deficiency
Hemochromatosis
Secondaries
Wilms tumor, Neuroblastoma
Infection-Acute
Viral hepatitis A-E
Dengue, typhoid, leptospirosis
Infection: Chronic
Tubercular, malaria, kala azar
Liver cirrhosis
Indian childhood cirrhosis
Budd Chiari, veno-occlusive disease
Chronic active hepatitis
Wilsons disease
Extra hepatic portal hypertension
Hepatic fibrosis
Cystic fibrosis
Glycogen storage disease
Gauchers, Niemann-Pick disease
Mucopolysaccharidosis
Hematological disorders
Hemolytic anemias
Leukemia, lymphoma
Cysts (congenital, hydatid)
Abscesses (amebic, pyogenic)
Fever: typhoid, dengue, malaria, tuberculosis

Family history and consanguinity: Wilsons disease,
thalassemias
Hepatotoxic drugs: anti-tubercular, anti-epileptic,
anti-cancer drugs
Anemia: hemolytic anemias, leukemias
Lymphadenopathy: disseminated tuberculosis,
malignancy (some other clinical clues to diagnosis are
given in Table 13.14.2).
Important Associated Features in
Differential Diagnosis of Hepatomegaly
Jaundice: Obstructive/ Hemolytic/ Hepatocellular. Each
type is associated with different group of diseases (See
Chapter 13.15 on Jaundice).
Splenomegaly is commonly associated with hepatomegaly because of common pathogenetic mechanisms.
Causes of predominant and massive splenomegaly are
seen in Table 13.14.3.
Ascites, edema and bleeding tendencies are signs of
liver damage. Drowsiness (precoma, coma) and
gastrointestinal hemorrhage (hematemesis, malena) are
ominous signs of impending hepatic failure (see chapter
13.21 on Fulminant Hepatic Failure).
TABLE 13.14.2: Associated clinical manifestations which

aid in diagnosis of hepatomegaly
Clinical features
Clues to diagnosis
Microcephaly/
Hydrocephalus
Intrauterine infections (e.g. Rubella,

Toxoplasmosis, CMV)
Cataracts
Galactosemia, Wilsons disease
KF rings
Wilsons disease
Tremors, dysarthria
Wilsons disease
Mental retardation
Galactosemia; lipid storage
Engorged neck veins-
Congestive heart failure, constrictive

pericarditis
Rickets
Wilsons disease, Tyrosinemia
Cystic kidneys
Congenital hepatic fibrosis
Skin rashes
Histiocytosis
Scheme of Investigations
The scheme of investigations should be directed
judiciously at detecting the etiology and the mechanism
of hepatomegaly as also the extent and severity of the
disease. (see Chapter 13.13 Liver and Biliary Tract). Special
additional tests are given in Table 13.14.4.
652
TABLE 13.14.3 Causes of massive hepatosplenomegaly

Liver
Predominant enlargement of
Spleen
Gauchers disease
Hemolytic anemias
Tumor (Hepatoma,
secondaries)
Extra hepatic portal

hypertension
Cyst (hydatid, abscess)
Chronic myeloid leukemia

(juvenile)
Chronic extrahepatic
cholestasis
Myelofibrosis
Chronic malaria, kala azar
Hypersplenism, tropical
splenomegaly
Progress of Liver Disease/Hepatomegaly

Important conclusions can be based on careful followup of hepatomegaly. Benign hepatomegaly associated
with common febrile illnesses of children usually recedes
completely within a few weeks. So also most cases of
acute viral hepatitis resolve within 3 to 6 weeks. On the
other hand continued hepatomegaly with signs of
progressive liver failure must be evaluated for chronic
liver diseases and cirrhosis (see Chapter on 13.18 and
13.19 on Chronic Liver Disorders and Cirrhosis).
BIBLIOGRAPHY
1.
Bhave SA, Bavdekar AR, Pandit AN. Neonatal cholestasis

syndrome in India: A diagnostic and therapeutic
challenge. Indian Pediatr 1996;33:75362.
TABLE 13.14.4 Special tests in diagnosis of

hepatosplenomegaly
Hemogram, ESR, rectic count,

Urine routine, culture
(See chapter 12.12 Liver and
Biliary System)
Liver biopsy
USG abdomen, CT scan
Radioisotopic scanning esp. for Neonatal cholestasis syndrome
Additional Special Tests
Viral markers
Autoimmune markers
TORCH titres
Metabolic studies
Metabolic screen (urine)
and confirmatory tests
Enzyme estimations
Urine succinylacetone
Copper studies
Ceruloplasmin, urinary
Cu
Cu stains on liver biopsy
Hepatic Cu
Alpha fetoprotein
Sweat chloride
Hepatitis A-E Dengue

Autoimmune hepatitis
for intrauterine infections
Galactosemia, Gauchers
disease, Niemann-Pick
Tyrosinemia
ICC, Wilsons disease

Hepatoblastoma, tyrosinemia
Cystic fibrosis
2. Kelly DA. Diseases of the liver and biliary system in

children. Oxford, U.K. Replika Press Pvt. Ltd., Blackwell
Science Limited, 1999.
3. Scriver CR, Beaudet AL, Sly WS, Valle D. (Eds) The
metabolic and molecular bases of inherited disease. 7th
edn. New York, USA Vol. II. McGraw Hill. 1996.
4. Walker-Smith JA, Hamilton JR, Walker WA (Eds).
Practical Pediatric Gastroenterology. (2nd edn). New
Delhi, India. Jaypee Brothers Medical Publishers (P) Ltd.,
1996.
653
13.15 Differential Diagnosis of

Jaundice in Infancy
MK Jain, Sunil Karande
COMMON CAUSES OF JAUNDICE IN INFANCY
Unconjugated
1. Hemolytic: Congenital spherocytosis, and elliptocytosis.
Red cell enzyme deficiency (G6PD)
Hemoglobinopathies
Autoimmune hemolytic anemia, viral infections
2.
3.
4.
5.
6.
Septicemia
Wilson's disease
Incompatible blood transfusion
Gilbert's syndrome
Crigler-Najjar syndrome type I and type II.
Dubin-Johnson syndrome
Rotor syndrome
Laboratory Work up in Hemolytic Jaundice
Hb, reticulocyte count, total WBC

Direct Coombs test
Urine microscopy
Red cell morphology
Peripheral blood smear for malarial parasite
Blood culture
Hb electrophoresis
Osmotic fragility of RBC
Conjugated
TABLE 13.15.1: The familial nonhemolytic

hyperbilirubinemias
Acute Hepato Cellular Disease

Viral, bacterial or parasitic metabolic abnormalities,
drugs, toxins, nutritional.
Chronic Hepatocellular Injury
Autoimmune (infective, vascular) (Table 13.15.1 and
Flow chart 13.15.1).
Cirrhosis
Post necrotic biliary or genetic

Infiltrative, e.g. Hodgkin's lymphoma
Intrahepatic cholestasis
Biliary hypoplasia syndrome
Benign recurrent cholangitis
Diseases of Extrahepatic Biliary Tree
Choledochal cyst
Choledocholithiasis
Roundworm obstruction
Sludges
Bile duct stricture
Familial conjugated hyperbilirubinemia
Types
Diagnostic points
Unconjugated hyperbilirubinemia
Clinical picture is of compensated
Primary
hyperbilirubinemia
hemolysis.
Gilbert's syndrome
Serum bilirubin increases with
fasting and falls with phenobarbitone. Mild deficiency of conjugating
enzyme in liver.
Crigler-Najjar syndrome
Type 1
Die young with kernicterus.
No conjugating enzyme in liver.
No response to phenobarbitone.
Type 2
Less severe deficiency of
conjugating enzyme in liver.
Response to phenobarbitone.
Conjugated hyperbilirubinemia
Dubin-Johnson
Blackish-brown melaninlike
syndrome
pigment on liver biopsy. No
concentration of cholecystographic
media.
Secondary rise in BSP test
characteristic.
Rotor syndrome
Normal liver biopsy. Normal
cholescystography. No uptake in
BSP test.
654

Flow Chart 13.15.1: Diagnostic approach to neonatal jaundice
Heinz body test

Test for red cell enzymes, e.g. G6PD, pyruvate kinase etc.
BIBLIOGRAPHY
1. Behrman RE, Kliegman RM,Balistreri WF et al: Metabolic
diseases of the liver. In: Nelson Test book of Pediatrics,
15th Edn., Philadelphia, WB Saunders 1996;113841.
2. Fevery J, Blanckaert N, Mclntyre N et al: Hyperbilirubinemia: In: Oxford Textbook of Clinical Hepatology,
1st Edn, Ed. Rodes J Oxford, Oxford University Press
1991;98591.
3. Sherlock S, Dooley J: Disease of the liver and biliary
system, 9th Edn., London, Blackwell Scientific Publications 1993;199213.
655
13.16 Viral Hepatitis

Malathi Sathiyasekaran, Ramaswamy Ganesh
INTRODUCTION
Viral hepatitis is a systemic viral infection marked by
diffuse hepatic cell necrosis and inflammation, which
leads to a characteristic constellation of clinical,
biochemical, and pathological changes. Several viruses
can cause hepatitis but the term viral hepatitis is
usually associated with disease due to hepatotropic
viruses. The major hepatotropic viruses are Hepatitis A,
B, C, D, E and G. and the viral hepatitis alphabet is
gradually expanding. Over the years, the newer
hepatotropic viruses namely TT and SEN virus have been
associated with transfusion hepatitis though they are less
common. Viruses such as Epstein-Barr, Herpes simplex,
Coxsackie B, Cytomegalovirus (CMV) and some exotic
viruses like Marburg and Ebola can also cause hepatitis
and should be considered in the differential diagnosis.
The two common presentations of viral hepatitis are
acute and chronic hepatitis, occasionally the initial
manifestation may be as an acute liver failure. The term
acute hepatitis is used when the illness is acute in onset
and usually lasts less than 4 weeks. The term chronic
hepatitis implies continuing hepatic inflammation for
more than 6 months which can either resolve or progress
to cirrhosis.
days but may persist even for 12 weeks in older children.

During the recovery phase, the constitutional symptoms
disappear, appetite improves and size of the liver
decreases .The biochemical abnormalities may persist for
1-2 months after the acute infection.
Chronic Viral Hepatitis
The two viruses which cause chronic hepatitis are
hepatitis B (HBV) and hepatitis C (HCV). In India chronic
hepatitis B is more common than chronic hepatitis C since
perinatal transmission plays a very significant role in
HBV infection.
HEPATITIS A
Epidemiology
Hepatitis A virus (HAV) is a 27 nm spherical, nonenveloped entero virus of Picorna viridea family
(Fig. 13.16.1) HAV infection is endemic in India and in
most developing countries. The exact incidence of the
disease is not known and it is difficult to estimate because
of the high proportion of asymptomatic cases. According
to WHO about 10-50 persons per 1, 00,000 are infected
annually and in India, 50-75 percent of acute sporadic
hepatitis in children is due to HAV. The majority of
Acute Viral Hepatitis (AVH)

In India, the common viruses causing sporadic hepatitis
are hepatitis A (HAV), hepatitis E (HEV) and hepatitis B
(HBV) whereas the epidemics are mainly due to HEV.
In younger children, the classical clinical symptoms may
be absent or may consist of only nausea, vomiting and
diarrhea. In older children the three stages of AVH
namely the prodrome, icteric stage and convalescence
may be more distinct. The clinical presentation is more
or less same whatever may be the viral etiology and hence
it may be difficult to differentiate them clinically. The
prodrome usually lasts for 2-7 days and is characterized
by nausea, vomiting, high colored urine, fever and right
hypochondrial pain. During the icteric stage, the child
has jaundice, pale stools and tender hepatomegaly. The
prodromal symptoms decrease and disappear with the
onset of icterus. The icteric stage usually lasts for 7-14
Figure 13.16.1: Hepatitis A virus
656
children acquire natural immunity by the age of 10 years

without developing symptoms of the illness. Recent
studies have shown a changing epidemiology with a
lower prevalence of anti HAV IgG in the higher
socioeconomic group exposing the susceptible older
children and adolescents to the infection at a later age.
Transmission
HAV is highly contagious and transmission is through
faeco-oral route either due to consumption of contaminated food or water. The virus is inactivated by boiling
for 5 minutes, autoclaving or UV radiation. Parenteral
transmission has been reported. Transmission occurs
during the preicteric stage of the disease. Antenatal HAV
infection does not result in increased complications or
clinical disease in the fetus or newborn. The virus can be
isolated from the liver, bile, stools and blood during the
late incubation period and pre icteric phase of the illness.
Natural infection confers life long immunity. There is
no evidence for chronic carrier state.
Pathogenesis
The ingested virus multiplies in the small bowel and
migrates via the portal vein to the liver. Although HAV
has a cytopathic effect in tissue culture, the hepatocyte
injury is secondary to a host immune response. HAV
infection causes periportal inflammation, pericentral
cholestasis without significant cellular inflammation.
hepatitis in susceptible children , red cell aplasia,

myocarditis, nephritis, cryoglobulinemia and Guillian
Barre syndrome due to circulating immune complexes.
The incidence of fulminant hepatitis or acute liver failure
occurs in less than 1% of acute infection. The case fatality
ranges from 0.15 to 3 per 1000. Co-infection with HEV or
HBV may increase the morbidity. HAV infection in
individuals with chronic liver disease of any age group
is associated with increased mortality.
Diagnosis
Acute HAV infection is confirmed by the presence of IgM
antibodies to HAV which is detected at the onset of
symptoms and remains positive for 4-6 months. Anti
HAV IgG indicates past infection and can be detected
within 8 weeks of onset of symptoms and continues to
remain positive indefinitely (Fig. 13.16.2). Polymerase
chain reaction (PCR) for detection of viral particles in
stool or blood is not done routinely and reserved only
for research purposes. The total serum bilirubin is
increased with the direct component showing variable
rise depending on the phase of illness. Serum transaminases are more than 20 times upper limit of normal,
these levels only indicate liver injury and do not correlate
with the degree of liver cell dysfunction. Prothrombin
time is an important predictor of severity of infection
and reflects severe hepatic synthetic defect and extensive
hepatocellular necrosis. A fall in serum albumin is
uncommon in uncomplicated HAV infection. Serum
The incubation period is 2 to 7 weeks and fecal shedding
occurs for 2-3 weeks before and 1 week after the onset of
jaundice. The characteristic features include an age
dependent expression of clinical illness, low rate of
fulminant disease and absence of chronicity. In children
less than 6 years of age, majority have an anicteric
hepatitis and only 10% develop typical illness with
icterus. In older children, 40-60% will present with
icterus whereas 70-80% of adults will manifest as icteric
hepatitis. In those presenting with jaundice the illness is
heralded by a mild prodrome and recovery occurs within
a period of 5 to 7 days. Older children can have atypical
manifestations such as ascites, pleural effusion, firm
hepatomegaly and disturbing prolonged cholestasis.
Extra hepatic manifestations are uncommon and include
evanescent skin rash, transient arthralgia, pancreatitis,
vasculitis, thrombocytopenia, triggering of autoimmune
Figure 13.16.2: Sequence of HAV serological

marker appearance

alkaline phosphatase may be normal or mildly elevated.
Lymphopenia and neutropenia may occur during the
course of illness.
Prevention
HAV infection is a disease of the developing countries
and therefore general measures to improve hygiene is
very essential to decrease the over all prevalence. Clean
and potable drinking water supply, hand washing and
hygienic preparation of food are important steps in
preventing the spread of Hepatitis A virus.
Immunization
Active Immunization
Effective and safe vaccine for HAV is available in India
though at present it is not indicated for universal
immunization. The vaccine is recommended on a one to
one named child basis for children especially from
higher socio economic group, adolescents and adults who
are leaving homes for education or employment without
past history of viral hepatitis or are antibody negative,
all children and adults with underlying chronic liver
disease and family contacts, all immunocompromised
individuals, household contacts of acute HAV infection
(within 10 days), children attending day care centers and
creches, travellers from abroad (eg NRIs) visiting India
or other endemic areas.
The inactive hepatitis A vaccine is administered
intramuscularly as a prime boost schedule on an elected
date (0) followed by a booster dose after 6 months. A
live attenuated human diploid cell vaccine for subcutaneous use is also available. Recently a novel inactivated
vaccine using virosome technology has been introduced.
IAP recommends two doses of HAV vaccine anytime
after 18 months of age.
Prognosis
The prognosis of HAV infection in those who recover is
excellent with no long term sequelae. Acute liver failure
is still associated with a high mortality and liver
transplantation is life saving.
HEPATITIS B
Hepatitis B (Fig. 13.16.3) virus stands unique in the group
of hepatitis virus with a potential to cause chronic
hepatitis, cirrhosis and hepatocellular carcinoma. It is a
complex hepadna virus which produces surplus protein
coat namely the surface antigen (HBsAg), earlier termed
as Australia antigen as it was first isolated from an
Australian aborginee. The intact HBV is the Dane
particle or virion, which is double shelled and 42 nm in
size. Serologically HBV is recognized by its three antigens
namely surface (HBsAg), core (HBcAg), and nucleo
capsid (HBeAg) antigens and their corresponding
antibodies namely antiHBs, antiHBc and antiHBe
(Fig. 13.16.3). HBV DNA can be detected quantitatively
and is a sensitive marker of active replication. HBV has
been classified into A to H genotypes. A genotype is
pandemic, B and C are prevalent in Asia, D is seen in
southern Europe, E in Africa, F in USA, UK and France
and H in Central America.
Epidemiology
The incubation period ranges from 60-180 days.
Transmission of HBV is by the parenteral route and
occurs by exposure to infected blood, blood products and
body fluids. The risk factors include frequent needle
pricks, intravenous drug abuse, transfusion with
Passive Immunization
HAV specific immunoglobulin is not available in India
and there are very few indications for passive immunization. The dose is 0.02 ml/kg of Immune globulin which
should be administered within two weeks after exposure
to HAV. It is indicated for newborns of HAV infected
mothers and children with chronic liver disease who are
exposed to HAV. The protection is immediate, effective
but temporary. Immunoglobulin prophylaxis is not
indicated for healthy household contacts.
657
Figure 13.16.3: Hepatitis B virus
658
improperly screened blood, acupuncture or tattoos,

sexual contact, institutional care and intimate contact
with carriers and perinatal exposure to an HBsAg
positive mother. HBV is present in high concentration
in blood, serum and body fluids such as vaginal
secretions, semen, saliva, nasopharyngeal secretions,
tears and sweat. HBsAg is inconsistently recovered in
breast milk of infected mothers and feeding of infants
under cover of active immunization is permitted. The
main source of infection is the chronic hepatitis B virus
infected individual. Depending on the prevalence of
HBsAg the world is divided into three endemic zones
namely low<2%, intermediate 2-8%, high >8% and India
lies in the intermediate zone.
Pathogenesis
HBV is predominantly a noncytopathogenic virus that
causes injury by immune mediated process and the
severity of injury reflects the degree of immune response.
Hepatocyte lysis occurs as a result of polyclonal and
multispecific immune response. The elimination of virus
infected hepatocyte is dependent on the recognition by
cytotoxic T lymphocytes of viral determinants in
association with HLA protein present on infected cell.
In India children with HBV infection presenting as
sporadic acute hepatitis occurs in 10-15 %. Most cases of
acute HBV infection in children are asymptomatic as
evidenced by the high positivity of serum markers in
persons without history of acute hepatitis. In those who
are symptomatic the prodrome of anorexia, nausea,
vomiting with or without fever may be quite marked
compared to HAV infection. Jaundice may last for 1 to 2
months and is accompanied by hepatosplenomegaly and
intense fatigue. Immune mediated extra hepatic
manifestations such as maculopapular or urticarial rash,
migratory arthritis or nephritis may be a presenting
feature. Papular acrodermatitis of childhood or GianottiCrosti syndrome may be a manifestation of HBV
infection.
Natural History
The risk of chronicity is inversely proportional to the age
of acquisition of the illness. A neonate born to a mother
who is HBsAg and HBeAg positive has about 90 percent
chance of acquiring the infection. This decreases to 30%
if the age of acquisition is 1 to 5 years and is 5 to 10 percent

if acquired after the age of 5 years. Children with chronic
hepatitis may progress to cirrhosis and/or hepatocellular
carcinoma (HCC).
There are four stages in the natural history of HBV
infection.
1. Replicative phase-Immune tolerance: This represents the
period of immune tolerance where the virus is
actively multiplying but there is no hepatic inflammation. In perinatal transmission this phase lasts
for many years and is associated with a low annual
HBeAg clearance of < 2% in children less than 3 years
and 4-5% in children more than 3 years, whereas in
horizontal transmission this stage is relatively short
and the annual HBeAg clearance is much more being
5-15%. Though treatment appears justifiable in the
immuno tolerant phase, no effective therapy is
available.
2. Replicative phaseimmune clearance: In this phase the
immune system of the host responds by hepatic
inflammation and direct cell lysis. If the immune
response is ineffective, this phase may persist for
many years. Maximum liver damage occurs in this
phase. The child may present with jaundice and
elevated transaminases and serologically is HbeAg
positive with high HBV DNA. A viral load level of
more than 105 DNA copies per ml is taken as the cut
off for considering therapy. It is important that
children in this phase of the illness are treated
appropriately because the long term prognosis
depends upon the duration of this stage. The results
of therapy depend upon the degree of underlying
liver damage when seroconversion occurs. The
treatment strategies aim to reduce the duration of this
phase of the disease.
3. Integrative phase-non replicative: When the immune
response of the host is successful, active viral
replication decreases. HBV DNA becomes undetectable and antibodies against HBeAg (HBe Ab) become
positive. The seroconversion to anti HBe is an
important event in the natural history of chronic
hepatitis B. The infection has cleared for all practical
purposes, even though the HBsAg remains positive
and integration would have occurred. This event is
characterized by a brief and self limiting rise in
transaminases followed by biochemical and histological remission. These children are infective to others
but at a much lower rate than HBeAg positive

individuals. They may go on to develop cirrhosis and
hepatocellular carcinoma. There is no indication to
treat these patients unless they have elevated liver
enzymes or an active disease on liver biopsy. These
findings would then suggest that the wild virus has
undergone mutation to a precore mutant. The
response of precore mutant infection to treatment is
not satisfactory.
4. Integrative phase viral clearance: In this phase there is
complete cessation of viral replication and the HBsAg
becomes negative. The person is completely cured of
the disease. Patients with acute Hepatitis B will
achieve this phase, but those with chronic infection
may not always reach this phase.
Interpretation of Serological Markers (Fig. 13.16.4)
HBsAg: This surface antigen appears 6 weeks after
infection and disappears by 3 to 6 months. The
persistence of this antigen for more than 6 months
indicates chronicity. HBsAg is only a marker of exposure
to the virus and is therefore positive both in acute and
chronic infection.
659
Anti HBs: This is a protective antibody and appears soon

after the disappearance of HBsAg and persists lifelong
though the titres may decrease. Anti HBs is also detected
following an effective immunization but unlike following
natural infection anti HBc will not be present. The
protective titre is more than 10 mIU/ml.
HBeAg: This antigen is detected soon after the appearance
of HBsAg and is a marker of infectivity and active viral
replication. It usually disappears by 6 weeks; persistence
of this antigen for more than 6 weeks indicates
progression to chronicity. It is detected in chronic
hepatitis due to wild virus infection but not in pre core
mutant infection. An infant born to a mother who is
HBsAg and HBeAg positive has more chance (about
80%) of acquiring the infection than an infant born to a
mother who is positive only for surface antigen.
Anti HBe: This is not a protective antibody. It appears
after the disappearance of HBeAg. The seroconversion
of HbeAg to antiHbe positivity during therapy for
chronic HBV infection indicates a good response to
treatment.
Figure 13.16.4: Sequence of HBV serological marker appearance
660
HBcAg (core antigen) is detected only in the hepatocyte

and not in serum. The ground glass hepatocytes seen on
histopathology indicate the presence of core antigen.
AntiHBc: This is also not a protective antibody but is a
useful marker in sero diagnosis. Anti-HBc IgM indicates
recent infection and anti HBc IgG indicates past infection.
HBV DNA: The presence of HBV DNA indicates active
viral replication and can be assessed qualitatively or
quantitatively. Quantitative measurement of the viral
load is necessary before commencing therapy in chronic
hepatitis. The fall in viral load is monitored during
therapy.
Diagnosis
Acute hepatitis B is diagnosed by the presence of HBsAg
and antiHBcIgM whereas in chronic hepatitis B the
serological markers can be detected according to the stage
of the disease. The presence of HBsAg more than
6 months indicates chronic infection; if HBV DNA is
present with or without HBeAg it indicates active
multiplication.The interpretation of the various viral
markers is shown in Table 13.16.1 and Figure 13.16.4.
Prevention
General measures: Since HBV is spread parenterally proper
screening of blood and blood products is necessary prior
to transfusion. Disposable needles should be used and
unnecessary needle pricks including tattooing avoided.
Common religious practices in India namely hair tonsure,
ear and nose boring should be performed with due
precaution only after immunization.
Immunization
Active immunization with hepatitis B vaccine is
recommended for all children. The current IAP
recommendation is to administer the recombinant
genetically engineered subunit HBV vaccine intramuscularly in 3 doses of 10 mg for children less than 12
years and 20 mg for those more than 12 years. The three
schedules endorsed by IAP are 0, 1 and 6 months or birth,
6 and 14 weeks or combination with triple antigen at 6,10
and 14 weeks. The genetically engineered recombinant
DNA vaccine is safe and immunogenic. It is preferable
to administer Hepatitis B Immunoglobulin (HBIG) within
6 hours of birth and hepatitis B vaccine to babies born to
HBsAg positive mothers using two separate syringes and
sites for injection. HBIG has also been recommended for
those with history of acute exposure to HBsAg infected
material (eg: needle stick injury).
HEPATITIS C
Hepatitis C virus (HCV) is an important cause of post
transfusion hepatitis and is a single stranded RNA virus
and is the only member of the genus Hepacivirus in the
family Flaviviridae. It is an enveloped, linear, single
stranded RNA flavivirus (Fig. 13.16.5) with 6 genotypes
and several subtypes based on genomic differences. The
various subtypes permit the virus to escape the host
immune surveillance.
Epidemiology
HCV is transmitted more often by blood and blood
products compared to body secretions. It is therefore
TABLE 13.16.1: Interpretation of serologic markers with SGPT in hepatitis B infection

HBsAg
HBeAg
antiHBe
antiHBc
antiHBS
HBV DNA
SGPT
Significance
+
+
+
+/-
IgM
IgG
High
High
> 2 times
UL of normal
Acute hepatitis
Chronic hepatitis-immune clearance
IgG
Low/not
detected
High
IgG
+
+
-
IgG
ULUpper limit
Normal
Normal
Recovery
Vaccination immunity
Chronic hepatitis Inactive
carrier
Immune tolerance
661
milder course in children. Acute liver failure occurs in <

1%.The symptoms of malaise, fatigue and jaundice are
mild; the transaminases are elevated for a longer period.
Spontaneous remission occurs in 40 to 60% of individuals
following acute HCV infection, 40-50 percent may
progress to chronicity and later to cirrhosis and
hepatocellular carcinoma. Sporadic hepatitis in children
due to type C hepatitis is rare. Children who require
repeated blood transfusion, e.g. Thalassemia major are
at a higher risk for type C infection.
Diagnosis
Figure 13.16.5: Hepatitis C virus
not as infective as HBV but results in more morbidity.

HCV is less common in children compared to adults with
a prevalence of 0.2% in children younger than 11 years
of age and 0.4% in children more than 11 years of age.
The risk factors for HCV transmission in children include
repeated blood transfusions, illegal drug usage and
unsafe sex. Perinatal transmission of HCV is much less
than which occurs in HBV infection and depends on the
maternal HCV viral load and HIV positivity status.
Pathogenesis
Chronic HCV infection is not a consequence of direct
cytopathic effect but rather an intermediate immune
response that is sufficient to induce hepatic cell
destruction and fibrosis but not sufficient enough to clear
the virus. Cell mediated immune responses and
elaborations by T cells of anti viral cytokines contribute
to containment of infection and pathogenesis of liver
injury. Certain characteristic features are identified on
histopathology such as periportal lymphoid aggregates,
steatosis and piling up of biliary epithelial cells with out
interruption of basement membrane in the liver. The
natural history of the disease depends upon several viral
and host factors. Genotype I do not respond to antiviral
therapy as well as non I genotypes and needs longer
duration of treatment
Detection of antibodies to HCV and HCV RNA helps in

the diagnosis of HCV infection. Enzyme immunoassays
for detection of antibodies are sensitive in high risk
populations but not in the low risk group. Recombinant
Immuno Blot Assay (RIBA) has a higher sensitivity in
low risk patient groups. Anti HCV antibody is not a
protective antibody and hence does not confer immunity
and is usually present with the virus. Detection of HCV
RNA is more sensitive and a viral load >105 copies/ml
of HCV RNA is taken as a cut off for initiating therapy.
Prevention
Screening of donor blood is essential in prevention of
HCV infection. Vaccines for HCV are on the pipeline but
are not yet available for regular use. Vaccine development has been impeded by the various HCV genotypes
and presence of quasispecies.
HEPATITIS D
Hepatitis D virus (HDV) or Delta agent is a unique
hybrid virus which requires HBsAg to replicate and was
first isolated from the chronic carriers of HBV. It is an
enveloped incomplete RNA virus 35-38 nm in size,
containing a small circular single stranded RNA, with
an outer coat formed by HBsAg.
Pathogenesis
Hepatocyte injury resulting from infection with HDV
may be caused by direct virus cytotoxicity, in contrast to
immune mediated injury associated with HBV. Replication is limited to the liver and the pathologic changes
in HDV infection are limited to this organ.
The incubation period of HCV infection is 7 to 9 weeks.

Acute HCV infection is insidious in onset and takes a
The clinical features depend on the status of the

underlying HBV infection. Acute HDV infection can
662
occur either as a co-infection with acute HBV infection

or as a superinfection in an asymptomatic or symptomatic chronic HBsAg positive child.
and preterm labor may be as high 60%. Acute liver failure

due to HEV is also seen more during pregnancy.
Coinfection follows simultaneous exposure to an

innoculum containing both HBV and HDV. The
incubation period is same as that for HBV infection. A
biphasic illness occurs which is uncommon in other forms
of hepatitis. The incidence of acute liver failure is as high
as 10 percent.
Diagnosis
Superinfection can occur in an asymptomatic HbsAg

positive child or in those with HBV related chronic liver
disease. It results in deterioration of the pre existing
condition with the appearance or deepening of jaundice
and worsening of ascites. Acute liver failure is as high as
20 percent.
Diagnosis
Coinfection with HBV is diagnosed by the presence of
HBsAg, anti-HBc IgM and low titres of anti-HDV IgM
whereas in superinfection, HBsAg is present with high
titres of anti-HDV IgM but without anti-HBc IgM.
Prevention
HDV can be prevented by taking all steps to prevent HBV
infection.
HEPATITIS E
Hepatitis E virus (HEV) is an important cause of both
sporadic and epidemic forms of hepatitis. It is a 27-32
nm RNA virus of calici group and is spread by faecooral route. Several strains have been identified based on
the nucleotide sequence. HEV has been the causative
organism in the major epidemics of hepatitis in India.
The 1978 epidemic in Kashmir was studied extensively
which gave several new insights to this virus.
The incubation period of HEV is between 3 to 9 weeks.
The illness is similar to type A hepatitis and chronicity
does not occur. During epidemics, children usually have
a subclinical infection and intrafamilial spread is
uncommon. Pregnant women are more symptomatic
than non pregnant women especially during the 2 nd
and 3 rd trimester. Pregnancy is complicated with a high
maternal mortality of 5-30%, still births, fetal wastage
The presence of anti-HEV IgM indicates recent infection.

Prevention
Vaccine against HEV is on the pipeline but is not available
for regular use at present.
HEPATITIS F
It is well documented that even after a detailed
serological study, 10 percent of children will not have
markers to the known viruses A to E. These could be
HBV variants with mutation, or a budding RNA virus.
French workers have identified an enteric virus in this
non A E group and call it the hepatitis French Virus
(HFV).
HEPATITIS G
Hepatitis G (HGV) virus is a single stranded RNA flavi
virus which shares limited identity with HCV. It is
distributed widely among the population and spreads
by parenteral route.
HGV has been linked to post-transfusion hepatitis,
chronic hepatitis and cirrhosis but it is unlikely that HGV
by itself can cause disease. Some workers feel that the
virus is still searching for a disease and is an innocent
bystander.
SEN and TT Virus: These viruses derive their identity from
the patients from whom they were isolated.
SEN virus is a single stranded, circular, non enveloped
DNA circo virus associated with transfusion associated
hepatitis. However its definite role in acute or chronic
hepatitis is still debated.
TT virus is also a single stranded DNA circovirus transmitted parenterally. It has also been associated with
transfusion associated hepatitis. The prevalence rates of
this virus in hemodialysis patients and blood donors are
reported as high as 50%. Isolation of this virus as the
aetiological agent in acute, chronic or fulminant hepatitis
has been inconsistent.

NON HEPATOTROPHIC VIRUSES
Several nonhepatotrophic viruses can cause hepatitis and
though they are less common in older children, they form
an important group in neonates and young infants.
Children with this form of hepatitis usually present with
features of the underlying illness such as the exanthem
in measles and varicella in addition to hepatomegaly and
elevated serum transaminases. The diagnosis is usually
made clinically and if necessary confirmed serologically.
Some of the important non hepatotrophic viruses causing
hepatitis are:
Measles virus: Measles presenting with anicteric hepatitis
is an atypical manifestation of the illness and usually
results in spontaneous recovery. Measles virus can
trigger autoimmune hepatitis type 1 within 3 months of
the infection in susceptible individuals.
Parvovirus B19: Human parvovirus B19 can present with
hepatic dysfunction, elevated transaminases and acute
liver failure with or without aplastic anemia.
Herpes Simplex 1 and 2(HSV): HSV hepatitis is usually
rare beyond the neonatal period unless the child is
immunocompromised. It may present as part of a
generalized herpetic disease in infants. In older children
it is rare and the mucocutaneous lesions may be absent.
The diagnosis is made by the presence of IgM antibodies
and the isolation of virus from the vesicles or other tissue.
Liver biopsy shows the characteristic inclusion bodies.
Dengue virus: Dengue fever presents with fever, hepatomegaly, rash, pleural effusion and features of capillary
leak. There is a moderate elevation of transaminases especially AST more than ALT. In the presence of Dengue
shock syndrome, the transaminases may be very high in
several thousands due to ischemic or hypoxic hepatitis.
This elevation of transaminases unlike in viral hepatitis
is associated with a significant rise in LDH which drops
sharply once the child is resuscitated. The diagnosis is
confirmed by the high hematocrit, low platelet and the
presence of IgM dengue antibodies.
Cytomegalovirus (CMV): Cytomegalovirus hepatitis
usually occurs in neonates presenting as prolonged
cholestasis of newborn and later may progress to
cirrhosis. In older children it may occur in recipients of
renal or liver transplant. The disease resembles EBV
related mononucleosis without pharyngitis and posterior
663
cervical lymphadenopathy. The diagnosis is made by

isolation of the virus from urine or saliva using PCR. A
four-fold rise in the antibody titre is also helpful in diagnosis. Liver biopsy demonstrates the characteristic
nuclear and cytoplasmic inclusion bodies.
Epstein Barr virus (EBV): Infectious mononucleosis caused
by EBV usually presents as prolonged fever with sore
throat, evanescent rash and lymphadenopathy. At times
these features subside and the child presents as acute
hepatitis with hepatosplenomegaly and elevated
transaminases. The diagnosis is confirmed by the
detection of IgM antibody to the viral capsid antigen.
Human herpes virus 6 (HHV 6): Liver dysfunction in
association with HHV 6 virus infection may present as
infectious mononucleosis like syndrome, hepatitis or
acute liver failure.
Varicella zoster: VZ virus causing liver disease is unusual
except in immunosuppressed children with HIV
infection or post transplant recipients.
Human Immunodeficiency Virus: Infants with HIV hepatitis
may manifest with cholestasis and later present with
chronic hepatitis. Liver involvement in HIV infected
individuals is indicative of a poor prognosis.
Other viruses: Echo virus, coxsackie and adeno virus may
present in neonates and infants with acute liver failure.
The differential diagnosis of acute viral hepatitis includes
all the causes of viral marker negative hepatitis apart
from congenital hyperbilirubinemia and some surgical
causes. It is important that this group is recognized since
specific therapy is available unlike in the viral marker
positive hepatitis where only supportive therapy is
recommended. In India the following conditions should
be considered.
1. Bacterial hepatitis: typhoid, tuberculosis, Brucella.
2. Protozoal: Malaria.
3. Spirochaetal: Leptospirosis
4. Drug induced or toxic hepatitis
5. Metabolic: Wilsons , Glycogen Storage disease
6. Biliary disease: Cholangitis, gallstone disease
7. Congenital hyperbilirubinemia: Gilberts syndrome,
Dubin Johnson.
664
Typhoid fever: Typhoid hepatitis can mimic AVH and

the differentiating features of toxemia, high fever and
hepatosplenomegaly if present may help in diagnosis.
Some children may also have minimal ascites and pleural
effusion similar to liver disease. The transaminases are
moderately elevated (3-20 times the upper limit of
normal) with an ALT/LDH ratio less than 4 whereas in
AVH it is >4. The diagnosis is confirmed by a positive
blood culture for Salmonella typhi.
Bacterial sepsis: Bacterial sepsis should be considered in
children presenting with fever, jaundice, hepatosplenomegaly and mild elevation of transaminases. Liver
involvement is secondary to parenchymal or biliary
invasion as a part of a systemic manifestation of sepsis.
The prolonged prothrombin time and the high mortality
is due to DIC and sepsis respectively rather than liver
failure.
Tuberculosis: Tuberculous hepatitis should be considered
in those children presenting with fever of unknown
origin, hepatomegaly, mild to moderate elevation of
transaminases and high alkaline phosphatase. Liver
biopsy shows the characteristic caseating granuloma.
Brucellosis: Brucellosis can occur in children who consume
unpasteurised milk and presents with fever, lymphadenopathy and elevated transaminases. The diagnosis
is confirmed by a high initial titre of 1:160 or a rising
titre done 2 weeks apart.
Leptospirosis: The clinical presentation may range from
inapparent infection, to features of acute hepatitis or fatal
disease. Jaundice, hepatosplenomegaly, fever, myalgia,
congested conjunctiva, bleeding manifestations, minimal
ascites and pleural effusion are some of the features.
Renal manifestations such as hematuria, albuminuria,
azotaemia, oliguria or anuria are findings in some
children. Apart from rise in serum bilirubin and
transaminases the CRP and CPK are elevated which may
help to differentiate it from viral hepatitis. A single high
antibody titre by Microscopic Agglutination Test (MAT)
or a rising titre 2 weeks apart helps in diagnosis.
Malaria: Malarial hepatitis or malarial hepatopathy (since
inflammatory cells are not a characteristic feature on
histology) is diagnosed when there is a 3 fold rise in
ALT with or without rise in conjugated hyperbilirubinemia, in the absence of clinical and serological evidence
of viral and drug induced hepatitis and with a clinical
response to antimalarials. It is usually seen with

P.falciparum but may occur in P. vivax infection. The exact
pathogenesis is unknown but could be due to impaired
bilirubin transport caused by blockage of reticulo
endithelial cells, microvilli damage or cyto -adherence
of parasites to the vascular endothelium leading to
stagnant anoxemia.
Drug induced liver disease (DILD): The common drugs
causing hepatitis are anticonvulsants, anti tuberculous
drugs, antimetabolites, NSAIDS, paracetamol, herbals
and indigeneous medications. It may be very difficult to
differentiate DILD from viral hepatitis. The child presents
with elevated transaminases with or without jaundice,
rash and hepatomegaly. The absence of prodrome and
the history of drug intake is a clue to diagnosis. The
challenge or onset of symptoms occurs within 5-90 days
of introducing the drug. On dechallenge, 50% drop in
transaminases occurs within 8 days of stopping the drug.
Autoimmune hepatitis (AIH): Autoimmune hepatitis
should be considered during the evaluation of acute
hepatitis. It is a progressive inflammatory liver disease
of unknown etiology presenting with elevated transaminases, hypergammaglobulinaemia., interface
hepatitis, non organ and liver specific antibodies and
good response to immunosuppressive treatment..
Children may present with type I or type II hepatitis. In
type I hepatitis, antinuclear antibody (ANA) and anti
smooth muscle antibody (ASMA) are present whereas
in the later LKM1 antibody is detected.
Obstructive jaundice: Obstructive jaundice due to
choledocholithiasis or biliary ascariasis can rarely mimic
acute hepatitis. Abdominal pain and features of
cholangitis are an important clue to diagnosis. The direct
bilirubin, alkaline phosphatase and ALT are elevated.
Ultrasound helps in identifying the site and cause of
obstruction.
Glycogen storage disease (GSD): In type I and III GSD , the
elevated transaminases may suggest anicteric hepatitis
but the presence of massive hepatomegaly and other
features such as short stature, doll like facies, voracious
appetite and early morning seizures will give a clue to a
diagnosis of storage disorder. Jaundice is not a presentation. Fasting hypoglycemia, elevated lactate and uric
acid levels are more suggestive of type I whereas elevated
CPK and moderate elevation of transaminases especially

AST are suggestive of type III. The liver biopsy shows
swollen hepatocytes with glycogen (PAS positive and
diastase sensitive) and steatosis in type I and PAS positive
cells without steatosis in type III.
Wilsons disease (WD): Wilsons disease should be
suspected in any child more than 3 years who presents
with jaundice, elevated transaminases and a firm liver.
Early appearance of free fluid, hemolysis, family history
and a set back in school performance are pointers to
suspect WD. The diagnosis is made by the presence of
KF ring, decreased serum ceruloplasmin and elevated
24 hour copper and confirmed by liver biopsy, dry copper
estimation and mutational studies.
Complications
AVH in children is usually a self limiting illness.
However atypical presentations can occur. The spectrum
of this illness includes:
1. Anicteric hepatitis
2. Classical hepatitis
3. Subacute hepatic failure
4. Chronic hepatitis (B, D, C)
5. Acute liver failure
6. Prolonged hyperbilirubinemia
7. Prolonged cholestasis
8. Relapse.
In addition, certain extrahepatic manifestations are
seen such as aplastic anemia, glomerulonephritis,
Guillain-Barre syndrome, myocarditis, pancreatitis,
urticaria, polyarthritis and papular acrodermatitis. All
the hepatotropic viruses can cause acute liver failure or
subacute hepatic failure. The morbidity and mortality is
higher in co infections but this is controversial.Chronic
hepatitis occurs as a complication only with hepatitis B,
C or D viruses and not with hepatitis A or E.
Investigations
The characteristic biochemical feature of hepatitis is the
detection of elevated transaminases more than twice the
upper limit of normal. In viral hepatitis, ALT is higher
than AST indicating cytoplasmic rather than mitochondrial injury. These are elevated during the acute phase
of the illness and fall during recovery. The other
investigations in AVH include complete blood counts,
urine for bile salts and pigments and liver tests such as
bilirubin, AST, ALT and alkaline phosphatase. Prothrom-
665
bin time is a useful test for assessing prognosis. Blood

glucose, blood urea, serum creatinine, total protein,
serum albumin, A/G ratio are included if hospitalized.
Investigations to confirm etiology are done as mentioned
in those with atypical manifestations. HBsAg is an
important screening test. Lepto IgM ELISA, blood Widal
and work up for Wilsons disease are included in the
panel of investigations. Ultrasound examination is done
to exclude liver abscess or gallstones. Liver biopsy is not
done in children with acute hepatitis but is essential in
those with suspected acute on chronic liver disease or
chronic hepatitis.
Management of Acute Viral Hepatitis
Most of the children with AVH will recover spontaneously and require only supportive treatment. During
the period of acute illness, the child should take adequate
calories in the form of a nutritious diet, avoid undue
physical exercise, hepatotoxic drugs and constipation.
The role of herbal hepatotrophic drugs in management
of acute viral hepatitis remains controversial. It is of
utmost importance to avoid unnecessary medications to
children with acute hepatitis, unless the drug is essential
and its mechanism of action is well understood. Water
soluble vitamins may be prescribed during acute
hepatitis. All children with acute hepatitis do not require
hospitalization unless there is persistent vomiting, fever,
fluid retention, altered sensorium or gastrointestinal
bleed. Ascites may be a presentation in some children
with AVH and can be treated with a short course of
spirinolactone. In the presence of spontaneous bacterial
peritonitis, antibiotics such as 3rd generation cephalosporins may be required. Fever if present during AVH
should be managed with tepid sponging and if necessary
paracetamol is administered at half the recommended
dose. NSAIDS should be strictly avoided. If the child is
on anticonvulsants such as sodium valproate or
phenytoin it can be changed to phenobarbitone and if
on antitubercular therapy with rifampicin, isoniazid and
pyrazinamide, they should be stopped and ethambutol
continued with streptomycin or fluoroquinolones. Older
children and adolescents may present with significant
and prolonged cholestasis or hyperbilirubinemia.
Cholestasis can be treated with ursodeoxycholic acid 20
mg/kg/day. Very rarely steroids may be required for
the management of severe cholestasis in type A hepatitis.
666
Specific Therapy
1. Hepatitis A: Since the majority (>95% )of children
with acute hepatitis A recover spontaneously without
any sequlae, no specific antiviral therapy is
recommended
2. Hepatitis E: Isolated Hepatitis E infection in children
is usually mild and does not require any specific
treatment.
3. Hepatitis B: In acute hepatitis B no antiviral therapy
is advised. These children should be followed up for
6 months to monitor spontaneous clearance of
HBsAg.
4. Hepatitis C: Children and adolescents with acute
hepatitis C acquired either by post transfusion or
following IV drug abuse should be monitored closely
for 12 weeks to establish spontaneous sero -conversion. Those who have persistent viremia (i.e) HCV
RNA positive for 12 weeks after the infection are the
candidates for treatment with Interferon (IFN). Since
the genotype plays a major role in the prognosis and
therapeutic response it should be tested before
therapy.
The current recommendation in adults is to initiate
treatment with IFN alpha or PEG IFN as early as
possible in asymptomatic patients infected with HCV
genotype 1, while treatment may be delayed in icteric
individuals with significant symptoms. Treatment
can also be safely delayed in patients with genotype
2 and 3 disease because these individuals clear acute
hepatitis C more often than those with genotype 1
and treatment success in chronic HCV is much better.
A shorter duration of therapy (12 weeks) compared
to that required for the treatment of chronic hepatitis
has been suggested.
5. Hepatitis D: Treatment is only supportive and liver
transplant may be required.
Treatment for Hepatitis due to Other

Non Hepatotropic Viruses
The treatment for hepatitis due to other viruses is also
usually supportive, Some specific antiviral agents such
as acyclovir for herpes simplex, ganciclovir for CMV and
HAART for HIV are available and may be used
judiciously.
PREVENTION
The most important aspect of therapy in hepatitis is the
prevention of the disease. The common viruses such as
HAV, HBV, HCV, HDV and HEV can be prevented by
improving personal, food and environmental hygiene,
avoiding unnecessary needle pricks; using disposable
syringes and screened blood for transfusion and active
immunization against HAV and HBV.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
Dienstag JL, Isselbacher KJ. Acute viral hepatitis. In

Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser
SL, Jameson JL eds. Harrisons principles of Internal
Medicine. (16 th Edn). USA; McGraw Hill, 2005;2:
1822-38.
Evans JS. Acute and chronic hepatitis. In Wyllie R, Hyams
JS (eds). Pediatric Gastrointestinal disease-Pathophysiology, Diagnosis, Management (2nd Edn): Philadelphia:
WB Saunders, 1999;600-23.
Novak DA, Suchy FJ, Balistreri WF. Disorders of the liver
and biliary system. In McMillanJA, Feigin RD, DeAngelis
C, Jones DM (Eds). Oskis PediatricsPrinciples and
Practice (4 th edn). Philadelphia: Lippincott: Williams
and Wilkins, 2006;2013-39.
Viral hepatitis. In Sherlock S, Dooley J (Eds). Diseases of
the liver and biliary system. 11th edn. UK Blackwell
Science 2007;267-319.
Yazigi N, Balistreri WF. Viral hepatitis. In Kliegman RM,
Behrman RE, Jenson HB, Stanton BF (Eds). Nelson text
book of Pediatrics (18th edn). Philadelphia: WB Saunders
2007;2:1680-90.
667
13.17 Chronic Hepatitis in Children

BR Thapa
Chronic hepatitis (CH) in children is defined as
continuing inflammation of liver parenchyma for
6 months or longer, leading to chronic liver injury that
resolves with or without treatment or progresses to
cirrhosis. It warrants a liver biopsy to establish the
pathological diagnosis. There are many diseases, which
primarily affect the liver and lead to CH.
Histopathological Classification,
Grading and Scoring
of fibrosis occurred following injury. There are several

scoring systems (Ishak et al, Scheuer PJ, Knodell et al,
Batts and Ludwig, METAVIR scoring) to define the
severity and extent of necroinflammation and fibrosis.
Knodells histology activity index (HAI) is widely used
to define CH. The more simplied scoring system of
grading and staging of liver histology is given in Table
13.17.2.
Etiology of CH
Pathologically, chronic hepatitis has been classified into

chronic persistent hepatitis (CPH), chronic active
hepatitis (CAH), and chronic lobular hepatitis (CLH)
based on the extent of liver parenchymal injury. The
distinctive features of the three types are given below in
Table 13.17.1. The original classification suggested by
DeGroote et al has been replaced by scoring the grades
of necroinflammation and stages of fibrosis. But in the
text, this has been retained as it is still mentioned in the
literature to explain the histopathology of liver with CH.
Very recently the histological classification has
undergone tremendous changes based upon
i. Etiology
ii. The grade of necroinflammation and
iii. The stage of fibrosis/cirrhosis.
There is always some evidence of etiology demonstrated on immunohistochemistry, special staining and
specific pathological features of underlying disease. The
necroinflammation is graded depending upon the extent
of necrosis and inflammation in portal tracts and in the
lobules. Similarly staging is done based upon the extent
Common causes of chronic hepatitis in children are:

Infections: HBV, HCV, HDV, CMV, rubella, HIV,
congenital syphilis, TTV, HGV.
Autoimmune: Three types:
1. Smooth muscle antibodies (SMA), antinuclear
antibody (ANA) positive
2. Liver kidney microsomal antibody (LKMA) positive
and
3. Soluble liver antigen and liver pancreas (SLA/LP)
positive
Metabolic: Wilsons disease, -1-antitrypsin deficiency,
galactosemia, fructosemia, tyrosinemia, etc.
Drugs: INH, ethyldopa, methotrexate, oxyphenacetin,
ketoconazole, etc.
Non-alcoholic steatohepatitis (NASH)
Cryptogenic hepatitis: Chronic hepatitis unclassified.
Chronic HBV Infection
Ten percent of patients with acute HBV hepatitis progress
to CH. Ninety percent of the infants with perinatally
TABLE 13.17.1: Characteristics of chronic hepatitis (DeGroote et al)

Chronic persistent hepatitis
Chronic lobular hepatitis
Chronic active hepatitis
It is characterized by portal triaditis
It resembles acute viral hepatitis

histologically
Its hallmark is piecemeal necrosis
Expanded portal tracts with

mononuclear infiltration
Predominantly, intra-acinar inflammation and necrosis
Erosion of limiting plates
Liver architecture and limiting

plate-intact
Rosette formation in zone 1, bridging

necrosis is also seen
668

TABLE 13.17.2: Grading and staging of chronic hepatitis on histology
Grade
Portal Periportal
Lobular
Stage
Degree of Fibrosis
Hepatic Architecture
None or minimal
None
Portal tracts not appreciably

enlarged, no septa
None or too mild

to affect size of portal
tract
Mostly periportal
Portal inflammation
Inflammation
but no necrosis
Mild limiting plate

(lymphocyte piecemeal)
necrosis
Severe focal cell

damage
Septal
Prominent septal fibrosis with

architectural distortion or
definite cirrhosis
Moderate limiting plate

(lymphocyte piecemeal)
necrosis
Severe focal cell

damage
Cirrhosis
Probable or definite cirrhosis
Severe limiting plate

(lymphocytic piecemeal)
necrosis
Bridging
necrosis
acquired HBV infection develop immune tolerance and

suffer from asymptomatic chronic hepatitis B (CHB)
infection. They show rise in transaminases, HBe and
DNA positivity and liver histology shows active
necroinflammation. Serology shows HbsAg positivity.
Presence of HBe and HBV DNA, serve as markers of
active viral replication. In presence of superinfection with
delta virus, HbsAg + anti HDV are positive. Liver biopsy
shows HbsAg containing hepatocytes having ground
glass appearance and may show core antigen (HbcAg)
in infected hepatocytes by immunohistochemistry (Figs
13.17.1A and B). Progression is slow but usually relentless
especially in HbeAg positive or combined hepatitis B and
D infection eventually leading to cirrhosis. Hepatocellular carcinoma (HCC) is a long-term complication.
Enlarged portal tracts,

periportal fibrosis, or portal-toportal septa without
architectural distortion
Figure 13.17.1A: Ground glass hepatocyte (HBsAg+)
Chronic HCV Infection

HCV infection runs a milder course. It invariably leads to
chronic liver disease (CLD). Cirrhosis is likely to develop
later. Serology for anti-HCV antibodies and HCV RNA is
positive. Histological features of chronic hepatitis C are
intense chronic portal inflammation with lymphoid aggregate and sometimes follicles with germinal centers, fat
accumulation and bile duct injury (Figs 13.17.2A and B).
Autoimmune Hepatitis (AIH)
Autoimmune hepatitis (AIH) is associated with other
autoimmune diseases like thyroiditis, pernicious anemia
Figure 13.17.1B: HBc antigen on immunostaining
Figure 13.17.2A: Chronic hepatitis C liver showing lymphoid

follicle, bile duct destruction in the portal tract and fatty change
in lobule
669
Figure 13.17.3: AIH interface hepatitis
there is underlying chronic liver disease. The histological

changes are mild to severe chronic hepatitis with or
without cirrhosis. Orcein staining shows increased
copper associated protein (Fig. 13.17.4). Rhodamine and
rubanic acid staining confirms increased copper deposits.
The diagnosis depends upon positive KF rings; low
serum ceruloplasmin and liver copper more than 250 mg
of dry weight.
-1-Antitrypsin Deficiency (AAT)
Figure 13.17.2B: HCV hepatitis lymphoid aggregate
and Coombs positive hemolytic anemias. It is associated

with hypergammaglobulinemia (IgG) and positive
antinuclear antibodies (ANA), smooth muscle antibodies
(SMA) or liver/kidney microsomal antibodies (LKM) or
SLA/LP. Exacerbations and remissions are common and
eventually lead to cirrhosis and its complications.
Histopathological features of autoimmune hepatitis are
severe inflammation, collapse of multiple acini,
numerous plasma cell infiltrate in the portal tract and
interface hepatitis (Fig. 13.17.3). The interface hepatitis
is akin to piece meal necrosis described in chronic active
hepatitis. Hepatocellular injury is in form of ballooning
of hepatocytes, regeneration of hepatocyte leading rosette
formation and confluent zone 3 hepatocellular necrosis.
The fibrosis sets in fast and leads to cirrhosis.
The disease may manifest as cholestasis during infancy.

In older children it may manifest as chronic liver disease.
Histopathology of liver biopsy shows PAS positive
diastase resistant granules, which are diagnostic of AAT.
Galactosemia
This autosomal recessive disorder manifests during
neonatal period after exposure to milk. The clinical
picture is characterized by neonatal hepatitis, cataract in
eyes, failure to thrive, vomiting and sepsis. The histology
Wilsons Disease
The disease occurs in 3 to 50 years age group. The hepatic
manifestation is quite varied. In majority of the situations
Figure 13.17.4: Wilsons disease orcein staining positive
670
of liver is characterized by portal triaditis, periportal

cholangiolar proliferation pseudoacinar transformation
and fatty change. Cirrhosis develops very fast.
Non-alcoholic Steatohepatitis (NASH)
NASH is well-recognized entity in children occurring
with increasing incidence of obesity and diabetics in
them. There may be enzyme rise and hepatomegaly.
Histopathology of liver is characterized by fatty
infiltration (microvesicular or macrovesicular or mixed),
ballooning of hepatocytes, mallory hyaline, neutrophil
infiltrate (satellitosis) and pericellar fibrosis (Fig. 13.17.5).
These changes are pronounced in zone 3 of the lobule
and are progressive and develop into cirrhosis.
Clinical presentation is chronic hepatitis is variable.
Acute hepatic illness with waxing and vaning course for
more than 6 months suggests chronic inflammation
occurring in the liver parenchyma. There may or may
not be overt features of chronic liver disease and portal
hypertension. In children asymptomatic hepatomegaly
picked up on routine examination may reveal chronic
hepatitis on liver biopsy. Suspect CH, if there is history
of hepatotoxic drugs, family history of liver disease,
relapse of acute hepatitis, hepatitis persisting for more
than 3-6 months and previous history of hepatitis B or C
infection. Look for non-hepatic manifestations of AIH
and Wilsons disease.
Clinically child shows jaundice, firm hepatomegaly,
splenomegaly, ascites and features of chronic liver
Figure 13.17.5: NASH Masson staining pericellular

fibrosis + fat
Figure 13.17.6: Course of chronic hepatitis
disease. There may be non-hepatic manifestations

depending upon the underlying etiology of liver disease
like AIH, Wilsons disease, galactosemia, etc. The overall
course of chronic hepatitis is given in (Fig. 13.17.6).
Investigations
1. Liver function tests: Serum bilirubindirect/indirect,
liver enzymes (ALT, AST); alkaline phosphatase; total
proteins and A/G ratio, and prothrombin time to
assess liver damage.
2. Ultrasound examination of abdomen is done to see
for the echotexture of liver, ascites and the collaterals
due to portal hypertension.
3. Upper gastrointestinal endoscopy is done to see for
esophageal varices in case of portal hypertension.
4. Every effort should be made to have an etiological
diagnosis. The investigations depend upon the age
of occurrence of the chronic hepatitis. Approach to
etiological diagnosis is given in (Fig. 13.17.7).
Viral markers: HBsAg, HBeAg, HBV DNA, coinfection anti HDV antibodies, anti HCV antibodies and HCV RNA
AIH markers: SMA, ANA, LKMA, SLA
Wilsons disease: KF ring, serum ceruloplasmin,
pre and post d-penicillamine urinary copper levels
and copper in the liver tissue.
Serum -1 Antitrypsin levels
During infancy: Intrauterine infection TORCH
work up, GALT levels, reducing substance in
urine, urinary succinyl acetone, etc.
5. Liver biopsy: The percutaneous liver biopsy is done
to study the morphological changes in the liver
671
Encephalopathy: Intake of proteins should be restricted.

Animal proteins should be avoided. Balance calories and
protein should be given to maintain normal growth in a
child.
Treatment of specific diseases: There is no specific treatment
of CH but certain potentially treatable conditions are:
Figure 13.17.7: Approach to the etiological diagnosis
parenchyma. The changes seen in the histopathology

and immunohistochemistry also give clue to the
diagnosis of the underlying disease as discussed
under specific conditions.
At times it is very difficult to differentiate cirrhosis from
CH. The liver biopsy is confirmatory. Based on the clinical
approach and investigations, various diseases leading to
CH can be differentiated from each other. But high index
of suspicion in a clinical setting can guide to reach to
definite diagnosis of CH.
Management
Management can be divided into 2:
Complications
Bleeding: Endoscopic sclerotherapy (EST) or endoscopic
variceal ligation (EVL) is the preferred mode to control
bleeding from esophageal varices. Bleeding due to
coagulopathy requires fresh blood transfusion and
vitamin K.
Ascites: Peritoneal fluid should be analyzed to rule out
infection. Spontaneous bacterial peritonitis (SBP) should
be treated with appropriate antimicrobial agents like,
cefotaxime or ciprofloxacin. Intake, of salt should be
restricted and diuretics help in controlling the ascites.
Chronic hepatitis B (CHB): Interferon (5 million units/m2

body surface area given subcutaneously on alternate days
for 6 months) is effective to treat chronic hepatitis B in
30 to 50 percent of cases whereas the results with
pegylated interferon therapy are encouraging (75%). But
strict criteria should be followed. For CHB the criteria
are disease for more than 6 months, raised liver enzymes,
positive HBe and HBV DNA and liver histology showing
core antigen positivity. Lamivudine is another promising
drug to treat CHB; possibly in combination with
interferon will be more effective. The treatment with
interferon is very costly.
Hepatitis C
Hepatitis C infection in majority leads to chronic liver
disease. This takes time to develop chronic hepatitis and
cirrhosis due to HCV. The enzyme rise is quite variable,
so histopathology of liver is mandatory to define the
necroinflammatory and fibrosis scoring based upon
which therapy with interferon (3-5 million units/m2 body
surface area given subcutaneously on alternate days for
12 months) is instituted. The results with pegylated
interferon with ribavarin are encouraging and the
response rate varies from 30 to 60 percent. The
indications for interferon therapy in children are acute
HCV infection with raised transaminases for more than
12 weeks and HCV infection with normal enzymes but
liver histology showing significant necroinflammatory
changes.
Autoimmune hepatitis: Steroids are very helpful but in
certain situations when growth retardation is problem,
azathioprine can be added. Prednisolone in dose of 2 mg/
kg/day is given, till clinical and biochemical improvement occurs. This is followed by maintenance dose till
the histological reversal is seen. The relapse of the disease
is very common, therefore the maintenance dose is given
for a prolonged period.
Wilsons disease: Avoid copper containing food items like
chocolate, nuts, mushrooms, shellfish, liver, etc. D-
672
penicillamine (10-20 mg/kg/day), a copper chelator is

very effective. Zinc can be given to prevent copper
absorption from gastrointestinal tract. Other alternate
drugs to treat Wilsons disease are trientine and
tetrathiomolybdate. The treatment is required for lifelong. Family screening should be done so that treatment
can be started at the earliest to the affected individual.
Galactosemia: Withdrawal of milk (Galactose) from diet
can stop the ongoing liver damage.
Fructosemia: This requires withdrawal of fructose from
diet to stop further progression of disease.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
Congenital Syphilis: This is treated with penicillin.

6.
NASH
Treatment lies in reduction of weight and appropriate
treatment of diabetes to have good control of blood sugar
levels. Prevention is very important and is not to put on
extra weight.
7.
8.
9.
Outcome
As shown before CPH, CLH and mild CAH can revert
back to normal whereas severe CAH invariably
progresses to cirrhosis. Certain situations like Wilsons
disease and AIH changes reverse back to normal with
specific therapy. Withdrawal of offending factors can
ameliorate the clinical picture in some of the metabolic
disorders.
10.
11.
12.
13.
Batts KP, Ludwig J. Chronic hepatitis: An update on

terminology and reporting. Am J Sug Pathol 1995;19:
1409-17.
Bedossa P, Poynard T and The French METAVIR
Cooperative Study Group. An algorithm for grading
activity in chronic hepatitis C. Hepatology 1996,24:
289-93.
DeGroote J, Desmet VJ, Gedigk P, et al. A classification
of chronic hepatitis. Lancet 1968;2:626-28.
Desmet VJ, Gerber M, Hoofnagle JH, et al. Classification
of chronic hepatitis: diagnosis, grading and staging.
Hepatology 1994;19:151320.
Gurkan F, Koeak N, Ozen H, Yuu A. Comparison of
standard and high dosage recombinant interferon L-2b
for treatment chronic hepatitis B in children. Pediatr
Infect Dis J 2000;19:52-56.
Ishak K, Baptista A, Bianchi L, et al. Histological grading
and staging of chronic hepatitis. J Hepatol 1995;22:
69699.
Jonas M M. Hepatitis C in children. Hepatol Review 2004,
1.23-31.
Knodell RG, Ishak KG, Black WG, et al. Formulation and
application of a numerical scoring system chronic active
hepatitis. Hepatology 1981;1:431-35.
Maggiore G, Bernard O, Harchonel M et al. Treatment
hepatitis in childhood. J Pediatr 1984;106:52930.
Mowat AP (Ed). Chronic hepatitis. In: Liver Disorders
in child 3rd edn. Butterworths and Co. Publishers
London, Oxford 1994;31729.
Scheuer PJ. Classification of chronic viral hepatitis: need
for reassessment. J Hepatol 1991;13:372-74.
Thapa BR, Joshi K, Singh V, Dilawari JB. Clinicopathological profile of chronic hepatitis in children. Indian J
Gastroenterol 1993;120:A74.
Wilinson SP, Portmann B, Cochrane AMG et al. Clinical
course of chronic lobular hepatitis. Q J Med 1978;4721.
13.18 Chronic Liver Disorders in Children

Chronic Liver Disease (CLD) includes a wide spectrum
of disorders with ongoing inflammation of liver tissue,
potentially progressing to cirrhosis or end stage liver
disease.
It may be six months in adults but in pediatrics it
maybe 3-6 months or more when one can include the
disease as chronic liver disease.
CLD at times may present as acute on chronic liver
disease, acute or fulminant viral hepatitis (HA V, HEV)
on top of silent Wilsons disease and eventually obscure

the nature of the original insult unless one has a high
degree of suspicion.
Histologically chronic hepatitis, cirrhosis or hepatic
fibrosis are included under this category which maybe
active or inactive depending on the presence of
biochemical or histological evidence of hepatocellular
necrosis, inflammation and fibrosis with varying degree
of regenerating nodules in advancing disease.

Incidence
CLD accounts upto 5% of pediatric ward admissions with
a mortality upto 20% in our set up. The changing pattern
of CLD during the last 25 years is given in the Table
13.18.1. Yacha et al had reported that CLD constitutes
36% of hepatobiliary diseases in their institution.
Causes of CLD
1. Biliary: Neonatal cholestasis syndrome (Extrahepatic
biliary atresia, choledocral cyst, ductal paucity (with
or without Watson Alagille syndrome), Progressive
familial intrahepatic cholestasis (PFIC), etc.)
2. Hepatic: Neonatal hepatitis, Hepatitis B, Hepatitis C,
TORCH, Autoimmune hepatitis, drugs and toxins.
3. Genetic/Metabolic: 1 Antitrypsin deficiency,
Wilsons disease, Glycogen storage disease III, IV,
Galactosemia, Tyrosinemia, Urea cycle disorders,
Neonatal hemochromatosis, Nieman Picks-type C,
Gauchers disease, Peroxisomal (Zelweiger
Syndrome) mitochondrial disorders or respiratory
chain defects, Cystic fibrosis and rarely Indian
Childhood cirrhosis.
4. Fibrocystic disorders: Carolis and congenital hepatic
fibrosis (both do not cause cirrhosis)
5. Vascular: Non cirrhotic portal fibrosis
Chronic Budd Chiari syndrome
Veno occlusive disease
6. Cardiac: Constrictive pericarditis
Chronic congestive cardiac failure
7. Nutritional: Hypervitaminosis A
Total Parenteral Nutrition
8. Cryptogenic or idiopathic.
673
NEONATAL CHOLESTASIS SYNDROME

(PROLONGED CHOLESTASIS OF INFANCY)
Diagnostic Criteria
Prolonged elevation of serum conjugated bilirubin more
than 1.5 mg% or more than 20% of total bilirubin beyond
the first 14 days of life, often presenting as jaundice, high
coloured urine with yellowish staining of diaper, varying
degree of acholic stools and hepatomegaly or hepatosplenomegaly.
The presentation can be even little later upto even
3 months of life.
Two major categories of presentation namely
neonatal hepatitis due to injury to liver cells and biliary
atresia due to complete obliteration of the biliary tree
due to cholangitis and progressive sclerosis and
narrowing of biliary tree with complete obstruction are
encountered frequently.
Basic clinical differences between EHBA and
Neonatal hepatitis are important in the management of
NCS (Table 13.18.1) to facilitate prompt surgical
consultation of extrahepatic biliary atresia infants before
4-6 wks of age.
The topic on neonatal cholestasis syndrome will be
discussed separately in the following chapter 13.20.
Chronic Heptitis is defined as continuing inflammation of the liver cells for a short period of more than 3-6
months, which may resolve spontaneously or with
treatment or progress to cirrhosis
Refer 13.17 chapters on chronic hepatits in children
for more details
Cirrhosis of the liver is a chronic liver disease almost
irreversible due to varieties of chronic liver disorders
TABLE 13.18.1: Basic clinical differences between NH and extra hepatic biliary atresia
Features
Neonatal hepatitis
EHBA
Age of onset
Gestation
General Appearance
Stool
Hepatosplenomegaly
Liver
Multisystem
involvement
Anytime in neonatal period

Preterm or SFD
May look sick
Incompletely acholic
Early
Mild to mod, soft
Often present
(Cataract, microcephaly, feeding
difficulty, septicemia, blue berry
naevus, seizures etc)
End of 1st week

Term baby
Well looking
Completely acholic (pale stool)
Late
Mod to large
Firm to hard
Rare
Polysplenia may be present
674
characterized by nodular, firm and shrunken liver with

evidence of portal hypertension, ascites and encephalopathy classically.
Refer chapter 13.19 on cirrhosis of the liver.
Metabolic Liver Diseases (MLD)
Incidence
Eight to forty-three percent in most of the centers with
GE services and includes Wilsons disease, GSD,
Tyrosinemia, 1 Antitrypsin deficiency, galactosemia,
neonatal hemochromatosis, inborn errors of bile acid
metabolism, fatty oxidation defects, and mitochondrial
and peroxisomal disorders and cystic fibrosis
Most of the above diseases are likely to progress to
cirrhosis.
Fibrocystic Diseases of the Liver
They are inhertited heterogenous disorders that include
congenital hepatic fibrosis (CHF) and Carolis syndrome.
The child usually presents with hepatosplenomegaly and
portal hypertension. Enlarged left lobe of the liver may
suggest CHF and liver biopsy is confirmatory showing
periportal fibrosis containing proliferating bile duct like
structures due to ductal plate malformation.
Non Cirrhotic Portal Fibrosis (NCPF)
The etiology is obscure and the syndrome is characterized
by periportal fibrosis and portal vein sclerosis due to
portal pyemia and occlusion of III and IV degree
intrahepatic branches of portal vein. Often seen in older
children and girls with splenomegaly and well tolerated
recurrent variceal bleeds due to NCPF in 2-10% of
patients of CLD. The diagnostic triad includes patent
splenoporto venal axis, absence of cirrhosis and presence
of portal venopathy involving third and fourth degree
intrahepatic portal venules.
Clinical Features of CLD
Often child with CLD may be asymptomatic in compensated liver disease and is also anicteric. Indication of
chronic liver disease in these children may be an
incidental finding of firm hepatosplenomegaly, isolated
firm splenomegaly, with increased transaminases or
increased alkaline phosphatase. Decompensated liver
disease often presents with liver synthetic functiom

failure, occurrence of complication and poor response to
medication. The features of CLD at presentation include
Muscle wasting
Growth failure
Edema
Ascites and jaundice
Firm liver
Hard or nodular liver
Enlarged left lobe
Firm splenomegaly
Complications of CLD
Cirrhosis, Portal hypertension and ascites, variceal bleed,
Coagulopathy, hepatorenal and hepatopulmonary
syndromes. Hypersplenism, recurrent infections due to
impaired immunity and later hepatocellular carcinoma
especially in chronic Hepatitis B and Tyrosinaemia-type
II.
Growth retardation, hepatic encephalopathy and
death are inevitable in the end stage of liver disease
Laboratory Investigations in CLD
Baseline investigations include:
1. Complete urine examination (including albumin,
sugar, bile salt, bile pigment, and urobilonogen) CBC
and reti count to identify hypersplenism or hemolysis.
2. Prothrombin time and activated partial thromboplastin time are sensitive indices of liver function. An
increased PT not responding to Vit K indicates poor
synthetic capacity of the liver and decompensated
hepatocellular disease.
3. Biochemical: Refer chapter 13.19 on cirrhosis of Liver
-Laboratory work up.
4. Liver Biopsy is the gold standard for diagnosis of any
chronic liver disease for confirmation of chronic
hepatitis, cirrhosis and hepatic fibrosis. The grading
of liver injury and staging of liver disease will help
in the prognosis and follow up of the patient. Certain
liver diseases like GSD, CHF and ductopenia have
typical histological findings.
The liver tissue can also be processed for estimation
of copper, special staining and enzyme analysis.
5. Specific investigations for etiology of liver disease
should be done as suggested in Chapter 13.19.

Biochemical Features of CLD
1. Persistent elevation of serum transaminases and
alkaline phosphatase (Eg: biliary disorders)
2. Reversal of albumin globulin ratio (serum albumin <
3.5G/100ml and serum globulin above 3G/100ml
3. Prolonged prothrombin time (despite vitamin K
injection)
Note: above laboratory support in correlation with clinical
findings of CLD like firm hepatosplenomegaly, prolonged jaundice pruritus, ascites, abdominal wall veins
and coagulopathy especially with a sib +ve history/death
due to chronic liver disease and consanguineous parents.
The gold standard test for confirmation of CLD is only
liver biopsy which will show significant fibrosis,
regenerating nodules and lobular disarray of liver cells.
indications for liver transplantations are biliary atresia,

ductal paucity, 1 Antitrypsin deficiency, tyrosinemia
type I, GSD type III and IV, PFIC, Wilsons disease and
primary biliary cirrhosis and fulminant hepatic failure.
KEY MESSAGES
Chronic Liver Disease in children is likely to progress to
cirrhosis and needs a complete work up for diagnosis,
confirmation of etiology and grading and staging of the
disease histologically. These children should be referred
to tertiary care centers where there is facility for pediatric
GE workup and follow up management
BIBLIOGRAPHY
1.
2.
Management of CLD
1. Aim of management is to reduce or prevent progression of the disease. Eg: Wilsons disease, auto
immune disease, hepatitis B and C and tyrosinemia.
2. To anticipate, prevent and treat complications
3. Supportive therapy includes nutrition and vitamins
and salt restriction, antibiotics, diuretics and growth
monitoring.
To select candidates for liver transplantation
Liver transplantation is an accepted modality of management of chronic liver disease currently and has changed
the lifestyle of these children with CLD. The commonest
675
3.
4.
5.
6.
7.
Ashish Bavdekar. Metabolic liver diseases, lAP speciality

series on paediatric gastroenterology 2008;(16):217-27.
Bavdekar AR. Wilsons diseaseA diagnostic dilemma.
Indian J Gastroenterology 2003;22-23.
Malathi SatyasekharanApproach to a child with CLD,
Indian J of Pract Pediatrics. Hepatology 2002;4(4):
362-69.
Sheila Bhave. Chronic liver disorders in children, lAP
speciality series on paed gastroenterology 2008;(14):
188-96.
Surendar Kumar A Yacha. Neonatal cholestasisfAP
speciality series pn ped.gastroenterology 2008;(13):
178-87.
Sutapa ganguly. Portal hypertension. IAP speciality
VS Sankaranarayanan, S srinivas. Chronic hepatitis in
children and cirrhosis of liver in children. Parthas
fundamentals ofpediatrics 2007;(11):354-61.
13.19 Cirrhosis of Liver

Cirrhosis of the liver is relatively a common form and
the end stage of chronic liver disease and is due to a
variety of etiologies (Table 13.19.1). Clinically established
cirrhosis is characterized by a shrunken (short liver span),
firm to hard nodular liver with evidence of portal
hypertension and varying degree of liver cell failure.
Pathologically, hepatic cirrhosis is characterized by

fibrosis, nodules created by regeneration of hepatocytes
and disruption of parenchymal lobular architecture of
the entire liver.1,8 Fibrosis is generally reversible.
Causes of Cirrhosis
Causes of cirrhosis in children are listed in Table 13.19.1.
676

TABLE 13.19.1: Etiology of cirrhosis in children
Young infants
Children < 4 years of age
Children > 4 years of age
Extra hepatic biliary atresia

Severe form of neonatal
hepatitis
Bile acid abnormalities
(PFIC, inborn error of bile
acid metabolism)
Tyrosinemia
Galactosemia
Congenital hemochromatosis
Post TPN
Extension of problems of
neonatal cholestasis
beyond infancy and more
than 2 yrs of age
Tyrosinemia
Alpha 1 antitrypsin
deficiency
Histiocytosis
Nieman pick disease
Drug induced (anti cancer,
anti epileptic, anti TB etc)
Veno occlusive disease
Chronic hepatitis
Wilsons disease and other
metabolic diseases
Cystic fibrosis
Hemochromatosis
Autoimmune chronic hepatitis
Cryptogenic
Pathogenesis of Cirrhosis
Chronic and persistent liver cell injury leads to cell death
(necrosis) replaced by scar formation (fibrosis) and
nodular formation (regeneration).Intracellular liver
enzymes and electrolytes are released from the injured
hepatocytes.
This results in changes in extracellular matrix increased collagen (especially type 3 and 4). This
produces perisinusoidal broad septa formation. Vascular
changes take place at sinusoidal level due to deposition
of Lamin causing arteriolar and venous intrahepatic
shunts. Ischemia, decreased synthetic liver function,
increased pressure effects result ultimately and the
viscious cycle of necrosis, fibrosis and nodular formation
continue ending in irreversibility even if the cause is
removed.
Clinical Features
Clinical clues for cirrhosis in history:
History of consanguinity/sib history of death due to
chronic liver disease - metabolic cause
Family history of neuro psychiatric disease - Wilsons
disease
Risk factors of hepatitis B/Hepatitis C like blood
transfusion, needle injury, tattooing, dental extraction
etc
History of ingestion of hepatotoxic drugsINH,
methotrexate, methyl dopa, sodium valproate,
ketoconazole, nitrofurantoin, prolonged TPN, etc.
Past history of neonatal cholestatic syndrome or

prolonged jaundice atleast two years ago.
History of seizures with abdominal distension Nieman picks disease, Gauchers
History of frequent feeds with dizzy spells on fastingGlycogen storage disease.
Cirrhosis should be suspected whenever there is
persistent jaundice, ascites, GI bleed, peripheral oedema,
family history of chronic liver disease or past history of
jaundice due to HBV, HCV, HDV or hepatotoxic drugs
with firm and nodular liver with abnormal tortuous
abdominal wall midline veins with palmar erythema,
clubbing and fatiguability.
General Clinical Examination in Cirrhosis
Examination will reveal features of hepatocellular failure
and features of decompensated liver disease.
Abdominal examination may reveal ascites, abnormal
and tortuous veins, nodular liver, splenomegaly and
opening of hernial orifices and peripheral and scrotal
oedema and other complications of cirrhosis.
Complications of Advanced and
Decompensated Cirrhosis
Ascites, encephalopathy, GI bleeds, hepatorenal
syndrome, hepatopulmonary syndrome (cyanosis)
spontaneous bacterial peritonitis and hepatocellular
carcinoma. (HBV, HCV and HDV cirrhosis).

Diagnosis
677
Liver Biopsy
Labarotary Investigations
HematologyBasic: Haemoglobin, total and differential
count, platelet count and peripheral smear.
Liver function tests: serum bilirubin and (conjugated +
unconjugated fraction), SGOT and PT.
Serum albumin and globulin ratio, Serum alkaline
phosphatase, GGTP and cholesterol.
Prothrombin time and activated partial thromboplastin time.
If ascites is present serum sodium, potassium.
Bicarbonate, chloride, urea and creatinine levels may
help.
Serology for hepatitis B (HBsAg, HbeAg, HBV DNA),
HCV (HCV elisa and HCV RNA), CMIV, EB virus, HIV
and TORCH group.
Screening for metabolic liver disease.
Biochemical Features of Cirrhosis Liver
1. Persistent elevation of serum transaminases and
serum alkaline phosphatases
2. Reversal of albumin: globulin ratio S.albumin (< 3.5
g/100 ml)
3. Prolonged prothrombin time (despite Vitamin K
injection).
Ultrasonogram
For splenoporto venal axis, echo texture of liver, portal
vein collaterals and minimal ascites, hepatoma, and
choledoccal cyst, extrahepatic biliary atresia, gallstones
can be easily identified by USG abdomen. Colour doppler
USG abdomen will provide more details about the portal
hypertension.
Liver biopsy is the gold standard and confirmatory for

chronic hepatitis and cirrhosis liver.
Presence of periportal fibrosis and necrosis, nodular
regeneration with loss of hepatic lobular architexture are
the confirmatory findings for cirrhosis
Helps in diagnosis, disease activity, classification,
follow up and identifying Differential diagnosis
1. Extrahepatic portal hypertension (absent liver cell
failure abdominal wall veins)
2. Chronic hepatitis (absence of nodular liver, abdominal wall veins and portal hypertension)
Course and Prognosis
It is variable, depending on Childs grading system
(Table 13.19.2).
Interpretation: Any two of the below will guide physician
Childs A: Patient with good liver dysfunction
Childs C: Patient with poor liver function and surgical/
invasive procedures will carry increased mortality in 90%
in non bleeding cirrhotics.
Management
1. Early detection and management of complications
due to decompensated cirrhosis.
2. There is no specific treatment per se that will arrest
or reverse the cirrhotic changes. Treatment of portal
hypertension, ascites and hepatic encephalopathy has
been discussed separately.
3. Treatment of specific cause if any, like Wilsons
disease, drug induced hepatitis and hepatitis B and
C.
4. Patients with compensated cirrhosis can lead a
normal life and no specific diet is helpful.
TABLE: 13.19.2 Childs prognostic grading of portal hypertension (Modified Pughs)

Prognosis
Compensated (A)
Guarded (B)
Decompensated (c)
Jaundice (bilirubin)
Mild or nil < 2 mg/dl
Moderate 2-3 mg/dl
Intense > 3 mg/dl
Ascites
Mild and treatable
Severe/refractory
Albumin
>3.5 g/dl
3-3.5 g/dl
< 3 g/dl
Encephalopathy
Past history
++
Prothrombin time
N or 1
X2
X many
678
5. Hepatic herbal supportives, antioxidants, liver cell

membrane protectives and maintenance of adequate
calories, fluid and electrolytes, vitamin especially fat
soluble vitamins are routinely recommended with
variable outcome.
6. Liver transplantation is the future hope in EHBA,
tyrosinemia, glycogen storage disease, acetyl
transferease deficiency and severe bile acid metabolic
defects (PFIC)
Encephalopathy
Encephalopathy is characterized by irritability, incoherent speech, mental confusion and violence (Grade l)
Drowsiness and somnolence, flapping tremor, fetor
hepaticus (Grade II), Exaggerated reflexes with upgoing
plantar reflex, stupor (Grade III) and Coma (Grade IV).
Metabolic complications like hypoglycemia, dyselectrolytemia, renal failure, Coagulopathy with bleeds,
hyperammonemia, convulsions etc may supervene in Gr

III and IV encephalopathy. Early detection of hepatic
encephalopathy can be by demonstrating constructional
apraxia (inability to draw or copy a star)
Predisposing Causes
GI bleed with excess protein in the bowel, rapid
abdominal paracentesis, intercurrent infection (Gram
negative septicemia) use of hepatotoxic drugs (morphine)
major surgical procedures and electrolyte imbalance
(diurectics)
Management Guidelines
Goal of therapy is to identify the complications of hepatic
encephalopathy and decompensated cirrhosis and
prevent by avoiding predisposing factors mentioned
above.
Disease
Defect
Clinical
Diagnosis
Treatment
Extrahepatic
biliary atresia
Atresia of EHB
passage
intrahepatic
biliary atresia
Persistent pale stools

in neonate
Firm big liver
Well fed neonate
Early cirrhosis
Kasai-Hepatico
porto
jejunostomy
within 6 wks of
life and follow
up
Liver
transplantation
chromosome
mutations
frequent
Autosomal
dominant
Jaundice
CLD in teenage
U/S screening
absent gallbladder
Liverbiopsy
Bile duct
proliferation, bile
stasis and plugs and
dense fibrosis with
cirrhosis
Hepatobiliary scanno isotope excretion
in intestine, even
after 24 hrs
(mebrefenin)
Preoperative
cholangiogram
urine porphins
normal
Red cell free
Protoporphyrin
increase
Viral, metabolic
drugs, TPN,
endocrine, etc or
idiopathic
(common)
Small for date

Sick and septic baby
Occasional yellow
stools
Multiorgan
involvement
Hepatosplenomegaly
Tests for etiologic

agents
Liver biopsy,
Giant cells+++ and
necrosis
Supportive care
Neonatal
Hepatitis
Prevention
carotene
Cholestyramine
UDCS for itch
Livertransplant
-Kidney
transplant
Prevention of
antenatal
infection
Contd...

Disease
Defect
Clinical
Post hepatic
cirrhosis
HBV, HCV or
HDV
Pat h/o 2 yrs ago

s/s of CLD
s/s of
decompensated CLD
macronodular
cirrhosis
Wilsons
disease
Copper binding
membrane
spanning protein
with P type
ATPase motifs
at chromosome
13 at 14 q 21
mutation C to A
transversion
Frame shift
autosomal
recessive
Inborn error of
bile acids
Synthesis of
primary bile
acids decrease
Erythropoietic
Protoporphyria
Ferrochelatase
decrease
Gene locus:18
ICC (Indian
child hood
cirrhosis)
Not clear
possibly
inherited
tendency+
copper triggered
Diagnosis
HBsAg,
HBeAg, antiHBcIGM
DNA polymerase,
R.T.PCR-HBV, antiHCV ABD,PCR,
anti HDV IGM
ABD. Liver biopsy
U/S endoscopy and
biochemical
(A;G,PT,PTT)
Hepatosplenomegaly CT scan/MRI brain
viral hepatitis,FHF
for deposition of
Chronic hepatitis,
copper in basal
features of cirrhosis ganglia,cortical
neuro-psychiatric
atrophy etc after
(choreoathetoid
ophthalmic opinion
movements,
for KFR,
dyslexia, dysarthria, S.Ceruloplasmin
ataxia)renal:tubular
reduced mostly test
dysfunction rickets
is a screening test
24 hrs urinary Cu
excretion is>
100 g/day
especially after
penicillamine
Liver copper being
gold standard is
usually above 250
g/g dry weight
Neonatal cholestasis Serum bile acids
cirrhosis
(CDCA and CA
Intense pruritus
decrease) urine,bile
acids increase
enzyme estimation
by spectrometry and
gaschromatography
Photosensitivity<6
Micro-hypoanemia
Yrs
Bone marrow:ring
Pain abdomen
sideroplastic iron
Insidious onset/AVH
onset H/o
copper utensils
3 stage CLDEarly (1-1 yr)
Intermediate(1-1 yr)
Late (6/12 year)6
months. Malignant
(6/12) hepatitis
6 mths to 4 yrs
Age: 6/12-4 years
Liver biopsy
creeping fibrosis
Mallory hyaline
rcein+ for liver
copper, no fatty
change
679
Treatment
Prevention
Symptomatic
and supportive
treatment of
variceal bleed.
PoSE, ascites
coagulopathy
HBV
immunization
Chelators D
penicillamine
(750 mg/m2)+
pyridoxine
Trientine
Triethylene
Tetramine
HCL,
ammonium
Tetra
thiomolybdate,
zinc, liver
transplant diet:
decrease the
intake of shell
fish,chocolate,
nuts
Genetic
counseling
Oral bile acides

(UDCA)
Liver transplant
Genetic
counseling
Local:UV and
sunscreens
Oral beta
Genetic
counseling
prenatal diagnosis
and MTP
D. penicillamine
Zinc
Steroids?
Remove copper
from diet
Contd...
680
Contd...
Disease
Defect
Clinical
Diagnosis
Treatment
Alpha 1
antitrypsin
deficiency
Abnormal A-1
AT in
endoplasmic
reticulum and
intracellular
hepatic
inclusions >
liver damage
Gene locus: 12Kb on
chromosome 14
Z AIAT and ZAIAT deficiency
common
Neonatal cholestasis
Chronic hepatitis
Cirrhosis +
Emphysema
Serum AIAT
decreases
PCR for nucleotides
in A-1AD at
Z mutation site
Prenatal
Liver transplant
Gene therapy
Aerosol AAT
for COPD
MTP after PND
Tyrosinemia
(Type 1)
Fumaryl
acetoacetate
decreases
Autosomal
recessive
Genelocus at
chromosome
15 qu 23-25
Neonatal cholestatis
CLD-Ch hepatitis
Cirrhosis
HCC
Renal: renal rickets
and tubular
dysfunction
Failure to thrive,
diarrhea and vomit,
anemia, bleeds and
neurological
Alpha fetoprotein
increases. LFT may
be normal
Confirmation by red
cell, lymphocyte,
cultured fibroblast
or liver analysis for
fumaryl acetoacetate
hydrolase (FAH)
Urine
succinylacetone is
increased PCR
Diet low
tyrosine
methionine and
PA Nacety
cystine
Enzyme
therapy
Anti oxidants
Liver transplant
+
Kidney
transplant
Prevention
Prenatal screening
and MTP
Prenatal screening
Cystic fibrosis
Mutations in
CFTR gen locus
at chromosome 7
at position
7q31abnormal
secretions
(mucoviscidosis)
in resp, pancreatic,
hepatobiliary and
GI tract
Meconium ileus,
neonatal cholestasis,
cirrhosis, rectal
prolapse COPD
corpulmonale
Glycogen
storage
disease
Autosomal
recessive
(except type VI)
enzyme defect in
the metabolic
pathways in
glycogen
breakdown
Usually type IV
(branching enzyme)
or type I (G-6phosphatase) or
type III
(debranching)
insufficient
glucose production
by liver
Common types
Massive liver,
Hypoglycemic spells
Chubby cheeks
Age of onset 1-2 yrs
Mutation: N
Sweat chloride
(> 60 mEQ/L)
Fecal chymotrypsin
(< 60 MS/GM)
Neonatal screening
(IRT) (serum
trypsinogen on filter
paper) CF genotyping
Prenatal > CV
sampling >
amniocentesis
Fasting blood
glucose decrease
Glucagon test (no
response rise of
blood glucose)
liver biopsy-large
liver cells
vacuolations
liver enzymes and
estimation
Treat of CLD
Genetic counseling
(Cholestasis,
prenatal diagnosis
pH, cirrhosis)
and MTP
Nutrition
copper (low fat,
MCT vits)
Pancreatic
enzymes
Somatic gene therapy
Frequent feed
with glucose
Raw, uncooked
corn starch
1.5 to 2 gms/kg
5 to 6 times a
day useful.
Liver transplant for
end stage liver
disease

Specific treatment includes:
To identify any site of bleeding by endoscopy and treat
appropriately (variceal bleed, gastric or duodenal
erosions etc).
Maintenance of fluid and electrolyte balance. Sodium
restriction may be required despite hyponatremia which
may be dilutional.
Potassium replacement for hypokalemia Diuretics
(spironolactone/loop diuretics) for edema and parenteral
IV glucose for hypoglucemia.
Infection: Culture studies of ascitic fluid and if
positive to treat infection as indicated.
Lactulose produces two liquid stools (15-30 ml twice
of thrice daily). It produces osmotic diarrhoea, prevents
absorption of ammonia from colon and prevents
proliferation of ammonia producing organisms.
Selective intestinal decontamination by administration of non absorbable antibiotics (norfloxacin,
neomycin).
Sedation (short acting benzodiazepines Oxazepam,
medozolam) preferred.
Coagulation defects to be corrected with fresh frozen
plasma or clotting factors and vit K (single dose).
Parenteral vitamins (Fat soluble and water soluble
especially B vitamins).
Orthoptic liver transplantation in selected tertiary
care liver transplant units-cost prohibitive.
Variceal bleed to be treated by somatostatin, octreotide, vasopressin or glypressin or endoscopic band
ligation or sclero/glue therapy and Sengstaken tube.
Specific causes of cirrhosis and management of treatable
causes like Wilsons disease, autoimmune hepatitis, drug
induced, hepatitis B and C etc recommended.
PORTAL HYPERTENSION
Clinical criteria includes variceal upper G I bleed,
splenomegaly, tortuous veins on anterior abdominal wall
away from umbilicus especially in intrahepatic type and
ascites getting localized in all end stage of cirrhosis in
the presence of portal hypertension. Cirrhotic portal
hypertension will have history suggestive of chronic liver
disease and clinical features of underlying cause for
portal hypertension. Nodular and shrunken liver,
681
abdominal veins and features of decompensation with

extrahepatic manifestations of chronic liver disease will
differentiate patients of extrahepatic portal hypertension
where the above features are absent until late stage.
However laboratory work up including ultrasound/
Doppler abdomen will help to identify the pathology in
the SPV axis. Pressure criteria: portal venous pressure>
10 mm of Hg (normal < 10 mm of Hg), Hepatic venous
pressure gradient: if more than 12 mm it is a useful
predictor of impending variceal bleed.
Abdominal ultrasound will give details about the
patency, size and collaterals of SPV axis and presence of
ascites. Echotexture of the liver and right sided plural
effusions and evidence of SOL in liver can be picked out
easily.
Oesophago gastro duodenoscopy not only helps to
identify the oesophageal and fundic varices and porto
hypertensive gastropathy but also facilitates endotherapy.
Identification of the cause of portal hypertension is
almost laboratory etiologic work of cirrhosis liver and
chronic hepatitis. Evaluation of hyper coagulable statecausing thrombosis of splenoportovenous axis includes
complete coagulation profile, protein S and C, antiphospholipid antibody, antithrombin and fibrinogen
estimation in selected patients, as specific therapy for this
is possible.
Liver biopsy will be the gold standard for confirmation of cirrhosis, noncirrhotic portal fibrosis,
congenital hepatic fibrosis, chronic biliary diseases
including biliary atresia, PFIC etc. Diagnosis of portal
hypertension should also include screening for hypersplenism, posttransfusion complications and work up for
minimal chronic hepatic encephalopathy like psychometry analysis.
Management of portal hypertension should include
emergency resuscitation of upper GI bleed [control of
bleeding with somatostatin and analogues or vasopressin
and glypressin, emergency endoscopy therapy and long
term prevention of variceal bleeds with propranalol (1
mg/kg/day) and isosorbide mononitrate]. Proper
counseling of close relatives for long term follow up and
the natural course of the illness is mandatory. Indication
for surgical management includes:
682
1. Recurrent rebleeds even after 4 to 6 endotherapy

sessions
2. Hypersplenism
3. Outstation patients (from remote places) where
medical treatment is not available
4. If patient is not fit for surgery or not willing for
surgery, TIPS (transjugular intrahepatic porto
systemic shunt) can be attempted.
Ascites: see chapter on ascites
BIBLIOGRAPHY
1.
Ashish Bavdekar. Metabolic liver diseases, lAP speciality

2. Bavdekar AR. Wilsons diseaseA diagnostic dilemma.
Indian J Gastroenterology 2003;22-23.
3. Hardy S, Kleinman ER. Cirrhosis and chronic liver
failure. Text book of liver disease in chidren2nd edition.
Eds Suchy FJ, Sokol RJ. Balistreri WF Lippincott Williams
and Wilkins: Phildelphia, 2001;89-127.
4. Kelly DA. Useful investigations in the assessment of liver

disease. Textbook of diseases of the liver and biliary
system in children. Deidre A Kelly 1999;3-8.
5. Malathi SatyasekharanApproach to a child with CLD,
Indian J of Pract. Pediatrics, Hepatology 2002;4(4):
362-69.
6. Sheila Bhave. Chronic liver disorders in children, lAP
speciality series on paed gastroenterology 2008;(14):
188-96.
7. Surendar Kumar A Yacha. Neonatal cholestasisiAP
speciality series pn ped.gastroenterology 2008;(13):
178-87.
8. Sutapa ganguly Portal hypertension. lAP speciality series
on paediatric gastroenterology 2008(15);196-216.
9. VS Sankaranarayanan, S srinivas. Chronic hepatitis in
children and cirrhosis of liver in children. Parthas
fundamentals of pediatrics 2007;(11):354-61.
10. Thapa BR, Bansal D .Management of upper gastrointestinal bleeding in children- portal hypertension-acute
variceal bleeding. Indian J of Practical pediatricsHepatology 2002;4(4):403-10.
13.20 Neonatal Cholestasis Syndrome

BR Thapa
INTRODUCTION
Neonatal cholestasis is a pathological condition in which
bile flow is affected. Neonatal cholestasis syndrome
(NCS) comprises of a heterogeneous group of hepatobiliary disorders responsible for cholestasis during
neonatal life. The cholestasis due to some disorders can
extend beyond neonatal period hence it is also referred
to as cholestasis of infancy. Most of the disorders have
linkage with insults during antenatal, natal and postnatal
periods. Main causes of NCS are infections, metabolic
disorders and extrahepatic biliary obstruction.
Epidemiology
The present scenario about the spectrum of illnesses is
changing fast, the premature babies are now being looked
after in neonatal specialized care units, the causes of
cholestasis due to sepsis, total parenteral nutrition (TPN)

and drugs are emerging as a large group.
Approach to Jaundice
Jaundice is a very common symptom encountered during
neonatal life. Approach to jaundice during neonatal
period and infancy is given (Fig. 13.20.1). This is also
called hyperbilirubinemia when defined by raised serum
bilirubin > 2 mg/dl. Based upon the composition of
serum bilirubin, this is divided into unconjugated and
conjugated hyperbilirubinemia. Unconjugated hyperbilirubinemia is very common during first few weeks of
life and the unconjugated bilirubin constitutes 80 percent
of total serum bilirubin level. This is characterized by
icterus, normal colored urine and yellow normal colored
stools. Most of the times it is attributed to physiological
jaundice or breast milk jaundice.
683
Figure 13.20.2: Normal yellow stool (1) and pale/alcoholic

stool in case of EHBA or severe cholestasis (2)
Classification
Figure 13.20.1: Approach to jaundice during infancy and

classification of cholestasis
Definition
Conjugated hyperbilirubinemia is defined when the
conjugated fraction of bilirubin is more than 20 percent
of the total serum bilirubin or when conjugated bilirubin
is more than 1.5 mg/dl in neonatal period and persists
beyond first 14 days of life then it is labeled as neonatal
cholestasis.This is associated with retention of bile salts
in the blood. Cholestasis is also defined as pathological
stage of reduced bile formation or flow and clinical
criteria are passage of high colored urine that stains the
diaper yellow and pale/white/acholic or intermittent
pale and yellow or yellow stools (Fig. 13.20.2). Cholestasis
is characterized by itching that may not be recognized
during early life but irritability is a common feature. After
6-months of life itching is quite apparent. These clinical
pointers are very important to differentiate between
cholestasis and unconjugated hyperbilirubinemia.
Histopathological definition of cholestasis is the
appearance of bile within the liver parenchyma
responsible for secondary cell injury.
Neonatal cholestasis is divided into two groups, intrahepatic cholestasis and extrahepatic cholestasis based
upon the nature and site of pathological lesions.
Intrahepatic cholestasis covers two important groups
hepatocellular cholestasis: neonatal hepatitis and paucity
of intrahepatic bile ducts (PIBD). Cholestasis can also be
classified into neonatal hepatitis and obstructive
cholangiopathy or obstructive cholestasis. Obstruction
could be at level of extrahepatic biliary tree and/or
intrahepatic biliary tree.
Predisposing Factors
Newborn infants are prone to develop cholestasis
because of immaturity of excretory function, inborn
errors of metabolism manifesting in early life and
inherent susceptibility to various viral, septic and toxic
insults. The immature liver cells are associated with
peculiar kind of pathological response to different kind
of noxious agents during neonatal life and infancy.
The ineffective enterohepatic circulation of bile
further compromises the excretory function. There is
gradual maturation of hepatocytes in respect to handling
of bilirubin, excretion of bile, synthetic functions and
enzyme system during infancy. The maturation of these
functions may be equivalent to adulthood by age of 4 to
6 months. Some biochemical markers of cholestasis like
684
alkaline phosphatase and glutamyl transpeptidase are

raised during early life. Serum unconjugated bilirubin,
and bile acids concentration are normally in higher
concentration in blood again suggesting that there are
clearance problems in neonatal liver. Due to these reasons
the neonatal hepatobiliary system is affected by various
infective, metabolic and obstructive causes faster as
compared to older children and adults.
Etiology
Various causes of cholestasis are given in Table 13.20.1.
Neonatal hepatitis is more common than EHBA. The
etiology of neonatal hepatitis is idiopathic if known
causes are ruled out.
Pathophysiology
The effects of cholestasis are devastating secondarily due
to retention of bile and results into widespread problems
with the advancing life, of the cholestatic infants and
children. Figure 13.20.3 gives the consequences of
prolonged cholestasis.
Approach to NCS
In NCS it is mandatory to differentiate between neonatal
hepatitis and EHBA. Neonatal hepatitis warrants medical
treatment whereas obstructive cholestasis largely EHBA
needs only surgical treatment and is effective, if done
within 60 days of life.
If the baby is passing pale or acholic or white stools
from very beginning or after few weeks of life one should
act very fast to make the diagnosis of EHBA. In EHBA
fibrosis sets in as early as 4 weeks of life.
EHBA babies are usually term born and have good
weight. Twenty percent of these babies may have
associated congenital malformations. Liver function tests
at times may not help to differentiate. Liver enzymes like
ALT and AST are nearly normal in EHBA but are always
raised in NH. Gamma GT may be raised in EHBA. In
EHBA prolonged PT usually responds to vitamin K
administration.
The approach to cholestasis to differentiate between
obstructive cholestasis and hepatocellular cholestasis is
given in Figure 13.20.4 whereas approach in late
presentation of EHBA is given in (Fig. 13.20.5).
Figure 13.20.3: Consequence of prolonged cholestasis
685
TABLE 13.20.1 Causes of cholestasis in infancy

A.
Extrahepatic
Correctable
Biliary atresia
Noncorrectable
Bile duct stenosis
Spontaneous perforation of bile duct
Common bile duct (CBD) stone
Primary sclerosing cholangitis (PSC)
B.
CBD ligation
CBD stricture
Biliary hypoplasia
Pancreatico-ductal anomaly
Choledochal cyst
Mass (neoplasia)
Intrahepatic
I Idiopathic neonatal hepatitis
II
Intrahepatic cholestasis: persistent
a. Nonsyndromic PIBD
b. Syndromic PIBD
c. Others
Arteriohepatic dysplasia (Alagille syndrome)
Progressive familial intrahepatic cholestasis (PFIC I, II, III and IV)
Byler disease
Trihydroxycoprostanic acidemia
Zellweger syndrome (cerebrohepatorenal syndrome)
III. Intrahepatic cholestasis: recurrent
a. Familial benign recurrent cholestasis
b. Hereditary cholestasis with lymphedema
c. Alpha 1 antitrypsin deficiency
d. Miscellaneous
Cystic fibrosis
Idiopathic hypopituitarism
Hypothyroidism
Multiple acyl-CoA dehydrogenase deficiency
IV. Hepatitis
a. Infections
Bacterial infections
Hepatitis B virus
Herpes virus
Coxsackie virus
Cytomegalovirus
ECHO virus
Rubella virus
HIV
Varicella virus
b. Metabolic disorders
A. Disorders of amino acid metabolism
Tyrosinemia
Hypermethioninemia
B. Disorders of lipid metabolism
Cholestasis associated with parenteral nutrition
Niemann-Pick disease type C.
Infantile Gaucher disease
C. Disorders of carbohydrate metabolism
Galactosemia
Fructosemia
Glycogen storage disease, III and IV
Others:
Malaria
Toxoplasmosis
Syphilis
Listeriosis
Contd...
686

TABLE 13.20.1 Contd...
V.
Genetic chromosomal disorders
Trisomy F
Down syndrome
Donohues syndrome (leprechaunism)

VI. Miscellaneous
Histiocytosis X
Shock
Carolis disease
Neonatal iron storage disease/hemochromatosis
Hemangioendothelioma
Figure 13.20.4: Algorithmic approach to differentiate EHBA from NH (<60 days)
687
Figure 13.20.5: Approach to late presentation of EHBA (>60 days of life)
Ultrasound
Ultrasound is a non-invasive modality to see the status
of liver parenchyma, dilated intrahepatic or extrahepatic
biliary tree and presence of gallbladder. Conditions like
choledochal cyst, bile plug syndrome, common bile duct
(CBD) stone and Carolis disease can be picked up with
great accuracy. Absence of gallbladder is correlated with
EHBA with low sensitivity and specificity (6070%). But
there is significant overlap. Even in severe cholestasis
gallbladder may not be defined because of less production of bile and it may be hypoplastic. Ultrasonographic triangular cord (TC) sign is a cone shaped fibrotic
mass in front of bifurcation of portal vein. This is very
specific for EHBA in expert hands.
Scintigraphy (HIDA Scan)
In severe cholestasis due to NH there may not be
excretion of dye even after adequate priming with
phenobarbitone 5 mg/kg/day or ursodeoxycholic acid
(UDCA) 20 mg/kg/day for 5 days. However, EHBA is

ruled out when dye is seen in duodenum (Figs 13.20.6A
and B). The sensitivity is very high to pick up severe
cholestasis whereas specificity to pick up EHBA is very
low 60 to 70 percent. In some centers this investigation
is not done routinely since there is wastage of 6 to 7 days
period.
Liver Biopsy
It is important to do liver biopsy. But for interpretation
there is need of an expert pathologist who is familiar with
developing neonatal liver and then reaction to various
toxic factors like infections, metabolic and obstructive
insults. In best hands histopathology can differentiate
NH and EHBA up to the tune of 95 percent. But in
5 percent cases there can be overlap.
EHBA is characterized by presence of proliferation
of interlobular ducts, plugged with bile casts and portal
tracts show fibrosis. The liver parenchyma may be
normal, or may show intrahepatocytic or canalicular
688
Figures 13.20.7A and B: (A) Classical histopathology of

EHBA, (B) EHBA with secondary cirrhosis
Figures 13.20.6A and B: (A) Showing dye into the duodenum
EHBA rules out, (B) Dye not seen in duodenum: EHBA or severe
cholestasis
cholestasis. But in advanced cases after 2 months of life

there may be full-fledged changes of secondary biliary
cirrhosis (Figs 13.20.7A and B).
In neonatal hepatitis there is marked parenchymal
injury suggesting focal necrosis, ballooning degeneration,
giant cell transformation (Fig. 13.20.8 showing giant cell
hepatitis), inflammatory infiltrate, pseudoacinar
formation and portal tract may show mild portal triaditis.
There is no fibrosis until the disease is chronic.
Diagnosis of PIBD can be made on histology if the
ratio of presence of bile ducts to portal tracts is less than
0.4 to 0.6. But liver biopsy should contain minimum
5 portal tracts to make the diagnosis of PIBD in a biopsy
specimen.
If the results of biopsy are equivocal (5%) and age is
less than 6 weeks, BRIDA scan and or repeat liver biopsy
Figure 13.20.8: Showing giant cell neonatal hepatitis
after 10 to 14 days should be done. The other modalities

used are MRCP and ERCP but all depends upon the
expertise available.

Magnetic Resonance
Cholangiopancreatography (MRCP)
This is a new noninvasive modality but experts are
required for interpretation of neonatal bile ducts.
Endoscopic Retrograde
Cholangiopancreatography (ERCP)
Problem with ERCP is technical failure and nonavailability of small diameter ERCP scopes in most of
the centers.
Laparoscopy
Laparoscopic visualization of hepatobiliary tree has not
been popularized in children.
Duodenal Intubation
Aspiration of duodenal fluid over 24 hours to see for bile
is popular procedure in Japan. This can be done during
scintigraphy to define the radioactivity in stomach and
duodenal fluid.
689
accordingly. If the infections have been ruled out

reasonably, the next choice is to do metabolic work up.
High index of suspicion of these disorders should be
based upon certain clinical pointers like family history
of previous sib death due to similar disorder, repeated
hypoglycemia, seizures, vomiting, failure to thrive, and
cataract. Preliminary metabolic work up includes urine
for reducing substances like galactose or fructose, serum
alpha-1 antitrypsin level, thyroid function tests, serum
amino acids, urine amino acids screening, eye examination, urinary succinyl acetone, and serum ferritin.
Based upon the suspected diagnosis the specific enzyme
estimation/genetic work up should be done.
Inspite of elaborate workup in 30 to 40 percent cases
of neonatal hepatitis the etiology can not be defined. This
group is labelled as idiopathic neonatal hepatitis or giant
cell hepatitis. Liver histology shows marked giant cell
reaction. Liver biopsy also gives clue towards metabolic
disorders at times.
Treatment
Neonatal Hepatitis
Intraoperative Cholangiography (IOC) or

Peroperative Cholangiography (POC)
This is the gold standard to confirm the diagnosis of
EHBA, when above given investigations do not suggest
EHBA. In presence of gallbladder IOC showing dye in
duodenum and after clamping the CBD showing dye in
intrahepatic radicles rules out EHBA. On the other hand
if dye is not going to duodenum or there is no extra
hepatic biliary tree also confirms EHBA. There is
advantage of taking wedge biopsy of liver. Kasais
portoenterostomy can be done simultaneously in EHBA.
Approach to Neonatal Hepatitis
Neonatal hepatitis is the most important cause of NCS
(60-70%). It is important to record detail history regarding
antenatal, natal and postnatal events, family history,
exposure to various drugs, maturity of the baby, neonatal
sepsis, intrauterine infections, various metabolic and
genetic disorders. Thorough clinical examination is
warranted. The clue to the etiological diagnosis should
come from good clinical evaluation of the case. Infections
in our set up are very important cause of neonatal
hepatitis. If there is direct clue to some metabolic or
genetic disorders the investigations should be done
Infections constitute a major cause of neonatal hepatitis

in developing countries. Bacterial infections must be
treated very effectively. Urinary tract infection remains
hidden infection in neonatal period that should be
diagnosed and treated energetically. Viral infections
perse do not require any specific therapy in this age group
but protozoal infections like malaria and toxoplasmosis
and congenital syphilis should be treated effectively.
Treatment of various metabolic disorders should be
started at the earliest. The offending agent should be
withdrawn promptly for example in case of galactosemia,
milk should be stopped immediately to avoid effect on
the developing brain. In case of fructosemia, fructose
containing food items must be withdrawn immediately.
Treatment of various endocrinologic and metabolic
disorders should be done accordingly. Genetic counseling and need of the antenatal diagnosis should be
stressed in the affected families.
Obstructive Cholestasis: EHBA
The necro-inflammation of the biliary tree leads to
fibrosis also called obliterative cholangiopathy. Exact
etiology is not clear so far. EHBA is a big challenge
worldover but it is more alarming problem in developing
690
countries. This constitutes 30 percent of the NCS seen at

our center. The late presentation of the disease is
responsible for development of cirrhosis. This is a stage
when it becomes untreatable and death is inevitable
within 2 years of life. Bile flow can be established in 80
90 percent cases after Kasais portoenterostomy if done
within 60 days of life. With the advancing age the bile
flow decreases. If the surgery is done within 2-3 months
the bile flow can be established in 4045 percent cases
whereas of surgery done after 3 months of age, the bile
flow can be established in 1020 percent of cases only. In
85 percent of EHBA patients, the extrahepatic biliary tree
is fibrosed and needs portoenterostomy and are called
noncorrectable EHBA. Fifteen percent of EHBA may
have part of CBD or hepatic duct patent and these require
choledochoduodenostomy and hence called as correctable EHBA.
This shows that diagnosis of EHBA should be done
early and surgery should be performed within 60 days
of life. Best time is 4 to 6 weeks of life.
Inspite of advancement in surgical skills the outcome
is not encouraging. Even after portoenterostomy onethird cases deteriorate in perioperative period and first
year of surgery and may require liver transplantation,
one-third develop complications of liver disease during
first decade of life and require liver transplantation,
whereas one-third survive beyond 10 years of life
abnormal liver functions.
One year survival reported is varying from 3071
percent. The highest survival rate is reported by Japanese
workers. One year survival in our country is 2530
percent. This shows that surgery is not fool-proof
treatment and needs liver transplantation. Good
prognostic factors for EHBA surgery are surgery done
under 60 days of life, minimal or no fibrosis on histology,
good bile flow after surgery and absence of cholangitis
in immediate postoperative period or first year of life
and availability of surgical expertise. In our set up late
presentation of the cases and cholangitis are the main
deterimental reasons for fatal outcome of these cases.
Choledochal cyst during infancy is also very
important cause of cholestasis (6%) and needs surgical
treatment.
procedure, progressive liver disease inspite of successful

Kasais procedure and late presentation of EHBA
(unoperated). Ten years survival is 85 to 90 percent in
various centers.
Liver Transplantation
PFIC 2 Type
Liver transplantation has revolutionized the outcome of

EHBA world over. The indications are failed Kasais
The presentation is similar to Byler disease but occurs in

non-Amish families also called Byler syndrome. The
PAUCITY OF INTRAHEPATIC BILE DUCT (PIBD)

The hypoplasia of bile ducts can occur in intrauterine
infections and in alpha 1 antitrypsin deficiency and is
selflimiting. The PIBD may occur in sporadic or in
syndrome form. There is paucity of bile ducts (<0.6) in
relation with portal vein and hepatic artery in the portal
tracts. The disease is progressive and leads to cirrhosis
during infancy and early childhood. This is considered
to be analogous to disappearing bile duct syndrome in
adults.
Alagille Syndrome (Arteriohepatic Dysplasia)
This is the commonest syndromic cause of PIBD and is
characterized by broad forehead, deep set widely spaced
eyes, long straight nose and mandible hypoplasia, ocular
abnormalities posterior embryostoxon, palmostenosis,
tetralogy of Fallot, butterfly vertebrae and tubulointerstitial nephropathy. Chronic cholestasis leads to lot
of complications like xanthomas, vit E. deficiency,
pruritus, growth retardation and defective spermatogenesis. This is linked with human jagged 1 gene (JAGI).
Progressive Familial Intrahepatic
Cholestasis (PFIC)
There are various types of PFIC.
PFIC 1 Type
In Amish families after Jacob Byler this is called Byler
disease. There is defect in the structure of bile canaliculi
membrane so excretion of bile is affected. The disease is
characterized by failure to thrive, marked pruritus,
rickets, steatorrhea and low gamma glutamyl transpeptidase (GGT) levels. The serum cholesterol is normal
but bile acids are raised. The disease is progressive and
develops in cirrhosis and hepatocellular dysfunction
during first decade of life. Liver transplantation is the
only definite treatment. PFIC 1 gene is mapped on
chromosome 18q12.

manifestations and outcome are similar to PFIC1 type
but GGT is high. There are transporter defects (bile salt
export pump, BSEP) and gene is mapped on chromosome
2q24.
PFIC 3 Type
There is high GGT and is absence of multidrug resistance 3 p glycoprotein with deficient translocation of
phosphotidyl choline across the canalicular membrane.
The disease is having milder course as compared to PFIC
1 and 2 types. Ultimately the disease progresses to
cirrhosis.
PFIC 4 Type
This is still under consideration when the cases of PFIC
cannot be classified.
There are certain syndromes like Aagenaes syndrome, Zellweger (cerebrohepato renal) syndrome and
inborn errors of bile acid metabolism (deficiency of
reductase, steroid dehydrogenase, isomerase hydroxylase). These are also responsible for intrahepatic
cholestasis and there is accumulation of abnormal bile
acids.
All there conditions are progressive despite of
treatment with UDCA and other supportive measures
and invariably require liver transplantation.
Metabolic Liver Disease
During neonatal period and infancy various important
metabolic disorders are pertaining to carbohydrates
(galactosemia, fructosemia, glycogen storage disease type
I, III and IV), proteins (tyrosinemia, urea cycle defects,
amino acid disorders, etc.) and fats (Niemann-Pick
disease type C, infantile Gauchers disease). These have
distinct clinical presentation and need enzyme estimation
for confirmation of the diagnosis.
Medical Treatment
Chronic cholestasis is responsible for various life
threatening consequences which need prolonged
therapy.
Pruritus: Pruritus is a most distressing symptom. It leads
to miserable life in term of lack of sleep, emotional
problems and children become mentally reckoned.
Various treatment modalities like cholestyramine,
phenobarbitone 5 mg/kg/day, rifampicin (10 mg/kg/
691
day), terfenadine, UDCA (2040 mg/kg) and phototherapy have been tried with variable results. UDCA
seems to be promising as it is one of choleretic drug. Some
times untreatable and unremitted pruritus becomes sole
indication for liver transplantation.
Malnutrition: Malnutrition is very common and is due to
obvious reasons mentioned in Fig. 13.20.1. Breastfeeding
should be encouraged in these babies. If anorexia is a
prominent feature nasogastric feeding is indicated. The
diet should have 200 calories/kg and protein 12 g/kg
body weight. The diet should be constituted by MCT (2
3% calories from PUFA), carbohydrates (glucose
polymers), minerals, trace elements and vitamins. MCT
rich available diets are coconut oil, simyl MCT,
Progestimil and Portagen. All vitamins should be given
in double the daily requirement.
Vitamin A: Vitamin A should be given 2500 to 5000 IU/
day. Monitor the vitamin A level. If blood level is less
than 30 mg/dl increase the oral dose by 10 folds or give
50,000 IU IM.
Vitamin D: Daily 400 to 1200 IU of vitamin D is
recommended. This can be given in form of 40,000 IU
IM monthly. 25-hydroxycholecalciferol 5 to 7 mg/kg can
be given daily. Monitor serum calcium, phosphate and
alkaline phosphatase and X-ray wrist at 2 months
interval.
Vitamin E: Vitamin E deficiency is now recognized very
often since the age of the children with cholestasis is
increasing. The dose of vitamin E recommended is 15 to
200 mg daily. Serum monitoring is mandatory. If levels
are lower side then higher dose should be given. Six
monthly neurological and yearly eye examination are
required.
Vitamin K: In case of prolonged cholestasis with
steatorrhea vitamin K 5 mg IM monthly should be given.
Treatment of other complications of liver disease like
ascites, portal hypertension, variceal bleed and encephalopathy should be done accordingly.
Liver failure due to metabolic conditions in neonatal
period and infancy is difficult to manage medically. Liver
transplantation have changed the outcome in western
world.
692
Prognosis and Outcome

Prognosis of NH is very good if diagnosed early and
appropriate treatment is instituted depending upon the
etiology. In idiopathic neonatal hepatitis 70-80 percent
recover whereas 10 to 20 percent may have progressive
liver disease and very small percentage of 1 to 2 percent
may develop cirrhosis. Death occurs due to sepsis,
bleeding or acute liver failure. In EHBA even after
successful portoenterostomy one-third die during 1 year
of operation, one-third die by 10 years of age whereas
one-third survive after 10 with some compromised liver
functions. With liver transplantation survival of EHBA
has improved to 90 percent in best centers.
4.
5.
6.
7.
8.
9.
BIBLIOGRAPHY
1.
Chardot C, Carton M, Spire Bendelae N et al. Is Kasais

operation still indicated in children older than 3 months
diagnosed with biliary atresia? J Pediatr 2001;138:
22428.
2. Chhabra M, Poddar U, Thapa BR, Singh K. Spectrum of
cholestasis of infancy. Indian J Gastroenterol 1996;15:
(Suppl 1) A 73.
3. Kader HH, Balisteri WF. In: Rd Behrman, RM Kliegman,
HB Jenson, (Eds): Cholestasis from Nelson text of
10.
11.
Pediatrics. Saunders company. (17th edition) 2003;

131419.
Kotb MA, Sheba M, EL Koofy N, et al. Evaluation of
Triangular cord sign in the diagnosis of biliary atresia
pediatrics 2001;108:41620.
Lai MW, Chang MH, Hsu SC, Cheng TS, Kao CL, Lee
CY. Differential diagnosis of extrahepatic biliary atresia
from neonatal hepatitis: a prospective study. J Pediatr
Gastroenterol Nutr 1994;18:121217.
McEvoy CF, Suehy FJ. Biliary tract disease in children.
Ped Clin North Am 1996;43:7598.
Paltiel HJ. Imaging of neonatal cholestasis. Semin
Ultrasound CT and MRI 1994;15:290305.
Poddar U, Thapa BR, Chhabra M, Rao KLN, Mitra SK,
Singh K. Choledochal cysts in infants and children.
Indian Pediatr 1998;35:61318.
Shah HA, Spivak W. Neonatal cholestasis: New
approaches to diagnostic evaluation and therapy. Ped
Clin North Am 1994;41:94366.
Thapa BR: In Sachdev HPS, Choudhary P (Eds): Role of
nutrition in liver and biliary disorders in nutrition in
children. Developing country concerns (First edition).
Cambridge Press, Kashmere gate New Delhi; 1994;
37689.
Whitington PI. Chronic cholestasis of infancy. Ped Clin
North Am 1996;43:126.
13.21 Fulminant Hepatic Failure

Rajiv Chandra Mathur
Definition
Etiology
Fulminant hepatic failure (FHF) is defined as the severe

impairment of hepatic dysfunction (INR > 1.5 +
encephalopathy or INR> 2 + encephalopathy) in the
absence of preexisting liver disease. Hepatic encephalopathy is a state of disturbed neurological function
associated with liver disease. Unlike in adults where
encephalopathy is central it may be absent, late or
unrecognized especially in neonates and infants.
Based on the onset of symptoms various presentations
have been proposed. Hyper acute liver failure is defined
as coagulopathy due to acute liver dysfunction of up to
10 days duration, acute liver failure is when it is more
than 10 days but less than 30 days and subacute liver
failure from 31 days to less than 6 months.
Etiology varies with age of presentation (Table 13.21.1).

The most common causes in neonates and infants are
metabolic liver disease, septicemia and neonatal
hemochromatosis. In children older than one year viral
hepatitis, drugs systemic infection and unknown causes
are the most common etiologies.
Pathology
Severe liver damage to the liver has already occurred by
the time of presentation. Histologic examination at the
time of presentation typically demonstrates confluent
necrosis with cell drop out and parenchymal collapse in
either a zonal or non zonal distribution. Many activated
sinusoidal lining cells, kupffer cells, stellate cells and

TABLE 13.21.1: Etiology of Fulminant hepatic failure
Neonates and infants
Older children
Septicemia
Inborn errors of metabolism
Tyrosinemia
Galactosemia
Hemochromatosis
Hereditary fructose
intolerance
Viral hepatitis A, B,B+D,E

Parvo virus,
Adeno virus
Herpes simplex
Hepatotoxic drugs*
Circulatory failure, Ischemic
disease
Hematological malignancy
Hodgkins disease
Leukemic infiltrates
Reyes syndrome
Autoimmune hepatitis type 2
Wilsons disease
Infections#
*Valproic acid, INH, Paracetamol, Halothane, Phenytoin, Ketoconazole

#CMV, Herpes, EBV, Leptospira, Dengue, Typhoid
endothelial cells are seen at the site of the hepatocyte

drop out. Marked cholestasis in the remaining parenchyma may occur and is a poor prognostic sign. There
may be sinusoidal dilatation, congestion and cirrhosis
specific to the underlying cause. In most cases of FHF a
variable degree of liver regeneration in the form of
proliferation of hepatocytes and ducts is evident.
Pathophysiology
FHF is characterized by marked splanchnic and systemic
arteriolar vasodilatation along with hyperdynamic
circulation and low arterio venous oxygen content
difference. Tissue hypoxia develops despite adequate
arterial oxygen and this contributes to the development
of multiorgan failure and is a marker of poor prognosis.
Microcirculatory plugging caused by formation of
micro thrombi as a consequence of activation and
consumption of platelets along with increased adhesion
of leukocytes to the endothelial wall. Increased activity
of cGMP results in vasodilatation.
Encephalopathy results from the accumulation of
unmetabolized ammonia, mercaptans, fatty acids and
GABA. Production of false neurotransmitters is enhanced
due to decreased aromatic and branched chain amino
acids in the blood. The cerebral metabolism is altered.
Decreased cerebral blood flow is due to impaired auto
regulation in FHF. In patients with grade III and IV
693
encephalopathy subclinical epileptiform activity is seen

and seen this exacerbates the oxygen demand.
Renal failure of various degrees occurs in FHF
patients. Hypovolemia caused by vasodilatation, micro
circulatory disturbance and acute tubular necrosis are
important contributing factors. Rapid deterioration in
nutritional status with depletion of muscle and fat stores
often occurs as a consequence of impaired gluconeogenesis and impaired glycogen storage. Hypoglycemia,
hypophosphatemia and hypomagnesaemia are common.
Metabolic acidosis is relatively frequent due to tissue
hypoxia, increased peripheral lactate production and
renal failure.
Reduced hepatic synthesis of clotting factors and
increased consumption of multiple clotting factors and
platelets contribute to the coagulopathy associated with
FHF. Children with FHF are susceptible to infections as
a consequence of impaired neutrophils and kupffer cell
phagocytic function and reduced complement levels.
Induced bacterial changes in the gut flora may also
contribute to this. The common infections that occur are
pneumonia, septicemia, urinary tract infection and
spontaneous bacteria peritonitis. A vicious cycle of
endotoxemia, circulatory collapse, tissue hypoxia,
increased bacteria translocation and leaky intestinal
mucosa contribute to multi organ failure.
Precipitating Factors
Stress, gastrointestinal bleeding, constipation, large
volume animal protein diet, rapid abdominal paracentesis, hypoglycemia, sepsis, CNS depressant drugs and
hypoxia are common precipitating factors.
FHF affects previously healthy children with no
recognized risk factors for liver disease. Children usually
present with hepatitis and worsening of symptoms over
a period of several days or weeks. Jaundice is the
presenting symptom in most children. A prodrome of
flu like illness may precede jaundice. Fever, anorexia,
vomiting, abdominal pain and fetor hepaticus are
common. Altered consciousness, mental changes present
later. Infants initially may present with poor feeding,
irritability and disturbances in sleep rhythm.
Hemorrhagic diathesis and ascites may develop later.
Patients should be observed for signs of hepatic
encephalopathy (Table 13.21.2).
694

TABLE 13.21.2: Grades of hepatic encephalopathy
Grade of
encephalopathy
Mental status
Behavior
Motor activity
Tone and Reflexes
Response to pain
pupils
Grade I
Alert oriented
Incoordination
tremor
Normal
Obeys
Normal
Grade II
Lethargic
confused
irritated
Stupor
arousable
Restless,
irritable,
confusion
Combative,
euphoric
Yawning,
grimacing
intention-tremor
Motor activity
marked intention
tremor
Tone brisk
reflexes
Localizes
Hyperactive
Up plantars,
clonus
Flexes
Hippus
Absent
Sustained clonus
Extends
Dilated
sluggish
Grade III
Grade IV
Unarousable
Sleeps
all times,
marked
confusion
Unconscious
TABLE 13.21.3: Supportive treatment of FHF

Goal
Intervention
Maintain hemodynamic
stability and electrolyte balance
Colloid, dopamine/dobutamine infusions.

Avoid fluid overload,
Prevention of stress ulcer
H2 Blocker
Sedation
Propofol
Optimize oxygen delivery
Oxygen, N acetyl cysteine & prostaglandin E 1 infusions.
Coagulopathy
Recombinant Factor VII a 5-10 ug/kg

FFP in active hemorrhage
Packed cell transfusion in hemodynamicaly destabilizing anemia
Plasmapheresis
Prevention and correction of

hypoglycemia
10-20 % dextrose
Prevention of hepatic
encephalopathy (Decrease ammonia)
Dietary protein restriction < 0.5 g/kg/day

Lactulose 1 mg/kg/6 hourly till 3 loose motions/day
L ornithine L aspartate infusion 1-2 g/day
Benzodiazepine antagonist (Flumazenil) for short reversal of
encephalopathy
Cerebral edema
Monitor ICP (Subdural transucer) Keep < 20-25 mmhg

Quiet environment, 30 head elevation, pyrexia control, sedation
20% mannitol infusion
Elective ventilation
Induction hypernatremia (145-155 meq/I) by 3% Nacl
Induction of Hypothermia (Core body temperature 32-33 C)
Sub clinical or clinical seizures
Phenytoin infusion, Thiopental infusion
Diet
High calorie 30-50 K cal/Kg 50% non protein calories

High carbohydrate, protein restriction BCCA rich vegetable protein
Prevention and treatment of infections
IV line care, infection surveillance

Prophylactic antibiotic & anti fungal
Renal failure
Maintain intravascular volume, pressure

Dialysis in established failure

Complications are often encountered in association
with grade III and IV encephalopathy. They include
cerebral edema, convulsions, hypoglycemia, dyselectrolytemia, metabolic acidosis, hypotension, sepsis,
gastrointestinal bleeding, coagulopathy, hepatorenal
syndrome and multi organ failure.
Investigations
These include serum bilirubin, AST, ALT, blood
ammonia, prothrombin time, blood sugar, serum
electrolytes, blood gas analysis, infection screening, viral
serological markers blood grouping and other tests
specific for the suspected etiology.
Management
Management in an intensive care is mandatory for all
patients with more than grade II encephalopathy.
Treatment is supportive but specific for multiorgan
dysfunction (Table 13.21.3). Specific therapies where
treatable etiologies can be identified needs to initiated
early.
Orthotropic liver transplant using whole, split or
auxiliary liver from either cadaver or living related
donors has shown promising results and is indicated
when there is severe liver damage. Extra corporeal liver
support provides temporary liver support in FHF. MARS
(Molecular Adsorbent Recirculating System) involves
usage of albumin, resin dialysate to remove protein
bound and low molecular toxins.
695
Prognosis
The overall mortality exceeds 60%. The prognosis may
vary with the cause of hepatic failure, severity of
encephalopathy and development of complications.
BIBLIOGRAPHY
1. Bansal S, Dhawan A. Acute liver failure. Indian Journal
of Pediatr 2006;73(10):931-34.
2. Bhaduri BR,Mieli-Vergani G. Fulminant hepatic failure
pediatric aspects. Semin Liver Dis 1996;16(4):349-55.
3. Chuansumrit A,Chantarojansin P ,Isarangkura S etal.
Recombinant activated factor VII in children with acute
bleeding resulting from liver failure and DIC. Blood
Caogul Fibrinolysis.2000;11(Supp 1): 5101-5105.
4. Cochran JB, Losek ill. Pediatr Emerg Care 2007;23(2):
129-35.
5. Dhawan A,Cheeseman P, Mieli-Vergani G.Approaches
to liver failure in children.Pediatr transplant. 2004;8:
84-588.
6. Kortsalioudaki C, Taylor RM, Cheeseman P, Bansal S,
Mieli- V ergani G, Dhawan A. Safety and efficacy of Nacetylcysteine in children with non-acetaminopheninduced acute liver failure. Liver Transpl. 2008
Jan;14(1):25-30.
7. Mathur RC. Management of difficult problems in
Fulminant hepatic failure. Indian J Pediatr 1995;4:
361-366.
8. Mathur RC, Chandra N, Mathur YC. Viral etiology and
outcome of Fulminant hepatic failure.J Fed Child Health.
1997;33:I:S 52.
9. Poddar U, Thapa B, Prasad A et al. Natural history and
manifestations in FHF. Arch Dis Child. 2002;87:54-56.
13.22 Ascites
Balvir S Tomar, Anurag Tomar
DEFINITION
Ascites is of Greek derivation (askhos) which refers to a
bag or sack. The word describes pathologic fluid
accumulation within the peritoneal cavity (Fig. 13.22.1).
BACKGROUND
Inside the abdomen there is a membrane called the
peritoneum which has two layers. One layer lines the
abdominal wall and the other layer covers the organs
inside the abdominal cavity. The peritoneum produces

a fluid that acts as a lubricant and allows the abdominal
organs to glide smoothly over one another. Sometimes
an excess of this fluid can build up between the two layers
and this is called ascites.
The accumulation of fluid in the abdominal cavity
can be associated with portal hypertension. This means
there is an increased blood pressure in the veins draining
the liver. The higher pressure can be caused by liver
damage. It can also be caused by impaired drainage in
696
Figure 13.22.1: Child with ascites
the lymph system. This system takes excess fluid and

particles away from the liver. Low levels of albumin and
other proteins in the blood also contribute to ascites. The
force that holds plasma water within the blood vessels is
reduced. Plasma water is lost into the abdominal cavity.
Albumin in the ascitic fluid pulls yet more fluid across
into this cavity. Blood flow to the kidneys might be
reduced. This leads to increased secretion of aldosterone.
This causes the kidneys to retain salt and water. Urinary
output is decreased, and fluid is retained. In some cases,
kidney disease contributes to impaired elimination of salt
and water. Fluid may leak from capillaries, the pancreas,
or the lymph system. Capillary fluid leakage can be
caused by inflammation or infection.
PATHOPHYSIOLOGY
The accumulation of ascitic fluid represents a state of
total-body sodium and water excess, but the event that
initiates the unbalance is unclear. Three theories of ascites
formation have been proposed.
A. Under filling theory: This suggests that the primary
abnormality is inappropriate sequestration of fluid
within the splanchnic vascular bed due to portal
hypertension and a consequent decrease in effective
circulating blood volume. This activates the plasma
renin, aldosterone, and sympathetic nervous system,
resulting in renal sodium and water retention.

B. Overflow theory: This suggests that the primary
abnormality is inappropriate renal retention of
sodium and water in the absence of volume depletion.
This theory was developed in accordance with the
observation that patients with cirrhosis have
intravascular hypervolemia rather than hypovolemia.
C. Peripheral arterial vasodilatation hypothesis: This
includes components of both of the other theories. It
suggests that portal hypertension leads to vasodilatation, which causes decreased effective arterial
blood volume. As the natural history of the disease
progresses, neurohumoral excitation increases, more
renal sodium is retained, and plasma volume
expands. This leads to overflow of fluid into the
peritoneal cavity. According to the vasodilatation
theory, the under filling theory is proposed to be
operative early and the overflow theory is proposed
to be operative late in the natural history of cirrhosis
(Fig. 13.22.3).
Although the sequence of events that occurs between
the development of portal hypertension and renal
sodium retention is not entirely clear, portal hypertension
apparently leads to an increase in nitric oxide levels.
Nitric oxide mediates splanchnic and peripheral
vasodilatation. Patients with ascites have greater hepatic
artery nitric oxide synthase activity compared to patients
without ascites.
Regardless of the initiating event, a number of factors
contribute to the accumulation of fluid in the abdominal
cavity. Elevated levels of epinephrine and nor epinephrine are well-documented factors. Hypoalbuminemia
and reduced plasma oncotic pressure favor the extravasation of fluid from the plasma to the peritoneal fluid,
and, thus, ascites is infrequent in patients with cirrhosis
unless both portal hypertension and hypoalbuminemia
are present. If the liver is damaged, it may produce less
blood protein. This may upset the bodys fluid balance
which causes fluid to build up in the body tissues,
including the abdomen.
Cancer cells can block the lymphatic system. The
lymphatic system is a network of fine channels, which
runs throughout the body. One of its functions is to drain
off excess fluid, which is eventually got rid of in the urine.
If some of these channels are blocked, the system cannot
drain efficiently and fluid can build up. The pathophysiologic mechanisms of ascites is shown in Table
13.22.1.
697
Figure 13.22.2: Pathophysiology of ascites

TABLE 13.22.1: Pathogenic mechanisms in ascites formation
A. Increased hydrostatic pressure
Cirrhosis (Fig. 13.22.3)
Hepatic vein occlusion (Budd-Chiari syndrome)
Inferior vena cava obstruction
Constrictive pericarditis
B. Decreased colloid osmotic pressure
End-stage liver disease with poor protein synthesis
Nephrotic syndrome with protein loss
Malnutrition
Protein-losing enteropathy
C. Increased permeability of peritoneal capillaries
Tuberculous peritonitis
Bacterial peritonitis
Malignant disease of the peritoneum
D. Leakage of fluid into the peritoneal cavity
Bile ascites
Pancreatic ascites (secondary to a leaking pseudocyst)
Chylous ascites
Urine ascites
E. Miscellaneous causes
Myxedema
Ovarian disease (Meigs syndrome)
Chronic hemodialysis
ETIOLOGY
NEONATAL ASCITES/CONGENITAL ASCITES
Ascites in the newborn (Fig. 13.22.4) can be grouped as:
I. Associated with hydrops
II. Isolated ascites
III. Ascites due to peritonitis
Associated with Hydrops
1. Cardiovascular (20% cases) (failure or poor output)
a. Rhythm disturbances: Heart block, auricular
tachycardia
b. Cardiac malformation: Hypoplastic left heart,
Ebsteins disease
2. Hematological disorders (10% cases) (Chronic in
utero anemia): Isoimmune hemolytic disease,
homozygous alpha thalassemia
3. Chromosomal (10% cases): Turner syndrome,
trisomy 13, 18 and 21
4. Infection (8% cases): TORCH group, syphilis
5. Renal (5% cases): Nephrosis, posterior urethral valve
698
Figure 13.22.3: Ascites formation in cirrhosis
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Figure 13.22.4: Ascites in neonate
Pulmonary (5% cases): Diaphragmatic hernia.

Gastrointestinal (5% cases): Atresia
Maternal conditions (5% cases): Toxemia, diabetes
Placenta or cord (rare): Cord compression, chorangioma
Miscellaneous (10% cases): Wilms tumors, neuroblastoma
Storage disease: Mucopolysaccharidosis VIII
Skeletal abnormalities: Osteogenesis imperfecta,
achondrogenesis
Cirrhosis: -1 antitrypsin deficiency
Liver failure: Neonatal hemochromatosis
Unknown (20% cases).
Isolated Ascites
1. Chylous: Congenital anomaly of lymphatic channels
2. Biliary: Spontaneous perforation of biliary tree
3. Pancreatic duct anomaly.
Peritonitis
1. Chemical: Bile, meconium
2. Bacterial.
ETIOLOGY IN CHILDREN
Associated with Portal Hypertension (Fig. 13.22.5)
1. Extrahepatic disorders
Venous obstruction: Splenic vein thrombosis, portal
vein thrombosis/cavernous transformation, BuddChiari syndrome, inferior vena cava obstruction
Miscellaneous: CHF, AV fistulae
Figure 13.22.5: Ascites with portal hypertension showing

dilated veins
2. Intrahepatic disorders
a. Biliary tract disease: EHBA, cystic fibrosis,
choledochal cyst, sclerosing cholangitis, intrahepatic cholestasis syndromes
b. Hepatocellular disease: Autoimmune hepatitis,
hepatitis B,C, Wilsons disease, antitrypsin
deficiency
c. Toxins: Ethanol, methotrexate, 6-mercaptopurine
d. Miscellaneous: Histiocytosis X, schistosomiasis.

OTHER CAUSES
Tuberculosis, heart failure, nephrotic syndrome,
pancreatitis, chlamydial infection and rheumatoid
arthritis.
ETIOLOGY OF ACUTE ASCITES
i. Venous obstruction: Budd-Chiari syndrome, portal
vein thrombosis, inferior vena cava obstruction,
splenic vein thrombosis, venoocclusive disease of
liver
ii. Peritonitis: Spontaneous perforation of bile duct
iii. Fulminant hepatic failure
ETIOLOGY OF ASCITES IN REFERENCE TO
NORMAL AND/OR DISEASED PERITONEUM
Normal Peritoneum
Portal hypertension (serum-ascites albumin gradient
[SAAG] > 1.1 g/dl)
Hepatic congestion, congestive heart failure,
constrictive pericarditis, tricuspid insufficiency,
Budd-Chiari syndrome
Liver disease, cirrhosis, alcoholic hepatitis, fulminant
hepatic failure, massive hepatic metastasis
Hypoalbuminemia (SAAG < 1.1 g/dl)
Nephrotic syndrome
Protein-losing enteropathy
Severe malnutrition with anasarca
Miscellaneous conditions (SAAG < 1.1 g/dl)
Chylous ascites
Pancreatic ascites
Bile ascites
Nephrogenic ascites
Ovarian disease
Diseased Peritoneum (SAAG < 1.1 g/dl)
Infections
Bacterial peritonitis
Fungal peritonitis
HIV-associated peritonitis
Malignant conditions
Peritoneal carcinomatosis
Primary mesothelioma
Pseudomyxoma peritonei
Hepatocellular carcinoma
699
Other rare conditions

Familial Mediterranean fever
Vasculitis
Granulomatous peritonitis
Eosinophilic peritonitis
PRESENTATION
History
Most cases of ascites are due to liver disease or due to
some precipitating factors deteriorating liver functions,
e.g. drugs (NSAIDs). History of abdominal distention,
increasing weight, respiratory embarrassment, associated pedal edema.
Risk Factors for Liver Diseases
Chronic viral hepatitis or jaundice

Intravenous drug use
Sexual promiscuity
Transfusions: Hepatitis C has been linked to
transfusions
Tattoos
Habitation or origination from an area endemic for
hepatitis.
Patients with a history of cancer, especially gastrointestinal cancer, are at risk for malignant ascites.
Malignancy-related ascites is frequently painful, whereas
cirrhotic ascites is usually painless.
EXAMINATION
Ascites needs to be differentiated from abdominal
distension due to other causes like gross obesity, gaseous
distention, bowel obstruction, abdominal cysts or masses.
The clinical manifestations of ascites can vary from an
asymptomatic patient to patients complaining of
increased abdominal girth, early satiety, and respiratory
distress depending on the amount of fluid accumulated
in the abdominal cavity. Flank dullness which is present
in about 90% of patients, is the most sensitive physical
sign.
Per abdomen: Increasing weight and abdominal girth (if
previous values are available), shifting dullness (Puddle
sign), fluid thrill, peritoneal tap (Table 13.22.2). Elicitation
of increased flank dullness to percussion with patient
supine and shifting dullness (> 1500 ml free fluid). The
physical examination should focus on the signs of portal
700

TABLE 13.22.2: Grading of ascites
Grade
Severity
Signs
Mild
Puddle sign (+)

Detected by ultrasound abdomen
II
Moderate
Shifting dullness (+)

No fluid thrill
III
Tense
Fluid thrill (+)

Respiratory difficulty (+)
TABLE 13.22.3: Staging of ascites

Stage
Signs
1+
2+
3+
4+
Detectable only after careful examination

Easily detectable but of relatively small volume
Obvious ascites but not tense ascites
Tense ascites
hypertension and chronic liver disease. Liver is examined

to see if it is enlarged or tender. The liver may be difficult
to palpate if a large amount of ascites is present
(Table 13.22.3).
MONITORING
Simple assessment of the progress of ascites may be made
by serial measurements of the abdominal girth. The tape
measure must be placed in the same position each time.
Serial measurement of weight also indicates fluid gain
or loss. This tends to be much faster than gain or loss of
fat or lean body mass.
Neck: Check for jugular venous distention.
Heart: Check for tricuspid murmur or signs of heart
disease.
Lungs: Examine for signs of fluid (heart failure).
Skin: May show cutaneous spider angiomas, palmar
erythema, Dupuytrens contracture, or large veins on the
abdomen.
Asterixis may be present, ascitis may be part of
generalized oedema. Patients with cardiac disease or
nephrotic syndrome may have anasarca.
Lymph nodes: For enlargement. A pathologic left-sided

supraclavicular node (Virchows node) suggests the
presence of upper abdominal malignancy.
The puddle sign indicates that as little as 120 ml of
fluid is present. When peritoneal fluid exceeds 500 ml,
ascites may be demonstrated by the presence of shifting
dullness or bulging flanks. A fluid-wave sign is notoriously
inaccurate.
INVESTIGATIONS
Confirming the presence of ascites
Finding the cause for the ascites
Assessing any complication due to the ascites
BLOOD TESTS
Complete blood counts

Complete urine examination
Liver Function Tests including plasma proteins
Clotting screen, especially if invasive investigations
are considered
White cell count: Normal ascitic fluid contains fewer than

500 leukocytes/ml and fewer than 250 polymorphonuclear leukocytes/ml. Any inflammatory condition can
cause an elevated white blood cell count. White cell count
when greater than 350/microliter is suggestive of
infection. A neutrophil count of more than 250 cells/ml
is highly suggestive of bacterial peritonitis. In tuberculous
peritonitis and peritoneal carcinomatosis, a predominance of lymphocytes usually occurs. If most cells are
polymorphonuclear, bacterial infection should be
suspected. When mononuclear cells predominated,
tuberculosis or fungal infection is likely. This is the single
most useful test. Only recent trauma gives false results.
To correct this, one PMN is subtracted from absolute
ascitic fluid PMN count for every 250 RBC. In old trauma,
PMN will have lysed so no correction is needed.
Red cell count: When greater than 50,000/microliter
denotes hemorrhagic ascites, which usually is due to
malignancy, tuberculosis or trauma.
IMAGING STUDIES
Chest and Plain Abdominal Films
Elevation of the diaphragm, with or without
sympathetic pleural effusions (hepatic hydrothorax),
is visible in the presence of massive ascites. More than

500 ml of fluid is usually required for ascites to be
diagnosed based on findings from abdominal films.
Many nonspecific signs indicate ascites, such as
diffuse abdominal haziness, bulging of the flanks,
indistinct psoas margins, poor definition of the intraabdominal organs, erect position density increase,
separation of small bowel loops, and centralization
of floating gas containing small bowel.
The direct signs are more reliable and specific. In 80
percent of patients with ascites, the lateral liver edge
is medially displaced from the thoracoabdominal wall
(Hellmer sign). Obliteration of the hepatic angle is
visible in 80 percent of healthy patients. In the pelvis,
fluid accumulates in the rectovesical pouch and then
spills into the paravesical fossa. The fluid produces
symmetric densities on both sides of the bladder,
which is termed a dogs ear or Mickey Mouse
appearance. Medial displacement of the cecum and
ascending colon and lateral displacement of the
properitoneal fat line are present in more than
90 percent of patients with significant ascites.
Ultrasound
Abdominal ultrasound can be used to detect ascites
in morbidly obese, to indicate appropriate site for
paracentesis, in patients with multiple abdominal
surgical scars and with serum alphafetoprotein, to
detect hepatic malignancy. It can detect as little as
100 mL of fluid in the peritoneal cavity. Uncomplicated ascites appears as a homogenous, freely mobile,
anechoic collection in the peritoneal cavity that
demonstrates deep acoustic enhancement. Free
ascites does not displace organs but typically situates
itself between them, contouring to organ margins and
demonstrating acute angles at the point at which the
fluid borders the organ.
The smallest amounts of fluid first tend to collect
in the Morison pouch and around the liver as a
sonolucent band. With massive ascites, the small
bowel loops have a characteristic polycyclic,
lollipop, or arcuate appearance because they are
arrayed on either side of the vertically floating
mesentery.
Certain sonographic findings suggest that the
ascites may be infected, inflammatory, or malignant.
Findings include coarse internal echoes (blood), fine
internal echoes (chyle), multiple septa (tuberculous
peritonitis, pseudomyxoma peritonei), loculation or
atypical fluid distribution, matting or clumping of
701
bowel loops, and thickening of interfaces between

fluid and adjacent structures. In malignant ascites,
the bowel loops do not float freely but may be tethered
along the posterior abdominal wall plastered to the
liver or other organs or they may be surrounded by
loculated fluid collections.
Upper gastrointestinal endoscopy: To confirm
esophageal/fundal varices
CT and MRI: Ascites is demonstrated well on CT scan
images. Small amounts of ascitic fluid localize in the
right perihepatic space, the posterior subhepatic space
(Morison pouch), and the Douglas pouch. A number
of CT features suggest neoplasia. Hepatic, adrenal,
splenic, or lymph node lesions associated with masses
arising from the gut, ovary, or pancreas are suggestive
of malignant ascites. Patients with malignant ascites
tend to have proportional fluid collections in the
greater and lesser sacs, whereas, in patients with
benign ascites, the fluid is observed primarily in the
greater sac and not in the lesser omental bursae.
INVASIVE PROCEDURES
Ascitic tap (Abdominal paracentesis)
ABDOMINAL PARACENTESIS
Abdominal paracentesis is the most rapid and perhaps
the most cost-effective method of diagnosing the cause
of ascites formation. Therapeutic paracentesis may be
performed for refractory or tense ascites.
Position
For large volume ascites: Supine with head slightly
elevated.
For low volume ascites: Lateral decubitus position.
For small volume ascites: Face down position or hand knee
position (Fig. 13.22.6).
Figure 13.22.6: Minimal ascites is tapped in knee chest position
702
SITE
1. Midline site: Below the umbilicus, this is avascular
area.
2. When midline site is inappropriate (presence of scar),
then a site two-finger breadth medial to the anterior
superior iliac spine is chosen.
3. Ultrasonic guidance is needed only in, specific
indications.
Technique
Needle is inserted, using a Z tract to prevent leakage of
fluid. This is achieved by retracting (with one glove hand)
the skin approximately 2 cm caudal in relation to the
deep abdominal wall and then slowly inserting the
paracentesis needle. The skin is not released until the
needle has penetrated the peritoneum or fluid flows.
When the needle is finally removed at the end to
procedure, the skin resumes its original position and seals
the needle pathway (Fig. 13.22.7).
Ascitic Fluid Analysis
Routine Tests Optional tests

Total protein Grams stain and culture
Albumin AFB smear and culture
Cell count Cytology
Amylase
Lactate dehydrogenase (LDH)
Glucose
Lab studies: Peritoneal fluid should be sent for cell count,

albumin level, culture, total protein, Gram stain, and
cytology for new-onset ascites of unknown origin.
Gross appearance: Most ascitic fluid is transparent and

tinged yellow. This may be attributed to either a
traumatic tap or malignancy. Bloody fluid from a
traumatic tap is heterogeneously bloody, and the fluid will
clot. Nontraumatic bloody fluid is homogeneously red and
does not clot because it has already clotted and lysed.
Neutrophil counts of more than 50,000 cells/ml have a
purulent cloudy consistency and indicate infection. It
may be red because of presence of red cells more than
10,000/cumm, milky if it is lipid laden, dark-brown because
of bilirubin, black/tea color in pancreatic ascites, cloudy
because of absolute neutrophilic count over 5,000/cumm.
Gross Appearance of Ascites
Color
Association
Translucent or yellow
Brown
Normal/sterile
Hyperbilirubinemia (most
common)
Gallbladder or biliary
perforation
Infection
Mild trauma at the site
Malignancy
Abdominal trauma
Cirrhosis
Thoracic duct injury
Lymphoma
Cloudy or tubid
Pink or blood tinged
Grossly bloody
Milky (chylous)
Total protein: In the past, ascitic fluid has been classified

as an exudate if the protein level is greater than or equal
to 2.5 g/dl. However, the accuracy is only approximately
56 percent for detecting exudative causes. The total
protein level may provide additional clues when used
with the SAAG. An elevated SAAG and a high protein
level are observed in most cases of ascites due to hepatic
congestion. Those patients with malignant ascites have
a low SAAG and a high protein level.
Gram stain: Gram stain is only 10 percent sensitive for
helping visualize bacteria in early-detected spontaneous
bacterial peritonitis. Approximately 10,000 bacteria/ml
are required for detection by Gram stain; the median
concentration of bacteria in spontaneous bacterial
peritonitis is 1 organism/ml.
Figure 13.22.7: Site of ascitic tap
Cytology: Cytology smear results are reported to be 58 to

75 percent sensitive for helping detect malignant ascites.

Positive in peritoneal carcinomatosis. Sensitivity
increased by centrifuging large volume.
pH when less than 7 suggests bacterial infection.
Classification of ascitic fluid infection
Type
Spontaneous
bacterial peritonitis
Culture-negative
neutrocytic
bacterascites
PMN count Bacterial culture

(cells/mm3) result
> 250
> 250
Monomicrobial
< 250
nonneutrocytic
bacterascites
Polymicrobial
< 250
bacterascites
Secondary
> 250
bacterial peritonitis
PMN, polymorphonuclear
neutrophil leukocyte
Positive
(one organism)
Negative
Positive
(one organism)
Positive
(polymicrobial)
Positive
(polymicrobial)
Serum Ascitis Albumin Gradient (SAAG): The SAAG is the

best single test for classifying ascites into portal
hypertensive (SAAG > 1.1 g/dl) and non-portal
hypertensive (SAAG < 1.1 g/dl) causes. Calculated by
subtracting the albumin concentration of the ascitic fluid
from the albumin concentration of a serum specimen
obtained on the same day.
Serum ascites albumin gradient (SAAG) = serum
albumin - ascitic fluid albumin
It correlates directly with portal pressure. The
accuracy of the SAAG results is approximately 97 percent
in classifying ascits. High albumin gradient and low
albumin gradient should replace the term transudate
and exudate, in the classification of ascites as accuracy
is not good in the latter. The test is accurate despite ascitic
fluid infection, diuresis, therapeutic paracentesis,
albumin infusion and etiology of liver disease
(Table 13.22.4).
Culture: The common bacterial infection of ascitic fluid
are monomicrobial with a very low bacterial concentration. The sensitivity with bedside inoculation of blood
culture bottles with ascites results in 92 percent detection
of bacterial growth in neutrocytic ascites.
703
TABLE 13.22.4: Types of ascites according to the level of

the serum-ascites albumin gradient (SAAG)
High gradient (> or = 1.1 g/dl)
Low gradient (< 1.1 g/dl)
Cirrhosis
Hepatitis
Nephrotic syndrome
Fulminant hepatic failure
Pancreatic ascitis
Cardiac ascites
Bowel obstruction/infarction
Portal vein thrombosis
Biliary ascites
Veno-occlusive disease
Postoperative lymphatic leak
Myxedema
Serositis in connective
tissue diseases
Massive liver metastases
Nephrotic syndrome
LDH: LDH estimation is often helpful in distinguishing

spontaneous bacterial peritonitis from gut perforation.
Lactate dehydrogenase > 225 mU/L, glucose < 50 mg/
dL, total protein > 1 g/dL and multiple organisms on
gram stain suggest secondary bacterial peritonitis
(ruptured viscus or loculated abscess).
Triglycerides: A high level of triglycerides confirms
chylous ascites.
Amylase: In pancreatitis or gut perforation it is markedly
elevated, usually greater than 2000 IU.
Bilirubin: An elevated bilirubin level suggest biliary or
gut perforation.
Complications of paracentesis: Include infection, electrolyte
imbalances, bleeding, and bowel perforation. Bowel
perforation should be considered in any patient with
recent paracentesis who develops a new onset of fever
and/or abdominal pain. All patients with long-standing
ascites are at risk of developing umbilical hernias. Largevolume paracentesis often results in large intravascular
fluid shifts. This can be avoided by administering
albumin replacement, if more than 5 liters is removed.
Indications for Admitting Patients of Chronic Liver
Disease with Ascites
1. For investigations of the cause of liver disease
2. Child not responsive to appropriate OPD basis
therapy
3. For intensive education of the patient in preparing
a diet limited to 88 mmol of sodium per day
4. For careful monitoring of serum and urine electrolytes and serum concentration of urea nitrogen and
creatinine
704
5. Grade III ascites with respiratory difficulty / distress

6. Ascites with suspected spontaneous bacterial
peritonitis
7. If a child develops diuretic induced complications
Electrolyte imbalances
Hyponatremia: Serum sodium < 125 mEq/L
Hypokalemia: Serum potassium < 3.0 mEq/L
Hyperkalemia: Serum potassium > 6.0 mEq/L
8. Hepatorenal syndrome
Increase in baseline serum creatinine by > 100%
or an absolute value of 1.5 mg/dl (even if the
patient is responding to diuretics)
Urinary Na+ < 10 mEq/L
Creatinine clearance < 0.75 mg/kg/min
9. Hepatic encephalopathy
10. Refractory ascites.
MANAGEMENT
1.
2.
3.
4.
5.
6.
7.
8.
Initial evaluation
Identify and treat the undelrying cause
Diagnostic ascitic fluid tap
Ascitic fluid analysis
Treatment of diuretic-sensitive ascites
Indications to stop diuretics
Treatment of refractory ascites
Spontaneous bacterial peritonitis
Non-drug Management
Bed rest: Upright position increases renin-aldosterone
activity, increased retention of sodium or water. Bed rest
reduces this activity.
Medical care: The goals of pharmacotherapy are to reduce
morbidity and to prevent complications.
Diet: sodium restriction (20-30 mEq/d) and diuretic
therapy constitute the standard medial management for
ascites and are effective in approximately 95 percent of
patients. Sodium restriction up to 5 mg per day in child
1-4 years, not greater than 20 mEq per day in child 4-11
years, not greater than 30 mEq per day in child 12-14
years.
Fluid restriction: It is the sodium restriction not the fluid
restriction, that results in weight loss. Fluid restriction is
only indicated when there is persistent hyponatremia,
serum sodium < 120 mEq/liter (reduced renal free water
clearance). Renal sodium retention is the phenomenon

primarily responsible for fluid retention and ascites
formation. It occurs months before impairment of renal
free water clearance.
Measurements of twenty-four hour urinary sodium
excretion (with measurement of creatinine to assess
completeness of collection). A major goal of treatment is
to increase urinary sodium excretion to > 78 mmol/day.
DRUGS
Diuretics
Spironolactone (Aldactone)
For management of edema resulting from excessive
aldosterone excretion. Competes with aldosterone for
receptor sites in distal renal tubules, increasing water
excretion while retaining potassium and hydrogen ions.
The peak effect of aldactone is approximately 3 days.
Dose: 2 to 3 mg/kg/day PO in divided doses q6-24h.
Contraindications: Documented hypersensitivity; anuria;
renal failure; hyperkalemia.
Precautions: Caution in renal and hepatic impairment;
may cause gynecomastia and impotence in men.
Furosemide (Lasix)
Increases excretion of water by interfering with chloridebinding cotransport system, which, in turn, inhibits
sodium and chloride reabsorption in ascending loop of
Henle and distal renal tubule. Dose must be individualized to patient.
Dose: 1 to 2 mg/kg/dose PO; not to exceed 6 mg/kg/
dose; do not administer >q6h 1 mg/kg IV/IM slowly
under close supervision; not to exceed 6 mg/kg. When
treating infants, titrate in increments of 1 mg/kg/dose
until a satisfactory effect is achieved.
Contraindications: Documented hypersensitivity; hepatic
coma; anuria; state of severe electrolyte depletion.
Precautions: Perform frequent serum electrolyte, carbon
dioxide, glucose, creatinine, uric acid, calcium, and BUN
determinations during first few months of therapy and
periodically thereafter.
Torasemide is three times more potent and longer acting
than furosemide.

Amiloride (Midamor)
A pyrazine-carbonyl-guanidine unrelated chemically to
other known antikaliuretic or diuretic agents. Potassiumconserving (antikaliuretic) drug which, compared with
thiazide diuretics, possesses weak natriuretic, diuretic,
and antihypertensive activity.
Dose: Not established fully in pediatric practice.
Contraindications: Documented hypersensitivity; elevated
serum potassium levels (>5.5 mEq/L); impaired renal
function, acute or chronic renal insufficiency, and
evidence of diabetic nephropathy. Monitor electrolytes
closely if evidence of renal functional impairment is
present, BUN >30 mg/100 ml, or serum creatinine level
>1.5 mg/100 ml.
Precautions: Potassium retention associated with use of
an antikaliuretic agent accentuated in presence of renal
impairment and may result in rapid development of
hyperkalemia. Monitor serum potassium level. Mild
hyperkalemia usually not associated with abnormal ECG
findings.
Metolazone (Mykrox, Zaroxolyn)
Helps treat edema in congestive heart failure. Increases
excretion of sodium, water, potassium, and hydrogen
ions by inhibiting reabsorption of sodium in distal
tubules. May be more effective in those with impaired
renal function.
Dose: 5 to 20 mg/dose PO q24h.
Contraindications: Documented hypersensitivity; hepatic
coma or anuria.
Precautions: Caution in hepatic or renal disease, diabetes
mellitus, gout, or lupus erythematosus.
Mannitol (Osmitrol)
Inhibits tubular reabsorption of electrolytes by increasing
osmotic pressure of glomerular filtrate. Increases urinary
output.
Dose: mannitol (20%) 2 ml/kg every 6 hours for 2 days
or 0.5-3.0 g/kg/dose 8th hourly.
Contraindications: Documented hypersensitivity, anuria,
severe pulmonary congestion, progressive renal damage,
severe dehydration, active intracranial bleeding, and
progressive heart failure.
705
Precautions: Carefully evaluate cardiovascular status

before rapid administration because a sudden increase
in extracellular fluid may lead to fulminating CHF. Avoid
pseudoagglutination. When blood is given simultaneously, add at least 20 mEq of sodium chloride to each
liter of mannitol solution. Do not give electrolyte-free
mannitol solutions with blood.
Which Diuretics in Pediatrics and When to
Increase Dose
Diuretics should be initiated in patients who do not
respond to sodium restriction. A useful regimen is to start
with spironolactone. The addition of loop diuretics may
be necessary in some cases to increase the natriuretic
effect. If no response occurs after 4 to 5 days, the dosage
may be increased stepwise.
Duration of Diuretics Therapy
To treat: Diuretic therapy is continued till ascites.
To prevent: In certain conditions like cirrhosis effective
doses of diuretics have to continued for months to years,
to prevent reaccumulation of fluid.
Indications to Stop Diuretics
Encephalopathy
Serum sodium < 120 mmol/L despite fluid restriction.
Serum creatinine > 2.0 mg/dl.
Clinically significant complications of diuretics.
Hyperkalemia and metabolic acidosis (spironolactone).
Diuretic-Resistant Ascites
For ascites resistant to medical therapy treatment options
include:
Therapeutic paracentesis
LeVeen or Denver (peritoneovenous) shunt
Liver transplantation
Extracorporeal ultrafiltration of ascitic fluid with
reinfusion
Transjugular intrahepatic portosystemic stent shunt
-BLOCKERS (PROPRANOLOL)
Lowers portal pressure and inhibits renin secretion or
combination of these effects, results increased natriuresis.
706
SURGICAL
Transjugular Interahepatic Portal-Systemic
Stent-Shunt (TIPSS)
A TIPSS is a side-to-side portal-systemic shunt placed
by an interventional radiologist (Figs 13.22.8 and 13.22.9).
TIPSS is an efficacious treatment for patients with
refractory ascites. Survival may be better than in patients
treated with serial large-volume paracentesis. TIPSS is
associated with suppression of antinatriuretic systems,
and an improvement in renal function and renal response
to diuretics. Although the main indication for TIPSS
remains variceal bleeding refractory to endoscopic
therapy, the procedure reduces the activity of the RAAS
and increases natriuresis and GFR. Shunt dysfunction
and development of encephalopathy remain the major
concerns in this patient group.
Figure 13.22.9: TIPS shunt from hepatic vein to portal vein
Peritoneovenous Shunt
Peritoneovenous shunts (e.g. LeVeen [Fig. 13.22.10] or
Denver) have been shown to have poor long-term
patency. They are associated with excessive complications, including peritoneal fibrosis, and confer no
survival advantage relative to standard therapy. It should
be reserved for diuretic-resistant patients who are
candidates for neither liver transplantation nor serial
large-volume paracentesis (because of multiple surgical
scars or distance from a physician able to perform
paracentesis).
This is the ultimate treatment modality available for
refractory ascites in end stage liver disease. By replacing
Figure 13.22.10: Peritoneovenous (Le Veen) shunt
Figure 13.22.8: Liver explaint showing metal mesh of a TIPS
the cirrhotic liver, portal hypertension and its underlying

mechanisms of ascites are corrected. Ideally transplantation should be done before hepato-renal syndrome
sets in. Scarcity of facility and exorbitant costs are
currently the limiting factors in our country. A patient
with cirrhosis, the development of ascites refractory to
standard medical therapy is associated with an approximately 50 percent 6-month survival, and an approximately 25 percent 12-month survival.

Surgical Portosystemic Shunting
Portocaval shunt operation involves the anastomosis of
the portal vein and the inferior vena cava, consequently
reducing the portal pressure. The shunt also produces a
marked diuresis and natriuresis. However, despite
reported efficacy, surgical portosystemic shunts are
rarely used in the treatment of advanced cirrhotic ascites,
because of the high incidence of post-shunt encephalopathy. In addition, surgical shunts may cause technical
difficulties during subsequent orthotopic liver transplantation.
FOLLOW-UP
Further Inpatient Care
Patients can actually be maintained free of ascites if
sodium intake is limited to 10 mmol/dl.
Twenty-four hours urinary sodium measurements
are useful in patients with ascites related to portal
hypertension in order to assess the degree of sodium
avidity, monitor the response to diuretics, and assess
compliance with diet.
For grade 3 or 4 ascites, therpaeutic paracentesis may
be necessary intermittently.
At hospital its important to monitor body weight and
the intake and output of fluids. Fluid restriction is
only necessary if the serum sodium concentration
drops below 120 mmol per liter. It is also important
to determine the sodium balance which can be
approximated by monitoring intake (diet, sodium
containing medications and intravenous solutions)
and urinary excretion because, a negative sodium
balance is a predictor of weight loss.
A reasonable goal for a patient without peripheral
edema is a negative sodium balance with a weight
loss of 0.5 kg per day.
Response to therapy is indicated by the following parameters:
1. Optimal decrease in body weight is 0.5 to 1 percent
every 24 hours as compared to the previous days
weight. Weight loss more than this would be harmful
and indicates rapid shift of body fluids and calls for
immediate reduction of diuretic dose.
2. Relief of abdominal distention as evidenced by
improvement of distress and decreasing abdominal
girth.
Achieving a negative sodium balance (when the
patient is excreting more sodium than the intake)
707
indicates good diuretic response. Inadequate

sodium restriction is an important cause of
diuretic resistant ascites and can be suspected if
the patient does not lose weight and fluid despite
an appropriate natriuresis.
Further Outpatient Care
When a patient is responding to medical treatment,
hospitalization is not necessary.
The best method of assessing the effectiveness of
diuretic therapy is by monitoring body weight and
urinary sodium levels.
In general, the goal of diuretic treatment should be
to achieve weight loss of 300 to 500 g/dl in patients
without edema and 800 to 1000 g/dl in patients with
edema.
Once ascites has disappeared, diuretic treatment
should be adjusted to maintain the patient free of
ascites.
Body weight, orthostatic symptoms, and serum
electrolytes, urea and creatinine are monitored.
COMPLICATIONS OF ASCITES
Umbilical Hernia
Some patients may develop or may show an increase in
the size of already existent umbilical hernia. Most hernias
recur after surgical repair unless the ascites is controlled.
Hydrothorax
Pleural effusion, particularly on the right side can
develop in some patients with ascites. It occurs due to
passage of fluid through small holes in the diaphragm.
These effusions may be very large.
Spontaneous Bacterial Peritonitis
Diagnosis
A diagnosis of SBP is made when an ascitic fluid bacterial
culture is positive (e.g. Escherichia coli, Klebsiella
pneumoniae, or pneumococcus) with an elevated ascitic
fluid absolute polymorphonuclear leukocyte count >250
cells/mm3, and symptoms and/or signs consistent with
infection (temperature >100 degrees F, chills, abdominal
pain, rebound tenderness, reduced bowel sounds)
without an evident intra-abdominal and surgically
treatable source of infection. A missed or delayed
diagnosis of spontaneous bacterial peritonitis (SBP) could
708
potentially lead to sepsis and significant morbidity and

mortality.
Treatment
Patients with a definitive diagnosis or presumptive
diagnosis of SBP, should be treated with antibiotics.
Treatment should not be delayed in those with a
presumptive diagnosis until a positive culture is
obtained. Those with positive ascitic fluid cultures in the
absence of a neutrophil response should also be treated
with antibiotics, if symptoms and/or signs of infection
are present.
When treating empirically a broad spectrum, nonnephrotoxic, antibiotic is administered intravenously, e.g.
cefotaxime (third-generation cephalosporin).
In well-characterized patients with SBP a 5-day course
is as efficacious as a 10-day course of intravenous
antibiotics.
Lack of antibiotic-induced clinical improvement is an
indication for repeat diagnostic paracentesis. If the ascitic
fluid PMN leukocyte count is lower and the culture
negative, a further course of antibiotic is given. If the
ascitic fluid PMN leukocyte count is higher and culture
yields a new organism, a different antibiotic is chosen.
Alternatively, if reculture yields the same organism
secondary bacterial peritonitis is suspected.
Co-treatment with intravenous albumin, 1.5 g/kg at
the time of diagnosis and 1 g/kg on day 3, reduces the
incidence of renal impairment and improves survival.
Oral ofloxacin has been reported to be as efficacious
as intravenous cefotaxime in the treatment of patients
with SBP, who are not azotemic, vomiting or in shock.
However, until more data are available, an intravenous
antibiotic regimen is preferred.
Follow-up Paracentesis
Necessary only if there are atypical features (symptoms,
clinical setting, ascitic fluid analysis, organism(s),
response to therapy) suggestive of secondary peritonitis.
Prevention
Cirrhotic patients, with low ascitic fluid total protein
levels (< 1 g/dl) or gastrointestinal hemorrhage or those
who have recovered from an episode of SBP, are at high
risk of developing SBP and are candidates for long-term
prophylactic therapy with oral antibiotics.
Oral antibiotic primary prophylaxis, with norfloxacin,
ciprofloxacin or cotrimoxazole, appears to be effective
in preventing an initial episode of SBP or a recurrence of
SBP. The emergence of infections caused by bacteria
resistant to specific antibiotics is a potential problem.
Prognosis
Depends on the underlying disorder, the degree of
reversibility of a given disease process, and the response
to treatment.
Patient Education
The most important aspect of patient education is
determining when therapy is failing and recognizing the
need to see a physician. Unfortunately, in most cases,
liver failure has a dismal prognosis. All patients must be
taught which complications are potentially fatal and the
signs and symptoms that precede them. Abdominal
distention and/or pain despite maximal diuretic therapy
are common problems, and patients must realize the
importance of seeing a physician immediately.
Monitoring of the Patient
The treatment of ascites depends on its cause. In the
majority of patients, cirrhosis leading to portal hypertension is the major cause. A particular value of
recognizing portal hypertension as a cause of ascites is
that medical management using diuretics and salt
restriction is often effective in portal hypertensive
patients. Conversely, ascites due to peritoneal inflammation or malignancy alone does not respond to salt
restriction and diuretics.
Low Albumin Gradient Ascites
The prognosis in patients who develop SBP is so poor,
that liver transplantation should be considered in all
survivors of SBP.
These patients usually do not have portal hypertension

and do not respond to salt restriction and diuretics.
Patients with Tuberculous peritonitis are cured by
antituberculous therapy. Pancreatic ascites may resolve

spontaneously, require endoscopic stenting or operative
intervention or need somatostatin therapy. Lymph leak
usually resolves spontaneously or may require surgical
intervention or peritoneovenous shunting: Chlamydial
peritonitis requires tetracycline therapy. Nephrotic and
lupus ascites may require steroids. Malignant requires
surgical debulking and chemotherapy. Ascites may
respond to aggressive dialysis.
Urinary Sodium
Twenty-four hours urinary sodium measurement is a
helpful parameter. When patient has no urinary sodium
excretion despite diuretics, recommend an alternative
treatment-paracentesis.
REFRACTORY ASCITES
Definition
Defined as fluid overload that is non-responsive to
restriction of dietary sodium to 88 mmol/day and
maximal dose diuretic therapy (furosemide + spironolactone), in the absence of ingestion of prostaglandin
inhibitors, such as non-steroidal anti-inflammatory
drugs. Ascites is also considered to be refractory when
there is intolerance of diuretic therapy.
Indications of failure of diuretic therapy include
minimal or no weight loss, together with inadequate
urinary sodium excretion (< 78 mmol/day).
Less than 10 percent of patients with ascites
complicating cirrhosis meet the criteria of the definition
of refractory ascites.
Management
709
Advanced cirrhosis is associated with a hyperdynamic circulation characterized by reduced systemic

vascular resistance secondary to splanchnic vasodilatation, which leads to effective hypovolemia. Intense
activation of the renin-angiotensin-aldosterone system
(RAAS) and the sympathetic nervous system, and
nonosmotic release of vasopressin occur, with consequent renal hypoperfusion. This becomes more accentuated as patients progress from decompensated cirrhosis
to the hepatorenal syndrome (HRS).
In patients with no urinary sodium excretion and a
dietary intake of 88 mmol sodium daily, the required
frequency is about every two weeks. The frequency is
influenced by the degree of compliance with the low
sodium diet. The sodium content of ascitic fluid is about
130 mmol/L. Thus, a 6 L paracentesis removes 780 mmol
sodium. Patients, who ingest 88 mmol sodium per day
and excrete 10 mmol sodium in non-urinary losses and
no sodium in the urine, retain 78 mmol sodium per day.
Accordingly, a 6 L paracentesis removes the sodium
retained over a period of 10 days, and a 10 L paracentesis
removes the sodium retained over approximately 17
days.
Intravenous colloid replacement, e.g. albumin 6 to 8
g/L ascitic fluid removed is recommended immediately
following a large-volume paracentesis (>5 L), to minimize
intravascular hypovolemia, activation of vasoconstrictor
and antinatriuretic systems, and impairment of renal
function. Dextran 70 is less efficacious than albumin. If a
paracentesis is <5 L, colloid replacement appears to be
unnecessary.
Novel Treatments in Ascites
Atrial Natriuretic Peptide
Serial Large-Volume Paracentesis

Serial large-volume paracentesis (6-10 L) are safe and
effective in controlling refractory ascites.
Therapeutic paracentesis volume of fluid to be
tapped: Up to 100 ml/kg safely at any time. How
frequently one should tap: large volume tap is indicated
in one sitting then frequent taps.
Atrial natriuretic peptide (ANP) normally increases

glomerular filtration rate (GFR) and natriuresis. Patients
with advanced cirrhosis and ascites have a reduced
natriuretic response to ANP despite elevated levels.
Exogenous ANP administration, together with the
splanchnic vasoconstrictor terlipressin to counter the
hypotensive effect of ANP, increases renal blood flow,
GFR and natriuresis in patients with refractory ascites.
Mechanism of Relief by Paracentesis

Taking out fluid from peritoneal cavity decreases
systemic venous congestion, increases GFR and renal
plasma flow which helps in producing diuresis.
Other Agents
Although not tested specifically for refractory ascites, a
number of agents have been tried in humans which may
710
increase diuresis in cirrhotic patients with ascites. These

include the V2 receptor antagonist, OPC-3126, Niravoline,
a k-opioid antagonist, and the adenosine-1-receptor
antagonist FK352. Future studies using these novel
agents may provide further information regarding their
efficacy in refractory ascites.
CHYLOUS ASCITES
Turbid, milky or creamy peritoneal fluid due to the
presence of thoracic or intestinal lymph having
triglyceride (fat) concentration of more than 1000 mg/
dl. If patient has nothing by mouth, then milky color will
fade and the fluid will look like transudate with
predominance of lymphocytes (85%).
Causes
Congenital anomaly of lymphatics lymphangiectasis,
obstruction of duct within its abdominal portion from
trauma, tumor, large lymph nodes, rupture of major
lymphatic channel, tuberculosis, filariasis, nephrotic
syndrome, cirrhosis, rheumatoid arthritis, other serositis.
PSEUDOCHYLOUS ASCITES
In chronic peritonitis/persistent ascites fluid have some
what similar color, from the degeneration of inflammatory products (leukocytes/tumor cell), and may be
confused with chylous fluid (Table 13.22.5).
Management
a. Dietary:
i. Low fat diet - containing medium chain triglycerides, because these are absorbed directly into
the portal circulation.
ii. High protein diet, and
iii. Parenteral nutrition supplementation.
b. Paracentesis
TABLE 13.22.5: Difference between true and
pseudochylous fluid
True chylous fluid
Pseudochylous fluid
1. Ether test- top thick layers

becomes clear fluid
Turbidity is unchanged
2. Alkali test- no change in color
Becomes clear (dissolves

cellular protein)
3. Fat globules stained by Sudan
Not stained
Duration of treatment may require several months

for effective medical management.
Surgical approach abdominal exploration to detect
the site of the leak.
Monitoring during Diuretic Therapy
The main concern during diuretic therapy is whether
there is too rapid fluid mobilization and diuretic induced
complications.
In OPD settings the patient needs to be assessed after
1 week of starting therapy and thereafter every 2 weeks.
At each visit compliance for low sodium diet, bed rest
and diuretic doses should be ascertained. Examination
for changes in weight, abdominal girth, pedal edema,
ascitic grading and subtle signs of spontaneous bacterial
peritonitis should be done. Weight loss of more than 1
percent per day or 4 to 6 percent per week of the previous
weight would indicate too rapid fluid mobilization and
natriuresis. This cautions us to evaluate renal functions
along with reduction in the dose of diuretics.
Evaluation of serum Na, K, blood urea and creatinine
and liver function tests would be useful in assessing
diuretic response and its attendant complications. Serial
measurement of fractional excretion of sodium is an
objective measure of the effectiveness of the diuretic
response. This requires simultaneous estimation of serum
and spot urinary sodium and creatinine concentrations.
At the earliest suspicion of spontaneous bacterial
peritonitis, an ascitic tap should be performed and
antibiotic therapy instituted. Admitted patients are
usually those who have resistant ascites or have
developed diuretic induced complications. Thus their
monitoring is more intense and repeated every 48 hours.
SUMMARY
The circulatory disturbances seen in advanced cirrhosis
lead to the development of ascites, which can become
refractory to diet and medical therapy. These abnormalities may progress and cause a functional renal failure
known as the hepatorenal syndrome. Management of
refractory ascites and hepatorenal syndrome is a
therapeutic challenge, and if appropriate, liver transplantation remains the best treatment. New therapeutic
options have recently appeared, including the transjugular intrahepatic portosystemic shunt and selective
splanchnic vasoconstrictor agents, which may improve
renal function and act as a bridge to transplantation.

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synthase activity in the splanchnic vasculature of patients
with cirrhosis: relationship with hemodynamic disturbances. J Hepatol 2001;35(4):452-6.
2. Arrovo V, Esptein M, Gallus G et al. Refractory ascites
in cirrhosis. Mechanism and treatment. Gastroenterology
1989;2:195.
3. Arroyo V, Gines P, Gerbes AL, Dudley FJ, Gentilini P,
Laffi G, Reynolds TB, Larsen HR, Scholmerich J.
Definition and diagnostic criteria of refractory ascites and
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4. Bernadi M, Santini C, Trevisani F. Renal function
impairment induced by change of posture in patients
with cirrhosis and ascites. Gut 1985;26:629-35.
5. Cardenas A, Bataller R, Arroyo V. Mechanisms of ascites
formation. Clin Liver Dis 2000;4(2):447-65.
6. Casado M, Bosch J, Garcia-Pagan JC et al. Clinical events
after transjugular intrahepatic portosystemic shunt:
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7. DAmico G, Luca A, Morabito A, Miraglia R, DAmico
M. Uncovered transjugular intrahepatic portosystemic
shunt for refractory ascites: a meta-analysis. Gastroenterology. 2005;129(4):1282-93.
8. DAmico G, Morabito A, Pagliaro L, Marublni E. Survival
and prognostic indicators in compensated and decompensated cirrhosis. Dig Dis Sci 1986;31:468-75.
9. Diseases of the peritoneum, mesentery and omentum.
In Wynngaarden JB, Smith LH, Bennet JC (Eds): Cecil
Textbook of Medicine, 20th edition. W B Saunders ny,
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10. Garcia-Tsao G. Current management of the complications of cirrhosis and portal hypertension: variceal
hemorrhage, ascites, and spontaneous bacterial peritonitis. Gastroenterology 2001;120(3):726-48.
11. Gerbes AL. Medical treatment of ascites in cirrhosis. J
Hepatol 1993;17(suppl):S4-S9.
12. Gines P, Cardenas A, Arroyo V, Rodes J. management
of cirrhosis and ascites. N Engl J Med 2004;350:1646-54.
13. Hardikar W. Ascites and encephalopathy in chronic liver
disease. Indian J Ped 2002;69:169-73.
14. Hardy SC, Kleinman RE. In Erederick JS (Eds): Cirrhosis
and Chronic Live Failure in Liver Diseases in Children
(1st edn) Mosby 1994;229-30.
15. Heneghan MA, Harrison PM. Pathogenesis of ascites in
cirrhosis and portal hypertension. Med Sci Monit
2000;6(4):807-16.
16. Idem. Low protein concentration ascitic fluid is
predisposed to spontaneous bacterial peritonitis.
Gastroenterology 1986;91:1343-46.
17. Inturri P, Graziotto A, Rossaro L. Treatment of ascites:
old and new remedies. Dig Dis 1996;14:145-56.
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18. Jeffery J, Murphy MJ. Ascitic fluid analysis: the role of

biochemistry and haematology. Hlsp Med 2001;
62(5):282-86.
19. Levy M. Pathophysiology of ascites formation. In: Epstein
M (Ed): The Kidney in Liver Disease, 3rd edn. Williams
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20. Lieberman FL, Denison EK, Reynolds TB. The
relation-ship of plasma volume, portal hypertension,
ascites and renal sodium retention in cirrhosis: the
overflow theory of ascites formation. Ann NY Acad Sci
1970;170:202-12.
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23. McVay PA, Toy PTCY. Lack of increased bleeding after
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24. Pare P, Talbot J, Hoefs JC. Serum ascites albumin
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27. Rector WG Jr, Reynolds TB. Superiority of the serumascites albumin difference over the ascites total protein
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14.1 Renal Anatomy and Physiology: Arvind Bagga ................................................................................................................................. 714

14.2 Diagnostic Evaluation: RN Srivastava, Aditi Sinha ............................................................................................................................. 715
14.3 Imaging of the Urinary Tract: Arvind Bagga, Aditi Sinha ................................................................................................................... 719
14.4 Developmental Anomalies: M Vijayakumar ........................................................................................................................................ 722
14.5 Acute Proliferative Glomerulonephritis: BR Nammalwar, T Vasanthi, M Vijayakumar ................................................................... 724
14.6 Renal Vasculitis: BR Nammalwar, N Prahlad ...................................................................................................................................... 729
14.7 Acute Renal Failure: Arvind Bagga, Aditi Sinha .................................................................................................................................. 737
14.8 Nephrotic Syndrome: RN Srivastava, Arvind Bagga ........................................................................................................................... 743
14.9 Urinary Tract Infection, Vesicoureteric Reflux and Reflux Nephropathy: M Vijayakumar, RN Srivastava ................................... 750
14.10 Obstructive Uropathy: Kumud P Mehta .............................................................................................................................................. 754
14.11 Disorders of Micturition: Kumud P Mehta .......................................................................................................................................... 755
14.12 Chronic Kidney Disease: KD Phadke, Pankaj Hari ............................................................................................................................ 757
14.13 Hypertension: Kumud P Mehta ............................................................................................................................................................ 761
14.14 Renal Tubular Disorders: Aditi Sinha, Arvind Bagga .......................................................................................................................... 763
714
14.1 Renal Anatomy and Physiology

Arvind Bagga
INTRODUCTION
The kidneys are situated retroperitoneally on each side
of the vertebral column. On cut surface, the pale outer
cortex and a dark, inner medulla can be easily distinguished. The medulla consists of 8 to 18 conical masses,
the pyramids. The base of a pyramid is at the corticomedullary junction and the apex towards the renal
pelvis forming a papilla. Each papilla contains 10 to 25
small openings that represent the distal ends of the
collecting ducts.
Kidneys receive 20-25 percent of the cardiac output.
While its chief functions are glomerular filtration, tubular
reabsorption and tubular secretion, the kidneys also play
an important role in vitamin D metabolism, hematopoiesis and blood pressure control.
The Nephron
Each kidney contains about one million nephrons, the
functional units. A nephron consists of a glomerulus,
proximal tubule, the thin limbs, the distal tubule and the
collecting segment. The glomerulus is made up of a tuft
of capillaries and a central region of mesangium
containing cells and matrix. The capillaries arise from
an afferent arteriole and eventually join to form an
efferent arteriole. The glomerulus is surrounded by the
Bowmans capsule lined by the parietal epithelium,
which is continuous with the visceral epithelium at the
vascular pole. The Bowmans capsule leads into the
proximal tubule.
The early part of the distal tubule on its ascent from
the medulla comes in contact with the afferent arteriole of
the glomerulus. The smooth muscle cells of the afferent
arterioles have renin containing cytoplasmic granules. The
juxtaglomerular apparatus (JGA) is composed of the
afferent and efferent arterioles, and specialized cells of the
distal tubule, the macula densa. The JGA is involved in
systemic blood pressure regulation, electrolyte homeostasis and tubuloglomerular feedback mechanisms.
Glomerular Filtration
The glomerular capillary hydrostatic pressure forces a
virtually protein free filtrate into the Bowmans space.
Crystalloids and low molecular weight substances such

as urea, glucose and amino acids are freely filtered. The
glomerular filter, composed of endothelial cells, the
glomerular basement membrane and the slit diaphragm
of the podocytes, restricts the filtration of protein
molecules.
The glomerular filtrate has almost the same composition as that of plasma. The normal glomerular filtration
rate (GFR) is about 100 to 125 ml/min/1.73 m2. The GFR
is determined by the degree of constriction of afferent
and efferent arterioles, and plasma colloid osmotic
pressure. Angiotensin II increases the GFR by a
preferential constriction of the efferent arteriole.
Autoregulation is the phenomenon where the GFR is
maintained despite fluctuations in systemic arterial
pressure. This is mediated through tubuloglomerular
feedback, where a marked fall in GFR results in excessive
reabsorption of Na+ and Cl- in the ascending loop of
Henle, reducing their concentrations at the macula densa,
which leads to renin release by the juxtaglomerular cells,
increased angiotensin II formation, constriction of
efferent arterioles and increase in the GFR.
Tubular Reabsorption
The proximal tubule reabsorbs about 65 percent of the
filtrate. The descending limb of Henle is the site of simple
diffusion of substances. The thick ascending limb of
Henle and the early distal tubule are almost impermeable
to both water and urea, but important for absorption of
sodium, potassium and chloride. This differential
permeability results in accumulation of sodium in the
medullary interstitium, which creates the hypertonicity
necessary for urinary concentration. The latter part of
distal tubule is involved in aldosterone controlled sodium
reabsorption and potassium secretion. The late distal
tubule and the cortical collecting duct contain specialized
cells, which actively secrete hydrogen ions against a steep
concentration gradient, necessary for maximum urinary
acidification. The small amounts of proteins that are
filtered through the glomerular barrier are normally
totally reabsorbed in the proximal tubule by pinocytosis.
Under usual circumstances, 65 percent of the
glomerular filtrate water is reabsorbed in the proximal
Diseases of Kidney and Urinary Tract

tubule, 15 percent in the loop of Henle, 10 percent in the
distal tubule and 9 percent in the collecting duct. Only 1
percent of glomerular filtrate water is excreted as urine.
Urinary Acidification
The role of the kidney is to stabilize plasma bicarbonate
at a level of 22 to 25 mEq/l. The filtered bicarbonate is
largely (80-85%) reabsorbed in the proximal tubule.
Maximum urinary acidification is achieved distally,
through excretion of titratable acid and ammonia.
Filtered sodium is exchanged for hydrogen ion along the
entire length of the nephron. Titratable acid is formed
by the buffering of hydrogen ions by phosphate in the
tubular fluid. Ammonia formed within the proximal
tubular cells diffuses into the lumen where it combines
with hydrogen ion to form ammonium ions. During
states of acidosis, the urine pH can be lowered to between
5.2 and 5.5.
Urinary Concentration
The tonicity of the body fluid is maintained constant
between 280 to 290 mOsm/kg. Expansion of intravascular volume causes activation of stretch sensors in
the atria, leading to an increase in atrial natriuretic
peptide. Sodium and water diuresis follows. An increase
in blood osmolality, on the other hand, is sensed by
osmoreceptors leading to increased ADH secretion. ADH
increases the permeability of water in the collecting ducts
through the insertion of aquaporins (water channels) that
allow passage of water from the lumen to the hyper-
715
osmotic interstitium. In the absence of ADH, the

collecting ducts are impermeable to the passage of water
and dilute urine is passed. During maximum urinary
concentration, the urinary osmolality may rise to 10001200 mOsm/kg.
Renal Function in the Newborn
Renal function in an infant is subnormal by adult
standards, especially in premature neonates, which puts
them at high risk of developing acute renal failure.
Glomerular filtration begins between 9 to 12 weeks of
gestation, initiating formation of urine and contributing
to accumulation of amniotic fluid. The GFR is low at birth
(10-20 ml/min/1.73 m2 in the first 3 days) but increases
rapidly to 75-80 ml/min/1.73 m2 by 8 weeks. The serum
creatinine level is high at birth, reflecting the maternal
value but falls to 0.4 mg/dl by the end of 2 weeks. Sodium
reabsorption is low; around 1 to 3 percent of the filtered
load is excreted. There is also limited bicarbonate
reabsorption and hydrogen ion excretion. Therefore, the
pH of urine of a newborn is inappropriately high for the
degree of acidemia.
BIBLIOGRAPHY
1. Kriz W, Elgar M. Renal anatomy. In: Johnson RJ, Feehaly
J (Eds): Comprehensive Clinical Nephrology. London:
Mosby 2000;1.1-1.10.
2. Srivastava RN, Bagga A. Renal anatomy and physiology.
In: Srivastava RN, Bagga A (Eds): Pediatric Nephrology,
4th edn. New Delhi: Jaypee Brothers 2005;1-19.
14.2 Diagnostic Evaluation

RN Srivastava, Aditi Sinha
There are only a few specific manifestations of renal
diseases in infants and children, whereas other features
are subtle and do not lead to a suspicion of a renal
disorder. Renal disease should be suspected in patients
with failure to thrive, unexplained fever, obscure anemia,
dyselectrolytemia and refractory rickets. A family history
of a renal disease should always be obtained.
Clinical Features of Renal Disease

Hematuria
The urine color may vary from frank red to shades of
brown, described as tea or cola-colored. A small quantity
of blood (1 mL in 1000 mL urine) is enough to make the
urine appear red; hematuria must be confirmed on urine
716
microscopy. In the absence of gross hematuria, the

persistent finding of hematuria (more than 5 red cells
per high power field) in at least two of three urinalyses,
performed over 2-3 weeks, warrants further evaluation.
Hematuria should be distinguished from other causes
of red urine, including hemoglobinuria, methemoglobinuria, urates and ingestion of rifampicin, red dyes or
beet. A brown discoloration of urine may be caused by
myoglobinuria, porphyria and alkaptonuria.
Blood in the initial urine suggests urethral origin
while terminal hematuria indicates bladder origin. If
hematuria is uniform throughout micturition, then gross
hematuria is most often due to a renal cause, e.g.
glomerulonephritis (GN). Hematuria may be glomerular
or extraglomerular in origin; distinguishing features are
listed in Table 14.2.1. Important causes of hematuria in
the newborn include renal vein thrombosis, renal artery
thrombosis, bleeding and clotting disorders, trauma due
to bladder catheterization, urinary tract infection,
autosomal recessive polycystic kidney disease and
obstructive uropathy.
Important causes of hematuria are listed in Table
14.2.2, and a protocol for evaluation in Figure 14.2.1.
Edema
Glomerulonephritis characteristically manifests with
facial puffiness and gross hematuria. Edema is turgid
and does not pit readily on pressure. In nephrotic
syndrome, edema develops insidiously, starting with
puffiness around the eyes and then involving the feet
and legs. Edema is soft and easily pits on pressure.
Abnormalities of Micturition
In a male infant, a poor urinary stream, especially in the
presence of a full bladder, suggests obstruction, most
TABLE 14.2.2 Causes of glomerular and

non-glomerular hematuria
Glomerular diseases
Non-glomerular causes
Acute postinfectious GN
Nephrolithiasis*
IgA nephropathy*
Hypercalciuria*
Benign familial hematuria*
Viral cystitis
Systemic infections
(malaria, leptospirosis,
infective endocarditis)
Membranoproliferative GN
Renal vein/artery thrombosis, AV

malformations
Focal segmental
glomerulosclerosis
Trauma, tumors*, exercise
Systemic lupus
erythematosus
Bleeding or clotting abnormality
Hydronephrosis
Henoch-Schonlein purpura
Renal cystic disease
Alports syndrome*
Medications: NSAIDs, anticoagulants, ritonavir, indinavir, cyclophosphamide
Goodpasture disease
Tuberculosis*
GN glomerulonephritis; NSAIDs non-steroidal anti-inflammatory

drugs
*Causes of recurrent hematuria; Hematuria with familial
association
commonly due to posterior urethral valve. Persistent

dribbling of urine indicates abnormal ureteric insertion
distal to the bladder neck. In all infants with meningomyelocele, a detailed evaluation should be done to detect
bladder dysfunction. Crying during micturition and
straining suggest obstruction. Retention of urine may be
due to neurogenic bladder or obstruction by stone or
tumor.
TABLE 14.2.1: Features distinguishing glomerular hematuria from non-glomerular hematuria

Features
Glomerular hematuria
Non-glomerular causes
Systemic complaints
Edema, oliguria, hypertension, rash,

arthralgia, fever
Fever, abdominal pain, dysuria, abdominal mass
Family history
Deafness, renal disease (Alport syndrome) Renal stones, cystic kidneys
Urine color, clots
Brown, tea/cola colored
Bright red, clots may be present
Proteinuria
2+ or more
Less than 2+
Dysmorphic red cells
More than 20%
Not common; less than 15%
RBC casts
Common
Absent
Crystals
Absent
Positive in few
717
Figure 14.2.1: Patients with isolated hematuria should be evaluated to distinguish glomerular from extra-glomerular hematuria.
Subsequent evaluation is tailored to the likely cause. RBC red blood cells; hpf high power field; C3 complement factor 3, ASO
antistreptolysin O; ANA antinuclear antibody; anti-dsDNA anti-double stranded DNA antibody; ANCA antineutrophil cytoplasmic
antibody
Oliguria
Polyuria
Anuria is no passage of urine. Oliguria is passage of

insufficient volume of urine, defined as < 500 ml/day/
1.73 m2 or < 0.5 ml/kg/hour. Decreased urine output is
an important feature of renal disease. A cause such as
gastroenteritis or other conditions that lead to prerenal
type of acute renal failure may be present. Oliguria is an
important feature of moderate or severe glomerulonephritis and other conditions causing serious glomerular injury, like hemolytic uremic syndrome.
Polyuria is passage of excessive amount of urine, 5-6 ml/

kg/hour or more. Impairment of urinary concentration
is a feature of obstructive uropathy and disorders
characterized by tubulointerstitial lesions, e.g. nephronophthisis. In infants, these symptoms are often not
noticed. A diagnosis of nephrogenic diabetes insipidus
is rarely made until complications develop. Conditions
causing persistent hypokalemia (distal renal tubular
acidosis) also result in polyuria.
718
Enuresis
In most children with nocturnal enuresis, there is no
evidence of renal disease. It is a benign and self-limiting
condition, usually remediable with patient education and
bladder training. Increased frequency or polyuria may
be due to urinary infections, bladder instability or
polyuria.
Other Features
Presence of dysuria, flank pain and cloudy urine suggest
urinary tract infections. Tenderness in the renal angle
and fever indicate pyelonephritis. Features suggestive
of chronic kidney disease include hypertension, growth
retardation and normocytic normochromic anemia.
Presence of palpable kidney/s suggests multicystic
dysplastic kidney, polycystic kidney disease and Wilms
tumor.
Laboratory Examination
Urine Examination
Careful examination, preferably of the first morning
urine is preferred. A midstream specimen is generally
adequate. In infants, a specimen obtained by suprapubic
bladder aspiration or transurethral catheterization is
preferred for culture. The urine specimen should be fresh
and relatively concentrated (appearing yellow). Formed
elements quickly disintegrate in dilute urine. If
processing is likely to be delayed, the sample may be
stored at 4C.
Urinary protein is measured with heat precipitation
method or with sulfosalicylic acid. The turbidity can be
graded from nil to 4+; 3+ or more indicates heavy
proteinuria. Proteinuria is always abnormal and a cause
should be looked for. Assessment of specific gravity is
required in patients with suspected defects in urine
concentration. Estimation of urine pH is useful in patients
with suspected renal tubular acidosis. Composite
dipsticks are available for urine pH, glucose, protein,
blood, leukocyte esterase and nitrite.
Microscopic examination: A fresh, centrifuged specimen
should be examined. Red cell casts indicate glomerular
inflammation. Clumping of neutrophils (white cell casts)
suggests acute pyelonephritis. Leukocytes may be absent,
despite significant bacteriuria. Red blood cells and
leukocytes can be counted under high power field (HPF)
and more accurately in a counting chamber. Normally,

1 to 2 of either of these may be seen per HPF in midstream
urine. More than 5 neutrophils/HPF with bacteriuria
suggests urinary tract infection. More than 5 red cells/
HPF in a centrifuged specimen is abnormal. Phase
contrast microscopy is helpful to examine red cell
morphology, casts and crystals.
Because of difficulties in accurately collecting 24-hr
specimens of urine, this is resorted to when definitely
needed (e.g. quantitative measurement of calcium,
phosphate, creatinine, magnesium, oxalate) for the
diagnosis of specific conditions and clearance studies.
In nephrotic syndrome and various forms of GN,
semiquantitative tests for protein or protein/creatinine
ratio in spot urine samples are sufficient.
Blood Tests
The normal level of blood urea ranges between 20 and
40 mg/dl. Various factors that reduce renal perfusion,
cause a reversible increase in blood urea levels. The levels
are also increased in excessive tissue breakdown, trauma,
gastrointestinal bleeding and use of corticosteroids and
tetracycline. Urea levels may be low in presence of
hepatic failure and on a low protein diet.
The level of serum creatinine varies inversely with
the glomerular filtration rate (GFR) of which it is a better
indicator than blood urea. Serum creatinine is not readily
affected by prerenal factors. However, serum creatinine
depends on muscle mass and may overestimate GFR in
presence of malnutrition. Hyperbilirubinemia (bilirubin
level > 5 mg/dl) interferes with the measurement of
creatinine. GFR may be estimated in children as follows:
height (in cm)
Glomerular filtration rate = k _______________________
serum creatinine
(mg/dL)
where, k = 0.33 for preterm infants; 0.45 for children
< 2-yr-old; 0.55 for older children.
Serum albumin is reduced in patients with nephrotic
syndrome proteinuria, occasionally below 1.5 g/dL. In
children with nephrotic syndrome, hypercholesterolemia
is typically present.
The levels of complement factor 3 (C3) in blood are
reduced in postinfectious GN, membranoproliferative
GN and lupus nephritis. In systemic lupus erythematosus
(SLE), C3 levels reflect disease activity; the normal range
is between 70 and 120 mg/dL.

Antinuclear antibodies (ANA) are antibodies directed
against chromatin associated or ribonucleoprotein
particles. They are not specific and may be increased in
many autoimmune diseases like SLE, juvenile rheumatoid arthritis, polyarteritis nodosa and autoimmune
hepatitis. Antibodies to double standed DNA (antidsDNA) is specific to SLE, while increased titer of
antineutrophil cytoplasmic antibody (ANCA) is seen in
a group of small vessel vasculitis, including microscopic
polyangiitis, Wegeners granulomatosis and renal limited
vasculitis.
Imaging Studies
The role of radiological and radionuclide imaging
techniques in discussed in Section 14.3.
Renal Biopsy
A renal biopsy is not necessary in uncomplicated cases
of poststreptococcal GN and corticosteroid responsive
nephrotic syndrome. Indications for kidney biopsy are
listed under specific conditions. The procedure must be
performed early in case of rapidly progressive glomerulonephritis, suspected SLE nephritis and renal vasculitis,
where early institution of specific therapy may improve
outcome.
719
The availability of disposable Tru-Cut needle and

biopsy gun has improved the yield of the procedure, with
relatively less risks. Prior to biopsy, a normal coagulation
profile and normal blood pressure must be ensured to
reduce the risk of bleeding. Patients with marked
azotemia should be dialyzed and receive intranasal
desmopressin 30-60 minutes prior to the procedure. The
renal histology is examined by light microscopy and
immunofluorescence. Electron microscopic examination
is useful for precise diagnosis of Alport syndrome,
membranoproliferative GN and thin glomerular
basement membrane disease.
BIBLIOGRAPHY
1.
David I. Clinical and laboratory evaluation of renal

function, 2nd edn. In: Edelmann CM, (Ed): Pediatric
Kidney Disease 2000;461-74.
2. Endre SK. Acute proliferative glomerulonephritis. In:
Avner ED, Harmon WE, Niaudet P, (Eds): Pediatric
Nephrology, 5th edn. 2004;543-56.
3. Indian Pediatric Nephrology Group, Indian Academy
of Pediatrics. Consensus statement on evaluation of
hematuria. Indian Pediatr 2006;43:965-73.
4. Srivastava RN, Bagga A. Diagnostic evaluation. In:
Srivastava RN, Bagga A, (Eds): Pediatric Nephrology,
4th edn. New Delhi: Jaypee Brothers 2005;58-69.
14.3 Imaging of the Urinary Tract

In the last thirty years the field of diagnostic imaging
has grown tremendously with a multitude of imaging
techniques available to the treating physicians. In view
of the considerable radiation exposure associated with
the use of radiocontrast agents, the use of radionuclide
procedures is preferred, wherever feasible. The indications for these investigations are discussed.
Plain X-ray of the Abdomen
A plain X-ray film of abdomen has a role in the detection
of small renal calculi and ureteric calculi without
proximal ureteral dilatation. It is also important for
evaluation of the spine in children with neurogenic
bladder, evaluating metastatic bone disease secondary

to malignancies and for changes of renal osteodystrophy.
Intravenous Pyelography (IVP)
The use of intravenous pyelography (IVP) (excretory
urography) has declined due to the advent of ultrasonography and radionuclide studies. IVP requires bowel
preparation and administration of an ionic contrast
(urograffin, 3-4 ml/kg) with films taken at 1-5 minutes,
10-15 minutes and a late pelvic film for the bladder.
Hydration is necessary to avoid contrast nephropathy.
The test should be avoided in neonates, since they do
not show adequate urinary concentration of the contrast.
720
Figure 14.3.1: Micturating cystourethrogram showing bilateral

grade V vesicoureteric reflux in a 3-yr-old boy with recurrent
urinary tract infections. The urethra is not visualized
Figure 14.3.2: Ultrasound study in a 6-yr-old boy showing

hydronephrosis; note enlarged kidney and dilated renal pelvis
Current indications for IVP include detailed evaluation

of structural anomalies, e.g. duplex kidneys and
horseshoe kidneys, and for ureteric calculi.
Micturating Cystourethrogram (MCU)
The MCU is an important procedure, necessary for
diagnosis and grading of vesicoureteric reflux (Fig.
14.3.1), and detection of abnormalities of bladder and
urethra. The contrast agent is introduced into the bladder
through a catheter; films are taken while the child is
voiding. Strict aseptic precautions should be observed
during the procedure. The IVP and MCU involve
considerable radiation exposure to the patient.
Ultrasonography
Ultrasound evaluation gives excellent information about
anatomical aspects. It is ideally suited for children since
it is painless and requires no sedation or administration
of a contrast agent. It can be carried out even at bedside,
and repeated as often as required. Ultrasound guidance
can be used in intervention procedures, e.g. for biopsy
or fine needle aspiration. Its major limitation is that it is
operator dependent. Considerable experience is required
for interpretation of findings in small children (Figs 14.3.2
and 14.3.3).
Change in the renal cortical echotexture and its
comparison with liver, spleen and renal medulla gives
non-specific information about the presence of renal
Figure 14.3.3: Ultrasonography showing dense medullary

nephrocalcinosis in a patient with hyperoxaluria
parenchymal disease. Measurement of renal size helps

assess its growth. Doppler evaluation is useful for
assessment of blood flow in major vessels.
Antenatal Ultrasound
Abnormalities routinely picked up during antenatal
ultrasonography include hydronephrosis, multicystic
kidney and enlarged bladder with posterior urethral
valves. Particular attention is directed towards the
amount of amniotic fluid, anteroposterior diameter of
renal pelvis and pelviectasis, renal echotexture,
appearance of the ureters and urinary bladder. A
distended bladder with bilateral hydronephrosis

suggests distal urinary tract obstruction as seen with
posterior urethral valves, while unilateral hydronephrosis with normal ureters and bladder suggests pelviureteric junction obstruction.
Computerized Tomography (CT)
CT gives excellent anatomical details and is especially
useful in evaluating abdominal or pelvic masses (e.g.
tumors or abscess). Non-contrast helical CT scans are
currently the most sensitive and specific technique for
detecting renal calculi. When used with contrast, CT can
detect a non-functioning or poorly functioning kidney.
The disadvantages are radiation exposure, the need for
sedation in young children and risks of contrast
nephropathy.
Radionuclide Imaging
Radionuclide methods are replacing conventional
radiocontrast studies such as IVP and renal angiography. Radionuclide procedures are noninvasive, highly
sensitive and expose the patient to a smaller amount of
radiation. They can be used to assess differential renal
function, evaluate kidneys even in advanced dysfunction, assess renal perfusion, identify cortical scars and
intrarenal masses and upper urinary dilatation.
The radionuclide techniques include: (i) renal
perfusion study (renography), (ii) renal static imaging,
(iii) clearance studies, and (iv) radionuclide cystography.
Renography
Renography monitors the arrival, uptake and elimination of a radiopharmaceutical by the kidney. 99mTc
labeled diethylenetriamine-penta-acetic acid (DTPA),
mercaptotriacetylglycine (MAG-3) and LL-ethylene
cysteine dimer (LL-EC) are commonly used agents.
DTPA is a purely glomerular agent, excreted by
glomerular filtration; MAG-3 and LL-EC are excreted by
glomerular filtration and tubular secretion.
A normal renogram has three phases: (i) a rapid rise
and fall, due to first pass perfusion, (ii) slow rise to a
peak due to arrival of the agent into the kidney, and (iii)
declining amplitude due to excretion (Fig. 14.3.4). The
peak of the curve depends on renal blood flow, renal
function, tubular transit and excretion. Therefore, the
peak is delayed in renal artery stenosis, renal parenchymal disease, low urine flow rate or an obstructive
process. Renal dynamic scans are useful in identification
721
of pelviureteric junction obstruction, evaluation of

differential and total renal function, assessment of
allograft function and perfusion, and diagnosis of
renovascular hypertension.
A diuresis renogram in which frusemide is used to
cause rapid diuresis, helps to differentiate obstructive
dilatation from nonobstructive dilatation of the upper
urinary tract. In the latter, there is a prompt clearing of
the radionuclide following an injection of frusemide. In
captopril renogram, administration of captopril temporarily reduces the renal blood flow and GFR, thereby
facilitating the diagnosis of renal arterial stenosis.
Renal Static Imaging
Renal static imaging gives a two-dimensional depiction
of the concentration and distribution of the radio-nuclide. The quality of renal images with 99mTc labeled
dimercaptosuccinic acid (DMSA) and glucoheptonate
(GHA) is excellent. 99mTc DTPA is an excellent agent for
visualizing the pelvicalyceal collecting system and
ureters. DMSA attains a high level of concentration in
renal cortex with a slow rate of urinary excretion and is
therefore particularly useful for demonstration and
monitoring of renal scarring (Fig. 14.3.4), identifying
ectopic kidneys and in detecting damage to kidneys and
recovery from trauma. GHA is filtered, partially
reabsorbed and retained in proximal tubular cells; GHA
imaging is useful when abnormalities in both the cortex
and collecting system need to be evaluated.
Clearance Studies
Radionuclide clearance studies can accurately assess
individual kidney function. Labeled chelating agents like
51Cr-ethylenediamine-tetra-acetic acid (EDTA) and 99mTc
Figures 14.3.4A and B: DTPA scintigraphy showing (A) normal

concentration and excretion of the radiolabeled agent through
both kidneys; (B) delayed image shows clearing of the radionuclide from both kidneys and its presence in urinary bladder
722
DTPA are used for estimation of GFR. 131I orthoiodohippurate is used for determination of effective renal
plasma flow.
Direct Radionuclide Cystogram
The diagnosis of vesicoureteric reflux and its grading is
made on radiocontrast MCU. However, radionuclide
cystography is more reliable and sensitive for detecting
VUR. The radiation dose to the patient is greatly reduced,
allowing repeated follow-up examinations. DRCG can
be done by instilling the radionuclide through a urethral
catheter or its direct injection into the bladder. Thereafter,
the patient is asked to void and rapid sequence images
of the urinary bladder are obtained during voiding. These
provide a visual representation of the rate of bladder
emptying, residual urine volume and evidence of VUR.
renal stones not diagnosed by ultrasonography, noncontrast helical CT is more useful than IVP or plain
X-ray. A MCU is necessary for the detection and grading
of vesicoureteric reflux and posterior urethral valves. For
follow-up evaluation of vesicoureteric reflux, direct
radionuclide cystography is satisfactory. DTPA scintigraphy is useful for assessment of differential kidney
function, detection of pelviureteric junction obstruction
and in allograft dysfunction. DMSA scintigraphy is the
most sensitive technique to detect renal cortical scarring.
BIBLIOGRAPHY
1. Bal CS, Kumar A. Radionuclide imaging. In: Srivastava
RN, Bagga A (Eds). Pediatric Nephrology, 4th edn.
Jaypee Brothers, New Delhi 2005;1-19.
2. Carty H, Wright N. Imaging in pediatric nephrology. In:
Webb N, Postlethwaite R (Eds): Clinical Pediatric
Nephrology, 3rd edn. Oxford University Press, Oxford
2003;113-34.
3. Gupta AK. Imaging of the urinary tract. In: Srivastava
RN, Bagga A (Eds): Pediatric Nephrology, 4th edn.
Jaypee Brothers, New Delhi 2005;30-44.
Clinical Applications
Ultrasound is the initial imaging in most patients with
suspected renal disease. It is often diagnostic or helps
guide the next investigation/s. In patients with suspected
14.4 Developmental Anomalies

M Vijayakumar
INTRODUCTION
Ultrasonographic (USG) examination during the
antenatal period often leads to detection of anomalies of
kidney and urinary tract. About 80 percent of antenatally
diagnosed uropathies are asymptomatic at birth. Some
antenatally detected hydronephrosis may be transient
and regress, while others may be progressive, leading to
severe renal dysfunction.
Fetal urine excretion starts by tenth week, contributing to the volume of the amniotic fluid. Bilateral loss
of renal function causes severe oligohydramnios.
Kidneys are visualized on USG by 15-17 weeks, and after
20 weeks renal growth can be measured. The length of
the kidney (in mm) approximates the fetal age in weeks.
Initially fetal bladder is empty, but if during the later
weeks of gestation, bladder is not visualized a renal
anomaly should be suspected. Table 14.4.1 list the
common anomalies detected on antenatal USG.
TABLE 14.4.1: Anomalies detected on fetal USG*
Hydronephrosis: unilateral, bilateral

Renal mass: neuroblastoma, renal tumor
Cystic kidney: solitary cyst, polycystic kidneys, multicystic
kidneys
Absent kidney: renal agenesis (unilateral or bilateral), ectopic
kidney.
*Hydronephrosis and multicystic kidneys are the most common

anomalies
Fetal Hydronephrosis
Fetal hydronephrosis may be unilateral or bilateral. The
chief cause include pelvi-ureteral junction obstruction
and vesicoureteric reflux (VUR). Severe urinary tract
obstruction result in renal dysplasia and pulmonary
hypoplasia. Postnatally, USG examination is done at 3-7
days of age. Blood levels of urea and creatinine are

measured. Milder degrees of hydronephrosis usally
regress spontaneously. Pelviureteric junction obstruction
is confirmed on DTPA renogram with frusemide
washout. Conservative management is carried out
initially. If there is progression of hydronephrosis with
fall in renal function, surgery is considered.
Posterior urethral valves (PUV) are the most
important cause of distal urinary tract obstruction and
present with dribbling of urine, distended bladder and
recurrent UTI. Occasionally, PUV may present with fetal
hydronephrosis of bilateral nature. The diagnosis is
confirmed by a MCU. Treatment involves resection of
the valves, which is done endoscopically.
Developmental Abnormalities
Presence of any of the clinical features listed in Table
14.4.2 either singly or in combination should lead to the
suspicion of renal anomalies.
TABLE 14.4.2: Clinical features suggestive of
renal anomalies
Single umbilical artery

Low set or malformed ears
Chromosomal disorders (Trisomy 13 and 18)
Tuberous sclerosis
Abent abdominal muscles (prune belly syndrome)
Myelomeningocele, sacral anomalies
Imperforate anus or genital anomalies
Aniridia (Wilms tumor)
Fetal compression syndrome, Potter facies, pulmonary
hypoplasia, oligohydramnios (renal agenesis)
Family history of renal disease (Alport syndrome, polycystic
kidney disease)
Renal Agenesis
Renal agenesis is the congential absence of identifiable
renal tissue. It may be unilateral or bilateral. Unilateral
renal agenesis is mostly detected incidentally. Bilateral
renal agenesis is a lethal disorder manifesting with
features of Potter syndrome characterized by oligohydramnios, pulmonary hypoplasia, low set ears, receding
chin, and malformed limbs, club feet and dislocated hip
joints.
Renal Hypoplasia and Dysplasia
The hypoplastic kidney is normal in shape and structure
but small in size with reduced number of nephrons and
no dysplastic elements. USG will show normal corticomedullary differentiation. The dysplastic kidney is small
723
with primitive tubules and immature glomeruli.

Mesenchymal and cartilaginous tissues are also present.
It may be unilateral or bilateral, and is associated with
obstructive or developmental anomalies of urinary tract.
Patients with severe bilateral dysplastic kidneys may
have features of Potter syndrome and end stage renal
disease sets in early in these cases.
Renal Ectopia and Fusion
Developmental interference with normal ascent and
rotation of the kidneys results in ectopia, malrotation and
fusion. Pelvic kidneys and horseshoe kidneys may be
associated with abnormalities of ureter and renal
vasculature. Various anomalies are often asymptomatic
but careful evaluation for other anomalies and long-term
observations are essential. During ascent into the
abdominal cavity the two kidneys come very near each
other and can fuse occasionally fuse together and the
common form of fusion is horseshoe kidney.
Multicystic Dysplastic Kidneys
A multicystic kidney is a non-functioning, large renal
mass consisting of cysts of varying sizes, which do not
communicate with each other. It is a common cause of
an abdominal mass in the neonate. The kidney tends to
involute and shrink. Surgical removal is rarely necessary.
Polycystic Kidneys
Polycystic kidneys may be inherited as autosomal
recessive or dominant. The severe form is the autosomal
recessive or dominant. The severe form is the autosomal
recessive type in which kidneys are large and palpable.
Renal failure may develop in the first few months of life.
Hepatic fibrosis is a constant associated feature.
Autosomal dominant polycystic kidney disease
(ADPKD) most often presents in the older age group,
but can occasionally be detected in children. Characteristic features include enlarged palpable kidneys,
hematuria, hypertension, urinary tract infection and
calculus formation. Genetic loci for the defect have been
identified on chromosomes 16 and 4. Ultrasound
examination of the parents and siblings should be done.
These children should undergo ECHO evaluation to rule
out mitral valve prolapse syndrome, which is increasingly diagnosed in them. The chances of chronic renal
failure occurring in them should be stressed to the parents
very clearly and early.
724
Other Anomalies
Multiple and aberrant renal arteries are very common
and renal arteriovenous malformation is a rare cause for
hematuria and hypertension. Retrocaval position of
ureter can be noted in few. Ureteral diverticulum and
ureterocele can be documented in few children on
evaluation of UTI and can cause obstruction if it is large.
Ectopic ureters and megacystic-megaureter syndrome
are some of the anomalies seen with ureter and bladder.
Pelviureteric junction obstruction and posterior urethral

valves are other anomalies seen in children.
BIBLIOGRAPHY
1. Nammalwar BR, Vijayakumar M. Genetic and developmental renal disease. In: Vijayakumar M, Nammalwar BR,
(Eds): Principles and Practice of Pediatric Nephrology, 1st
Edn, Jaypee Brothers, New Delhi 2004; 424-35.
2. Srivastava RN, Bagga A. Developmental abnormalities.
In: Srivastava RN, Bagga A, (Eds): Pediatric Nephrology,
3rd Edn, Jaypee Brothers, New Delhi 2005;70-80.
14.5 Acute Proliferative Glomerulonephritis

BR Nammalwar, T Vasanthi, M Vijayakumar
Acute proliferative glomerulonephritis (APGN) is
essentially a histological description denoting a clinical
condition termed as acute nephritic syndrome (ANS). It
is a glomerular injury due to wide spectrum of infectious
agents with glomerular inflammation. APGN is
histologically characterized by diffuse proliferation (all
most all the glomeruli) of all the cell components of the
glomerulus namely endothelial cells, mesangial cells and
minimally epithelial cells; accompanied by invasion of
inflammatory cells into the glomerulus. ANS is clinically
characterized by acute onset of hematuria (micro or
macro) oliguria, edema, proteinuria, arterial hypertension and uncommonly azotemia. It includes a number
of clinical conditions (Table 14.5.1).
Among all causes of ANS, the most frequent is the
postinfectious glomerulonephritis (PIGN). Among the
causes of PIGN, the commonest type is poststreptococcal
glomerulonephritis (PSGN) (Table 14.5.2). PSGN is a
prototype of APGN or ANS and hence discussed in this
chapter. In ANS other than PIGN, the glomerular
proliferation is often focal or segmental and infrequently
diffuse proliferation as in SLE, but even here infiltration
with inflammatory cells is minimal or absent.
Definition
PSGN is characterized by rapid onset of hematuria,
oliguria, edema, proteinuria with or without hypertension. There is often preceding pharyngitis or
pyoderma as a common antecedent infection due to
group A- hemolytic streptococcus with a latent period.
TABLE 14.5.1: Causes of acute glomerulonephritis

Postinfectious glomerulonephritis (PIGN)
Poststreptococcal glomerulonephritis (PSGN)

Shunt nephritis
Other systemic infections
Systemic vasculitis
Henoch Schonlein Purpura (HSP)

Systemic lupus erythematosis (SLE)
Wegeners granulomatosis (WG)
Polyarteritis nodosa (PAN)
Primary glomerular
disease
IgA nephropathy
Membranoproliferative glomerulonephritis (MPGN)
Rapidly progressive glomerulonephritis
(RPGN)
Focal segmental glomerulosclerosis
(FSGS)
Familial diseases
Alport syndrome
Familial glomerulopathy
Epidemiology
The disease is seen all around the world, but more so in
the tropics secondary to poor hygiene, hot climate and
high humidity. PSGN account for 21% of children
admitted in hospital for acute renal failure in developing
countries. It is endemic in nature but can occur in
epidemic due to intimate contact, overcrowded living
condition and poor sanitation. PSGN is essentially a
disease of preschool and early school age children, rarely
it occurs in children less than 2 years. Recurrence is
uncommon in postpharyngeal infection but may rarely

TABLE 14.5.2: Common infections causing PIGN
Bacteria
Viruses
Parasites
Group A- hemolytic Streptococcus

Streptococcus viridans
Streptococcus pneumonia
Staphylococcus aureus
Salmonella
Leptospirosis
Varicella
Mumps
Hepatitis B and C
Cytomegalo virus
Ebstein Barr virus
Measles
Echo virus
Coxsackie virus
HIV virus
Toxoplasma
Plasmodium malariae
Rickettsia
Filariasis
Schistosoma mansoni
occur in postpyoderma. The strains of Group A-

hemolytic streptococci associated with APGN are
Rebecca Lancefields M-types 1,2,4,12,18 and 25 in
pharyngitis and 49, 55, 57 and 60 in pyoderma. These
are known as nephritogenic strains. A lipoproteinase that
makes serum opaque (opacity factor) has been used to
subdivide M proteins into class I (opacity factor negative)
corresponding to serotypes that cause rheumatic fever
and class II (opacity factor positive) that corresponds to
serotypes that cause pyoderma and acute glomerulonephritis. In recent years, streptococcus zooepidemicus
(group C) has been responsible for an epidemic of PSGN.
Pathogenesis
The symptomatology of PSGN is due to glomerular
injury. The exact mechanism is not clear. The most
accepted mechanism of glomerular injury is immune
complex mediated but the nephrotogenic antigen is still
not definite. Recent evidence has demonstrated that M
protein is not the decisive factor in streptococcal
nephritogenicity.
Mechanism of Injury
Trapping of the circulating streptococcal M antigen
with antibody to the antigen in the glomeruli followed
by deposition of complement and the triggering of
725
the inflammatory process resulting in damage to the

glomerular basement membrane and the adjoining
cell components.
In situ immune complex formation between
antistreptococcal antibodies and glomerular planted
antigens.
Molecular mimicry between streptococcal and renal
antigen; the normal glomerular tissue acting as auto
antigen reacts with the circulating antibody formed
against streptococcal antigen.
Direct complement activation by streptococcal
antigens deposited in glomeruli.
The autologous IgG becomes autoimmunogenic after
being desialysed by streptococcal neuraminidase.
Cellular immune mechanisms have also been implicated. Macrophages and T-cells were shown to
infiltrate the glomeruli. Infiltration of mononuclear
cells may be promoted by chemotactic factors of the
complement system, over expression of the intracellular adhesion molecule-1, and lymphocyte
function-association antigen-1, increased circulating
levels of IL-6, IL-8, tumor necrosis factor-, and
monocyte chemotactic protein-1.
Streptococcal Nephritogenic Antigen

In addition to M antigen, other antigens related to
streptococcal cell cytoplasm such as endostreptosin,
nephritis-associated streptococcal plasmin receptor,
(NAPLr), streptococcal histone-like proteins, cationic
cystenine proteinase-SpeB and its precursor zSpeB
are antigens against which antibodies are raised
which mediate glomerular injury. Streptokinase has
been removed from the list of candidate nephrotogenic antigens in PSGN.
Certain host factors must play a major and decisive
role in determining who gets post-streptococcal
nephritis. Constitutional differences among families
were assumed to be responsible for a familial
predisposition.
Pathology
It is essentially a diffuse and generalized proliferation of
all cell components of the glomeruli with invasion of
inflammatory cells (Figs 14.5.1 and 14.5.2). Rarely there
are epithelial crescents. In PSGN epithelial cell proliferation is minimal or moderate. Most cases exhibit one or
two layers of hyperplastic parietal epithelial cells focally.
726

deposits are described. Stary sky is a fine granular
deposition of C3 and IgG along the capillary walls.
Mesangial pattern is due to deposition of C3 in the
mesangial cells. The garland type is characterized by
dense deposit along the capillary walls. Electron
microscopic studies show subepithelial lumpy bumpy
electron dense deposits in the capillary wall on the subepithelial side of the glomerular basement membrane.
These deposits disappear by about 6 weeks after the onset
of the disease.
Pathophysiology
Figure 14.5.1: Normal glomeruli. Glomeruli are well spaced

out (blue arrow); Capillary loops are clearly visible with (green
arrow) normal masangium
The diffuse proliferation of the glomeruli leads to

obliteration of the capillary lumen and hence decreased
GFR. In the presence of decreased filtrate, preserved
tubular function and enhanced absorption of fluid with
solute in the distal and collecting tubule, there is
decreased urine production resulting in oliguria. The
decreased filtration leads to retention of fluid and solutes
resulting in increased vascular and interstitial volume
leading to hypertension, azotemia and its associated
complications.
Figure 14.5.2: Light microscopy showing diffuse proliferative

glomerulonephritis [Glomeruli appears crowded and there is
(green arrow) proliferation of endothelial cells, increase in cells
of (blue arrow) mesangium with mesangial hypercellularity]
Well-formed crescents are seen in a significant proportion

of the glomeruli in a smaller number of pediatric cases.
In this situation, the outcome is less favorable. The
cellular infiltration consists of polymorphs, eosinophils,
T.lymphocytes and macrophages. Immunofluorescent
studies show finely granular staining for IgG, IgM, C4,
C3, C1q, fibrinogen and factor B, along the capillary loops
and within the mesangium. Three types of immune
Typical manifestations consist of preceding streptococcal

infection of throat or skin followed by a latent period of
10-14 days after pharyngitis or 2-3 weeks after pyoderma,
early morning periorbital edema, hematuria with rapid
onset of generalized edema and hypertension. Hematuria
can be gross in about 30% of children while microscopic
hematuria is present in all. Edema is due to retention of
salt and water. Hypertension is the low renin type due to
retention of water and salt which leads to expansion of
the extracellular fluid volume with suppression of the
rennin angiotensin aldosterone axis. Hypertension can
present as headache and drowsiness followed by seizures.
Children can present with orthopnea, tachypnea,
tachycardia and distended jugular vessels and rarely as
cardiac failure. Uncommonly some may present as
isolated hematuria, isolated hypertension with minimal
urine findings and nephrotic syndrome with microscopic
or macroscopic hematuria and rarely as rapidly progressive renal failure known as RPGN. The urine is dark
reddish brown in color and is described as coco-cola color
or gingili oil colour. Rarely urine may be clear on passing
but becomes reddish brown in color on standing after a
few hours.

Clinical conditions resembling PSGN are few. Features
like absence of preceding infection, decreased latent
period, recurrence, insidious onset, systemic manifestations such as fever, rash, arthralgia, organomegaly and
family history of renal disease will rule out PSGN. The
presence of nephrotic proteinuria, renal failure,
macroscopic hematuria or hypertension for more than 4
weeks are unlikely in PSGN. D-negative HUS, IgA
nephropathy and MPGN are three clinical conditions in
children that closely resemble PSGN. MPGN is suspected
when there is recurrence of nephritic features with severe
proteinuria and persistently low serum complement level
even after 6 weeks of the disease. HUS is recognized by
thrombocytopenia, anemia with elevated LDH and
serum bilirubin levels.
727
be identified.
Chest skiagram shows pleural fluid and mild
cardiomegaly due to pericardial effusion. Gross
cardiomegaly can be seen with severe volume
overload and is an impending sign of cardiac failure.
Consolidation can be seen in streptococcal pneumonia. Presence of pulmonary infiltrates should
suggest systemic vasculitis.
USG abdomen shows bilaterally enlarged kidneys
with mild parenchymal changes and rarely loss of
corticomedulary differentiation. Free fluid in the
abdomen and pleural fluid are other common
findings.
Renal biopsy is indicated when any of the above
criteria for PSGN are not met with or when nephrotic
syndrome accompanies acute nephritic syndrome or
in persistent or progressive renal failure.
Laboratory Findings
Urine analysis: Proteinuria, mild to moderate is
observed. Massive proteinuria is uncommon.
Presence of dysmorphic or crenated RBCs and RBC
casts are diagnostic. WBCs, hyaline casts and granular
casts are present. Minimal urine findings may be
present in children with severe clinical features.
Renal function tests: Blood urea, creatinine levels are
usually normal, they may be elevated. Free water
excretion is impaired, leading to hyponatremia.
Decreased GFR and indiscriminate intake of potassium rich food can cause hyperkalemia. Serum total
proteins can be elevated due to increased gamma
globulins. Serum cholesterol levels are normal.
Serology: ASO titres will be high in pharyngitis and
can be normal in pyoderma. Use of streptozyme test,
which measures anti-hyaluronidase, ASO titre, antideoxyribonuclease-B, anti-nicotinamide and adenine
dinucleotidase has higher sensitivity particularly in
postpyoderma states. In the future, the etiological
diagnosis of children with ANS due to nephritogenic
streptococcal infection will depend on the demonstration of rising antibody titres to SpeB/zSpeB or NAPLr
antigens.
Total hemolytic component, C4 and C3 are low. LE
cells, antinuclear antibody, antinuclear cytoplasmic
antibodies studies are indicated when there are
associated systemic features.
Low hemoglobin is due to dilution. Occasionally
thrombocytopeia and coagulation abnormalities can
Treatment
Children with moderate edema, anuria or oliguria,
hypertension, or moderate renal failure need
hospitalization.
Bed rest is indicated in the above conditions to
encourage venous return, increased stimulation of
atrial natriuretic hormone and to increase urine
output.
Fluid intake in the first 24 hours is restricted to
insensible water loss. Subsequently the input is
regulated by urine output added to insensible water
loss.
Restriction on salt intake is advocated in the presence
of edema, hypertension and renal failure and is
limited to no added salt to the diet during cooking.
With onset of diuresis to more than 1 ml/kg/hr and
control of hypertension, salt can be gradually
increased by 1 gm every third day and fluid intake
modified to match the urine output.
Protein is restricted to 0.6-1.0 gm/kg/day in the
presence of renal failure.
Hypertension should be treated promptly with
parenteral furosemide, calcium channel blockers,
ACE inhibitors or hydralazine. Use of ACE inhibitors
in the presence of renal failure needs monitoring of
serum potassium.
Volume overload sufficient to produce cardiac failure
can be treated with salt and fluid restriction and IV
furosemide.
728
Hyponatremia and hyperkalemia should be treated

with restriction of fluid intake and food containing
high potassium. Use of calcium resin salts is helpful
in the presence of fluid overload, wherein sodium
resin salts can worsen hypertension and fluid
retention.
Antibiotics are indicated in the presence of infection
as infection can prolong the activity of disease and
spread of nephritogenic strains. Ampicillin /
amoxycillin is a good choice.
Immunosuppressive: There is no clear evidence of
beneficial effects except in RPGN. Pulse methyl
prednisolone 0.5-1.0 g/1.73 m 2 for 3 or 5 days
followed by oral prednisolone has been reported to
have beneficial effect. Use of IV cyclophosphamide
in addition has also been reported.
Complications
Hypertensive encephalopathy is a consequence of
failure to monitor blood pressure at regular interval
or inadequate treatment. BP monitoring at frequent
intervals is the best way to prevent hypertension.
Control of seizures is followed by use of intravenous
furosemide, salt and fluid restriction. Sublingual/oral
nifedipine (0.25-0.5 mg/kg/dose) can bring down
blood pressure fairly rapidly. It can be repeated on 2
occasions at about 30 minutes intervals. Serious side
effects have been reported in adults hence it should
be administered in children with caution. Fortunately
since hypertension in these children is acute in onset
and cerebral vessels are healthy, cerebrovascular
accidents are unlikely. For hypertensive emergency
in a hospital setting, IV nitroprusside (0.5-2.0 mcg/
kg/min) or IV labetalol (0.5-1.0 mg/kg/hr) in
addition to IV furosemide is recommended.
Pulmonary edema can at best be managed with
intravenous furosemide at a dose of 2-3 mg/kg given
as slow IV pushes at the rate of 4 mg/mt. This can
avoid the uncomfortable burning sensation in the
body or hypotension.
Renal failure of mild to moderate degree can be
managed conservatively.
Dialysis is indicated in the presence of severe

hyperkalemia, acidosis, pulmonary edema, uncontrollable hypertension and progressive renal failure.
Peritoneal dialysis is simplest and easily available
method. Other renal replacement therapy such as
continuous renal replacement therapy, slow ultrafiltration and hemodilaysis are alternate choice.
Prognosis
Spontaneous improvement usually begins in a weeks
time with diuresis followed by loss of edema and
improvement in blood pressure. The total duration of
illness rarely exceeds 4 weeks. Often recurrence of
hematuria occurs associated with URI, a week or two
after resolution of disease and does not require any
intervention. Typically serum complement returns to
normal at about 8 weeks. Proteinuria subsides usually
by about six months and microscopic hematuria may
persists upto one year. Some children with PSGN
develop RPGN and minor sequelae, which may not
become apparent for several years and progress into
chronic renal failure. Some children with systemic
vasculitis can present with isolated renal disease.
Therefore it is in the best interest of children that they be
followed serially for many years for at least a period of
2-5 years.
BIBLIOGRAPHY
1. Endre Sul Yok. Acute proliferative glomerulonephritis.
In: Ellis D Avner, William E Harmone, Patrick Niaudet,
(Eds): Pediatric Nephrology, 5th Edn, Lippincott
Williams and Willkins, Philadelphia 2004;601-13.
2. Mikhael R, Postlethwaite R. Postinfectious glomerulonephritis. In: Chochat P, et al (Eds): ESPN Handbook,
European Society for Pediatric Nephrology 2002;268-74.
3. Rodriguez-Iturbe B, Batsford S. Pathogenesis of postreptococcal glomerulonephritis a century after Clemens
von Pirquet. Kidney Int 2007;17:1094-1104.
4. Tasic V. Postinfectious glonerulonephritis. In: Geary DF,
Schaefer F, (Eds): Comprehensive Pediatric Nephrology.
1st Edn, Mosby Elsevier: Philadelphia 2008;309-17.
5. Vijaykumar M, Nammalwar BR. Acute proliferative
glomerulonephritis and crescentic glomerulonephritis.
In: Nammalwar BR, Vijayakumar M (Eds): Principles and
Practice of Pediatric Nephrology. Jaypee Brothers: New
Delhi 2004;167-78.
729
14.6 Renal Vasculitis

BR Nammalwar, N Prahlad
Vasculitis is defined as inflammation of the blood vessels.
The blood vessels involved vary from small vessels like
capillaries to large vessels like aorta. The vessels show
partial or completely obliteration which is often
immunologically mediated or sometimes due to nonimmunological causes like atherosclerosis and thrombotic obliteration. Symptoms vary depending upon the
type of vessel and the organ system that is involved.
Kidney being a vascular organ is consequently involved
in these disorders as a part of the multiorgan involvement. Renal involvement includes inflammation and
necrosis of the blood vessels, proliferation of the
glomerular cell components, deposition of immunoglobulins and interstitial tissue damage, leading to
malfunction of the kidneys and renal failure. They
commonly present as severe hypertension, chronic
glomerulonephritis, proteinuria and/or hematuria. They
can be classified based on the size of the blood vessel
involved. Hitherto, there has been, with certain
exceptions much reliance on adult classification systems
and criteria that have not proved entirely satisfactory. A
recent International Consensus Conference held at
Vienna in June 2005 proposed an acceptable classification
of childhood vasculitis as well as criteria for classifying
specific subcategories of vasculitic disease affecting the
young (Table 14.6.1 and Fig. 14.6.1).
TAKASAYU ARTERITIS (TA)
Definition
It is a segmental inflammatory vasculitis of unknown
cause that usually begins in the subclavian vessels and
progressively involves the carotids, aorta and renal
arteries and rarely pulmonary vessels (Fig. 14.6.2). It is
known as a pulseless disease, owing to its involvement
of the aortic arch and subclavian vessel, resulting in
reduced blood flow in brachial artery and hence absence
of pulse or poor pulse volume.
Epidemiology
This disease is more common among girls with a female
to male ratio of 9:1. It commonly affects children between
10-20 years.
TABLE 14.6.1: Classification of childhood vasculitis based

on the size of the blood vessels involved
A. Predominantly large vessel vasculitis
Takayasus arteritis
B. Predominantly medium-sized vessel vasculitis
Juvenile polyarteritis nodosa
Cutaneous polyarteritis
Kawasaki disease
C. Predominantly small vessel vasculitis
a. Granulomatous
Wegners granulomatosis
Churg Strauss disease
b. Non-granulomatous
Microscopic polyangitis
Henoch Scholein purpura
Isolated cutaneous leukocytoclastic vasculitis
Hypocomplementemic urticarial vasculitis
D. Other vasculitis
Behcets disease
Vasculitis secondary to infection (including hepatitis
B-associated PAN), malignancy and drugs including hypersensitivity vasculitis
Isolated vasculitis of the CNS
Cogans syndrome
Unclassified
Pathology
All three layers of the large vessels and its branches show
mononuclear cell inflammation with variable admixture
of multinucleated giant cells. Focal destruction of the wall
leads to aneurysm formation and occasionally even
rupture. More commonly there is fibrosis of the wall with
narrowing of the vascular lumen with parenchymal
atrophy. Glomerulonephritis is seen occasionally.
Fifty percent of children present commonly with
hypertension or symptoms of end organ effect due to
hypertension, namely cardiac failure, headache,
dizziness, visual disturbance and seizures. They also
present with asymmetric pulse, bruit over the subclavian,
brachial and abdominal vessels. There are two phases of
the disease. The prepulseless phase is characterized by
nonspecific symptoms like fever, malaise, headache,
730
Figure 14.6.1: Classification of vasculitis based on the size of the blood vessels
may present with dizziness, headache, syncope and

stroke. Dermatological manifestations like erythema
nodosum and pyoderma gangrenosum are seen.
Secondary to pulmonary artery involvement, children
may present with hemoptysis, shortness of breath and
pulmonary hypertension. Few can present as angina,
which is due to aortic or coronary arteritis. Any one
criteria listed in the Table 14.6.2 in addition to the
angiographic abnormalities is diagnostic of TA.
TABLE 14.6.2: Diagnostic criteria for Takayasu arteritis
Figure 14.6.2: Abdominal aortogram showing area of dilatation

(black arrow) and narrowing (red arrow) in Takayasu arteritis
(Courtesy: Prof. V Tamilarasi)
myalgia, arthralgia and weight loss. As arterial

involvement advances, symptoms of end organ ischemia
appear and signal the start of the pulseless phase. Child
presents with hypertension and end organ dysfunction
like hypertensive encephalopathy and congestive cardiac
failure. The hypertension is secondary to coarctation of
aorta and not due to renal involvement. Due to
compromised arterial blood flow to the brain, children
Decreased peripheral artery pulse(s) and / or claudication of

extremities
A blood pressure difference of >10 mmHg
Bruits over the aorta and / or its major branches
Hypertension
Presence of angiographic abnormalities of the aorta or its major
branches by conventional, CT or MR (a mandatory criteria)
Laboratory Findings
There may be widening and calcification of aorta on plain
abdominal radiograph. Angiography, demonstrating
narrowing or occlusion with or without aneurysms of the
major arteries makes the diagnosis of TA. Doppler
ultrasound and MRI are other techniques, which have a
role. Digital subtraction angiography has allowed
diagnosis to be made with less contrast. It is classically

anti-nuclear antibody (ANA) and antineutrophil
cytoplasmic antibody (ANCA) negative disease. It is
characterized by elevated acute phase reactants like ESR
and CRP and is associated with anemia. Often a positive
mantoux reaction is observed in these children suggesting
a distant possibility of tuberculous etiology. This disease
should be considered in children presenting with
hypertension associated with fever and elevated ESR.
Treatment and Outcome
Therapy with steroids is the first line of treatment. In
situations wherein the child is resistant to steroids,
combination of steroids with cyclophosphamide or
methotrexate has been tried. The combination of steroids
and methotrexate has shown to result in higher remission
rate and the need for lower maintenance dose of steroids.
Reconstructive surgery and percutaneous transluminal
angioplasty used for treating stenosis of the descending
thoracic and or abdominal aorta have been found
moderately successful. Hypertension in children is well
controlled with blockers, diuretics and vasodilators.
ACE inhibitors have to be used with caution as it can
precipitate renal failure. The long-term prognosis of TA
is generally good but ultimately most of them progress
into severe renal failure or die as a consequence of
uncontrollable hypertension.
JUVENILE POLYARTERITIS NODOSA (PAN)
Definition
Earlier PAN was classified as classical PAN (c PAN),
which was a necrotising vasculitis with aneurysmal
nodules along the walls of medium sized and small sized
muscular vessels like the coronary, hepatic, mesenteric and
renal arteries, without involvement of arterioles, capillaries
and venules, and as microscopic polyarteritis or
polyangitis which involved arterioles, capillaries or
venules. It also defined as PAN where ANCA is negative
and microscopic polyangitis (MPA) where ANCA is
positive. However, in childhood, PAN may also have small
vessel involvement. Hence, it should be classified as
juvenile PAN. Recently new criteria for the classification
of juvenile PAN has been developed (Table 14.6.3).
Epidemiology
PAN is seen in children between 3-16 years with a
median age of 9-10 years. It commonly affects males with
a preponderance of 2.5:1.
731
TABLE 14.6.3: Classification criteria for juvenile

polyarteritis nodosa
A systemic illness characterized by the presence of at least 2 of
the following 7 criteria:
1. Skin involvement (livedo reticularis, tender subcutaneous
modules, other vasculitic lesions)
2. Myalgia or muscle tenderness
3. Systemic hypertension, relative to childhood normative data
4. Mononeuropathy or polyneuropathy
5. Abnormal urinalysis and/or impaired renal function
6. Testicular pain or tenderness
7. Signs or symptoms suggesting vasculitis of any other major
organ system (gastrointestinal, cardiac, pulmonary or central
nervous)
In the presence of (one of the below as a mandatory criteria)
Biopsy showing small and mid-size artery necrotizing vasculitis
Or antiographic abnormalities (aneurysms or occlusions) or
angiographic
From Ozen S, Ruperto N, Dillon MJ, Bagga A et al. EULAR/PRES
endorsed consensus criteria for the classification of childhood
vasculitis. Ann Rheum Dis 65: 936-941, 2006.
Etiopathogenesis
An immune complex mediated mechanism has been
postulated as an initiating factor for the vasculitis.
Another view proposed is the formation of autoantibody
to the vascular endothelium. Similar changes have been
observed with drugs like penicillin, sulfonamide and
amphetamine administration. PAN is also associated
with hepatitis B infection wherein antigen antibody
immune complexes are seen in the walls of the blood
vessels.
Pathology
In the kidney, PAN affects the medium sized muscular
arteries while MPA involves smaller arteries and
arterioles. Renal biopsy of PAN shows necrotising
vasculitis without crescentric or necrotising glomerulonephritis, which differentiate it from MPA wherein there
is evidence of crescentric or necrotising glomerulonephritis.
Clinical Features
PAN is a multisystem disease that has varied presentation. They normally present with fever, weight loss,
weakness, testicular pain, ischemic heart symptoms,
arthalgia and myalgia. PAN can present with cutaneous
features like livedo reticularis or inflammatory nodules
with or without gangrene (Figs 14.6.3 and 14.6.4).
Renovascular hypertension is seen in 1/3 of the affected
732

aneurysm. Reliable non-aneurysmal signs are perfusion
defect, presence of collateral artery, lack of crossing of
peripheral renal arteries and delayed emptying of small
renal arteries. In the kidney, the interlobar and arcuate
arteries are mainly involved, with rare involvement of
renal arteries. Vasculitis can be confirmed by a biopsy of
the skin, sural nerve, testis or skeletal muscles. Renal
biopsy reveals necrotising vasculitis without evidence
of cresentic or necrotising glomerulonephritis.
Figure 14.6.3: Gangrene of fingers in polyarteritis nodosa
Treatment consists of oral steroids with IV cyclophosphamide. Antiplatelet adhesive agents, plasma exchange
and high dose IV immunoglobulins have been tried.
Azathioprine, cyclosporine or mycophenolate mofetil are
useful in maintaining remission. Children with nephrotic
proteinuria, renal insufficiency, cardiomyopathy, and
CNS or GIT involvement have bad prognosis. The
mortality is around 10%, which is mostly due to severe
infections or chronic renal failure.
Cutaneous Polyarteritis
Figure 14.6.4: Child with severe arthritis and healing

gangrene in polyarteritis nodosa
children. Renal failure may be seen on presentation or

during the course of the disease. Abdominal pain and
hematochezia signify bowel involvement. It may also
present as peripheral neuropathy or organic psychosis.
Rarely, renal symptoms may be in the form of isolated
proteinuria, nephritic or nephrotic syndrome or renal
failure.
Laboratory Findings
Investigations reveal anemia, polymorphonuclear
leucocytosis, thrombocytosis and elevated ESR and
C-reactive protein positivity. ANCA is detected with both
cytoplasmic and perinuclear patterns. The most valuable
procedure is renal and hepatic angiography, which
shows multiple aneurysms. High-resolution selective
angiography is required to detect small peripheral
Cutaneous polyarteritis is characterized by the presence

of subcutaneous nodules, painful non-purpuric lesions
with or without livedo reticularis, myalgia, arthralgia and
non-erosive arthritis. Skin biopsy shows necrotizing, nongranulomatous vasculitis, ANCA tests are negative and
there is often an association with serologic and
microbiologic evidence of streptococcal infection.
Kawasaki Disease (KD)
Kawasaki disease is a systemic childhood vasculitis
characterized by persistent fever of at least 5 days
(mandatory criterion) plus four of the following five
being present: changes in the peripheral extremities or
perianal area, polymorphous exanthem, bilateral
conjuctival congestion, changes in the lips and oral cavity
and/or inflammation of the oral and pharyngeal mucosa
and cervical lymphadenopathy. In the presence of
coronary artery involvement detected on echocardiography and fever, fewer than four of the five remaining
criteria are considered sufficient. It is a systemic medium
vessel vasculitis. KD is believed to have an infective basis
and may be super antigenic induced. Renal involvement
is characterized by involvement of interlobar arteries and
can present a few months after an episode of Kawasaki
733
disease as hypertension. They can present as acute renal

failure secondary to interstitial nephritis. Uncommonly
hematuria, proteinuria and pyuria have been reported.
Ultrasonogram has shown nephromegaly, echogenic
kidneys with increased corticomedullary differentiation.
Laboratory investigations will show polymorphonuclear leucocytosis and thrombocytosis. Treatment
involves aspirin, high dose IV immunoglobulins and
antiplatelet adhesive therapy with aspirin given for 2-3
months. Steroids have been tried when no response to
the above treatment is noted.
HENOCH SCHONLEIN PURPURA (HSP)
Definition
HSP is a benign systemic vasculitis which involves small
vessels. It involves multiple organ systems and is
characterized by crops of purpura on the buttock and
lower limbs accompanied by gastrointestinal tract, joints
and renal symptoms (Figs 14.6.5 and 14.6.6). In 1994
Consensus Conference on Nomenclature of Systemic
Vasculitis, defined HSP as a small vessel vasculitis
involving capillaries, arterioles and venules with IgAdominant immune deposits typically involving skin, gut
and glomeruli and associated with arthralgia or arthritis.
Recently the European League Against Rheumatism
(EULAR) and the Pediatric Rheumatology Society has
proposed a classification for HSP. Diagnosis of HSP
Figure 14.6.6: Purpuric rashes involving

the genetalia in HSP
requires at least one of the following four should be

present: diffuse abdominal pain, any biopsy showing
predominant IgA deposition, arthritis or arthralgia and
renal involvement (any hematuria and/or proteinuria)
in the presence of palpable purpura which is a mandatory
criterion.
Epidemiology
It is the most frequent vasculitis seen in children. It
commonly affects males, frequently in the first decade
of life. The median age of presentation is 4-5 years and
the mean age of renal involvement is 6-10 years.
Pathogenesis
Figure 14.6.5: Palpable purpuric rash

involving lower limb in HSP
The pathogenesis of HSP is believed to be an immune

complex-mediated disease characterized by the presence
of polymeric IgA 1 containing immune complexes in the
dermal, gastrointestinal and glomerulocapillaries. IgA is
the predominant immunoglobulin in secretions acting as
a defence against viral and bacterial agents. HSP and IgA
nephropathy are triggered by respiratory infection.
Though HSP is preceded by a respiratory infection, there
is no clear evidence for a pathogenic role of Group-A
streptococcus. A variety of other infections and food
allergens have been implicated. The principal problem is
persistent depositions of IgA in the mesangium. Various
theories for the IgA deposition are: (1) Immune response
secondary to a specific antigen as evidenced by the
734
presence of IgA immune deposits within the glomeruli,

(2) Affinity of circulating IgA to various molecules like
glycoprotein in the kidney to cause its accumulation and
hence renal involvement, (3) Abnormal glycosylation of
IgA leading to high tendency for self-aggregation and
formation of macromolecules which escape clearance by
hepatic receptors and accumulate in the mesangium of
the kidney. This abnormal accumulation along with
defective catabolism of this abnormal IgA from the
mesangium leads to persistent depositions of IgA in the
mesangium. The interaction of this IgA with Fc receptor
on mesangial cells results in cellular activation, mediator
synthesis and release of variety of cytokines (IL-6, IL-1,
TNF- and TGF-), vasoactive factors (PG, thromboxane,
leukotrienes, nitrous oxide and PAF) by the mesangial
cells, thus leading to glomerular damage. This is worsened
by the increased production of IgA by B cells along with
abnormal activity of T suppressor cells. Several reports
have postulated HLA Class II gene polymorphism to be a
risk factor for HSP.
In about 2/3 of children, the disease is triggered by
infections (streptococcus, yersinia, mycoplasma,
toxoplasma, varicella, measles, rubella, HIV). The acute
illness starts with fever and malaise. The skin lesions
typically begin as red macules to later become utricarial
and purpuric and involve mainly the extensor surface of
limbs, buttocks, back and occasionally face and genitalia.
The purpura always involves the ankle. Subcutaneous
edema may be seen. Gastrointestinal symptoms like
colicky abdominal pain and hematochezia occur due to
bowel hemorrhage, intussusception or perforation .The
arthritis is moderate to severe involves the ankles and
knees and is oligoarticular in nature. Renal involvement
is noted in 35-65% of these children. Hematuria alone or
with mild proteinuria is always present and is transient.
Some have macroscopic hematuria, which is transient,
but recurs with a respiratory infection. 80% have
nephritic syndrome within 4 weeks of onset of rash.
About 2/3 of children with renal involvement have
nephrotic range of proteinuria and nephrotic syndrome.
Hypertension is noted in 25% of the affected children.
Renal insufficiency is usually mild but acute renal failure
can occur. In severe cases, acute nephritic syndrome,
which progresses to nephrotic syndrome and then to
renal failure occurs (Table 14.6.4).
TABLE 14.6.4: Clinical manifestation of HSP

Skin
GIT
Joints
Kidney
Palpable purpura
Abdominal pain
Vomiting
Hematemesis
Intussusception
Bowel perforation
Intestinal infarction
Ankle and knee, oligoarticular synovitis
Nephritis.
Microscopic / Macroscopic hematuria
Mild proteinuria
Nephrotic proteinuria
Renal failure
Hypertension
Nephrotic syndrome
Laboratory Findings
The diagnosis of HSP is essentially clinical and by
demonstrating that purpura is not due to thrombocytopenia or defective clotting mechanism. The serum
IgA may be elevated in 50-70 % of HSP. High levels of
IgA-ANCA may also be seen. A skin biopsy is done only
when the diagnosis is in doubt, which typically shows
leukocytoclastic vasculitis with fragmentation of
leukocyte nuclei in and around arterioles, capillaries and
venules, surrounded by infiltrating neutrophils and
monocytes in the presence of nuclear dust in the walls of
the arterioles. Deposits of IgA and C3 are seen in the
dermal capillaries and IgA deposit in the skin is
diagnostic of HSP. Renal biopsy is neither recommended
nor necessary in all cases of HSP except in case of
nephritis with nephrotic range of proteinuria, renal
failure and nephrotic syndrome. Renal biopsy shows
focal and segmental proliferation with necrotic lesions
and crescents. Tubulointerstitial changes parallel the
severity of glomerular injury. Granular mesangial
deposits of IgA are seen in all glomeruli and are
characteristic of HSP nephritis. Electron dense deposits
may be found in a subendothelial paramesangial location
together with fibrin like material. Severity and prognosis
depends on the histological class as explained in Table
14.6.5.
Treatment and Prognosis
The treatment is essentially symptomatic. In mild cases
treatment is with analgesics like paracetamol for pain
and antispasmodics for relief of abdominal pain. It is

TABLE 14.6.5: HSP nephritis pathology classification of
International Study of Kidney Disease in Children
Class I
Minimal change
Class II
Pure mesangial proliferation without crescents
Class III
Mesangial proliferative glomerulonephritis with

< 50% crescents
a. IIIa Focal
b. IIIb Diffuse
Class IV
Mesangial proliferative glomerulonephritis with

50-75% crescents
a. IVa Focal
b. IVb Diffuse
Class V
Mesangial proliferative glomerulonephritis >75%

crescents
c. Va Focal
d. Vb Diffuse
Class VI
Membranoproliferative (mesangiocapillary)
glomerulonephritis
necessary to monitor urine for active sediments in the

first 2-3 months after the appearance of rashes. When
abdominal pain is severe, a small dose of steroids is
useful. Children who present with nephritic syndrome
unassociated with renal failure, hypertension or massive
proteinuria need no active treatment and can be
monitored. When they present as nephritic syndrome
associated with either nephrotic proteinuria or renal
failure, a renal biopsy is warranted. Endocapillary
proliferation and crescents by renal biopsy warrants more
aggressive therapy with IV methylprednisolone and
cyclophosphamide. The outcome of the disease depends
on the severity of renal involvement. The overall risk of
children with HSP nephritis going into ESRD is 2%. With
more severe renal involvement, the risk increases to 2530%. Children with group I to IIIa histological findings
have better outcome with return of normal renal
functions or persistent urinary abnormalities. Children
in groups IIIb, IV and V have persistent proteinuria and
hematuria and may progress to ESRD. When compared
to adults the outcome of children with HSP nephritis is
similar. The overall risk of going into ESRD is 27%.
Wegeners Granulomatosis (WG)
Wegners granulomatosis is a necrotising granulomatous
vasculitis of the upper and lower respiratory tract
associated with glomerulonephritis. It is an idiopathic
inflammatory systemic disease with predilection for the
upper and lower respiratory tract and glomerulo-
735
nephritis. The criteria for WG have been defined as the

presence of 3 of the following 6 criteria: abnormal
urinalysis, granulomatous inflammation on biopsy, nasosinus inflammation, subglottic, tracheal or endobronchial
stenosis, abnormal chest X-ray or computed tomography
(CT) and PR3 ANCA or cytoplasmic ANCA staining.
Incidence
It is a rare disease of the pediatric age group. The mean
age of presentation is 15.4 years with a range from 9.3 to
19.4 years.
Etiopathogenesis
WG is an exaggerated immune response to inhaled
antigen. No specific exogenous or endogenous antigens
have been identified. The immune complexes may be
formed in situ or circulating immune complexes may be
deposited. Alternatively cell mediated immune mechanism can be the cause of the granulomatous vasculitis.
Clinical features include those of PAN with unique
features of subglottic stenosis, opaque sinuses, nasal
septum disease and chronic lower respiratory infection
like symptoms. In less than 10% of the children the
kidneys are not involved. Hematuria, proteinuria and
renal insufficiency are common. Gross hematuria and
hypertension are unusual. Pauci immunenecrotizing
glomerulonephritis is the histological feature. Biopsy of
the involved tissue show ANCA positivity with
granulocytic cytoplasmic pattern and the antibody
directed against proteinase 3.
Treatment is similar to PAN and MAP. Therapy includes
steroids, cyclophosphamide, antiplatelet adhesive
therapy, plasma exchange and antimicrobial therapy
such as with cotrimoxazole. Remission is maintained
with long-term steroids and azathioprine or cyclosporin.
The long-term mortality and morbidity is high.
CHURG STRAUSS SYNDROME (CSS)
This syndrome is a systemic necrotizing vasculitis with
hypereosinophilia and extravascular granulomas usually
occuring in a patient with asthma. It is a paucimmune
736
small vessel vasculitis characterized by preceding history

of asthma, eosinophilia, parenchymal infiltrates associated with rhinitis and nasal polyposis. It is a multisystem
disease involving the GI tract, lungs, kidneys, skin and
peripheral nerves. It has been postulated that CSS occurs
in three phases: a prodromal phase, an allergic phase
(asthma and /or allergic rhinitis), an eosonophilic phase
(tissue and peripheral eosinophilia) and a vasculitis phase
(with multi organ involvement). Six criteria have been
developed by the American College of Rheumatology for
the diagnosis of this condition. The criteria include asthma,
eosinophilia (>10% or absolute eosinophil count of >1500),
mononeuropathy or polyneuropathy, histological
evidence of vasculitis, paranasal sinusitis and non-fixed
pulmonary infiltrates. The kidneys are involved after a
period of 2-30 years. It can present as acute renal failure
due to vasculitis, which responds well to steroids, or
obstructive uropathy due to eosinophilic granuloma.
Laboratory investigations reveal eosinophilia, anemia,
elevated WBC counts, positive CRP, elevated ESR and
high serum IgE levels. Proteinuria and hematuria may be
seen. Steroids form the mainstay of treatment given alone
or in combination with cyclophosphamide. Plasma
exchange has been tried but do not offer any advantage
over steroids. Once remission is attained, cyclophosphamide is replaced by azathioprine. Relapses are
common within one year of diagnosis.
Microscopic Polyangitis (MPA)
MPA is a small vessel vasculitis affecting arterioles,
capillaries and post-capillary venules. Clinically children
presents with glomerulonephritis, purpura and occasionally pulmonary hemorrhage. It is difficult to
distinguish it from WG and RPGN.
Clinical features
Usually presents with proteinuria, hematuria, hypertension and renal impairment. The presenting features
are more of glomerulonephritis with hypertension while
in PAN it is essentially systemic features and hyper-
tension without evidence of crescentric or necrotising

glomerulonephritis by renal biopsy. Investigations reveal
positive ESR and a high titre of myeloperoxidase ANCA
or positive perinuclear ANCA staining. Renal biopsy is
diagnostically valuable revealing characteristically pauci
immune crescentic necrotizing glomerulonephritis.
Treatment is similar to that of PAN utilizing steroids,
cyclophosphamide and antiplatelet adhesive agents.
Plasma exchange has been tried. Long-term alternate day
steroid therapy, azathioprine have been tried for
maintenance. The mortality with ESRD is more than 50%.
A protective effect is seen with cyclophosphamide.
Renal Limited Disease
These are rare situations wherein a child presents with
isolated progressive renal failure with clinical features
of glomerulonephritis. The renal biopsy will show a
crescentic glomerulonephritis with no immune complexes but have a positive ANCA.
BIBLIOGRAPHY
1. Bakkaloglu A, Ozen S. Wegeners Granulomatosis,
Microscopic polyangitis, and childhood polyarteritis
nodosa. In: Geary DF, Schaefer F (Eds): Comprehence
Pediatric Nephrology. 1st Edn, Mosby Elsevier,
Philadelphia 2008;353-8.
2. Dillon KJ, Sirin A. Systemic vasculitis. In: Chochat P,
et al. (Eds): ESPN Handbook, European Society for
Pediatric Nephrology 2002;291-5.
3. Dillon MJ, Ozen S. A new international classification of
childhood vasculitis. Pediatr Nephrol 2006;21:1219-22.
4. Rudolph P Valentini, William E Smoyer. Renal vasculitis.
In: Ellis D Avner, William E Harmone, Patrick Niaudet
(Eds): Pediatric Nephrology, 5th Edn, Lippincott
Williams and Willkins, Philadelphia 2004;835-63.
5. Vasanthi T, Nammalwar BR, Vijayakumar M. Renal
vasculitis and lupus nephritis. In: Nammalwar BR,
Vijayakumar M (Eds): Principles and Practice of Pediatric
Nephrology, 1st edn, M/s.Jaypee Brothers, New Delhi
2004;216-24.
737
14.7 Acute Renal Failure

INTRODUCTION
Acute renal failure (ARF) is characterized by a rapid
deterioration of renal function, resulting in retention of
nitrogenous wastes and biochemical derangements.
Anuria or oliguria (urine volume less than 500 ml/1.73
m2/24 hours; in infants less than 0.5 ml/kg/hr) is the
most prominent feature of ARF. However, in a proportion of patients the urine output may be normal or only
slightly reduced (non-oliguric ARF). An increase in the
blood levels of urea and creatinine suggests the diagnosis in such cases. ARF usually occurs in patients with
previously normal renal function, but it occasionally may
be superimposed on preexisting renal disease (acute-onchronic renal failure).
A lack of a standard definition of ARF has resulted
in failure to identify the condition early enough to
implement appropriate action. The lack of a definition
also makes it difficult to compare data across the world.
Recently, the term acute kidney injury (AKI) has been
proposed to represent the spectrum of acute renal
dysfunction. Criteria for diagnosis and staging of AKI
have been recommended (Table 14.7.1). AKI is considered to be present when there is an abrupt (within
48 hours) reduction in kidney function, defined as an
absolute increase in serum creatinine of > 0.3 mg/dl or a
percentage increase of creatinine by > 50% or a reduction
in urine output (< 0.5 ml/kg/hr for > 6 hr). The diagnosis
of AKI thus requires that two values of creatinine be
estimated within 48 hours; in cases where the diagnosis
is based on urine output alone, reversible causes like
urinary tract obstruction and dehydration should be

excluded. Common causes of ARF are listed in Table
14.7.2.
Geographical and Regional Variations
The etiology of ARF varies regionally. In infants, acute
gastroenteritis with severe dehydration used to be the
commonest cause of ARF. Widespread use of oral
rehydration in the management of diarrhea has led to a
marked decline in the incidence of severe dehydration.
For several years, hemolytic uremic syndrome (HUS) was
a leading cause of ARF at most referral centers, but its
incidence has recently declined. Acute glomerulonephritis and acute tubular necrosis (each due to various
underlying causes) are presently the commonest
conditions associated with ARF. In coastal regions of
India, Orissa and in rural areas, snakebite is a major cause
of ARF. In some parts of Kerala, leptospirosis is
frequently encountered. Acute intravascular hemolysis
following exposure to oxidant drugs in G-6-PD deficient
subjects and falciparum malaria, may lead to acute
tubular necrosis. Major surgical proce-dures especially
open heart surgery and road traffic accidents, are other
important causes. Post-renal causes are uncommon in
children.
Pre-renal ARF
In pre-renal type of ARF, the functional integrity of the
kidney is preserved and renal dysfunction is reversible with
restoration of the underlying hemodynamic abnormality.
TABLE 14.7.1 Staging of acute kidney injury*

Stage
1
2
3**
Serum creatinine criteria
Urine output criteria
Increase in serum creatinine of >0.3 mg/dl or >150% to 200%

(1.5- to 2- fold) from baseline
Increase in serum creatinine to >200% or 300% (>2- to 3-fold)
from baseline
Increase in serum creatinine to >300% (>3-fold) from baseline
(or serum creatinine of >4.0 mg/dl with acute increase of >0.5 mg/dl)
Less than 0.5 ml/kg per hour for >6 hr

Less than 0.5 ml/kg per hour for >12 hr
Less than 0.3 ml/kg per hour for >24 hr, or
anuria for 12 hr
* Only one criterion (creatinine or urine output) should be fulfilled for definition and staging
**Patients receiving renal replacement therapy (RRT) are considered in stage 3
738

TABLE 14.7.2. Causes of acute renal failure
Pre-renal
Renal
Acute tubular
necrosis
Acute gastroenteritis, blood loss, shock,

sepsis, fulminant hepatitis, congestive
heart failure
Prolongation of pre-renal insult, malaria,
intravascular hemolysis, sepsis, nephrotoxic drugs, snakebite and other envenomations
Glomerulonephritis
Acute glomerulonephritis (poststreptococcal, other infections), crescentic glomerulonephritis
Interstitial nephritis
Acute interstitial nephritis (drugs,

infections)
Vascular
Thrombotic microangiopathy (hemolytic

uremic syndrome), small vessel vasculitis,
renal vein thrombosis, renal artery
obstruction
Post-renal
Obstructive uropathy, neurogenic bladder
Characteristically, there is severe decrease in renal

perfusion and a fall in glomerular filtration but tubular
function is maintained with increased reabsorption of
sodium, water and urea. The renal perfusion is restored
following correction of pre-renal factors, e.g. repletion of
fluids in hypovolemia.
Although various conditions that lead to pre-renal
failure can progress to acute tubular necrosis, it is difficult
to predict when that transition may occur or the duration
of circulatory impairment necessary for its development.
More than one factor is often operative. Thus, renal injury
is compounded when dehydration is associated with the
administration of nephrotoxic agents.
Post-renal ARF
Bilateral obstruction at pelviureteric junction or ureters,
and obstruction at the bladder outlet or urethra by calculi,
blood clots and pus debris may cause post-renal ARF.
Renal Causes
Renal causes of ARF may be grouped into that involving the tubules, glomeruli, interstitium and blood
vessels and microvasculature.
Acute Tubular Necrosis
Renal hypoperfusion leads to a spectrum of conditions
ranging from typical pre-renal ARF, to an intermediate
stage, which is slowly reversible over 1 to 3 days, and

established ARF with acute tubular necrosis. In more
extreme instances, cortical necrosis may be present. Thus,
there is progressively severe renal injury, which is
inversely related to the chances of recovery.
A variety of renal insults can lead to acute tubular
necrosis. Common causes include renal hypoperfusion
following extracellular fluid volume contraction, e.g. in
acute gastroenteritis, severe renal vasoconstriction,
nephrotoxic agents, sepsis and shock.
G-6-PD deficiency with intravascular hemolysis: Exposure
to oxidant drugs, most notably antimalarials (chiefly
primaquine), sulphonamides, nitrofurantoin and
naphthaquinolones, and occasionally infections may
result in acute intravascular hemolysis in patients who
are G-6-PD deficient. The extent of hemolysis depends
upon the amount of drug taken and the degree of enzyme
deficiency. In severe cases, there is rapid onset of pallor,
weakness, mild jaundice and hemoglobinuria. Renal
tubular damage is indicated by elevation of blood urea
and creatinine levels. Occasionally, G-6-PD deficiency
with intravascular hemolysis may develop in a child
having viral hepatitis; extremely high levels of serum
bilirubin and other features of liver dysfunction may be
seen.
Snakebite: Snakebites are serious in children because of
the relatively large volume of venom injected. ARF may
develop due to intravascular hemolysis, shock and direct
tubular injury. Prompt administration of antivenom and
supportive treatment may reduce the severity of the
manifestations.
Sepsis: Serious infections and septicemia account for a
large proportion of ARF in the neonates and infants.
Shock and consumption coagulopathy are often associated.
Hemolytic Uremic Syndrome (HUS)
HUS is characterized by a triad of microangiopathic
hemolytic anemia, thrombocytopenia and acute renal
failure. On peripheral smear, red cells show fragmentation and schistocyte formation, which is caused by
mechanical injury as these cells traverse the damaged
microvasculature. HUS is mostly seen in infants and
young children. In India, and other developing countries,
HUS is associated with dysentery due to Shigella
dysenteriae 1. Shigella (shiga) toxin enters the circulation

and leads to endothelial cell damage in the renal microvasculature, followed by local coagulation. In developed
countries, HUS follows a diarrheal illness caused by
strains of verotoxin producing enterohemorrhagic E. coli
(verotoxin being similar to shiga toxin).
The patients present with acute onset of pallor,
oliguria, hypertension, occasional petechiae and sensorial
changes. Biochemical abnormalities, in addition to
hematologic features, reflect the severity of renal
insufficiency. Urinalysis may show microscopic hematuria and mild proteinuria, but heavy proteinuria and
gross hematuria are rare. There is no specific treatment
for HUS. The management consists of standard measures
for ARF, and treatment of anemia and hypertension. The
prognosis is related to the severity of renal involvement;
those with extensive damage and renal cortical necrosis
have a poor outcome. Even patients who recover from
the acute illness may develop progressive renal
insufficiency.
Occasionally, HUS is seen without a preceding
diarrheal illness (D negative, atypical HUS). The
underlying etiology is heterogeneous and includes
disorders of complement regulation, infection with
S. pneumoniae, systemic lupus erythematosus and medications (quinine, cyclosporine, oral contraceptives). The
clinical features are similar to typical HUS; hypertension
is severe and renal failure may be prolonged. The longterm outcome of patients with D- HUS is unsatisfactory.
ARF in the Newborn
Because of the immaturity of the kidney with a low renal
blood flow, the tubules are particularly susceptible to
injury. Birth asphyxia, respiratory distress syndrome,
shock, sepsis and use of nephrotoxic drugs are important
causes of ARF. Obstructive lesions such as bilateral pelviureteric junction obstruction and posterior urethral
valves are frequently detected in this age group.
Diagnostic Approach to ARF
In a child having oligoanuria, it is important to look for
pre-renal factors that lead to renal hypoperfusion. A
history of diarrhea, vomiting, fluid or blood loss should
be sought and an assessment of fluid intake in the
previous 24 hours made.
In pre-renal ARF, renal blood flow and glomerular
filtration rates decline but tubular reabsorption of salt
and water continues. Thus, there is oliguria with low
739
urine sodium, high urine osmolality, increased plasma

urea to creatinine ratio and low fractional excretion of
sodium. In intrinsic renal failure (acute tubular necrosis)
in a setting of renal hypoperfusion, there is diminished
tubular function with high urine sodium and dilute urine.
Several indices (Table 14.7.3) help to differentiate prerenal from established renal failure. Fractional excretion
of sodium is the most sensitive and reliable index. These
indices are however, not useful in patients with nonoliguric renal failure, and those receiving diuretics.
TABLE 14.7.3: Differences between pre-renal ARF and
established ARF (indices for neonates are in parentheses)
Indices
Pre-renal
ARF
Established
ARF
Urinary sodium (mEq/L)
<20 (<30)
>40 (>60)
Urinary osmolality (mOsm/kg)
>500 (>400)
<300 (<350)
Blood urea to creatinine ratio
>20 :1
<20 :1
Urine osmolality/plasma
osmolality
>1.5 (>2)
<0.8-1.2 (<1.1)
Fractional excretion of
sodium (percent)
<1 (<3)
>1 (>10 )
Fractional excretion of sodium (percent) =

urine sodium serum creatinine 100
__________________________________________________
serum sodium urine creatinine

In pre-renal ARF, expansion of the intravascular
volume leads to improved renal perfusion and an
increase in urine output. Dehydration is corrected by
infusion of 20 ml/kg of an isotonic solution (0.9% saline
or Ringers lactate) over 45 to 60 minutes. During this
period, the patients vital signs are monitored and care
taken to avoid overhydration. If there is still no clinical
improvement, a clinical decision should be made
regarding the patients intravascular volume status, as
further fluid administration could be potentially
hazardous in a child with oligoanuria. Assessment of the
central venous pressure may be needed, since clinical
assessment may be difficult. If urine output has not
improved despite volume repletion or if the patient
shows features of overhydration, frusemide (1-2 mg/kg)
may be administered intravenously to induce diuresis.
If these measures fail to result in diuresis, a diagnosis of
established ARF is made.
Varieties of interventions have been examined to
prevent ARF and reduce the need for renal replacement
740
therapy. Current evidence suggests that there is no

indication for the use of intravenous mannitol, low-dose
dopamine and diuretics for this purpose. In view of lack
of benefit and presence of adverse effects, their use is
not recommended.
Clinical Features
The child with ARF may have altered sensorium and
convulsions due to advanced uremia or hypertensive
encephalopathy. The breathing may be rapid and deep
due to acidosis. There may be peripheral or pulmonary
edema. Blood pressure may be elevated, or there may be
hypotension indicating volume depletion.
Clinical features that suggest an underlying cause,
include a history of fluid or blood loss with severe
dehydration (acute tubular necrosis); edema, hematuria
and hypertension (acute glomerulonephritis); dysentery,
pallor and petechiae (HUS), or sudden pallor, passage
of dark red urine and jaundice (acute intravascular
hemolysis). Severe hypertension is suggestive of
glomerulonephritis or atypical HUS. A history of
interrupted urinary stream and palpable bladder or
kidney, suggests an obstructive uropathy, and that of
abdominal colic, hematuria and dysuria suggests a
urinary tract calculus or infection. Anuria may occur in
urinary tract obstruction, renal cortical necrosis, bilateral
vascular occlusion, severe glomerulonephritis or
vasculitis.
ARF may occasionally be superimposed on chronic
renal disease. Features such as failure to thrive, hypocalcemia, hyperphosphatemia, hypertensive retinopathy, renal osteodystrophy and small contracted
kidneys indicate an underlying chronic renal disease. Use
of nephrotoxic drugs, rapid increase in hypertension,
infections and hypovolemia may precipitate ARF in a
child with pre-existing renal damage.
Appropriate investigations should be performed to
confirm the diagnosis. Peripheral blood smear examination showing features of microangiopathic hemolysis,
thrombocytopenia, increased reticulocyte count and
elevated levels of LDH suggests HUS. Throat swab
culture for Streptococcus, titers of ASO and other
streptococcal antibodies and serum complement should
be done in patients suspected to have acute glomerulonephritis. In glomerular and vascular disease, urinary
protein excretion is increased to 3+ or 4+, along with red

cells and red cell casts. Presence of eosinophils in the
urinary sediment suggests interstitial nephritis.
Ultrasonography is a useful imaging tool in renal
failure because of its non-dependence on renal function.
It allows visualization of the size of kidneys and the
pelvicalyceal system, structural anomalies and calculi.
Renal biopsy is indicated in the following:
i. Patients where the etiology of ARF is not identified,
especially in context of a systemic disease, e.g.
vasculitis.
ii. Unremitting ARF lasting longer than 2-3 weeks:
biopsy may identify a cause such as crescentic
glomerulonephritis, or assess the extent of damage
and outcome, e.g. acute cortical necrosis.
iii. Suspected drug toxicity, e.g. interstitial nephritis, or
in a renal transplant recipient treated with cyclosporine.
Immediate Management of ARF
Immediate attention should be directed towards
detection and management of life-threatening complications. Clinical evaluation includes measurement of blood
pressure, fundus examination and a search for signs of
congestive heart failure and fluid overload, acidosis and
anemia. Immediate investigations include estimation of
levels of hemoglobin, urea, creatinine, electrolytes and
bicarbonate. An electrocardiogram (ECG) is done to
detect potassium cardiotoxicity and an X-ray film of the
chest for pulmonary edema.
Hyperkalemia
Urgent treatment is instituted depending upon the blood
potassium levels and ECG changes. If serum potassium
is below 6.5 mEq/L or there are mild ECG changes, such
as peaked T waves, administration of 7.5 percent solution
of sodium bicarbonate in a dose of 1-2 ml/kg over 15 to
30 minutes may reduce serum potassium level. If the level
is more than 6.5 mEq/L or more ominous ECG changes
(widened QRS complex or sine wave) are present slow
infusion of 0.5 ml/kg of 10 percent calcium gluconate
over 5 to 10 minutes should be given, with ECG being
monitored. This should be followed by the administration 0.5-1 g/kg of 50 percent glucose solution and 0.2
units of insulin for each gm of glucose administered. The
administration of bicarbonate and insulin-glucose will
acutely reduce the serum potassium level, and calcium
741
infusion will prevent fatal cardiac arrhythmias without

lowering serum potassium level. Intravenous or inhaled
salbutamol also lowers the levels of serum potassium.
The action of potassium binding resins (calcium or
sodium resonium 1 g/kg orally or rectally) is slow and
these are used in chronic situations to prevent hyperkalemia.
correction of acidosis. The estimated deficit is administered according to the formula: 1/2 deficit weight in
kg 0.5 = mEq of sodium bicarbonate. If severe acidosis
is present as indicated by deep and rapid breathing and
blood gas measurements are not available, sodium
bicarbonate 2 to 3 mEq/kg should be administered by
an IV infusion over 15-30 minutes.
Pulmonary Edema and Heart Failure
Anemia
The child may have overhydration, pulmonary edema

and congestive heart failure, which result from administration of excessive amount of fluid either orally or
intravenously. The child should be placed in a sitting
position and given oxygen. The CVP should be monitored. If the patient is in shock, dopamine 5-10 mg/kg
body weight per minute is administered by IV infusion,
using minimum amount of fluid that contains no sodium
or potassium. If the condition does not rapidly improve,
the patient should be managed by endotracheal
intubation and assisted ventilation with positive endexpiratory pressure. Administration of IV frusemide (23 mg/kg) may induce some diuresis. Rotating tourniquets and venesection may occasionally be life-saving.
While these measures are being carried out, peritoneal
dialysis with hypertonic glucose should be started.
Packed red cells in aliquots of 3 to 5 ml/kg should be

infused. In the presence of fluid overload, partial
exchange transfusion may be required. Blood pressure
should be carefully monitored.
Hypertensive Encephalopathy
A rapid rise in blood pressure, usually associated with
retention of sodium and water (as in acute glomerulonephritis), may lead to encephalopathy presenting with
headache, vomiting and altered sensorium. Loss of
vision, hemiparesis and seizures may be present. The
immediate management aims at reducing the blood
pressure to safe levels (95th percentile for age, sex)
without causing it to fall precipitously and produce
cerebral ischemia. The medication of choice is IV infusion
of sodium nitroprusside (labetalol or nicardipine are
preferred alternatives, if available) in incremental doses
until the desired effect is produced. During infusion,
blood pressure levels are monitored closely. If the above
agents are not available, oral nifedipine (0.25-0.5 mg/
kg) may be used with careful measurements of blood
pressure. If there is evidence of fluid overload, coadministration of IV frusemide is useful.
Acidosis
A patient with a blood pH of below 7.2 and serum
bicarbonate level less than 12 mEq/L needs prompt
Standard Supportive Care of ARF

In a child with ARF in whom serious complications are
absent or have been adequately treated, standard
supportive care is instituted. Such management is based
on close attention to the intake of fluid and electrolytes,
provision of proper nutrition, prevention and treatment
of infections, careful monitoring and dialysis.
Diet
Adequate nutrition improves survival in ARF. A diet
containing 0.8 to 1 g/kg protein of high biologic value
and 80 to 120 Cal/kg should be given. Carbohydrates
and fats are allowed liberally. Volume restriction during
oliguria often imposes severe limits on the calories that
can be provided. Dietary restrictions are eased once
dialysis is instituted.
Management of Infections
Various infections (respiratory and urinary tract,
peritonitis and septicemia) are the immediate cause of
death in many patients. All procedures must be performed
with strict aseptic techniques, IV lines should be carefully
watched and skin puncture sites cleaned and dressed. Oral
hygiene should be ensured. Devitalized tissue and
collections of blood should be surgically removed. Sepsis
is suggested by hypothermia, persistent hypotension,
hyperkalemia and a disproportionate rise of blood urea
as compared to creatinine (indicating a catabolic state).
Once infection is suspected, appropriate specimens should
be taken for culture and antibiotics started.
Standard charts should be consulted to modify the
dose and dosing interval of various antibiotics.
742
Fluid and Electrolyte Balance

Fluid and electrolyte intake in a patient with ARF is crucial. The daily fluid requirement amounts to insensible
water losses (300-400 ml/m2) and the urinary output.
The former should be replaced with 10 percent glucose
solution. Urinary losses and those from vomiting,
diarrhea and aspiration should be replaced with 0.45
percent sodium chloride in 5 percent glucose solution.
Potassium containing fluids should not be given. It is
usually possible to administer the required amounts of
fluid by mouth, unless there is persistent vomiting.
Hyponatremia: Serum sodium less than 130 mEq/L may
be present at the initial diagnosis of ARF or develop later
during the course of management. In both instances,
hyponatremia is the result of excessive fluid administration rather than increased sodium loss. Profound
hyponatremia when associated with sensorial alteration
or seizures requires prompt correction. Serum sodium
concentration should be increased by 5 to 10 mEq/L over
a 60 to 120 minute period by infusion of 3 percent saline;
12 ml/kg of this solution will raise serum sodium by 10
mEq/L. It is emphasized that sodium administration is
usually not required to correct hyponatremia associated
with ARF and fluid restriction is the primary mode of
therapy. Sodium administration is hazardous in patients
with excessive body water and may cause hypertension
and congestive heart failure.
Hyperkalemia: Serum potassium levels should be
measured daily. Ion exchange resin (sodium or calcium
resonium) may be used to prevent hyperkalemia.
Hyperphosphatemia, hypermagnesemia and hypocalcemia:
Once ARF has persisted for a few days, hyper-phosphatemia (5-8 mg/dl) and hypermagnesemia may occur.
Hypocalcemia is usually asymptomatic because of
associated acidosis. However, tetany or convulsions may
be precipitated by excessive alkali therapy. Calcium
gluconate or carbonate may be administered with meals
at a dose of 30-50 mg/kg elemental calcium. Hyperphosphatemia is treated with aluminum hydroxide gel, which
chelates and prevents absorption of ingested phosphate.
Specific therapy: Therapy with high dose IV corticosteroids initially, followed by oral prednisolone is
recommended in patients with ARF secondary to rapidly
progressive glomerulonephritis, systemic vasculitis and
acute interstitial nephritis. Plasmapheresis and/or
infusion of fresh frozen plasma may be indicated in a

subset of subjects with atypical HUS.
Monitoring
The child should be closely monitored. Accurate record
of intake and output, and weight should be maintained.
Laboratory tests are carried out depending upon the
stability of the condition, progression of ARF and presence of complications. A careful physical examination
should be done at least twice a day.
Diuretic Phase in ARF
The clinical course of acute tubular necrosis is often
characterized by 3 phases: oligoanuria, diuresis and
recovery. The duration of oliguria may be just a few hours
to several weeks; in uncomplicated acute tubular
necrosis, it usually lasts for 5 to 10 days. Subsequently
there is a progressive rise in urine output, which may
reach 2-3 liters per day accompanied by increased losses
of electrolytes since tubular reabsorption is still impaired.
The diuretic phase should be managed by replacement
of urinary output with 0.45 percent saline. Potassium
supplementation may be necessary.
Renal Replacement Therapy
The absolute indications for dialysis include severe or
persistent hyperkalemia, congestive heart failure,
pulmonary edema, severe acidosis (total CO2 content
<10-12 mEq/l) and encephalopathy secondary to uremia
or hyponatremia. Early dialysis should be performed in
HUS and in hypercatabolic states, e.g. extensive trauma
and infections.
All modalities of renal replacement (peritoneal
dialysis, hemodialysis, continuous hemofiltration) can
be used during ARF. The choice of the procedure
depends on the age and size of the patient, cardiovascular
status, availability of vascular access, integrity of
peritoneal membranes and the expertise available at the
center. In young children, peritoneal dialysis is preferred
since it is simple to perform, requires minimum
equipment and does not require vascular access.
Critically sick children often tolerate this mode better
than hemodialysis due to the slow rate of fluid removal
and correction of metabolic abnormalities. A wide range
of PD catheters is available, permitting dialysis at all ages
and for different durations. Hemodialysis is more

effective in ARF associated with hypercatabolic states
(e.g. extensive trauma, sepsis, burns).
Continuous hemofiltration is a technique whereby
excessive fluid is removed without dialysis. It is
particularly useful for the management of critically sick
patients with hemodynamic instability, severe fluid
overload and in patients with major surgical procedures,
burns, heart failure and septic shock, especially when
conventional hemodialysis or peritoneal dialysis is not
possible. The procedure is hemodynamically gentler and
fluid is removed in a controlled manner. Different modes
include continuous arteriovenous hemofiltration
(CAVH), continuous venovenous hemofiltration (CVVH)
and continuous arteriovenous hemodiafiltration
(CAVHD).
Prognosis and Outcome
The derangements caused by ARF can be reversed by
optimal management and dialysis. The eventual recovery
and the long-term outcome depend upon the underlying
condition. The prognosis is good in acute tubular necrosis
and intravascular hemolysis, when complicating factors
are absent. The outcome is poor in infants with sepsis,
presence of multi-organ failure, cardiac surgery and
delayed referral. The outcome, in crescentic glomerulo-
743
nephritis and HUS, depends on the severity of renal

injury.
If ARF is prolonged beyond 2 to 3 weeks, multiple
dialyses may be required. Maintenance of nutrition and
prevention of infections become crucial as patients may
die of infection and inanition before significant recovery
of renal function. Many survivors of ARF in the neonatal
period and childhood continue to have some degree of
functional abnormality, which may not be immediately
apparent. It is therefore necessary that survivors of ARF
in childhood remain under long-term observation with
monitoring of urinalysis and measurement of blood
pressure.
BIBLIOGRAPHY
1. Andreoli SP. Acute renal failure. Curr Opin Pediatr
2002;14:183-8.
2. Bagga A. Management of acute renal failure. Indian J
Pediatr 1999;66:225-39.
3. Besbas N, Karpman D, Landau D, Loirat C, et al. A
classification of HUS and TTP and related disorders.
Kidney International 2006;70:423-31.
4. Gulati A, Bagga A. Acute kidney injury: Standardizing
terminologies. Indian J Pediatr 2008;75:526-7.
5. Moghal NE, Embleton ND. Management of acute renal
failure in the newborn. Semin Fetal Neonatal Med
2006;11:207-13.
14.8 Nephrotic Syndrome

RN Srivastava, Arvind Bagga
INTRODUCTION
Nephrotic syndrome is characterized by heavy proteinuria, hypoalbuminemia (serum albumin < 2.5 g/dL),
hyperlipidemia (serum cholesterol > 200 mg/dL) and
edema. The clinical and biochemical features of nephrotic
syndrome result from heavy proteinuria (more than
40 mg/m2/hour). Sustained proteinuria is followed by
hypoalbuminemia, lowered plasma oncotic pressure and
edema.
In about 95 percent cases of nephrotic syndrome, there
is a primary glomerular abnormality. The remainder is
caused by renal involvement in diverse conditions, such
as systemic lupus erythematosus, Henoch-Schnlein
purpura, amyloidosis and hepatitis B. More than
80 percent children with idiopathic nephrotic syndrome

show insignificant glomerular abnormalities on light
microscopy (minimal change nephrotic syndrome,
MCNS), whereas others have several distinct glomerular
lesions. The former usually respond to corticosteroid
therapy with complete remission and have an excellent
long-term prognosis. Those with significant glomerular
abnormalities usually do not respond to corticosteroids
and in a majority of cases, there is increasing renal damage
and a poor outcome.
Mechanisms of Proteinuria
The glomerular capillary wall consists of three layers:
fenestrated endothelium, glomerular basement
744
membrane (GBM) and epithelium. The endothelial lining

contains pores of 70 to 100 nm diameter. The endothelial
surface is negatively charged due to the presence of
polyanionic surface glycoprotein, podocalyxin. The
endothelium prevents blood cells from being filtered and
contributes to the charge selective barrier.
The GBM contains a meshwork of negatively charged
molecules rich in heparan sulfate, proteoglycans and
sialoproteins. These negative sites are important for
maintaining the normal structure and function of the
filtration barrier. The GBM acts as a semipermeable filter,
preventing the passage of macromolecules while
allowing fluid and low molecular weight solutes. The
slit diaphragm between adjacent podocytes is also an
important component of the glomerular filter.
Normally, negligible amounts of albumin and
globulin are excreted in urine. Small molecules, which
are less than 20,000 daltons such as beta-2 microglobulin
are freely filtered, but almost completely reclaimed by
the proximal tubule. Heavy proteinuria is usually due
to a glomerular abnormality. As a result, proteins that
are not normally filtered or filtered in very small amounts
pass readily into the urinary space and are excreted in
the urine.
Pathogenesis of Nephrotic Syndrome
In minimal change nephrotic syndrome (MCNS), light
microscopy does not disclose significant abnormalities.
Deposits of immune reactants are not seen on immunofluorescence examination, serum levels of complement
(C3) are normal and circulating immune complexes are
absent. However, immunologic mechanisms seem to be
involved in the pathogenesis of MCNS. The remission
that occasionally follows measles, association with
allergy, and response to immunoactive agents (steroids,
immunosuppressive and immunomodulatory drugs)
suggest an underlying immune dysfunction. However,
the precise mechanism of proteinuria is not clear.
A proportion of patients with nephrotic syndrome
show genetic mutations of proteins (nephrin, podocin,
actinin) required for integrity of the slit diaphragm. Such
patients do not respond to therapy with corticosteroids.
Finally, some patients with nephrotic syndrome show
histological abnormalities of the glomerulus (focal
segmental glomerulosclerosis, membranoproliferative
glomerulonephritis), which disrupt the glomerular filter
resulting in proteinuria.
Figure 14.8.1: A 2-year-old girl with nephrotic syndrome and

anasarca. Note ascites and facial puffiness
Clinical Features
The disease usually starts between the ages of 2 to 6 years;
60 to 70 percent are boys. When the disorder first occurs
after the age of 10-12 years, the chances of presence of a
significant underlying glomerular lesion are greater.
The onset is insidious with swelling around the eyes
and facial puffiness, which may be mistakenly ascribed
to allergy, conjunctivitis, mumps or dental infection. The
swelling gradually increases to involve the extremities
and abdomen and if untreated, may become massive
(Fig. 14.8.1). Occasionally, generalized swelling over the
body may develop acutely and be associated with gross
hematuria and oliguria. Such cases present a mixed
picture of nephrotic syndrome and acute nephritis, which
requires urgent detailed investigations and a renal
biopsy.
Evaluation
The patient should be examined to detect any associated
infection. The height, weight and blood pressure is
recorded. Regular weight record helps monitor the
decrease or increase of edema. Physical examination is
done to detect infections and underlying systemic
disorder, e.g. systemic lupus erythematosus and Henoch
Schonlein purpura.
745
Urinalysis
Treatment of the Initial Episode
Nephrotic range proteinuria is present if early morning

urine protein is 3+/4+ (on dipstick or boiling test), spot
protein/creatinine ratio > 2 mg/mg, or urine albumin
excretion > 40 mg/m2 hr. Precise quantitative assessment
of proteinuria, including 24-hr urine protein measurement is seldom necessary. Urine microscopy is done to
look for red cells; persistent microscopic hematuria
suggests the likelihood of an underlying significant renal
histologic lesion.
Adequate treatment of the initial episode, both in terms

of dose and duration of corticosteroids, is necessary.
Evidence from multiple studies suggests that appropriate
therapy of the initial episode is an important determinant
of long-term outcome. It is recommended that the initial
episode be treated with prednisolone at a dose of 2 mg/
kg body weight given daily for 6 weeks. The dose of
prednisolone is then reduced to 1.5 mg/kg administered
on alternate days, as a single morning dose, for another
6 weeks, after which it is discontinued. Shorter duration
of initial therapy is not recommended and may predispose to a higher risk of subsequent relapses.
Prednisolone should preferably be given after meals;
treatment with antacids is necessary in patients with
gastritis. Most patients respond to prednisolone with
complete disappearance of proteinuria within 2 weeks;
only a minority responds beyond 4 weeks of treatment.
The use of other corticosteroid preparations, including
methylprednisolone, dexamethasone, betamethasone,
triamcinolone, hydrocortisone or deflazacort is not
recommended.
A small proportion of patients has only one episode
of the disease, and is then cured. However, most patients
suffer from relapses for several years. About 30 percent
patients have infrequent relapses (three or fewer relapses
in one year), 40 percent frequent relapses and the
remainder needs almost continuous treatment with
prednisolone to maintain remission (steroid dependence). Table 14.8.2 lists standard definitions used for
defining the course of nephrotic syndrome.
Blood Examination
Blood is examined for levels of urea, creatinine, proteins
and cholesterol. In MCNS, blood urea levels are normal
unless edema is massive with associated oliguria.
Persistently elevated urea and creatinine suggest the
presence of significant renal histologic lesions. Hypoalbuminemia (serum albumin < 2.5 g/dl) and hyperlipidemia (total cholesterol > 200 mg/dl) are present. Serum
IgG levels are usually low and IgM raised. Serum C3
levels may be decreased in patients with membranoproliferative GN.
Appropriate laboratory tests should be done when a
collagen vascular disorder or renal vasculitis is suspected.
An X-ray film of chest and a Mantoux test are carried
out to exclude tuberculosis.
MANAGEMENT
Clinical and laboratory evaluation identifies children
likely to have MCNS. In such patients, a standard course
of prednisolone is instituted. Indications for renal biopsy
are listed in Table 14.8.1.
TABLE 14.8.1: Indications for kidney biopsy
At onset
Age at onset less than one year
Gross hematuria, persistent microscopic hematuria or low
serum C3
Sustained hypertension
Renal failure not attributable to hypovolemia
Suspected secondary cause of nephrotic syndrome
After initial treatment
Proteinuria persisting despite 4 weeks treatment with daily
corticosteroids
Before treatment with cyclosporine A or tacrolimus
Treatment of Relapse
A relapse is often precipitated by an upper respiratory
infection. The patient should be examined for infections,
which should be treated before initiating corticosteroid
therapy. Appropriate therapy of an infection might rarely
result in spontaneous remission, avoiding the need for
treatment with corticosteroids.
Prednisolone is administered at a dose of 2 mg/kg/
day (single or divided doses) until remission. Subsequently, prednisolone is given in a single morning dose
of 1.5 mg/kg on alternate days for 4 weeks, and then
discontinued. The usual duration of treatment for a
relapse is thus 5-6 weeks. In case the patient is not in
remission despite two weeks treatment with daily
746
TABLE 14.8.2: Definitions related to nephrotic syndrome

Remission
Urine albumin nil/ trace (proteinuria

< 4 mg/m2/h) for 3 consecutive morning
specimens
Relapse
Urine albumin 3+/4+ (proteinuria > 40 mg/

m 2 /h) for 3 consecutive morning
specimens, having been in remission
previously
Frequent relapses
Two or more relapses in initial 6-months,

or more than three relapses in any
12-months
Steroid dependence Two consecutive relapses when on

alternate day steroids or within 14 days of
its discontinuation
Steroid resistance
Absence of remission despite therapy with

daily prednisolone at a dose of 2 mg/kg
per day for 4 weeks
prednisolone, the treatment is extended for two more

weeks. Patients showing no remission despite 4 weeks
treatment with daily prednisolone are labeled as steroid
resistant and managed accordingly.
Infrequent Relapses
Patients with infrequent relapses are managed using the
aforementioned regimen for each relapse. Such children
are at a low risk for developing steroid toxicity.
Frequent Relapses and Steroid Dependence
Patients having frequent relapses or steroid dependence
require repeated courses of prednisolone may develop
serious steroid toxicity, including cushingoid features
(obesity, hirsutism, striae), hypertension, impaired
glucose tolerance, posterior subcapsular cataract,
emotional problems and growth retardation. Alternative
regimens in such patients are listed below:
i. Long-term alternate day prednisolone: Following
treatment of a relapse, prednisolone is tapered to
maintain the patient in remission on alternate day
dose of 0.5-0.7 mg/kg, which is administered for
9-18 months. Long-term alternate day prednisolone
is effective in maintaining a remission or reducing
the number of relapses. It has few side effects and
does not seem to interfere with growth. Breakthrough relapses are treated with standard treatment of relapse. If the prednisolone threshold, to
maintain remission, is higher or if features of steroid
toxicity are seen, additional use of the following
immunomodulators is recommended.
ii. Levamisole: Levamisole is beneficial in reducing

relapse rates in patients with frequent relapses and
steroid dependence. It is administered at a dose of
2 mg/kg on alternate days for 12-24 months. Cotreatment with prednisolone at a dose of 1.5 mg/kg
on alternate days is given for 2-4 weeks; its dose is
gradually reduced by 0.25 mg/kg every 4 weeks to
a maintenance dose of 0.5 mg/kg that is continued
for six or more months. Occasionally, it might be
possible to discontinue treatment with corticosteroids. The chief side effect of levamisole is
leukopenia; flu-like symptoms, liver toxicity,
convulsions and skin rash are rare.
iii. Cyclophosphamide: Treatment with cyclophosphamide may induce sustained remission in some
patients. Cyclophosphamide is given at a dose of
2-2.5 mg/kg/day for 12 weeks. Prednisolone is coadministered at a dose of 1.5 mg/kg on alternate
days for 4 weeks, followed by 1 mg/kg for the next
8 weeks; steroid therapy is tapered and stopped over
the next 2-3 months. Total leukocyte counts should
be monitored every 2 weeks; treatment with
cyclophosphamide is held if the count falls below
4000/mm3. An increased fluid intake and frequent
voiding help prevent hemorrhagic cystitis. Other
side effects are alopecia, nausea and vomiting; the
risk of gonadal toxicity is limited with a single
(12-week) course of cyclophosphamide. Therapy
with a related agent, chlorambucil, is currently not
recommended.
iv. Calcineurin inhibitors: Cyclosporine (CsA) causes
specific and reversible inhibition of T-helper
lymphocytes. The dose of CsA is 4 to 5 mg/kg per
day (100-150 mg/m2 per day) and is given for
12-24 months. Prednisolone is co-administered at a
dose of 1.5 mg/kg on alternate days for 2-4 weeks;
its dose is gradually reduced by 0.25 mg/kg every
4 weeks to a maintenance dose of 0.25-0.5 mg/kg
that is continued for six or more months.
Occasionally, treatment with corticosteroids may be
discontinued. Relapses often occur when therapy
with CsA is discontinued. Side effects of therapy
include hypertension, gum hypertrophy, hirsutism
and nephrotoxicity; hypercholesterolemia and
elevated transaminases rarely occur. Tacrolimus is
an alternative agent, preferred in adolescents
because of lack of cosmetic side effects.
747
Figure 14.8.2: Management of steroid sensitive nephrotic syndrome. The evidence for efficacy is strongest for cyclophosphamide
and cyclosporin. Levamisole has a modest steroid sparing effect and is a satisfactory initial choice for patients with frequent
relapses or steroid dependence. Treatment with cyclophosphamide is preferred in patients showing steroid toxicity or severe
relapses. The lack of renal, hemodynamic and metabolic toxicity with mycophenolate mofetil makes it an attractive alternative to
calcineurin inhibitors (Indian Pediatric Nephrology Group. Management of steroid-sensitive nephrotic syndrome. Indian Pediatr
2008; 45:203-14; with permission)
v. Mycophenolate mofetil: Prolonged therapy with this

agent, an inhibitor of purine metabolism, is found
effective in reducing relapse rates in patients with
frequent relapses and steroid dependence. Principal
side effects include gastrointestinal discomfort and
leukopenia.
A protocol summarizing the specific management of
patients with steroid sensitive nephrotic syndrome is
shown in Figure 14.8.2.
change nephrotic syndrome may show initial steroid

resistance.The treatment of these conditions is not well
established. Treatment with oral cyclophosphamide is
not satisfactory. Other regimens that have been used with
variable success include high dose IV pulse methylprednisolone with oral cyclophosphamide, monthly
pulses of IV cyclophosphamide, and oral treatment with
cyclosporine or tacrolimus. Patients with persistent
proteinuria have an unsatisfactory long-term outcome
and are at risk of progressive kidney failure.
INITIAL STEROID RESISTANCE

A renal biopsy is carried out in patients with steroid
resistance to determine the underlying glomerular lesion.
Mesangial proliferative glomerulonephritis, focal
segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (MPGN) account for
most of these cases. An occasional patient with minimal
CONGENITAL NEPHROTIC SYNDROME

The features of nephrotic syndrome may be present
rarely at birth or develop within the first 3 months of
life. Congenital syphilis and other intrauterine infections
are rare causes. The Finnish type, an autosomal recessive
condition, is relatively more common and is caused by
748
mutations in the nephrin (NPHS1) gene. There is no

specific treatment and chronic renal failure develops
quite early. A correct diagnosis is important for
prognosis, therapy and genetic counseling. The Finnish
type of congenital nephrotic syndrome can be diagnosed
antenatally at 15 to 18 weeks gestation by elevated alphafetoprotein concentration in the amniotic fluid and
maternal serum.
Advances in genetic diagnostic techniques including
positional cloning and sequencing have enabled us to
identify genes in several forms of familial and congenital
nephrotic syndrome. Denys Drash syndrome (infantile
nephrotic syndrome, male pseudohermaphroditism,
Wilms tumor; biopsy showing diffuse mesangial
sclerosis) and Frasier syndrome (nephrotic syndrome, XY
females, increased risk of gonadoblastoma, biopsy
suggestive of FSGS) are two forms of nephrotic syndrome
associated with WT1 gene mutation. Other genes
implicated include NPHS2 (podocin), actinin 4 (ACT4)
and laminin.
GENERAL CARE
Diet
A balanced diet, adequate in protein (1.5-2 g/kg) and
calories is recommended. Not more than 30% calories
should be derived from fat and saturated fats avoided.
Salt restriction is not necessary in most patients with
steroid sensitive nephrotic syndrome, but may be
recommended in those with persistent edema. Unnecessary restrictions in diet, salt intake and physical activity
are avoided. Diuretic induced losses of potassium may
be replaced by potassium supplements.
Edema
Hypoalbuminemia with reduction in colloid osmotic
pressure results in hypovolemia, which triggers various
sodium retaining mechanisms leading to accumulation
of salt and water in the body. Since treatment with
corticosteroids usually leads to diuresis within 5-10 days,
diuretics are avoided unless edema is significant.
Diuretics should also not be given to patients with
diarrhea, vomiting or hypovolemia.
Patients with persistent edema might require
treatment with oral frusemide (1-3 mg/kg daily). Patients
requiring higher doses and prolonged duration of
treatment with frusemide should receive potassium
sparing diuretics, e.g., spironolactone (2-4 mg/kg daily).

Blood pressure should be monitored frequently. A
gradual reduction of edema, over one week, is preferred.
Use of large doses of diuretics carries a hazard of inducing
sudden diuresis, which may aggravate hypovolemia and
precipitate acute renal failure. Therapy with IV albumin
(20%) is costly and the results are transient since most of
the infused albumin is rapidly lost in the urine. However,
it is necessary in patients with refractory edema, where
repeated administration might be necessary.
Infections
Bacterial infections in children with nephrotic syndrome
cause considerable morbidity, and are the commonest
cause of death. The factors responsible for the high
susceptibility to infections include urinary loss of factor
B and immunoglobulins, inadequate antibody response
and defective opsonization. Immunosuppressive
therapy, edema and ascites are contributory factors.
Peritonitis is the most common serious infection.
Others include pneumonia, meningitis, osteomyelitis,
arthritis and cellulitis. A majority of infections are due
to Streptococcus pneumoniae, but Gram-negative
organisms such as E. coli and Hemophilus influenzae are
also responsible. Tuberculosis also is more common in
children with nephrotic syndrome, particularly those
requiring prolonged corticosteroid therapy.
The clinical features of infections are often masked
and subtle. Infections must be suspected in any patient
with nephrotic syndrome who looks sick, has fever and
abdominal pain, vomiting and diarrhea. Appropriate
investigations should be done and treatment instituted.
Ascites predisposes to peritonitis and it is important to
treat relapses early and prevent edema. The administration of pneumococcal and varicella vaccines is recommended. Immunocompromised patients with varicella
should be administered oral/IV acyclovir depending on
its severity.
Immunization
The child should receive all recommended vaccines.
Patients receiving prednisolone at a dose of 2 mg/kg/
day or greater, or 20 mg/day or greater (if weighing
>10 kg) for more than 14 days are considered immunocompromised. Live agents should not be administered
to these patients. Live vaccines are administered once
the child is off immunosuppressive medications for at

least 6 weeks. Administration of some vaccines, e.g.
hepatitis B, measles-mumps-rubella or meningococcal
vaccines may rarely precipitate a relapse.
All children with nephrotic syndrome should receive
immunization against pneumococcal infections and
against varicella.
Coagulation Abnormalities
Nephrotic syndrome may be complicated by thrombosis
of major veins or arteries. An increase in platelet
aggregation and hepatic synthesis of clotting factors, and
urinary loss of clotting inhibitors contribute to the
hypercoagulable state. Renal vein is a common site of
thrombosis and is suspected in patients with oligoanuria,
hematuria or flank pain, especially following an episode
of dehydration. Major arteries (femoral and mesenteric)
and axillary and subclavian veins and cerebral venous
sinuses may also be involved. Saggital sinus and cortical
venous thrombosis may follow episodes of diarrhea and
present with convulsions, vomiting, altered sensorium
and neurological deficits. The diagnosis can be confirmed
by ultrasound examination, angiography or in suspected
pulmonary vein thrombosis by ventilation perfusion
scans. Treatment consists of correction of dehydration
and other complications, and use of heparin (IV) or lowmolecular-weight heparin (subcutaneously) initially,
followed by oral anticoagulants on the long-term. There
is no role for prophylactic treatment with anticoagulants
in patients with hypoalbuminemia.
Blood sampling in children with nephrotic syndrome
should be done only from superficial veins. Diarrhea and
volume depletion should be promptly treated.
749
and low cholesterol. Persistent, severe hyperlipidemia

in steroid resistant nephrotic syndrome may be treated
with lipid lowering agents.
Calcium, Vitamin D Metabolism
Hypocalcemia in nephrotic syndrome is due to a
reduction in protein bound calcium secondary to
hypoalbuminemia. Occasionally, low ionized calcium
levels are seen, which result from urinary loss of vitamin
D binding globulin and 25-hydroxyvitamin D3, and may
cause tetany. Patients on prolonged (> 3 months)
treatment with steroids should receive daily supplements
of oral calcium (250-500 mg daily) and vitamin D (125250 IU).
Hypovolemia and Acute Renal Failure
Patients with nephrotic syndrome in relapse are sensitive
to a reduction of blood volume. This complication can
occur due to unsupervised use of diuretics especially if
accompanied by septicemia, diarrhea or vomiting.
Prolonged renal hypoperfusion may result in renal
tubular necrosis. The diagnosis is suggested by moderate
to severe abdominal pain, hypotension, tachycardia, cold
extremities and poor capillary refill; hematocrit and blood
levels of urea and uric acid are elevated. Management
consists of rapid infusion of normal saline at a dose of
15-20 mL/kg over 20-30 minutes; this is repeated if
clinical features of hypovolemia persist. Infusion of 5%
albumin (10-15 mL/kg) or 20% albumin (0.5-1 g/kg) may
be used in subjects who do not respond despite two
boluses of saline.
Corticosteroid Side Effects
This may occur due to the disease state or secondary to

steroid therapy. Initial drugs used include ACE
inhibitors, calcium channel blockers or adrenergic
antagonists, keeping the blood pressure at less than the
90th percentile.
Prolonged therapy may be associated with significant

side effects including increased appetite, impaired
growth, behavioral changes, risk of infections, salt and
water retention, hypertension and bone demineralization. All patients should be monitored for cushingoid
features and blood pressure; 6-monthly record of height
and weight, and annual evaluation for cataract is
recommended.
Hyperlipidemia
Steroids during Stress
Hyperlipidemia is an important feature of nephrotic

syndrome. Patients with severe and persistent hyperlipidemia should maintain normal weight for height. The
diet should contain less than 30 percent fat, with equal
amounts of polyunsaturated and saturated fatty acids
Patients who have received high-dose steroids for more

than 2 weeks in the past year are at risk of suppression
of the hypothalamo-pituitary-adrenal axis. These
children require supplementation of steroids during
surgery, anesthesia or serious infections. Corticosteroids
Hypertension
750
are supplemented, as parenteral hydrocortisone at a dose

of 2-4 mg/kg/day, followed by oral prednisolone at 0.31 mg/kg/day. This is given for the duration of stress
and then tapered rapidly.
Reduction of Proteinuria
Persistent heavy proteinuria in steroid resistant nephrotic
syndrome itself may cause progression of glomerular
injury. Angiotensin converting enzyme inhibitors, such
as enalapril, reduce the amount of filtered protein, by
causing efferent arteriolar dilation and reducing
glomerular filtration pressure. Thus, proteinuria is
reduced which leads to rise in serum albumin levels.
relapses between the ages of 12-15 years, and recover

without any residual renal dysfunction. However, in a
given case, it is not possible to predict when the relapses
would cease. In a small proportion, there is development
of late steroid resistance and renal biopsy may show
abnormalities other than minimal change. In such cases,
the prognosis is guarded. The outcome of nephrotic
syndrome in patients with significant renal pathology
or steroid resistant nephrotic syndrome is variable.
Patients with persistent nephrotic range proteinuria are
at risk for progressive kidney disease. The long-term
outcome of congenital nephrotic syndrome, secondary
to mutations involving the NPHS1 gene, is unsatisfactory.
Patient and Parent Education

Parental motivation and involvement is essential in the
long-term management of these children. They should
learn how to examine urine for protein at home (using
dipstick, sulfosalicylic acid or boiling test) and maintain
a diary showing results of urine protein examination,
medications received and intercurrent infections. Parents
should also ensure a normal activity and school
attendance; the child should continue to participate in
all activities and sports.
OUTCOME IN NEPHROTIC SYNDROME
The outcome in patients with minimal change nephrotic
syndrome is satisfactory. Most patients stop getting
BIBLIOGRAPHY
1. Bagga A, Mantan M. Nephrotic syndrome in children.
Indian J Med Res 2005;122:13-28.
2. Hodson EM, Willis NS, Craig JC. Corticosteroid therapy
for nephrotic syndrome in children. Cochrane Database
Syst Rev 2007 Oct 17;(4):CD001533.
3. Hodson EM, Willis NS, Craig JC. Non-corticosteroid
treatment for nephrotic syndrome in children. Cochrane
Database Syst Rev 2008 Jan 23;(1):CD002290.
4. Indian Pediatric Nephrology Group, Indian Academy
of Pediatrics. Management of steroid-sensitive nephrotic
syndrome: Revised guidelines. Indian Pediatr 2008;
45:203-14.
5. Vats AN. Genetics of idiopathic nephrotic syndrome.
14.9 Urinary Tract Infection, Vesicoureteric

Reflux and Reflux Nephropathy
M Vijayakumar, RN Srivastava
URINARY TRACT INFECTIONS
Urinary tract infections (UTI) are common during
childhood and often associated with congenital
anomalies of the urinary tract and vesicoureteric reflux
(VUR), which together consititute an important cause of
chronic renal failure.
UTI is identified by significant bacteriuria on culture
of urine. It may be confined to the bladder and urethra
and is known as lower tract infection or dysuria
frequency syndrome. It is indiacated by dysuria,
frequency and suprapubic pain. In renal parenchymal

involvement (pyelonephritis), otherwise known as upper
tract infection, there are fever, chills and flank pain.
occasionally, asymptomatic bacteriuria is identified on
screening of healthy children.
UTI is more frequent in male neonates due to a higher
incidence of urinary tract anomalies. In older girls, lower
tract UTI is common, because of the short female urethra,
which is readily colonized with pathogenic organisms,
In the newborn period, renal involvement occurs by the

hematogenous route. Thereafter, in infants and older
children, bacteria enter the urethra and ascend into the
bladder. E.coli is the most common organism causing
UTI. E.coli that most often produce pyelonephritis have
special fimbriae on their surface through which they
attach to the uroepithelium. Bacteria have several
virulence factors, which leads to cell invasion and
inflammation. Other pathogens include Proteus
(common in uncircumcised boys), Streptococcus faecalis,
Klebsiella and Pseudomonas.
Obstruction to urine flow anywhere along the urinary
tract, VUR, instrumentation, urinary calculi, constipation
and pinworm infestation predispose to UTI. The host
defense mechanism chiefly consists of a normal urine
flow, which washes away the bacteria. The presence of
secretory IgA and antibacterial property of bladder
mucosa may have some role.
Clinical Features
Newborn period: The neonate may have features of
septicemia, jaundice, vomiting and shock.
Infant: There may be nonspecific symptoms such as
unexplained fever, diarrhea, vomiting and failure to
thrive.
Older child: The child has dysuria, frequency and
suprapubic pain. Fever, flank pain and toxic appearance
suggest renal parenchymal involvement.
Diagnosis
The diagnosis of UTI is suggested by detection of bacteria
and neutrophils on microscopic examination of a
carefully collected fresh sample of urine. Mild proteinuria, leukocyturia (>5 WBC/HPF in centrifuged urine
and >10 WBC/mm3 in uncentrifuged urine) and bacteria
on gram stain can indicate UTI. Enhanced urinalysis
using uncentrifuged urine and Neubauer counting
chamber along with gram staining of urine sediment is
found useful to get at the suspicion of UTI early. More
than 10 WBCs/mm3 with a positive gram staining will
indicate the possibility of UTI to a very reasonable extent.
The popular rapid tests like Nitrite or Greiss test and
leucocyte esterase tests have problems of false positivity
and negativity. Bacterial enzyme nitrate reductase can
convert the urinary nitrate to nitrite, which can be
751
detected. If sufficient time is not allowed for incubation

of bacteria with urine, the tests become negative as in
children with increased frequency. Even if UTI is caused
by a bacterium that does not contain nitrate reductase as
in streptococcal species, false negative results are seen
Similarly leucocyte esterase test detects leucocytes in
urine, which can be present in UTI as well as in other
conditions like interstitial nephritis or glomerulonephritis. A better method of utilizing these rapid tests
is by getting a combined positive tests for leucocyte
esterase and nitrite in a child with clinico-biological
features of upper tract UTI. A positive enhanced
urinalysis with positive rapid test will definitely indicate
UTI with certainty.
In urine culture, more than 105 colonies/ml indicates
significant bacteriuria whereas a colony count less than
104 is usually due to urinary contamination. A colony
count between 104 to 105/ml may be significant, if the
child has polyuria or has received antibiotics. In older
children, a midstream urine specimen is obtained. Urine
samples may be obtained by suprapubic bladder
aspiration or urethral catheterization in neonates and
infants where collecting midstream urine sample is
difficult. Imaging studies are considered in all children
with UTI. A child below the age of 2 years should have
an ultrasound (USG) study, DMSA renal scan and a
micturation cystourethrogram (MCU) with first attack
of UTI. Recent evidences state that this can be extended
up to 5 years of age. Older children are usually screened
by an USG following the first UTI. MCU should be done
in all children with recurrent UTI, and where USG or
DMSA scan shows anomalies or cortical scarring. A plain
X-ray film of abdomen detects bony deformities like spina
bifida and calculi. USG demonstrates renal anomalies,
dilated or irregular plevicalyceal system and renal
parenchymal scars. MCU may show VUR, bladder
thickening due to lower tract obstruction, posterior
urethral valves and can help in the assessment of residual
urine. Direct radionuclide cystogram is found useful as
a repeat test for documenting VUR on follow-up and
should not be used as the initial screening test as it
may not give details of the anatomy of bladder and
urethra.
Delay in diagnosis results in delayed treatment which
causes extensive morbidity. Most of the times, this is due
to vague symptomatology of UTI in young children and
infants. Young age, delay in initiating antibacterial
therapy, wrong choice of antibiotics, short duration of
752
therapy, recurrences and associated disorders like

vesicoureteric reflux are essential risk factors for renal
scarring. Growing kidneys up to 2 years of age and even
up to 5 years of age are at the risk of developing renal
scars and utilimately ending up with end stage renal
disease in adulthood due to renal parenchymal damage
that can occur in early childhood with upper tract
infection or otherwise known as acute pyelonephritis.
Asymptomatic bacteriuria: On screening of normal school

children, significant bacteriuria occasionally is detected.
The organisms are of low virulence that colonise the
lower tract. No treatment is necessary. But adolescent
females presenting with asymptomatic bacteriuria need
USG evaluation of the urinary tract to rule out renal
anamolies as chances of acute pyelonephritis occurring
during pregnancy in these individuals should be
remembered.
Management
If UTI is suspected clinically and suggested by urine
microscopy, treatment should be started promptly
without waiting for the result of urine culture. The initial
treatment is based on clinical evaluation of the severity
of UTI and the age of the patient.
Neonate and infant: Ampicillin and gentamicin are given
for a period of 10-14 days; cefotaxime or ceftriaxone may
be used instead.
Older children: Amoxicillin or co-trimoxazole orally are
the drugs of choice; oral cephalosporins may be also used.
The duration of therapy is 7-10 days. Patients who have
high fever, systemic toxicity or flank pain should receive
parenteral drugs as described for infants above.
Fever should be controlled and a liberal fluid intake
provided. The antibiotics may be modified, once the
culture and sensitivity results are available. With effective
treatment, symptoms disappear within 24-48 hours,
urine microscopy does not show bacteria and the culture
becomes sterile. Failure to respond suggests bacterial
insensitivity to the drugs, lack of compliance to treatment
or presence of complicating factors such as obstructive
urotpathy.
Chemoprophylaxis: Drugs used for chemoprophylaxis are
co-trimoxazole (1-2 mg/kg/daily) or nitrofurantion
(1-2 mg/kg daily), which is given in the night as a single
dose. The chief indication is in the management of VUR;
the aim is to keep the bladder urine sterile. The duration
of chemoprophylaxis is 6 months to two years, depending upon the associated anomalies and the problem of
recurrence.
Management of recurrent UTI: Recurrent UTI indicate
presence of complicating factors such as VUR, obstruction, neurogenic bladder or other abnormalities. A
through clinical examination and imaging studies are
mandatory.
VESICOURETERIC REFLUX (VUR) AND

REFLUX NEPHROPATHY
VUR implies passage of urine into the ureter and kidney
during micturition. Normally, the long submucosal and
intravesical segment of the ureter at the ureterovesical
junction closes when bladder contracts, effectively
preventing VUR. Incompetence of ureterovesical junction
due to shortening and lack of obliquity of the submucosal
and intravesical segments results in VUR. VUR can be
primary as an isolated defect or secondary associated
with other anomalies like posterior urethral valve or
neurogenic bladder. Voiding dysfunction should be
remembered in a child with VUR as this is recently
considered to complicate the disorder of VUR.
Thirty to forty percent of all children and 40-60
percent of neonates with UTI have VUR. UP to one-third
of children with UTI having VUR, develop renal scars.
Primary VUR may have a genetic basis and occur in
siblings.
Pathogenesis of Renal Scars
During micturition VUR allows the rise in intravesical
pressure to be transmitted to the ureter and renal pelvis,
which enables urine to enter papillary collecting ducts
and renal tubules (intrarenal reflux). Thus, pathogenic
organisms present in the bladder urine reach the renal
parenchyma and initiate inflammation and subsequent
scar formation. Reflux nephropathy indicates renal
parenchymal damage due to VUR.
The calyceal clubbing seen on IVP is a result of
papillary distortion and retraction following scar
contraction. The DMSA renal scan is a sensitive technique
to detect renal scars (Fig. 14.9.1).
Diagnosis
VUR is diagnosed and graded by a conventional MCU
done with radio contrast. Radionuclide cystogram using
Figure 14.9.1: 99mTc DMSA renal scan. Posterior view at 4

hours, following an intravenous injection of the radiotracer
showing bilateral cortical scarring (arrows)
DTPA also detects VUR, but the MCU can clearly show
abnormalities of the bladder and urethra. Hence
radionuclide cystogram is not useful in male infants as a
screening procedure as it will miss anatomical anomalies
of the urethra and bladder, which is more common in
females. Radionuclide cystogram is found to detect VUR
in some children where MCU failed to detect it as
radionuclide cystogram is more sensitive and specific
compared to MCU.
In mild to moderate VUR (grade I-III), there is reflux
into the non-dilated ureter or dilated ureter and upper
collection system. In severe VUR (grade IV-V), there is
reflux into grossly dilated ureter, pelvis and calyces.
Clinical Features
The child may have recurrent UTI with or without a
structural anomaly of the urinary tract. Those with reflux
nephropathy and marked renal parenchymal scarring
may present with chronic acidosis, hypertension or renal
failure.
Management of VUR
Children with VUR and otherwise normal urinary tract
are treated with long term chemoprophylaxis with
nitrofurantion (1-2 mg/kg body weight, as a single daily
night dose) or co-trimoxazole (1-2 mg/kg/day trimethoprim). Training the child for double or triple micturition
to reduce the residual urine is also beneficial. Urine
examination (microscopic and culture) is done if UTI is
suspected on follow-up. Yearly radionuclide cystography
is done to assess VUR. Grade I-III VUR resolves and even
753
higher grades may disappear in 80-90 percent of children.

Surgical indications will include non-resolution of VUR
by 5 years of age, VUR grades III-V associated with
bilateral renal scarring after 2 years of age, recurrent
breakthrough UTIs in children with VUR on uroprophylaxis, parents who are living in remote communities
and are not very confident about giving uroprophylaxis
or convinced about it and these are the same people who
in the event of suspected UTI will not do cultures, VUR
associated with paraureteric diverticulum or in duplex
systems as resolution in uncommon in this subset. Today
there are two options for correction of VUR. Subureteric
injection of Deflux or Macroplastique; is a day care or
out patient technique which is 70% effective in eliminating VUR which is grade III or IV. Cost of the implant
is the only limiting factor. A day care minimal access
extravesical ureteric reimplant technique is now quite
popular in the US. This is also suitable only for Grade III
or IV VUR. The most effective method of reflux
eliminating is surgery by ureteric reimplantation. The
scar can be placed in a transverse direction just above
the public symphysis so that it becomes obscured by the
pubic hair line.
The problem of voiding dysfunction should be
remembered in recurrent UTI as well as in children with
VUR and failure to manage this will not eliminate the
problem of recurrent UTI and will lead to failure of VUR
management done either medically or surgically.
Treatment of constipation and voiding dysfunction play
a major role in the management of VUR in children in
the present day care.
BIBLIOGRAPHY
1. Indian Pediatric Nephrology Group: Indian Academy
of Pediatrics, Consensus statements on management of
urinary tract infection. Indian Pediatr 2001;38:1106-15.
2. Srivastava RN, Bagga A. Urinary tract infection. In:
Srivastava RN, Bagga A (Eds): Pediatric Nephrology, 3rd
Edn, Jaypee Brothers, New Delhi 2005;235-64.
3. Vijayakumar M, Prahlad N, Sharma NL, Nammalwar
BR. Urinary tract infection (UTI). In: Suraj Gupta (Ed):
Recent advances in Pediatrics-17-Hot topics. 1st Edn,
Jaypee Brothers Medical Publishers, New Delhi 2007;
348-57.
4. Vijayakumar M, Prahlad N. Urinary tract infection in
children. In: Vijayakumar M, Nammalwar BR (Eds):
Principles and Practice of Pediatric Nephrology, 1st Edn,
Jaypee Brothers, New Delhi, 2004;348-57.
754
14.10 Obstructive Uropathy

Kumud P Mehta
Obstructive lesions of urinary tract, i.e. the pelvis, ureter,
bladder or urethra can be congenital or acquired (calculi,
ureteral stricture due to tuberculosis, postoperative
fibrosis). A list of common lesions is given in Table 14.10.1.
Obstruction may be partial or complete requiring surgery
for relief of back pressure, dilation and progressive renal
damage. Obstructive uropathy is an important cause of
end-stage renal disease (ESRD). The age of the child, and
severity and duration of obstruction, determine the extent
of renal damage. The increase in ureteric pressure is
transmitted to renal pelvis and tubules, causing a fall in
glomerular filtration rate. There is impairment of tubular
function characterized by decreased ability to concentrate
and acidify urine, decrease in potassium excretion and
reduced responsiveness to ADH. These abnormalities lead
to polyuria, hyperkalemia, hyperchloremic metabolic
acidosis with inappropriately high urine pH (distal renal
tubular acidosis type IV).
The mechanical effects of high pressure on the ureters
and pelvicalyceal system result in their dilatation,
tortuosity and loss of peristalsis. Urinary infection causes
further loss of peristalsis. Obstruction below the level of
the bladder results in distension of the bladder with
thickened walls and later, formation of diverticuli that
may obstruct the ureters. In cases of posterior urethral
valve the proximal urethra dilates. Due to poor emptying,
stagnation of urine occurs which predisposes to infection
and stone formation.
Obstruction in utero can cause irreversible renal
damage and renal dysplasia, due to adverse effect of
obstruction on the development of kidneys. Relief of
obstruction usually does not improve renal function in
such cases.
TABLE 14.10.1: Common obstructive lesions
Pelviureteric junction (unilateral or bilateral)
Calculi in pelvis, ureter or urinary bladder
Diverticuli or ureteroceles (obstructing ureter or ureterovesical junction)
Posterior urethral valves
Bladder neck obstruction
Phimosis, paraphimosis, meatal stenosis
Neurogenic bladder, neuropathic bladder
Diseases of spinal cord like meningomyelocele, lipomeningocele, tethered cord can lead to functional
obstruction due to detrusor, sphincter dyssynergia.
Clinical Features
A neonate with obstructive uropathy may present with:
i. Distention of abdomen due to unilateral or bilateral
renal masses (hydronephrosis) and poor urinary
stream with distended firm bladder;
ii. Excessive crying and irritability, poor feeding, and
occasionally hematuria.
In older children there may be abdominal pain due
to distention of kidney or bladder, voiding dysfunction
such as straining, dribbling, daytime enuresis, polyuria,
frequency and urinary tract infections.
It is possible to diagnose obstructive uropathy by
antenatal US around 25 to 26 weeks of gestation.
Investigations
US can demonstrate dilation of the pelvicalyceal system,
ureters and bladder, hydronephrosis, cortical thickness
and scarring. MCU is done to detect posterior urethral
valves. Radionuclide renal scan using 99mTc DTPA can
confirm obstruction at pelviureteric junction and provide
differential renal function. Failure of radiotracer pooling
in renal pelvis to washout after an intravenous injection
of frusemide indicates organic obstruction. Intravenous
pyelography is useful in older children, to define
accurately the anatomical site of obstruction or detect
radiolucent calculus in pelvis or ureter.
Treatment
Appropriate surgical treatment is done to relieve the
obstruction. Long-term follow-up is necessary to look for
urinary tract infections and treat associated complications. Renal dysplasia and renal scars already present
before the relief of obstruction may eventually lead to
ESRD over a period of 10 to 15 years.
BIBLIOGRAPHY
1.
Koff SA. Obstructive uropathy: Clinical. In Pediatric

Barratt TM, Avner, Harman WE, (Eds): Nephrology (4th
edn). Williams & Wilkins, Baltimore 1999;887-96.
755
14.11 Disorders of Micturition

Kumud P Mehta
Disorders of micturition result from abnormal bladder
function. Main functions of urinary bladder are storage
of urine at low pressure till maximum capacity is reached
and then complete evacuation of bladder at a convenient
time and place. Periodic voiding occurs due to coordinated contraction of detrusor muscle with relaxation
of bladder sphincter under the influence of nervous
system both somatic, sympathetic and parasympathetic.
Centers in brain, brain stem and spinal cord send
inhibitory and facilitatory impulses to detrusor and
sphincter muscles in a cycle. Disruption of this cycle
results in disorders of micturition.
Bladder Innervation
The chief nerve supply to the bladder is through pelvic
nerves (S 2-3 segments), which contain both sensory and
motor fibers. The former detect the degree of stretch of
the bladder wall and posterior urethra, which serves to
initiate the reflexes, leading to bladder emptying. The
motor nerve fibers are parasympathetic and innervate
the external sphincter muscle and control its voluntary
contraction. Once the bladder is full, stimuli reach the
external sphincter through the pudendal nerves.
Voluntary relaxation of that sphincter leads to micturition. Higher centers in pons and cortex also control
micturition. These are mostly inhibitory and override the
micturition reflex, until it is convenient to void.
Causes of disorders of micturition are:
1. Congenital anomalies of spinemeningomyelocele,
lipomeningocele, tethered spinal cord, sacral
agenesis.
2. Congenital anomalies of urinary tractposterior
urethral valves, vesicourteral reflux, duplex kidney,
ectopic ureter.
3. Urinary tract infections, calculi.
4. Non-neurogenic bladder dysfunction, Hinmanns
syndrome or Ochoa syndrome (facial dysmorphism
and bladder dysfunction) are associated with daytime
incontinence.
Common clinical manifestations of disorders of micturition
are poor stream, dribbling, straining in infants with
posterior urethral valves. Early diagnosis by ultrasono-
graphy of KUB and micturating cystourethrography

helps in early repair of valves with release of obstruction
that can prevent progressive renal damage. In older
children night time or day time enuresis is commonly
associated with functional disorders of micturition.
Children with enuresis should be evaluated for specific
cause as suggested in the flowchart given in Figure
14.11.1
Enuresis
Bladder control is normally achieved between 1-5 years.
A majority of children are dry during the day by the age
of 2-3 years and at night by 3-5 years.
Nocturnal enuresis (involuntary voiding at night with
daytime control), is a common condition affecting 10-15
percent children above the age of 5 years. It is three times
more common in boys. There is a spontaneous tendency
to remit and the prevalence is about 3 percent at the age
of 10 years and less than 1 percent in adults. Enuresis is
a benign condition but often leads to significant
emotional and psychological problems in the child and
the family.
The etiology of nocturnal enuresis is not well
understood. The disorder is often familial and in a large
proportion, one of the parents or siblings was also
enuretic. Inadequate or inappropriate toilet training may
play a role. Emotional stress may precipitate bedwetting
in a previously continent child. It has been suggested
that children with enuresis have smaller maximum
bladder capacities which become normal after they
recover.
Enuretic children tend to be heavy sleepers. More
recently, it was observed that enuretic children had lower
noctural ADH secretion rate, as compared to normal
subjects. It is more likely that enuresis is due to a delay
in the maturation of the neurological mechanisms
involved in the bladder control, which improve with
increase in age. Psychological and behavior problems are
common in such children and disappear after enuresis
is no longer present.
Treatment of Nocturnal Enuresis
Reassurance and sympathetic handling of the problem
are important. Punishment or humiliation of the child
must be avoided.
756

may be associated. In some cases, there is a dysfunction
of detrusor which may be hyperactive and may contract
on stress or physical exercise. Urgency of micturition
may be present. The child is unable to hold urine
and voids precipitately. Oxybutinin is beneficial in some
cases.
Pollakiuria
Rarely a child begins to void extremely frequently, at
30-60 minutes intervals. There is no dysuria or pain. It
creates great anxiety in the parents and interferes with
schooling. No organic cause seems to be present. The
disorder is most probably related to some stressful
situation. The condition resolves gradually. In persistent
cases, psychiatric evaluation may be carried out.
Figure 14.11.1: Algorithm for evaluation of enuresis
in a child
Strict fluid restriction at and after the evening meal and

waking the child during night may be effective, but
compliance with such a regimen is difficult. Imipramine
in a dosage of 50 mg daily for a child below the age of
10 years is beneficial but most children relapse when the
drug is stopped. Higher doses, more than 75 mg/day,
are of no additional benefit. The side effects of
imipramine include restlessness, headache, abdominal
pain and weight loss; accidental poisoning may cause
coma, convulsions and arrhythmias. In general,
imipramine therapy should be discouraged.
A moisture alarm is a conditioning device, in which
an alarm is activated when the child passes urine. The
response of urination is inhibited when the child wakes
up. Eventually, a conditioning process is established and
the child wakes up before the micturition-induced alarm
goes off. The parents and the child should be explained
the use of the alarm device. If the alarm does not awake
the child, imipramine may be added to the therapy.
Administration of arginine vasopressin (desmopressin) as a nasal spray is also effective. Relapse occurs in
more than half of the cases when it is stopped. Hyponatremia is an uncommon side effect.
Daytime Incontinence
Wetting during the daytime is uncommon. It may be a
manifestation of a behavior disturbance. Fecal soiling
Giggle Micturition
Involuntary voiding during sudden laughter or straining
is occasionally seen in schoolgirls and adolescents, and
may cause considerable embarrassment. The underlying
abnormality may be an instability of bladder with
inappropriate detrusor contraction. The precipitating
event if identified, should be avoided and the child asked
to empty the bladder regularly.
Infrequent Voiding (Lazy Bladder Syndrome)
In this rare disorder, the child does not void until the
bladder is stretched to the limit. Gradually, the bladder
enlarges, and may not empty completely. Recurrent UTI
may develop. Chronic constipation may occur for the
same reason. Regular voiding should be advised.
Neuropathic Bladder
Important causes of neuropathic bladder include spina
bifida, sacral agenesis, autonomic neuropathy, transverse
myelitis, spinal cord tumors and trauma.
The treatment aims to prevent deterioration of renal
function and achieve continence. Any associated
anomaly should be appropriately treated. Medical
management is essentially based on clean intermittent
catheterization. Regular bladder emptying at 3-4 hourly
intervals may improve continence and increase bladder
capacity. In children with VUR, long-term chemoprophylaxis or surgery should be considered.

Urodynamic study is useful in selected cases in
providing details of bladder function and capacity,
co-ordinated action of detrusor muscle contraction and
sphincter relaxation to decide therapy with oxybutynin,
bethacholine and clean intermittent catheterization to
reduce post-void urine and back pressure that can cause
progressive kidney damage.
757
BIBLIOGRAPHY
1. Atala A, Bauer SB. Bladder dysfunction In: Barratt (Ed):
Pediatric Nephrology, 4th ed, Avner Harmon Lippincott
William and Wilkins, 1999;913-31.
2. Churchill BM, Abramson RP, Washl EF. Dysfunction of
lower urinary tract PCNA 2001;48:1587-1630.
3. Dharnidharka VR. Primary nocturnal enuresis. Indian
Pediatr 2000;37:135-49.
14.12 Chronic Kidney Disease

KD Phadke, Pankaj Hari
Chronic kidney disease (CKD) implies persistent renal
damage or decreased glomerular filtration rate (GFR)
with a risk of developing progressive loss of renal
function. It is usually of gradual onset and there may be
no symptoms in the early stages.
CKD signifies structural or functional abnormalities
of the kidneys for 3 months, as manifested by either:
1. Kidney damage, with or without decreased GFR, as
defined by:
Pathologic abnormalities
Markers of kidney damage
Urinary abnormalities (e.g. proteinuria)
Blood abnormalities (e.g. renal tubular
syndromes)
Imaging abnormalities
2. GFR < 60 min/1.73 m 2, with or without kidney
damage.
Etiology
The important causes of CKD are listed in Table 14.12.1.
In infancy and early childhood congenital renal
anomalies predominate, whereas the incidence of
acquired renal diseases progressively increases throughout childhood.
Obstructive uropathy (23%), renal aplasia/dysplasia
(18%), reflux nephropathy (9%) and FSGS (8%) are more
common disorders progressing to CKD. Recent studies
have shown that FSGS is emerging as a more common
etiology leading to CKD. Regardless of the primary cause,
glomerular and tubular adaptive changes to initial insult
TABLE 14.12.1: Important causes of CKD
Congenital disorders
Malformations
CKD has been staged into five stages according to GFR.

Stage Description
1
2
3
4
5
GFR (ml/min/
1.73 m2)
Kidney damage with normal or GFR

Kidney damage with mild in GFR
Moderate in GFR
Severe in GFR
Kidney failure (end stage renal disease)
90
60-89
30-59
15-29
< 15 or
dialysis
The above staging is not applicable for children

below 2 years of age since GFR will progressively
increase from birth to reach adult values by 2 years of
age.
Renal hypoplasia, dysplasia

Neurogenic bladder
Hereditary disorders Nephronophthisis

Polycystic kidney disease
Alports syndrome
Congenital nephrotic syndrome
Acquired disorders
Glomerular
disorders
Focal segmental glomerulosclerosis

(FSGS)
Crescentic glomerulonephritis
Membrano proliferative glomerulonephritis
Vascular disorders
Tubulointerstitial
disorders
Reflux nephropathy
Interstitial nephritis
758
occur in the remaining nephrons. These changes finally

lead to global deterioration of kidney function. Final
histopathology findings are similar regardless of cause
which reveals global sclerosis, tubular atrophy and
interstitial fibrosis.
Clinical Features
The symptoms of CKD may be due to metabolic
derangements resulting from renal dysfunction or due
to the specific features of the underlying disease. The
early symptoms are vague and non-specific such as
weakness, anorexia, nausea and failure to thrive. When
renal function deteriorate significantly; anemia,
osteodystrophy and growth failure are noticed. The late
manifestations of CKD are gastrointestinal bleeding,
pericarditis, congestive cardiac failure, altered sensorium
and seizures. A careful history and clinical examination
provides useful clues to the diagnosis of the underlying
etiology (Table 14.12.2). Important signs to be looked for
in chronic kidney disease are growth failure, pallor,
rickets (Fig. 14.12.1), hypertension, altered sensorium and
fluid overload.
Figure 14.12.1: A 10-year-old body with chronic kidney

disease with short stature and deformities of the lower limbs
Laboratory Evaluation
The laboratory investigations are aimed at assessing the
severity of renal dysfunction, associated metabolic
abnormalities, and identifying the cause of CKD
(Fig. 14.12.2).
Baseline Investigations
Urine: Proteinuria, hematuria, microscopy
24 hours protein or protein/creatinine ratio
Blood: Hb, peripheral smear, transferrin saturation,
serum ferritin; urea, creatinine, electrolytes,
bicarbonate
calcium, phosphorous, alkaline phosphatase
HbsAg; renal ultrasound.
TABLE 14.12.2: Clinical assessment of the etiology of CKD
History
Diagnosis
Recurrent fever, dysuria,

pyuria
Reflux nephropathy
Poor urinary stream, urinary

retention, incontinence
polyuria, polydipsia, acidosis
Obstructive uropathy, neurogenic

bladder
Tubulointerstitial disease
Positive family history
Alports syndrome, polycystic

kidney disease, cystinosis
Edema, hematuria,
hypertension
Glomerulonephritis
Figure 14.12.2: Algorithm for evaluation of CKD

(MCUmicturating cystourethrography,
DMSAdimercaptosuccinic acid scan)
Additional Investigations for Etiology

Micturating cystourethrogram
Radionuclide imaging
Renal biopsy.

MANAGEMENT OF CKD
The action plan for the various stages of CKD has been
outlined in Table 14.12.3.
Conservative Management
Aims of conservative management are:
Correction of the reversible component of renal
dysfunction
Preservation of renal function
Treatment of metabolic problems
Addressing psycho-social issues
Optimization of growth
Preparation for treatment of end stage renal disease
(ESRD).
Infections, accelerated hypertension, volume
depletion, obstruction to urine flow, congestive cardiac
failure and drug nephrotoxicity can acutely exacerbate
renal dysfunction (acute-on-chronic renal failure).
Correction of these factors may improve renal function.
The measures for retarding the progression of CKD
aretreatment of hypertension, prevention and
treatment of recurrent urinary tract infections, use of
proteinuria lowering agents like angiotensin converting enzyme inhibitors and avoidance of nephrotoxic
drugs.
Dietary Advice
Dietary therapy is aimed at allowing normal growth and
development. Protein restriction may produce protein
calorie-malnutrition and hence is not recommended in
children. A CKD diet should therefore consist of
100 percent recommended dietary allowance for calories
and proteins. As renal function declines, dietary
TABLE 14.12.3: Stages of CKD and action plan
Stages
GFR (ml/min/
1.73 m2)
Action
> 90
2
3
4
60-89
30-59
15-29
< 15
(or dialysis)
Diagnosis and treatment

Treatment of comorbid conditions
Slowing of progression
Estimating progression
Evaluating and treating complications
Preparation for kidney replacement
therapy
Replacement
759
restrictions in potassium and phosphorous become

necessary. Hyperkalemia usually occurs when the GFR
falls below 10 ml/min/1.73 m2. Salt should be restricted
in patients with hypertension and fluid overload.
Appropriate daily supplementation of minerals and
vitamins should be provided, especially when child is
started on dialysis.
Renal Osteodystrophy (ROD)
Bone and mineral metabolism is affected early in CKD.
Several factors contribute to development of ROD which
is now called as mineral bone disease. These include
phosphate retention, hypocalcemia, impaired renal
calcitriol synthesis, alteration in PTH secretion, calcium
sensing receptors, and aluminium toxicity. The spectrum
of disease ranges from high turnover state (hyperparathyroidism, osteitis fibrosa) to low turnover state
(rickets/osteomalacia, adynamic bone disease). Early
symptoms are nonspecific and include bone pain, muscle
weakness. Long standing disease results in growth
retardation and skeletal deformities.
Laboratory and radiological studies are routinely
done; confirmation with bone biopsy is rarely required.
Aim of therapy is to prevent or reverse hyperparathyroidism, maintain normal mineralization and growth.
Restriction of dietary phosphate and administration of
phosphate binders such as calcium carbonates lower
serum phosphate and suppresses hyperparathyroidism.
The serum levels of phosphorus should be maintained
between 3.5-5.5 mg/dl (1.13-1.78 mmol/L) during
adolescence and between 4-6 mg/dl for children between
the ages of 1-12 years. Aluminium hydroxide should be
avoided due to the risk of aluminium toxicity. Vitamin D
is essential to raise the serum calcium and suppress
parathormone secretion. Therapy with short acting
vitamin D analogs such as calcitriol or 1-alpha-hydroxy
D is preferred. Care should be taken that the product of
calcium and phosphorous does not exceed 55 mg2/dl2 in
child above 12 years and 65 mg2/dl2 in younger children.
Osteotomy may be required to correct bony deformities.
Hypertension
Hypertension is a common complication of advanced
stages of CKD. Some patients remain hypertensive
despite salt and fluid restriction and diuretics and may
require treatment with antihypertensives drugs.
Hypertension in patients with proteinuria and glome-
760
rular filtration rate >30 ml/min/1.73 m 2 should

preferably be treated with angiotensin converting
enzyme inhibitors (e.g. enalapril). Beta-adrenergic
blockers (atenolol,) and calcium channel antagonists
(nifedipine, amlodipine) are also effective. Patients with
severe hypertension, uncontrolled with the above
medications, may require addition of clonidine or
prazosin. Angiotensin converting enzyme inhibitors may
help in retarding the progression of CKD; however, they
should be cautiously used as they may cause reduction
in GFR and worsen hyperkalemia.
Metabolic Acidosis
Metabolic acidosis occurs when the GFR falls below
25 percent of the normal. It should be corrected with
sodium bicarbonate (2-3 mEq/kg/day). The dose should
be titrated to maintain a serum bicarbonate level of
20 mEq/l.
Anemia
Several clinical features like fatigue, anorexia, poor
cognitive performance, decreased exercise capacity along
with left ventricular hypertrophy has been associated
with anemia. Inadequate production of erythropoietin
by peritubular interstitial cells in cortex is the most
important cause for anemia. Other contributing factors
include nutritional deficiency of iron, folic acid, decreased
RBC survival, and increased blood loss.
Administration of recombinant human erythropoietin (rHuEpo) along with adequate iron supplementation results in dose dependent increase in hemoglobin
level and cessation of transfusion requirement. The initial
dose varies between 50 to 150 IU/kg/dose thrice a week
given subcutaneously. The selected hemoglobin target
should generally be in the range of 11.0 to 12.0 g/dL.
Patient should be monitored for worsening of hypertension. After the desired hematocrit is achieved, the dose
is adjusted to maintain that level. Supplements of iron
and folic acid are given. Patients on hemodialysis should
receive intravenous iron supplementation. Inadequate
response to erythropoietin may occur due to iron
deficiency, chronic infection, aluminum toxicity and
severe hyperparathyroidism. Blood transfusions should
be avoided to prevent sensitization and blood borne
infections.
Growth
Inadequate calorie intake, acidosis, salt depletion and
secondary hyperparathyroidism result in poor growth.
Abnormalities of the growth hormone-insulin like
growth factor (GH-IGF) axis are also reported. With
optimum dietary management, children with GFR > 25
ml/min/l.73 m2 grow steadily. The administration of
recombinant human growth hormone improves height
velocity of children with CKD. The high cost of this
treatment, however, limits its use.
Children with CKD should be immunized against
hepatitis B. Those planning to undergo renal transplantation should also receive varicella vaccine.
RENAL REPLACEMENT THERAPY
Once ESRD is reached, renal replacement like dialysis
or transplantation becomes essential to sustain life.
Dialysis Treatment
In peritoneal dialysis (PD), the peritoneum is the semipermeable membrane across which the exchange of
solutes and fluid takes place (blood in the peritoneal
capillaries on one side and the dialysis fluid in the
peritoneal cavity on the other side). The major types of
PD are intermittent peritoneal dialysis (IPD), continuous
ambulatory peritoneal dialysis (CAPD) and continuous
cyclic peritoneal dialysis (CCPD). The parents can be
trained to perform exchanges. The cost of this treatment
is high. Peritonitis is likely to occur if aseptic precautions
are not followed meticulously.
Hemodialysis requires institutional facility having
dialysis machines, dialyzers (artificial kidney) and
technical expertise. It also needs a vascular access which
is difficult to obtain in young children weighing less than
20 kg. During a hemodialysis session blood is circulated
through an extracorporeal circuit that includes a hollow
fiber dialyzer. Anticoagulation of the circuit is usually
achieved by systemic heparnization. The procedure
requires continuous monitoring. The procedure needs
to be performed three times every week.
Renal Transplantation
Renal transplantation is the ideal treatment of ESRD in
children. Dialysis treatment is offered till transplantation
becomes possible. An adult kidney can be successfully
transplanted into a child. The donor can be living related

or a deceased donor. The Indian government passed
Human Organ Transplantation Act in 1994, recognizing brainstem death. This act has paved way for
cadaveric organ transplantation (Deceased donor
transplantation). Intensive hemodynamic monitoring is
needed during intraoperative and immediate postoperative period. The major complications of transplantation include rejection, infection, hypertension,
drug toxicity and recurrence of the primary disease.
Lifelong immunosuppression is required to prevent
rejection. The usual immunosuppressive therapy is a
combination of prednisolone, azathioprine or mycophenolate mofetil and a calcineurin inhibitor such as
cyclosporin A or tacrolimus. Excellent rehabilitation is
obtained in most children with functioning grafts. They
can attend their school normally and lead a near normal
life. The results of pediatric renal transplantation at
experienced centers are excellent and 1 year graft survival
rate has been more than 90% giving children a fresh lease
of life.
Deterrent factors for pediatric transplantation in India
include lack of awareness regarding renal transplantation
among the general public as well as medical professionals, financial issues, lack of experienced centers,
lack of suitable donors, ill developed deceased donor
program.
761
PREVENTION OF CKD
A significant proportion of cases of CKD can be
prevented by early detection and appropriate management of the underlying condition, e.g. prompt relief of
urinary tract obstruction and early diagnosis and
treatment of vesicoureteric reflux. Early immunosuppressive therapy can reverse renal dysfunction due
to crescentic glomerulonephritis and prevent its
progression to CRF. Routine antenatal sonography and
systematic evaluation of children with urinary tract
infection are other useful strategies.
BIBLIOGRAPHY
1. Fine RN, Whyte DA, Boydstun I. Chronic renal failure.
In: Avner Ed, Hartnan WE, Niaudet P (Eds): Pediatric
Nephrology (5th edn). Williams and Wilkins, Baltimore,
2004.
2. Hari P, Singla IK, Kanitkar M, Bagga A. Chronic renal
failure in children. Indian Pediatr 2003;40:1035-42.
3. Moudgil A, Bagga A. Evaluation and treatment of chronic
renal failure. Indian J Pediatr 1999;66:241-53.
4. NKF K/DOQI clinical practice guidelines for chronic
kidney disease 2000.
5. Phadke K, Iyengar A, Karthik S, Kumar A, Olakkengil S.
Pediatric renal transplantation: The Bangalore
experience. Indian Pediatr 2006;43:44-7.
14.13 Hypertension
Kumud P Mehta
INTRODUCTION
Hypertension in children is defined as blood pressure
values above the 95th percentile for the corresponding
age, height and sex. Values beyond 99th percentile denote
severe hypertension.
An acute rise in blood pressure is a usual feature of
acute glomerulonephritis and also may be associated
with hemolytic uremic syndrome, Guillain-Barr
syndrome, severe burns, disorders of central nervous
system, lead poisoning and porphyria. Important causes
of sustained (chronic) hypertension are listed in Table
14.13.1. They can be chiefly grouped into renal parenchymal, renal vascular and endocrine disorders. Essential
hypertension is being increasingly recognized in
children.
Sustained hypertension in children is mostly secondary to an underlying renal or other disorder.

Diagnostic evaluation of a child with hypertension
includes identifying the cause, demonstrating target
organ damage and identifying risk factors for cardiovascular injury. A thorough history and clinical examination
can give clues to the underlying etiology (Table 14.13.2).
Clinical Features
Chronic hypertension is often asymptomatic and
detected on incidental examination. Headache is an
important feature, although in a majority of children who
complain of headache, some cause other than hypertension is responsible. More often the presenting feature
is related to a complication of hypertension. These
762

TABLE 14.13.1: Causes of sustained hypertension
Renal parenchymal
Primary or secondary
glomerulonephritis
Reflux nephropathy
Polycystic kidney disease
Hereditary nephritis
Renovascular
Renal artery stenosis, arteriovenous

fistulae, aorto arteritis (Takayasus
disease) (Fig. 14.13.1)
Endocrine
Cushing's disease, congenital adrenal

hyperplasia, hyperaldosteronism,
pheochromocytoma
Miscellaneous
Essential hypertension,
neuroblastoma, Wilms tumor,
coarctation of aorta
Figure 14.13.1: Renovascular hypertension.

Arrow indicates renal artery stenosis
TABLE 14.13.2: Evaluation of a child with hypertension

Clinical
Investigations
Edema, hematuria
Purpura, joint
pains
Urine for hematuria,

proteinuria, RBC casts,
BUN, S. creatinine
ASO Titer, Serum C3
ANA
Recurrent UTI
Weak femorals
Abdominal bruit
Renal lump/s
If no clinical
clues but
symptomatic
hypertension
Diagnosis
Glomerulonephritis; Post
streptococcal,
lupus, HSP,
other chronic
GN
Urine culture ultrasound Chronic/recur(USG) for pelvicalyceal rent pyelodilatation
nephritis
99Tc DMSA renal scan
Renal scars,
reflux nephropathy
USG, color Doppler
Renal artery
stenosis
Digital subtraction
Aorto arteritis
angiography
USG of KUB
Hydronephrosis
Polycystic
kidneys
Renal tumors
CT scan for adrenals
Adrenal causes
urinary VMA, MIBG
scan
BUNBlood urea nitrogen, ASOAntistreptolysin O,

C3Complement factor 3, ANAAntinuclear antibody,
HSPHenoch Schonlein purpura, GNGlomerulonephritis,
DMSAdimercaptopuric luceinic acid, CTContrast tomography,
VMAVarillylmandelic acid, MIBG131I metaiodobenzyl guanidine
include epistaxis, facial paresis, and ocular symptoms

such as momentary loss of vision (Table 14.13.3).
Uncommonly, a rapid increase of blood pressure may
TABLE 14.13.3: Clinical features consistent with

hypertension
Neonates
Irritability, lethargy
Cardiomegaly
Vomiting, seizures
Palpitations/tachycardia
Sweating, pallor or cyanosis
Failure to thrive
Older children
(In addition to above)
Fatigue, nausea
Headache
Encephalopathy
Blurred vision
Epistaxis
Facial nerve palsy
Polydipsia, polyuria
lead to hypertensive encephalopathy (manifested by

sensorial disturbance, seizures), left ventricular failure
and pulmonary edema.
Treatment of Hypertensive Emergency
Hypertensive emergency may be treated with nifedipine
0.25 to 0.5 mg/kg per dose orally or sublingually which
reduces blood pressure within 10 minutes. However, the
fall of blood pressure is not controlled and is often
unpredictable. Intravenous sodium nitroprusside
(0.58 g/kg/minute) by continuous infusion has a
potent hypotensive effect and is the method of choice.
Intravenous labetalol infusion is also effective. Intravenous frusemide removes excess water and sodium and
is particularly useful in patients with acute glomerulonephritis.

Treatment of Chronic Hypertension
763
TABLE 14.13.4: Drugs for long-term

treatment of hypertension
In a large majority of patients with hypertension, the

underlying causative disorder is not curable (e.g. chronic
glomerulonephritis, reflux nephropathy). In such cases,
appropriate antihypertensive medications are given. The
aim of the treatment is to reduce the blood pressure levels
to below 90th percentile for the age. The most commonly
used agents are beta blockers (propranolol, atenolol),
calcium channel blockers (nifedipine), and angiotensin
converting enzyme inhibitors. A diuretic such as
hydrochlorthiazide is usually added. The cost of drugs
is an important consideration, since the treatment must
be given for long periods. A list of important drugs is
tion, increased exercise, salt restriction and potassium

supplementation in the diet. If necessary, appropriate
medications may be used to keep the blood pressure
levels below the 90th percentile for the age.
Essential Hypertension
BIBLIOGRAPHY
Often an underlying cause cannot be identified in an

obese older child or adolescent with a family history of
essential hypertension. The blood pressure values are
only mild to moderately elevated, and there is no target
organ damage. Such cases are labeled as essential
hypertension. The treatment consists of weight reduc-
Drug
Initial
Maximum
(mg/kg/day)
Nifedipine
Captopril
Enalapril
Propranolol
Atenolol
Hydrochlorthiazide
0.25-0.3
0.3
0.1
1-2
1
1
1-3
5
0.5
6-8
3
2
1.
Mehta KP. Hypertension. In Gupte S (Ed): Recent Advances in Pediatrics. Jaypee Brothers, New Delhi, 1996;
270-97.
2. National High Blood Pressure Education Program.
Working group on hypertension control in children and
adolescent. Update on the 1987 Task Force Report of
Blood Pressure. Pediatrics 1996;98:649-58.
14.14 Renal Tubular Disorders

Aditi Sinha, Arvind Bagga
INTRODUCTION
In comparison to glomerular diseases, renal tubular
disorders are rare. Because of their non-specific or vague
manifestations, tubular disorders are frequently missed
or detected late. With early diagnosis, satisfactory
treatment is possible in several of them. A correct
diagnosis is also necessary for genetic counseling. In a
primary tubular renal disorder, there is no significant
impairment of glomerular filtration or tubulointerstitial
involvement. A tubular disorder may be congenital or
acquired. It may involve a single function of the tubule
(e.g. renal glucosuria, nephrogenic diabetes insipidus)
or multiple functions (e.g. Fanconi syndrome). A primary
tubulopathy is usually congenital and hereditary and
often involves a single tubular function. Secondary
derangements of tubular function are usually acquired,
and involve multiple functions.
Common renal tubular disorders are listed in
Table 14.14.1.
The diagnosis of a tubular disorder requires accurate

measurements of GFR and quantitative determinations
of various substances in the blood and urine for the
evaluation of functions of the proximal tubule (i.e. tubular
handling of sodium, glucose, phosphate, calcium,
bicarbonate and amino acids) and distal tubule (urinary
acidification and concentration).
Renal Tubular Acidosis
Renal tubular acidosis (RTA) comprises a group of
tubular transport defects characterized by an inability
to appropriately acidify the urine with resultant
metabolic acidosis. The underlying abnormalities consist
of an impairment of bicarbonate reabsorption or
excretion of H+ ions or both. Two major varieties are
observed: distal RTA (type I) and proximal RTA (type
II); type IV characterized by hypoaldosteronism and
hyperkalemia is rare. In all forms of RTA, plasma anion
gap (Na+ - [Cl- + HCO3-]) is normal (8-16 mEq/L). The
764

TABLE 14.14.1 Common disorders of renal tubule functions
Segment
Function
Disorder
Proximal tubule
Phosphate transport
Glucose transport
Amino acid transport
Bicarbonate transport
Sodium, potassium, chloride transport
Proton secretion
Sodium, chloride transport
Sodium, potassium transport
Hypophosphatemic rickets
Renal glucosuria
Isolated, generalized amino aciduria
Proximal renal tubular acidosis, Fanconi syndrome*
Bartter syndrome
Distal renal tubular acidosis
Gitelman syndrome
Pseudohypoaldosteronism
Liddle syndrome
Nephrogenic diabetes insipidus
Ascending limb of Henle

Distal tubule
Collecting duct
Water transport
*Dysfunction of the proximal tubule (Fanconi syndrome) may be primary or secondary to various disorders (e.g., galactosemia, Lowe
syndrome)
urine anion gap (Na+ + K+ - Cl-), which provides an

estimate of renal ammonium production, is positive.
Type I RTA: Distal RTA is characterized by severe
rachitic deformities, failure to thrive and features of
hypokalemia. There is a severe metabolic acidosis due
to impaired capacity of the distal nephron to secrete H+
ions. The urine is inappropriately alkaline; proximal
tubular reabsorption of bicarbonate is normal. Persistent
acidosis results in buffering of H+ ions in the bone with
release of calcium, hypercalciuria and nephrocalcinosis.
Investigations show blood pH below 7.2, bicarbonate
below 15 mEq/L and low serum potassium (often below
2.5 mEq/L). The urine pH is more than 6 and there is
mild bicarbonaturia; hypercalciuria and hypocitraturia
are often associated.
Hypokalemia should be corrected before correction
of acidosis. Acidosis is treated by administration of alkali
solution, 2 to 3 mEq/kg/day and increased until the
blood bicarbonate levels become normal. Adequate longterm treatment results in healing of rickets and
improvement in growth. The alkali therapy is required
lifelong.
Type II RTA: Proximal RTA is characterized by impaired
proximal tubular reabsorption of bicarbonate, the
fractional excretion of bicarbonate being more than
15 percent. In children proximal RTA is usually seen as
a part of global proximal tubular dysfunction (Fanconi
syndrome) when glucosuria, amino-aciduria, phosphaturia and low molecular weight proteinuria are present
in addition to bicarbonaturia.
Clinical features include failure to thrive, and growth

retardation. Irritability, anorexia and listlessness are
present. Rachitic deformities are rare in isolated proximal
RTA but common in Fanconi syndrome. The blood pH
and bicarbonate levels are low and urine pH is relatively
alkaline. However, if the blood bicarbonate level is below
15 mEq/L (spontaneously or following an acid load), the
urine pH reduces to 5.5 or lower.
Sodium bicarbonate is given, initially at a dose of
5-8 mEq/kg/day; part of the alkali may be given as
potassium citrate. The requirement of bicarbonate
supplements is higher in patients with proximal RTA.
Correction of acidosis results in striking increase in the
growth velocity.
Type IV RTA: It is associated with hypoaldosteronism
or resistance to the action of aldosterone, either isolated
or in the context of chronic kidney disease, e.g.
obstructive uropathy. Nephrocalcinosis and urolithiasis
are absent and bone lesions are rare. Older children may
develop type IV RTA due to advanced tubulointerstitial
renal diseases leading to mineralocorticoid resistance,
drugs or with mineralocorticoid deficiency. In younger
children, genetic defects like pseudohypoaldosteronism
may be suspected.
A summary of the findings in different types of RTA
and their differences is provided in Table 14.14.2.
Fanconi Syndrome
In Fanconi syndrome, there is global dysfunction of the
proximal tubule. Glucosuria, phosphaturia and generalized amino aciduria are present. There is, in addition,
impaired reabsorption of bicarbonate (type II RTA),
765
TABLE 14.14.2: Investigations to differentiate types of renal tubular acidosis (RTA)
Plasma potassium
Urine pH*
Urine anion gap
Urine ammonium
Fractional bicarbonate excretion
Urine calcium excretion
Other tubular defects
Nephrocalcinosis
Bone disease
Proximal RTA
Distal RTA
Type IV RTA
Normal/low
<5.5
Positive
Low
>10-15%
Normal
Often present
Absent
Common
Low/normal
>5.5
Positive
Low
<5%
High
Absent
Present
Often present
High
<5.5
Positive
Low
5-10%
Normal/low
Absent
Absent
Absent
*Urine pH should be assessed during the state of metabolic acidosis
sodium, potassium and organic acids. The plasma

concentrations of glucose and amino acids are within the
normal range, but those of phosphate are low. Fanconi
syndrome may be primary (idiopathic) or secondary
(associated with various conditions, e.g. cystinosis, lead
toxicity, galactosemia and Wilson disease).
During infancy polyuria, polydipsia, growth
retardation and fever are common symptoms. Vitamin
D refractory rickets is a striking feature.
Treatment: The underlying primary condition should be
detected and appropriately managed. Urinary losses of
various substances should be replaced orally. Supplements of sodium, potassium, bicarbonate and phosphate
are often required; ad lib water intake is allowed. Some
patients require an additional supplemental dose of
vitamin D3. Rickets may heal with correction of
hypophosphatemia and acidosis.
Cystinosis
Cystinosis is an autosomal recessively inherited
condition characterized by deposition of cystine crystals
in the cornea, conjunctiva, bone marrow, leukocytes,
lymph nodes and other organs. There is an enzymatic
defect in the transport of cystine from lysosomes to
cytosol, leading to very high levels of free cystine within
the lysosomes. The chief symptoms are polyuria,
polydipsia, failure to thrive, vitamin D resistant rickets
and photophobia. End-stage renal disease develops
before the age of 10 years.
The diagnosis is confirmed by the demonstration of
elevated leukocyte cystine levels. Cystine crystals are
seen in the cornea on slit-lamp examination and in the
bone marrow. Management of manifestations of Fanconi
syndrome and oral therapy with cysteamine is beneficial.

Renal transplantation is successful but does not correct
the disorder, and cystine continues to accumulate in nonrenal tissues resulting in late-onset of hypothyroidism
and diabetes mellitus.
Renal Glucosuria
Renal glucosuria is a benign disorder in which there are
large amounts of glucose in the urine, with normal blood
glucose levels. The renal threshold for glucose reabsorption is lowered to variable degrees. There is no other
defect of proximal tubular function. No treatment is
necessary.
Nephrogenic Diabetes Insipidus
Nephrogenic diabetes insipidus (NDI) is a rare, X-linked
recessive disorder, characterized by tubular unresponsiveness to the antidiuretic hormone. Clinical features
include polyuria and polydipsia, irritability, poor
feeding, failure to thrive and recurrent episodes of
dehydration and fever. The patients often undergo
extensive investigations to find a cause for fever.
The urinary osmolality is usually less than 150
mOsm/kg. Serum sodium levels are high in infancy,
when they may be more than 160 mEq/L, with corresponding increase in osmolality. Hypernatremia is less
common once the child has free access to water. The
diagnosis is confirmed by failure of urinary osmolality
to rise, following either water deprivation or administration of vasopressin. The presence of low urine
osmolality (< 300 mOsm/kg) in patients with elevated
plasma osmolality (>300 mOsm/kg, serum sodium >145
mEq/L), either at baseline or after water deprivation, is
766
diagnostic of diabetes insipidus. Following administration of vasopressin, the increase of urine osmolality
in patients with nephrogenic DI is nil or minimal. The
urine osmolality increases by >50% in patients with
central DI.
Treatment consists of provision of adequate amounts
of water to compensate for the urinary losses. Hydrochlorothiazide at a dose of 1-3 mg/kg/day combined
with sodium restriction leads to significant reduction of
urine volume. Co-treatment with indomethacin or
amiloride is useful.
Bartter Syndrome
Bartter syndrome is characterized by variable presentation with polyuria, failure to thrive, normal to low blood
pressure, hypokalemia, hypochloremia and metabolic
alkalosis; plasma levels of renin and aldosterone are
raised. There is urinary wasting of potassium, sodium
and chloride.
Treatment with supplementation of potassium and
administration of indomethacin is usually satisfactory,
although serum K + levels may not increase above
3.5 mEq/L.
Urolithiasis
Patients with stones either in the bladder or upper
urinary tract may present with hematuria, pain abdomen
and urinary tract infections. Isolated vesical calculi are
seen in children consuming a cereal based diet lacking
in animal proteins. They are chiefly composed of
ammonium acid urate and calcium urate.
Renal stones are usually secondary to an underlying
disorder, chiefly idiopathic hypercalciuria, hyperoxaluria
and recurrent urinary tract infections. Hypercalcemia,
renal tubular acidosis, cystinuria and hyperuricosuria are
rare causes. A metabolic cause is more likely if there is a
positive family history, nephrocalcinosis, sterile urine,
recurrent stones or presence of clinical features like
failure to thrive, rickets or polyuria. All patients
presenting with renal stones or nephrocalcinosis should
be evaluated to determine the etiology. Investigations

include estimation of blood levels of urea, creatinine,
electrolytes, calcium, phosphorus, magnesium, pH and
bicarbonate. Urine is examined for crystals and casts;
estimation of spot and 24-hr urine calcium, creatinine,
uric acid and protein is recommended. Sodium nitroprusside test for cystine and 24-hr urinary oxalate is
required in patients with recurrent or multiple stones.
Treatment should be directed at the underlying cause;
a high fluid intake and low salt diet is advised in all
patients. Patients with idiopathic hypercalciuria benefit
from modest salt restriction, and administration of
potassium citrate; refractory cases might need treatment
with thiazide diuretics.
Cystinuria
Cystinuria is an autosomal recessive disorder characterized by a defect in transport of the four dibasic amino
acids: cystine, ornithine, lysine and arginine, causing
their increased urinary excretion. Cystine is relatively
insoluble and may lead to calculus formation. The stones
are typically radiopaque and urinalysis shows hexagonal
cystine crystals. The urinary cyanidenitroprusside test
gives a magenta red color. The four amino acids can be
identified on paper chromatography; plasma concentrations are usually normal. A high fluid intake and
alkalization of urine increase the solubility of cystine. Dpenicillamine may dissolve calculi as well as prevent
their formation.
BIBLIOGRAPHY
1. Bagga A, Bajpai A, Menon S. Approach to renal tubular
disorders. Indian J Pediatr 2005;72:771-6.
2. Bagga A, Sinha A. Evaluation of renal tubular acidosis.
3. Soriano RJ. Renal tubular acidosis. Pediatr Nephrol 2000;
14:1121-36.
4. Srivastava RN, Bagga A. Urolithiasis. In: Srivastava RN,
Bagga A, (Eds): Pediatric Nephrology, 4th edn. New
Delhi: Jaypee Brothers 2005;379-89.
15.1 Anemia in Children: MR Lokeshwar, VP Choudhry ............................................................................................................................. 768

15.2 The Value of a Complete Blood Count in Children: Zeenat Currimbhoy .......................................................................................... 771
15.3 Anemia in the Newborn: Jayashree A Mondkar, Mamta Manglani, Armida Fernandez ..................................................................... 775
15.4 Nutritional Anemias in Infancy and Childhood: Niranjan Shendurnikar, Omprakash Shukla, Sushil Madan .................................. 780
15.5 Nutritional Anemias in Adolescence: Sushil Madan .......................................................................................................................... 785
15.6 Thalassemia: MR Lokeshwar, Nitin Shah, Swati Kanakia, Mamta Manglani ....................................................................................... 794
15.7 Sickle Cell Disease: VS Dani ................................................................................................................................................................ 816
15.8 Red Cell Membrane Disorders: Rashmi Dalvi, Bharat Agarwal, R Agarwal ....................................................................................... 820
15.9 Autoimmune Hemolytic Anemia: Bharat Agarwal, Rashmi Dalvi ....................................................................................................... 822
15.10 Bone Marrow Failure Syndrome: Nitin Shah, MR Lokeshwar ............................................................................................................ 824
15.11 Physiology of Hemostasis: Approach to a Bleeding Disorder: Renu Saxena ................................................................................ 828
15.12 Platelet and Bleeding Disorders: VP Choudhry, Amit Upadhyay ....................................................................................................... 831
15.13 Disseminated Intravascular Coagulation (DIC): Anupam Sachdeva, VP Choudhry ......................................................................... 843
15.14 Bleeding Disorders in the Newborn: Jayashree A Mondkar, Mamta Manglani, Armida Fernandez ................................................. 854
15.15 Hematopoietic Growth Factors: Purvish M Parikh, MR Lokeshwar .................................................................................................... 858
15.16 Transfusion Medicine and Component Therapy in Pediatrics: RK Marwaha, Sudeshna Mitra, Deepak Bansal ........................... 861
768
15.1 Anemia in Children

MR Lokeshwar, VP Choudhry
INTRODUCTION
Anemia is global problem of immense public health
significance. It is an ancient disease, and commonest
chronic malady of mankind and seen all over the world.
Anemia is defined as reduction of red blood cell
volume or hemoglobin concentration, and hematocrit
below the range of values occurring in healthy persons,
or two standard deviations below the mean for the
normal population, age and sex.
Anemia is reduction in oxygen carrying capacity of
blood as a result of reduction in:
Red cell mass -Red cell count / HCT
Hb. concentration.
Although a reduction in the amount of circulating
RBCs and hemoglobin decreases the oxygen carrying
capacity of the blood, few physiological disturbances
occur until hemoglobin level falls below 7 to 8 g/dl.
Below this level pallor becomes evident in the skin and
mucus membrane. Physiologic adjustment to anemia
includes tachycardia, increased cardiac output, shift in
the oxygen dissociation curve and deviation of blood

flow towards vital organs and tissues.
CLASSIFICATION
Anemia is not a specific entity but an indication of an
underlying pathologic process or disease.
Anemia may be classified as
Mild Anemia
< 10 gm%, but < normal for the
age.
Moderate Anemia 7-10 gm%
Severe Anemia
< 7 gm%
Very Severe Anemia < 5 gm%
Useful classification of the anemia of childhood divides
them into two broad groups
Those resulting primarily from decreased or
ineffective (inadequate) production of red blood cells
or hemoglobin;
Those in which increased destruction or loss of red
cells is predominant mechanism.
TABLE 15.1.1: Shows age specific Indices
Term (Cord)
1-3 days
2 wks
1 month
6 mth-2 yr
2-6 yrs
6-12 yrs
12-18 yr Male
12-18 yr Female
Hb (g %)
Mean (2SD)
Hct(%)
Mean(-2SD)
MCV(fl)
Mean(-2SD)
MCHC %
Mean(-2SD)
Retic(%)
WBC/mm3x 1000, Platelets

Mean(+2SD)
(103/mm3)
16.5 (13.5)
18.5 (14.5)
16.6 (13.4)
13.9 (10.7)
12.0
12.5 (11.5)
13.5(11.5)
14.5 (13)
14.0(12)
51 (42)
56 (45)
53 (41)
44(33)
36
37(34)
40 (35)
43(36)
41(37)
108 (98)
108 (95)
105 (88)
101 (91)
78
81(75)
86(77)
88(78)
90(78)
(33.0)(30)
33.0 (29)
31.4 (28.1)
31.8 (28.1)
33.0
34(31)
34(31)
34(31)
34(31)
(3-7)
(1.8-4.6)
(0.1-1.7)
(0.5-1.0)
(0.5-1.0)
(0.5-1.0)
0.5-1
18.1 (9-30)
18.9 (9.4-34)
11.4 (5-20)
10.8 (4-19.5)
10.6
8.5(5-15.5)
8.1(4.5-13.5)
7.8 (4.3-13.5)
7.8(4.5-13.5)
290
192
252
(150-350)
Adapted from Harriet Lane Handbook, Kevin B Johnson, Jaypee Brothers Medical Publishers, New Delhi, India, pp 231.(1)
TABLE 15.1.2: Shows hemoglobin and hematocrit cut off values used to define anemia in
people living at sea level (WHO criteria)
Age/Sex Group
6 months 5 yrs.
5 11 yrs.
12 13 yrs.
Non-pregnant women
Pregnant women
Men
From WHO/UNICEF/UNO 1997
Hb. level below Gm/dl.

<11.0
<11.5
<12.0
<12
<11
<13
HCT level below%

33
34
36
36
33
39
Pediatric Hematology
769
TABLE 15.1.3: Shows the important causes of anemia in childhood

Anemia resulting primarily from inadequate production of red blood cells or hemoglobin.
1. Marrow failure
Aplastic anemia involving more than one cell line with or without congenital anomalies.
Congenital
- Fanconies Anemia, Dyskaratosis Congenita, etc.
- Acquired
- Idiopathic.
Infection, Chronic inflammatory disorder, Renal disease, Liver disorders, and Endocrine disorders, Chemicals, Physical
agents, Metabolic products, Immune mechanism.
Decreased numbers of red blood cell precursors in the marrow.
Pure red blood cell anemia - Congenital pure red blood cell anemia (Diamond Blackfan Syndrome)
Acquired pure red blood cell anemia-Transient erythroblastopenia of childhood. (e.g. TEC)
2. Marrow replacement
Malignancies and infiltrative disorders, Leukemia, Hodgkindisease. Neuroblastoma
Osteopetrosis,
Storage disorders (Gaucher, Nimennpick),
Myelofibrosis
Congenital dyserythropoietic anemia
Ineffective erythropoiesis-Thalassemia.
Chemotherapy
3. Deficiency of specific factors
Megaloblastic anemia
Folic acid deficiency or malabsorption
B12 deficiency - malabsorption or transport disorders, orotic aciduria
Microcytic anemia
Iron deficiency
Pyridoxine responsive and X-linked hypo chromic anemia
Lead poisoning
Copper deficiency.
4. Impaired erythropoietin production
Chronic renal disease
Hypothyroidism
Hypopitutrism
Chronic infection and inflammation
Malignancy
Protein malnutrition
Anemia resulting primarily from increased destruction or loss of red cells
1. Loss of red cells from the body.
Acute Hemorrhage
Chronic Hemorrhage
2. Hemolytic anemia- Excess Destruction
Intracorpuscular Defect (Intrinsic defect of red blood cells)
Extracorpuscular Defect (Extrinsic defect of red blood cells)
Intra Corpuscular Defect (Intrinsic defect of red blood cells)
Membrane defect (Membranopathy)
Hereditary spherocytosis / Elliptocytosis / Stomatocytosis.
Paroxysmal Nocturnal Hemoglobinuria.
Pyropyknocytosis.
Enzymatic defect (Enzymopathy) -Non-spherocytic Hemolytic anemia
Defect in enzymes of Glycolytic Pathway - Pyruvate Kinase, Hexokinase and other enzyme defects.
Defect in enzymes of the Pentose phosphate pathway and glutathione Complex -G6PD deficiency.
Defect in Synthesis of Hemoglobin (Hemoglobnopathy)
Hb S, C, D, E, etc alone or in combination.
Thalassemia group of disorder.
Extra-corpuscular Defect (Extracellular defect of red blood cells)
Immunologic disorder
Contd...
770
Contd...
Passive acquired antibodies (Hemolytic disease of New born).

Rh. isoimmunization
A/B isoimmunization
Other minor blood group incompatibility
Active antibody formation
Idiopathic autoimmune hemolytic anemia
Warm and cold agglutinin diseases
Symptomatic-Lupus, Lymphoma
Drug induced
Non-immunologic disorder
Toxic drugs, Chemical agents-Heavy metals, Oxidants,
Infections Malarial, Clostridia, Bacterial Toxins
Physical trauma-Microangiopathic,Thermal injury, HUS
Miscellaneous-Hypersplenism
Modified from Nelsons Textbook of Pediatrics and Hematology of Infancy and ChildhoodNathan and Oski, Smiths Disease of
Infancy and Childhood
MORPHOLOGICAL CLASSIFICATION
Anemia can be evaluated by complete blood count
(Table 15.1.1).
1. Hemoglobin (Hb) values are expressed in gm/liter
2. Mean corpuscular volume (MCV) represents mean
size of RBC.
3. Mean corpuscular Hb concentration (MCHC) detects
cellular dehydration.
4. Increased MCHC occurs in hereditary spherocytosis
and other membrane abnormalities like eliptocytosis
(ovalocytosis), stomatocytosis, and sickle cell
anemia.
Figure 15.1.2: Microcytic Hypochromic RBC
(MCV < 80 Fl, MCH < 29 pg)
Figure 15.1.1: Normocytic Normochromic (MCV = 80-94Fl.

MCH - 29pg-34pg)
Figure 15.1.3: Macrocytic Hypochromic Anemia MCV > 94Fl
MORPHOLOGIC CLASSIFICATION
Morphologic classification is often used, the red blood
cell being characterized by their mean corpuscular
volume (MCV) as
Microcytic Hypochromic anemia
MCV < 80 Fl,
MCH < 29 pg
MCHC < 30%
TABLE 15.1.4: Proposed classification of anemic disorders

based on MCV and RDW
Low MCV
High MCV
Aplastic
anemia
RDW High
Megaloblastic
anemia
Immune
hemolytic
anemia
IDA
Chronic liver
disease
Malignancies,
myelofibrosis,
myelotoxic
drugs
(Modified from Nelsons Textbook of Pediatrics)
Reticulocyte count: Reticulocyte count (corrected), is the

mirror image of bone marrow activity which is markedly
reduced (<1%) in hypoplastic or aplastic anemia whereas
reticulocyte count is increased in hemolytic anemia.
BIBLIOGRAPHY
1.
2.
RDW Values in Various Diseases

RDW is the coefficient of variation of red cell volume
distribution. RDW is the objective documentation of
subjective anisocytosis. It gives degree of red cell
anisocytosis. Normal range: 11.5 to 14.5 %.
It helps in distinguishing Iron Deficiency Anemia
(IDA) from beta thalassemia trait, two common causes
of microcytic anemia in clinical practice.
Normal MCV
RDW Normal Thalassemia Normal

trait
Macrocytic anemia
MCV > 94 cmm.
Normocytic Normochromic anemia
MCV - 80-94 cmm.
MCH - 29 pg to 34 pg
MCHC - 30-36%
Classification of anemia based on red cell parameter
derived from blood cell counter. (RDW and MCV as a
diagnostic aid in anemia).
Anemia in childhood may also be classified by
variation in cell size and shape, as reflected by alteration
in the red blood cell distribution width. A knowledge of
both the MCV the RDW can be helpful in the initial
classification of the anemia of childhood (Table 15.1.4)
771
3.
4.
5.
6.
7.
Bertil Glader. The Anemias Nelsons Textbook of

Pediatrics Ed. R Klingman, HB Gleson, RE Burman
Bonita Stanton, 18th Edition.
Denis Miller. Anemias: General considerations on
Smiths Blood Diseases of Infancy and Childhood. Denis
R Miller, Howard A Pearson. 4th Edition. P91, The CV
Mosby Company: Saint Louis, 1978.
Harriet Lane Handbook, Kevin B Johnson. Jaypee
Brothers Medical Publishers: New Delhi, India, 231.
Hematology of Infancy and childhood-Nathan and Oski,
Philip Lanzkowasky Hematologic references Manual of
Pediatric Hematology and Oncology, 630-31.
SM Lewis, BJ Bain, I. Bates Reference ranges and normal
values. Dacie and Lewis Practical Hematology. P13.
WHO/UNICEF/UNO, 1997.
15.2 The Value of a Complete

Blood Count in Children
Zeenat Currimbhoy
MEASUREMENT OF COMPLETE
BLOOD COUNT (CBC)
The components of CBC are hemoglobin (Hb), hematocrit
(HCT/PCV), mean corpuscular volume (MCV), mean
corpuscular hemoglobin concentration (MCHC), red
blood cell (RBC) Count, red cell distribution width

(RDW), WBC count and platelet count. In addition a
blood smear is examined for cellular morphology and
for a WBC differential count. A reticulocyte count
completes the examination. Instruments are available
today to do CBC.
772
HEMOGLOBIN, MCV, RBC COUNT AND MCHC

Hemoglobin level more then 2 SDs below the mean
constitutes anemia. Mean corpuscular volume (MCV)
and red cell distribution width (RDW) show size and
size distribution respectively. Increased RBC size or
macrocytosis (increased MCV) points to hemolysis or
marrow failure or folic acid/Vit B12 deficiency, and
decreased RBC size or microcytosis (decreased MCV) to
iron deficiency or anemia of chronic disease or
thalassemia. Normal or elevated MCV in anemic children
with increased reticulocyte (retic) counts is the result of
hemolysis and without increased retics is due to acquired
aplastic anemia. Mean corpuscular Hb concentration
(MCHC) detects cellular hydration and although not
picked up by electric impedance instruments, e.g. Coulter
counter /Sysmax, it can be measured by light scatter
instruments e.g. Technicon Series, Cell dyne. Increased
MCHC occurs in hereditary spherocytosis and sickle cell
anemia and normal newborns. It is low in iron deficiency.
INTERPRETATION
For interpretation, the clinician must have a working
knowledge of normal values of the components of the
CBC. Hemoglobin (Hb) values vary with age. The
normally high Hb of 19 gm/dl at birth decreased to 18
gm/dl at one week of age. Thereafter it falls gradually
to reach a nadir of 10.5 g/dl by 7 to 10 weeks of age.
(Prematures reach their nadir earlier and recover later).
Thereafter, Hb remains initially around 11 g/dl and later,
after the age of 6 months, over 12g/dl.
To keep any cell number constant, the amount of cell
destruction must equal the amount effectively produced.
In case of RBCs, if this balance is upset in favor of former
(excessive cell destruction) or the latter (decreased

production), anemia results which is reflected in a
decrease in Hb concentration (Table 15.2.1). A third
reason why the cell counts may be upset is
maldistribution as occurs when the spleen is enlarged
and hence contains an increased amount of blood
(hypersplenism).
When Hb is decreased, further RBC parameters that
prove helpful in diagnosis are MCV, MCH, RDW and
retic count. Iron deficiency appears if external iron is not
supplied and the diet is poor in iron by 6 months of age;
hence Hb screening is valuable if routinely done at 9
to 12 months of age. MCV and RDW estimations aid in
the diagnosis of iron deficiency and RDW differentiates
it from thalassemia minor (Table 15.2.2). Additionally,
Hb is normal or near normal in a thalassemia trait, but
the RBC count is higher than normal to explain
hypochromia in red cell.
Iron deficiency and thalassemia major are usually
detected between 6 months and 2 years of age. Both show
hallmark of hypochromia on peripheral blood (PB)
smears and a low MCV, but unlike iron deficiency,
several nucleated red cells (NRs) are present in a major
thalassemic smear.
If iron deficiency is on the way of being corrected
with iron therapy (at least 1g/dl of Hb rise within one
month), and then the Hb gets stuck at 8 to 9g/dl,
suspect and underlying chronic infection which may
show hypochromia. Serum ferritin solves this problem.
It is low in iron deficiency (<15 mg/dl).
Reticulocyte is evident when the marrow attempts
to make up for the blood loss. If RBC destruction
(hemolysis) is due to malaria, retic count rises to
compensate, unless there is a complication iron and/or
TABLE 15.2.1: The RBC balance
folic acid deficiency. In congenital hemolytic anemias
with continuous hemolysis, Hb is low only if the bone
marrow cannot compensate for red cell destruction, e.g.
in congenital spherocytosis, if the Hb normal and the
retic count is elevated, it implies a state of a compensated
hemolytic anemia. Peripheral blood smears are helpful
in diagnosing nonspecific and specific types of hemolysis
by the presence of nucleated red cells (NRs),
polychromatophilia, Howell-Jolly bodies, fragmented
cells, spiculated RBCs, sickle cells, basophilic stippling,
rouleaux formation, spherocytes, macrocytes etc.2 The
MCV is high with severe hemolyis and there may also
be an increase in WBC and platelet counts. If in a
peripheral blood smear NRs are increased, a correction
must be made in the WBC count thus:
NR
Corrected WBC count = WBC count
NR + 100
Increased MCV (macrocytosis) if due to extravascular

RBC loss from hemolysis, will show a reticyulocytosis
and hyperbilirubinemia, but if due to bone marrow
failure (aplastic anemia), will show a reticulocytopenia.
Anemia with a normal MCV and reticulocytes can also
be due to hemolysis, and in the absence of reticulocytes,
it may be due to chronic infection or chronic
inflammation.
WBC, Granulocytes, Lymphocytes
WBC counts lack sensitivity and specificity, hence must
be viewed in the context of the illness. An erroneous
773
concept is that polymorphonuclear (PMN) leukocytosis

exclusively implies a bacterial infection.
Normal WBC counts and differentials are given in
Table 15.2.3.
If after the neonatal period (i.e. after 1 month of age)
children display over 500 bands/mm3 (non-segmented
neutrophils), it suggests an infection, often bacterial, but
may be viral, irrespective of the WBC count.
Leukopenia is frequently associated with viral
infections. Lymphocytes with atypical lymphocytes
(which should be counted separately from regular
lymphocytes) are encountered in EBV, CMV, HBV, HAV
and HIV infections.
Eosinophilia is seen in parasitic infections and allergic
reactions (Table 15.2.3).
In a suspected immunodeficiency, absolute
lymphocyte count (WBC count lymphocyte %) is
frequently less than normal for age, and demands
further specific investigations (Table 15.2.3). Testing for
Primary Immunodeficiency Disease (PID) should be
considered in any infant/child presenting with recurrent
infections. Its later consequences are autoimmunity and
malignancy.
If NRs and immature granulocytes are present in a
peripheral blood smear (i.e. a leuko-erythroblastic
reaction), beware of an underlying malignancy (e.g.
neuroblastoma).
A leukemoid reaction is a WBC count of more than
50,000/mm3 and with an increase in immature granulocytes or in lymphocytes A granulocytic leukemoid
reaction with myelocytes, metamyelocytes, bands and
TABLE 15.2.2: RDW and MCV as an aid in diagnosis

MCV low
RDW
normal
MCV normal
RDW
high
MCV high
RDW
normal
RDW
high
RDW
normal
Thalassemia trait
Iron deficiency
Normal
Mixed deficiency
Aplastic anemia
Folate deficiency
Chronic disease
S-beta thalassemia
Chronic disease
Early iron or folate

deficiency
Pre-leukemia
B12 deficiency
HbH
Sickle/Hbc trait
Hemoglobinopathy
Immune hemolysis
Fragmentation
(HUS, DIC)
Hereditary
speherocytosis,
Chemotherapy,
CML, hemorrhage
Myelofibrosis
Cold
agglutinins
Sideroblastic
anemia
(Ref. Waters, MC and Abelson, HT Pediatric Clinics of North America 1996;43:599-622)

MCV low (67m3) and RDW high = Iron deficiency
MCV low (67m3) and RDW normal = Thalassemia trait and
The low MCV cannot be corrected with iron therapy
HUS = Hemolytic uremic syndrome

DIC = Disseminated IV coagulation
CML = Chronic myelogenous leukemia
RDW
high
774

TABLE 15.2.3: Age-specific leukocyte differential
Total leukocytes*
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Age
Mean (range)
Mean (range)
Mean (range)
Mean
Mean
Birth
12 hrs
24 hrs
1wk
2wks
1mth
6mths
1yr
2yrs
4yrs
6yrs
8yrs
10yrs
16yrs
21yrs
18.1 (9-30)
22.8 (13-38)
18.9 (9.4-34)
12.2 (5-21)
11.4 (5-20)
10.8 (5-19.5)
11.9 (6-17.5)
11.4 (6-17.5)
10.6 (6-17)
9.1 (5.5-15.5)
8.5 (5-14.5)
8.3 (4.5-13.5)
8.1 (1.5-13.5)
7.8 (4.5-13.0)
7.4 (4.5-11.0)
11 (6-26)
15.5 (6-28)
11.5 (5-21)
5.5 (1.5-10)
4.5 (1-9.5)
3.8 (1-8.5)
3.8 (1-8-5)
3.5 (1.5-8.5)
3.5 (1.5-8.5)
3.8 (1.5-8.5)
4.3 (1.5-8)
4.4 (1.5-8)
4.4 (1.5-8.5)
4.4 (1.8-8)
4.4 (1.8-7.7)
61
68
61
45
40
35
32
31
33
42
51
53
54
57
59
5.5 (1-11)
5.5 (2-11)
5.8 (2-11.5)
5.0 (2-17)
5.5 (2-17)
6.0 (2-5-16.5)
7.3 (4-13.5)
7.0 (4-10.5)
6.3 (3-9.5)
4.5 (2-8)
3.5 (1.5-7)
3.3 (1.5-6.8)
3.1 (1.5-6.5)
2.8 (1.2-5.2)
2.5 (1-4.8)
31
24
31
41
48
56
61
61
59
50
42
39
38
35
34
1.1
1.2
1.1
1.1
1.0
0.7
0.6
0.6
0.5
0.5
0.4
0.4
0.4
0.4
0.3
6
5
6
9
9
7
5
5
5
5
5
4
4
5
4
0.4
0.5
0.5
0.5
0.4
0.3
0.3
0.3
0.3
0.3
0.2
0.2
0.2
0.2
0.2
2
2
2
4
3
3
3
3
3
3
3
2
2
3
3
From Dallaman PR. In Rudolph AM, editor, Pediatrics, 20th ed. New York: Appleton-Century-Crofts; 1996.
Numbers of leukocytes are x 103 /mm3; ranges are estimates of 95% confidence limits; percents refer to differential count.
Neutrophilis include band cells at all ages and a small number of metamyelocytes and mydelocytes in the first few days of life.
neutrophils has to be distinguished from chronic

myelogenous leukemia (CML). Heperleukocytosis
increases Hb, HCT, RBC and MCV value in electronic
cell counters.
Infants with a low absolute lymphocyte count (ALC)
of <1500/ mm3 suggests a diagnosis of severe combined
immunodeficiency (SCID), which ends up in early death
if not treated-hence, SCID is a pediatric emergency, and
ALC is considered to be the most useful screening
diagnostic test of SCID from birth (Tabel 15.2.4).
Peripheral blood smears may reveal leukocyte
abnormalities, e.g. cytoplasmic inclusions, or a marked
shift to the left with immature granulocytes or blasts, or
a leuko-erythroblastic reaction, or decreased lymphocytes or thrombocytopenia thereby emphasizing the
importance of blood smears in the detection of both RBC
and WBC abnormalities.
Platelet Count
The previously neglected platelet size and counts are now
being easily done in CBC machines. Large platelets are
picked up by CBC machines (mean platelet volume) and
visually in PB smears. They occur in immunomediated
platelet destruction as new young platelets produced by
the marrow enter the peripheral blood in an effort to
compensate. Thrombocytopenia is commonly due to
autoimmune idiopathic thrombocytopenic purpura

(AITP) in which platelet count often falls below
20,000/mm3 . For rough calculations 1 platelet/oil
immersion field corresponds to 10,000 to 15,000
platelets/mm3. It is worthwhile to look for evidence of
leukemia (blasts/high WBC count, and low PMN count)
when thrombocytopenia is present. In leukemia or in
aplastic anemia, a pancytopenia (RBC, WBC and platelet
cytopenia) is present. Thrombocytosis is commonly
associated with infections, and can occur in iron
deficiency and hemolytic anemias and post-splenectomy.
TABLE 15.2.4: ALC at various ages (absolute counts
( 109/L): Median and percentiles (5th to 95th percentiles)
Age
ALC
Neonatal
1wk 2 moths
2-5 moths
5-9 moths
9-15 moths
15-24 moths
2-5 yrs
5-10 yrs
10-16 yrs
Adult
4.8 (0.7-7.3)
6.7 (3.5-13.1)
6.9 (3.7-9.6)
6.0 (3.8-9.9)
5.5 (2.6-10.4)
5.6 (2.7-11.9)
3.3 (1.7-6.9)
2.8 (1.1-5.9)
2.2 (1.0-5.3)
1.8 (1.0-2.8)
ALCAbsolute lymphocyte count
In conclusion, the often routinely done CBC and PB
smears provide an excellent framework on which the
clinician can recognize and diagnose a disease,
direct therapy, prognosticate, and also counsel patients
and parents with genetic conditions, e.g. Thalassemia
major.
Infants with a low absolute lymphocyte count (ALC)
of < 1500/mm3 suggests a diagnosis of Severe Combined
immunodeficiency (SCID) which ends up in early death
if not treated-hence SCID is a pediatric emergency, ALC
is considered to be the most useful screening diagnostic
test of SCID from birth.
775
Testing for primary immunodeficiency diseases (PID)

should be considered in any infant/child presenting with
recurrent infections. Its later consequences are autoimmunity and malignancy.
BIBLIOGRAPHY
1.
Brugnara C and Platt OS. The Neonatal Erythrocyte and

its disorders. 519-55 Nathan and Oskis Hematology of
Infancy and Childhood. Philadelphia: WB Saunders 2003.
2. Harriet Lane Handbook. 16th ed. VI Gunn C. Nechyba
Mobsy 2002.
3. Walter MC and Abelson HJ, Pediatric Clinics of North
America 1996;43:599-622.
15.3 Anemia in the Newborn

INTRODUCTION
Anemia during the first week of life is defined as a
hemoglobin value less than 14 gram/dl.
NORMAL HEMATOLOGICAL VALUES IN THE
NEWBORN
The mean cord blood hemoglobin of healthy term infants
ranges between 14 and 20 g/dl with a mean of
16.8 gm/dl.
Shortly after birth the Hb concentration increases by
as much as 6 gm/dl depending on the amount of
placental transfusion. The redistribution of body fluids
with decrease in plasma volume after birth also accounts
for this rise. Failure of hemoglobin to rise during this
period is a marker of blood loss.
Hemoglobin levels return to cord blood values by the
end of the first week. A significant Hb decrease during
this time even if absolute values of Hb are within the
normal range is also suggestive of hemorrhage or
hemolysis.
Beyond the first week of life, Hb concentrations
decrease in both term and preterm infants. To reach
minimal levels of 9.4 14.5 gm/dl in term infants by 7 to
9 weeks of age. This physiological anemia occurs
because of a decline in erythrocyte mass due to the
following reasons:
In utero the fetal oxygen saturation is low at around
45%, erythropoietin levels are high and RBC production
is rapid. Reticulocyte counts are 3-7% reflecting

erythropoiesis. With improved oxygen saturation to 95%
after birth, the erythropoietin levels become undetectable
hence RBC production stops, reticulocyte counts are low
and the hemoglobin level falls (Table 15.3.1).
This factor coupled with a reduced life span of fetal
RBCs results in anemia that is not a functional one as
oxygen delivery to the tissue is adequate as the levels of
Hb A and 2,3DPG increase.
At 8-12 weeks, hemoglobin levels reach their nadir
(Table 15.3.2), oxygen delivery to the tissues is impaired,
erythropoietin production is stimulated and hemoglobin
starts increasing.
The hemoglobin and RBC count fall earlier and to a
greater extent in preterm infants leading to anemia of
prematurity.
TABLE 15.3.1: RBC Values in term and preterm
infants during the first week of life
Term Infants
Cord blood
Day 1
Day 3
Day 7
Preterms
<1500 grams
Cord blood
Day 7
Hb (gms/ dl)
Hct %
Reticulocyte (%)
17.0 (14-20)
18.4
17.8
17.0
53 (45-61)
58
55
54
<7
<7
<3
<1
16.0 (13-18.5)
14.8
49
45
<10
<3
776

TABLE 15.3.2: Hemoglobin nadir in babies in the
first year of life
Maturity of baby at birth
Hemoglobin level
at nadir
Time of nadir
Term babies
9.2-11.0
6-12 wks
Premature babies
(1200-2500gm)
8.0-10.0
5-10 wks
Small premature babies

(<1200gm)
6.5-9.0
4-8 wks
CAUSES OF PATHOLOGIC ANEMIA IN THE

NEWBORN
The 3 basic mechanisms for the development of anemia
in any patient are
1. Blood loss.
2. Shortened RBC life span or hemolysis
3. Inadequate red blood cell (RBC) production.
Blood Loss
Blood loss can occur in the fetus, at birth or in the postnatal period.
The bleeding may be acute or chronic.
A. Obstetric causes of blood loss include:
Abruptio placentae.
Placenta previa.
Incision of placenta at cesarean section.
Rupture of a normal umbilical cord.
Malformations of placenta and cord velamentous
insertion, vasa praevia.
Rupture of anomalous insertion of cord and
hematoma of cord.
B. Occult blood loss before birth or during delivery
could be due to:
Feto-maternal bleeding
Fetofetal bleeding as occurs in: Twin-to-twin
transfusion
Feto-placental bleeding. If the neonate is accidentally
held above the placenta for a time after delivery, a
fetal-placental transfusion may result in blood loss.
C. Bleeding in the neonatal period may be due to:
Birth trauma resulting in intracranial bleeding,
cephalhematoma, sub galeal hemorrhage, retroperitoneal bleeding.
Hemorrhagic disease of newborn now called vitamin

K deficiency bleeding (VKDB) resulting in bleeding
from gastrointestinal tract, umbilicus, intracranial
bleed.
Sepsis with DIC.
Intrauterine TORCH infections.
Iatrogenic anemia due to excessive blood sampling.
Shortened Red Blood Cell Life Span or Hemolysis
The average life span of a neonatal RBC is only one half
to two thirds that of the RBC life span in an adult. Cells
of the most immature infants may survive only 35-70
days. Hemolytic anemia which further shortens RBC
survival can occur in the newborn for a variety of reasons:
Immune hemolytic anemia: Placental transfer of
maternal antibodies directed against fetal red cell
antigens is the most common cause of neonatal
hemolysis. This occurs as a consequence of maternal
sensitization to fetal antigens that have leaked into the
maternal circulation. Immune hemolysis may be due to
Rh, ABO or minor blood group incompatibility. When
an Rh negative mother conceives an Rh positive baby,
fetal red cells may cross the placenta and sensitize the
maternal immune system. On subsequent exposure to
Rh positive cells across the placenta, the antibodies
produced by the maternal immune system may cross the
placenta and cause hemolysis of fetal red cells. Similar
situation may arise with mothers with blood group O
and babies with blood group A or B.
Maternal auto immune hemolytic disease: Antibodies
from the mother cross the placenta and result in fetal
red cell hemolysis.
Non-immune Hemolytic Anemia in the Newborn may
occur due to
RBC membrane defectHereditary spherocytosis,
metabolic defects, hemoglobinopathies, infection or
disseminated intravascular coagulation.
Inadequate Red Blood Cell Production
Diminished RBC production could be due to:
Diamond-Blackfan syndrome,
Fanconis anemia,
Congenital leukemia,
Congenital infections with parvovirus, etc.
Osteopetrosis
Infections that cause anemia due to reduced red cell
production include parvovirus B19, CMV, toxoplasmosis,
congenital syphilis, rubella and herpes simplex. Maternal
infection with parvovirus B19 causes fetal anemia which
is severe enough to lead to intrauterine death, due to
hydrops. In addition to anemia, parvovirus infections
cause marked reticulocytopenia. Thrombocytopenia may
also occur.
Diamond Blackfan Syndrome also called pure red cell
aplasia, occurs either due to a lack of erythroid stem cells
or immune suppression of stem cell differentiation.
Inheritance seems to follow an autosomal ressessive
inheritance. The disorder should be suspected in any
newborn with anemia and reticulocytopenia, normal
platelets and leucocytes. Musculo-skeletal abnormalities,
triphalyngeal thumbs may occur in a third of patients.
The diagnosis is confirmed by examination of bone
marrow aspirate which reveals a virtual absence of
erythroid precursors.
Apnea: severe, anemia may result in respiratory

depression, manifested by increased periodic breathing
and apnea.
Tachypnea, tachycardia decreased activity and
lethargy are frequently attributed to anemia, with
subjective improvement subsequent to transfusion. Poor
growth, inadequate weight gain despite adequate caloric
intake often is attributed to AOP.
Tachycardia may occur.
Flow murmurs may occur.
Metabolic acidosis may be detected.
APPROACH TO DIAGNOSIS
Obstetric
History
ANEMIA OF PREMATURITY
Anemia of prematurity (AOP) is an exaggeration of the
physiologic anemia of infancy. The Hb nadir is therefore
reached earlier and is lower than in term babies and can
be as low as 7.8 to 9.6 gm/dl. Shortened survival of RBCs
to an average of 60 days (120 days life span in adult RBCs)
and rapid body growth with relative hemodilution are
the contributory factors. Besides, iatrogenic blood losses
may be higher, vitamin E deficiency is more common in
small preterm infants.
Birth History
Maternal
History
Infants, who have suffered chronic blood loss in utero,

vary in their clinical state at delivery from a hydropic
infant with severe anemia to an asymptomatic infant.
Often the pallor is marked and disproportionate to the
evidence of distress.
Few symptoms are universally accepted as attributable to anemia; however, the following are among
the symptoms attributable to AOP:
Feature
Inference
APH
Procedures like
Amniocentesis
Fetal blood loss

Feto maternal
Hemorrhage
Traumatic delivery
Concealed hemorrhage,
subgaleal hemorrhage,
ICH
Twin Delivery
Twin to twin
transfusion syndrome
Precipitate delivery
Ruptured cord, ICH
Drug ingestion like

aspirin, warfarin,
anticonvulsants
Early onset
hemorrhagic disease
Family History Anemia in other

male children
CLINICAL PRESENTATION OF
BABIES WITH ANEMIA
Acute hemorrhage before, during or after delivery is
poorly tolerated by the neonate and results in a neonate
who is pale, shocked, has acute distress, shallow, rapid
and often irregular respiration, tachycardia, weak or
absent peripheral pulses, low blood pressure and no
hepatosplenomegaly. Such babies may have normal
hemoglobin level initially but can fall rapidly in the first
6-8 hours.
777
Clinical
Presentation
G6PD Deficiency
H/O attacks of
jaundice with
gallstones
Hereditary
spherocytosis
GI bleed on day
2-3 in a well baby
Vitamin K deficiency
bleeding (VKDB)
Bleeding in a sick
baby
Repeated blood
collections especially
in small preterms
asphyxia and shock
pallor with CHF
Sepsis with DIC
Anemia, jaundice,
hepato-splenomegaly
Iatrogenic anemia
Acute blood loss
Chronic severe blood
loss, immune hydrops
Iso immune
hemolysis
SGA with anemia,

hepato splenomegaly, Intrauterine infection
jaundice
778
LABORATORY INVESTIGATIONS IN A CASE OF

NEONATAL ANEMIA (TABLE 15.3.3)
Investigations should be tailored to requirements of the
patient based on history and examination. These include:
Hemogram with peripheral smear for RBC
morphology.
Reticulocyte count (normal 3-7%) and RBC indices
to differentiate anemia due to hemorrhage and
hemolysis (elevated reticulocyte count) from anemia
due to bone marrow suppression (low reticulocyte
count).
Blood group and Coombs test, to detect blood group
incompatibility.
Serum bilirubin (indirect or unconjugated) elevated
levels suggest hemolysis.
G6PD estimation.
KleihauerBetke test on mothers blood to detect the
presence of fetal RBCs in maternal circulation.
Urine and stool examination for occult blood.
Hemoglobin electrophoresis if alpha thalassemia
suspected.
Bone marrow examination to confirm diagnosis of
hypoplastic anemia.
MANAGEMENT OF NEONATAL ANEMIA
Anemia with Shock
Therapy of acute hemorrhagic anemia is directed at
rapid expansion of the vascular space with 20 ml/kg of
isotonic saline or Ringers lactate, followed by either type
specific crossmatched whole blood or packed red cells
resuspended with saline.
In infants with severe anemia or hypoxia, O Rh

negative RBCs are an acceptable alternative.
Anemia with Congestive Heart Failure
Transfusion is required in infants in whom anemia may
be contributing to congestive heart failure. Furosemide
1mg/kg followed by a packed cell transfusion of 10-15
cc/kg may be given 3 ml/kg of packed cells or 6 ml/kg
of whole blood raises the hemoglobin by 1gm/dl. In
severely anemic babies with CHF, where large volume
of packed cells are required, a partial exchange
transfusion with packed red cells may be carried out to
reduce circulatory overload.
Anemia due to Hemolysis
Double volume exchange transfusion for hyperbilirubinemia followed by a top up packed cell
transfusion if required.
Other Indications for Packed Cell Transfusion
Besides transfusion for hemorrhagic shock, adoption of
transfusion protocols takes a variety of factors into
account, including hemoglobin levels, degree of
cardiorespiratory disease, and traditional signs and
symptoms of pathologic anemia.
Transfusion for phlebotomy losses is not routinely
required.
TABLE 15.3.3: Differential diagnosis based on findings of lab. studies

Reticulocytes
Bilirubin
Coombs test
RBC morphology
Diagnostic possibilities
Normal or
decreased
Normal
Negative
Normal
Physiologic anemia of infancy or prematurity;

congenital hypoplastic anemia; other causes of
decreased production
Normal or
Increased
Normal
Negative
Normal
Acute hemorrhage (fetomaternal, placental,

umbilical cord, or internal hemorrhage)
Chronic fetomaternal hemorrhage
Increased
Increased
Positive
microspherocytes
Immune hemolysis (blood group incompatibility

or maternal autoantibody)
Normal or
Increased
Increased
Negative
Spherocytes
Elliptocytes
Hypochromic microcytes
Spiculated RBCs
Hereditary spherocytosis
Hereditary elliptocytosis
Alpha-or gamma-thalassemia syndrome
Pyruvate-kinase deficiency
Schistocytes and RBC

fragments
Bite cells (Heinz bodies
with supravital stain)
Normal
Disseminated intravascular coagulation;

other microangiopathic processes
Glucose 6 phosphate
dehydrogenase deficiencyInfections;
Enclosed hemorrhage
(Cephalhematoma)
Hypochromic microcytes
779
24 Hrs tachycardia >180 ;

tachypnea >80
that care for premature infants should have the ability

to determine laboratory values using very small volumes
of serum.
The use of non-invasive monitoring devices, such as
transcutaneous hemoglobin oxygen saturation, partial
pressure of oxygen, and partial pressure of carbon
dioxide, may allow decreased blood drawing. Oral iron
therapy 2-6 mg/kg /day in preterm babies, starting by
4-6 weeks and continued till weaning has been
adequately achieved is an important preventive measure.
Increased O2 requirement from

previous 48 Hrs
BIBLIOGRAPHY
RBC Transfusion for Premature

Central
Hematocrit Hemoglobin
For infants requiring significant

ventilation (FiO2 > 40%,
pressor support)
< 40%,
< 12 g/dl
For infants requiring minimal

ventilation (FiO2 > 35%)
< 35%,
< 10 g/dl
Infant requiring supplemental O2
Weight gain < 10 g/kg/d for 4 days

on 100 calories/kg/d
Increase in apnea >10; >3 requiring
bagging undergoing surgery
< 25%,
< 8g/ dl
Recombinant Erythropoietin Treatment

Multiple investigations have established that premature
infants respond to exogenously administered
recombinant human EPO with a brisk reticulocytosis and
that the drug appears to be safe. Modest decreases in the
frequency of PRBC transfusions have been documented
primarily in premature infants who are relatively large.
No agreement regarding timing, dosing, route, or
duration of therapy exists. In short, the cost-benefit ratio
for EPO has yet to be clearly established, and this
medication is not accepted universally as a standard
therapy for the individual with AOP. Babies on
erythropoietin therapy should receive oral iron therapy.
Provision of adequate amounts of vitamin E, vitamin B12,
folate, and iron are important to avoid exacerbating the
expected decline in hemoglobin levels in the premature
infant.
PREVENTION OF ANEMIA
Reducing the amount of blood taken from the premature
infant diminishes the need to replace blood. Hospitals
1. Al-Kharfy T, Smyth JA, Wadsworth L, et al. Erythropoietin therapy in neonates at risk of having
bronchopulmonary dysplasia and requiring multiple
transfusions. J Pediatr 1996;129:89-96.
2. Bowden RA, Slichter SJ, Sayers M, et al. A comparison
of filtered leukocyte-reduced and cytomegalovirus
(CMV) seronegative blood products for the prevention
of transfusion- associated CMV infection after marrow
transplant. Blood 1995;86:3598-603.
3. DeMaio JG, Harris MC, Deuber C, Spitzer AR: Effect of
blood transfusion on apnea frequency in growing
premature infants. J Pediatr 1989;114:1039-41.
4. Lachance C, Chessex P, Fouron JC, et al: Myocardial,
erythropoietic, and metabolic adaptations to anemia of
prematurity. J Pediatr 1994;125:278-82.
5. Ohls RK: A multicenter randomized double-masked
placebo-controlled trial of early erythropoietin and iron
administration to preterm infants. Ped Res 1999;45:1268.
6. Roberts IAG, Murray NA. Haematology in Rennie JM.
Robertons Textbook of Neonatology 4th edition.Elsevir
Churchill Livingstone 2005;739-772.
7. Ringer SA, Richardson DK, Sacher RA, et al. Variations
in transfusion practice in neonatal intensive care.
Pediatrics 1998;101:194-200.
8. Strauss RG: Erythropoietin in the pathogenesis and
treatment of neonatal anemia. Transfusion 1995;35:
68-73.
9. Strauss RG: Practical issues in neonatal transfusion
practice. Am J Clin Pathol 1997;107:S57-63.
10. Widness JA, Seward VJ, Kromer IJ, et al. Changing
patterns of red blood cell transfusion in very low birth
weight infants. J Pediatr 1996;129:680-87.
780
15.4 Nutritional Anemias in

Infancy and Childhood
Niranjan Shendurnikar, Omprakash Shukla, Sushil Madan
Nutritional anemias are a condition in which hemoglobin
concentration of a given individual is below the normal
level due to deficiency of one or more nutrients needed
for hemopoiesis and the hemoglobin can be increased
by the supplementation of the deficient nutrients. These
main nutrients are iron, folate, vitamin B12, proteins and
vitamin E.
IRON DEFICIENCY ANEMIA
Iron deficiency anemia is currently the most widespread
micronutrient deficiency and affects nearly 1.5 billion
people globally. Infants, preschool children, adolescents
and women of child bearing age are at greatest risk of
developing iron deficiency and its resultant anemia.
Presently available data have shown that about one-third
of worlds population suffers from iron deficiency
anemia, and of which 90 percent lives in third world
countries. Seventy-four percent of children between the
age of 6 to 35 months are anemic. In developing countries,
52 percent of pregnant women and about 35 to 40 percent
of non-pregnant women suffer from iron deficiency
anemia. The high prevalence of iron deficiency anemia
is accounted for by the combination of limited iron stores
at birth, timing of umbilical cord clamping, timing and
type of complementary food introduction and frequency
of infections. If not corrected it leads to increasing severity
of anemia, reduced work capacity, increased susceptibility to infection and greater risk of death associated
with pregnancy and child birth.
Iron Requirements During Childhood
Understanding of iron requirements, intakes and
bioavailability is essential to explain the vulnerability of
some individuals to develop iron deficiency anemia. The
iron released from the senescent red cells during the first
8 to 12 weeks of life (a period of quiescent erythropoiesis)
is stored in the body and helps to maintain erythropoiesis
up to 4 to 6 months in a normal term infant and up to 2
to 3 months in the low birth weight infant. Normal infants
at birth have about 75 mg of iron per kg body weight,
two-thirds of which is present in red blood cells. Infants

and children should continue to absorb 0.8 to 1.0 mg of
iron daily to reach the adult body stores of 4 to 5 grams.
Iron requirements are highest in infancy during period
of rapid growth. Iron is also required more in first few
years of life, during adolescence, menstruation,
pregnancy and lactation.
Normal body losses of iron are about 20 g/kg/day
and most of these losses occur by the shedding of cells
from intestinal mucosa. These losses are small and are
relatively constant but may increase many folds in the
presence of diarrhea, dysentery and parasitic infestations.
Certain factors protect infants from becoming iron
deficient in first few months of life. These include
(i) preferential delivery of iron to the fetus during the
pregnancy particularly during last 3 months of gestation,
(ii) placental transfusion to the newborn immediately
after the birth when the cord is allowed to pulsate before
being clamped, (iii) exclusive breast-feeding for first six
months of life, due to the better bioavailability of iron
from the breast milk. Adolescence is a period of rapid
growth, weight gain and blood volume expansion. The
overall iron requirement increases from a preadolescent
level of approximately 0.7 to 0.9 mg iron per day to as
much as 2.2 mg iron per day or perhaps more in heavily
menstruating young women. A much larger amount of
iron is actually needed to meet the growth requirements
of adolescence and even a marginal iron deficiency
during this period of growth can precipitate anemia.
Malnutrition, chronic infections and worm infestations
also contribute to a high prevalence of anemia. The causes
of iron deficiency anemia are shown in Table 15.4.1.
Dietary Iron
The dietary iron comes from two sources: Heme and nonheme, the later being the major source of iron in diet and
is found in varying degrees in all foods of plant origin.
Heme iron is present in meat, fish and poultry, but the
intake of these products is generally low. Heme iron is
better absorbed than non-heme iron and is not influenced
by dietary factors.
TABLE 15.4.1: Causes of iron deficiency
Decreased Iron Stores
Preterms, small-for-dates, twins
Decreased Intake/Assimilation
Delayed weaning, malnutrition
Iron poor diet
Malabsorption syndromes, chronic diarrhea
Chronic infection
GI surgery
Increased Losses
GI bleeding
Malaria
Hookworm infestation
Peptic ulcer, diverticulitis
Bleeding diathesis
Fetomaternal hemorrhage
Repeated venous sampling
Increased Demands
Prematurity, LBW
Recovery from PEM
Adolescence
Additional sources of iron in the diet include the

exogenous sources originating from soil dust, water and
cooking of foods in iron pots but the bioavailability of
iron is less and the contribution insignificant. Breast milk
even in spite of low levels of iron (0.5 mg/liter) has a
better absorption and bioavailability as compared to
cows milk. Good sources of iron in the diet include
pulses, dals, green leafy vegetable, bajra, dates, nuts,
jaggery, meat and fish. Administration of 50 mg of
vitamin C increases iron absorption by two- fold (Table
15.4.2).
Clinical Features
Iron deficiency is a systemic disorder involving multiple
systems rather than a purely hematological condition
associated with anemia. The peak incidence of iron
deficiency in children occurs between 6 months to 3 years
and in adolescents 11 to 17 years.
781
Symptomatology depends upon the rate of fall in

hemoglobin and hemostatic adjustment of various
systems. As the fall of hemoglobin is gradual, the onset
of symptoms is insidious. Initially pallor, anorexia and
irritability may be noticed. Later, hyperdynamic
circulation leads to palpitation, shortness of breath,
fatigue, reduced exercise tolerance and congestive heart
failure. Gradual onset of pallor may escape notice even
when the hemoglobin falls to 4 to 5 gm percent.
Platynychia, koilionychia, glossitis, stomatitis, angular
cheilosis may be observed, especially with long-standing
anemia. The triad of dysphagia due to esophageal webs,
koilonychia and splenomegaly in a patient with IDA is
known as Plummer- Vinson or Paterson-Kelly syndrome
and are not common in children. Mild degree of
hepatosplenomegaly is also not uncommon in IDA.
Pica is a well documented feature of anemia in
children and is manifested as craving for unedible things
such as dirt, clay (geophagia), ice (phagophagia), laundry
starch (amylophagia), salt, cardboard, etc. and are seen
in almost 70 to 80 percent of patients and are usually
cured by prompt iron therapy. Growth retardation and
altered host immune responses are other associated
features of IDA in children. Blue sclerae are also
occasionally observed in iron deficiency in children and
adolescents.
Iron deficiency anemia is associated with impaired
performance on a range of mental and physical functions
in children including physical coordination and capacity,
mental development, cognitive abilities, social and
emotional development. Other health consequences
include reduced immunity, increased morbidity,
increased susceptibility to heavy metal (including lead)
poisoning. Such changes may be related to functional
changes in iron containing enzymes at cellular level.
Recent observations have indicated that IDA, at a time
of crucial brain growth and development may produce
permanent and irreversible abnormalities in these
functions.
Tests for Iron Deficiency
TABLE 15.4.2: Sources and contents of iron

Milk (liter)
Human milk (0.5 mg), Cows milk

0.020.3 mg
Foods
80100 grams
a) Pulses (9-11 mg), Cereals (411 mg)

Green-leafy vegetables (1018 mg)
b) Ripe banana (0.9 mg), Mango (1.3 mg)
Melon (7.5 mg)
c) Meat, fish, poultry (1025 mg)
Additional sources- Cooking in iron pots, water, soil, dust
Iron deficiency anemia develops sequentially from the

depletion of stored iron, iron deficient erythropoiesis to
iron deficiency anemia (Table 15.4.3). Laboratory tests
are needed to establish the diagnosis of IDA and to
determine its cause.
Hemoglobin, red cell count and hematocrit are
decreased in IDA. MCV, MCH and MCHC are also
reduced. Peripheral blood film shows hypochromia,
microcytosis, poikilocytosis and target cells. Reticulocyte
782
TABLE 15.4.3: Laboratory tests in iron deficiency anemia
Depletion of stainable iron from bone marrow

Reduction of serum ferritin levels (less than 15 mg/ml)
Elevation of RDW (more than 14.5%)
Low serum iron (less than 75 mg/dl) and
Increased total iron binding capacity (TIBC) (more than 470
mg/dl)
Low transferrin saturation (cut off values for infants and
children, 12% and 14% respectively)
Increased red cell protoporphyrin concentration
count is usually normal unless the child has had an acute,

recent blood loss or has received hematinics. Occasionally
platelet counts may be increased. These tests may be less
reliable in cases of mild iron deficiency anemia. Some of
these tests may be altered due to the presence of
inflammation, liver disease, diurnal variations and recent
iron intake. A low MCV with and elevated RDW is
strongly suggestive of iron deficiency anemia.
Hemoglobin levels and assay of hematocrit are
commonly used screening tests to detect IDA.
Differential diagnosis of microcytic hypochronic
anemia is iron deficiency anemia, anemia of chronic
infection, thalassemias, sideroblastic anemia and lead
poisoning. An algorythm for child with microcytic
hypochromic anemia is shown in Figure 15.4.1.
Management
The basic principle of management of IDA needs
correction of anemia and the eradication of underlying
cause. Oral iron therapy is the ideal mode of treatment
for IDA. The treatment is safe, economical and as effective
as the parenteral therapy. Various iron salts available
include ferrous sulfate, ferrous fumarate, ferrous
gluconate, ferric salts, ferrous glycine sulfate and iron
polymaltose complexes. Ferrous compounds are 4 to 10
times better absorbed than ferric compounds. Iron salts
of carbonate, citrate, choline citrate and pyrophosphates
are not efficiently absorbed. Hemoglobin containing
preparations do not offer additional advantage over
simple ferrous salts. The currently recommended dosage
is for infants and children 3 mg/kg/day of elemental
iron, as higher doses are unnecessary, may increase side
effects and reduce the patient compliance (Table 15.4.4).
The iron requirements for different ages are often
defined in terms of body weight. However, in a community setting, it is not feasible to use this approach. It is
recommended that one dose should be used for all
children 6 to 36 months of age. With due consideration
to the safety issues, it is recommended that 20 mg iron
be used for anemia prophylaxis for all the children in
this age-group. The daily dosage of Iron Folic Acid (IFA)
supplement (20 mg elemental iron + 100 mcg folic acid)
is recommended for children in the current NNACP
(National Nutritional Anemia Control Program).
Adolescents require 60 mg of elemental iron per day
in case of mild anemia, and 120 mg/day, (60 2) for
moderate and severe anemia. Therapy should continue
for eight weeks after the blood values have returned to
TABLE 15.4.4: Iron amount and percentage

iron absorption
Preparation
Figure 15.4.1: Approach to microcytic hypochromic anemia
Iron
compound
Elemental
iron (mg)
per tablet
Percent iron
absorption
(mg) per tablet
Ferrous fumerate
200
66
33
Ferrous gluconate
300
36
12
Ferrous sulfate
(7H2O)
300
60
20
Ferrous sulfate,
anhydrous
200
74
37
Ferrous sulfate,
(1H2) (exsiccated)
200
60
30
normal. Addition of ascorbic acid (50 mg/day) and iron
administration in divided doses between the meals help
to promote iron absorption. Suboptimal response to oral
iron therapy may be due to poor compliance, inadequate
dosage, associated infection, occult blood loss or other
causes of hypochromic microcytic anemia such as
thalassemia minor, lead poisoning or anemia of chronic
infection.
Assessment of response to treatment is made by
reticulocyte count, which rises after 2 to 4 days of therapy.
Approximately two months are required to achieve a
normal hemoglobin level (Table 15.4.5). Recent studies
have demonstrated the efficiency of weekly/twice
weekly oral iron supplementation. Human beings have
gut mucosal turnover between five and six days and
greater iron absorption may be achieved by iron
administration to new gut cells.
Parenteral iron therapy is indicated only when there
is intolerance to oral iron, persistent non-compliance or
gastrointestinal bleeding aggravated by oral iron therapy.
Iron dextran is a complex of ferric hydrochloride and
high molecular weight dextran. Intravenous injections
cause severe reactions and hence are rarely used in
children. Iron dextran can be administered by the
intravenous route either by infusion methods to bolus
(single total) dose. The dose can be calculated as:
Iron (mg) = Wt. in kg. Hb deficit (gm/dl) 4
Life threatening anaphylactic reactions may occur
and thus these infusions should be given in hospital
settings only. Other side effects may include fever,
abdominal cramps, pain, skin rash, arthralgia and serum
sickness like picture.
Transfusion Therapy
Blood transfusion may be needed in most severe cases
of IDA when the hemoglobin concentration is below 3
TABLE 15.4.5: Response to iron therapy in
iron deficiency anemia
1224 h
Replacement of iron enzymes; subjective

improvement; decreased irritability; increased
appetite
3648 h
Initial bone marrow response; erythroid

hyperplasia
4872 h
Reticulocytosis, peaking at 57 days
430 days
Increase in Hb level
13 mo
Repletion of stores
783
to 4 gm/dl, or when superimposed infection may

interfere with the therapeutic response. Careful
precautions must be taken to avoid overloading the
circulation and precipitating cardiac failure. Packed red
cells may be slowly administered, preferably 2 to 3
ml/kg at one time.
Prevention of IDA
Appropriate nutritional strategies are an important factor
in prevention of IDA. The basic approaches to the
prevention of IDA include:
1. Protection and promotion of breastfeeding, for as long
as possible, along with timely weaning is effective in
preventing IDA. Low birth weight infants need iron
supplementation from the age of 2 months.
2. Dietary modification and consumption of larger
amounts of habitual foods increases total iron
consumption by 25 to 30 percent. Processes like germination (sprouting of green gram) and consumption
of green leafy vegetables would be additional longterm methods for prevention of IDA.
3. Periodic deworming with anti-helminthic drugs for
hookworm infestation and schistosoma should be
considered in endemic areas.
4. Supplementation with medicinal iron is considered
necessary to reduce the extent of anemia in developing countries. Administration of one pediatric (small)
tablet containing 20 mg iron and 100 g folic acid
daily for 100 days every year has been recommended
by National Nutritional Anemia Control Program.
School-based intervention consisting of once or twice
weekly distribution of iron and folic acid tablets
through school or welfare centers can be recommended as an appropriate strategy to combat IDA in
the adolescent girls.
5. Food and salt fortification with iron are evolving
rapidly and would be one of the most effective
ways to control IDA. Salt fortification gives an iron
content of 1 mg per gram of salt in the preparation.
6. Iron deficiency is prevented by increasing the use of
iron-rich foods, targeted fortification of foods for
children and the use of iron drops. In the future,
microencapsulated iron sprinkles may be useful
strategy for treating and preventing iron deficiency
in infants and this can be supplemented with other
micronutrients such as vitamins A, C, D and folic acid
and zinc.
784
7. Various contact points like measles immunization (9

months), DPT booster (1618 months) and take home
ratios in ICDS scheme (wherever followed) should
be utilized for distribution of IFA.
Nutritional Megaloblastic Anemias
Megaloblastic anemia is caused by the deficiency of either
folate or vitamin B12 or both. These deficiencies could
arise due to:
1. Decreased intake: Vitamin B12 deficiency is observed
with strict vegetarian diets, malnutrition and in
breast-fed infants of mothers with low serum B12
levels. Folate content of goats milk is extremely low.
Cooking vegetables for long time in boiling water
would also reduce the folate content of diet.
2. Impaired absorption: Failure to secrete intrinsic
factor, intestinal diseases such as celiac disease,
regional ileitis and ileal resection lead to vitamin B12
malabsorption.
3. Defective utilization: Drugs such as phenytoin and
pyrimethamine interfere with folic acid metabolism.
4. Increased demands: Needs for folate and vitamin B12
are increased during infancy, especially in premature
babies due to rapid growth. The requirements also
increase during recovery from PEM, and chronic
hemolytic anemias.
Peripheral blood smear is one of the best indicator of
megaloblastic anemia. This shows presence of
macroovalocytosis of RBCs, hypersegmented neutrophils
(3% neutrophils with more than 5 lobes) and raised MCV.
There may be evidence of leukopenia and thrombocytopenia in severely deficient states.
Treatment
Treatment of folate deficiency needs 100 to 200 g of
folate daily. However, it is given in dose of 1 to 5 mg of
folate per day for 14 to 21 days for therapeutic response
and for replenishment of stores. Good sources of folate
in diet are fresh leafy vegetables, legumes, nuts and meat.
Goats milk is a poor source of folate. Vitamin B12
deficiency in infant is suitably treated with 100 to 200
g of vitamin B12 given intramuscularly, on alternate
days for 2 to 3 weeks, or oral dose of 100 g/day.
Treatment with folate alone can produce hematologic
response in vitamin B12 deficiency, but does not correct,
the neurological damage caused by vitamin B 12
deficiency, thus all megaloblastic anemias should be
treated with adequate doses of both folate and vitamin
B12. Anemia unresponsive to folate or B12 may be caused
by certain metabolic disorders or antimetabolic drugs.
BIBLIOGRAPHY
1.
Clinical Features
The commonest age is 3 to 18 months with maximum
number of cases being in 9 to 12 months. These children
appear sicker than the degree of anemia warrants.
Anorexia, mental apathy and fatiguability are early
symptoms. Sore tongue, papillary atrophy, glossitis and
diarrhea can occur. Hyperpigmentation of the dorsum
of hand and knuckles is an important finding. Tremors,
failure to thrive and developmental regression are also
observed.
Vitamin B12 deficiency is an important cause of
neurological abnormality characterized by degeneration
of some peripheral nerves, selected columns in spinal
cord and defective cerebral function. Symptoms of
megaloblastic anemia due to folate/vitamin B 12
deficiency are similar but folate deficiency does not cause
neuropathy.
2.
3.
4.
5.
6.
7.
Choudhary P: Management of iron deficiency anemia in

clinical practice. In: Sachdev HPS, Choudhary P (Eds).
Nutrition in children Developing country concern. New
Delhi, 1994;236-44.
Demeyer EM: Prevention and control of iron deficiency
anemia through primary health care. Geneva, WHO,
1989;8-33.
Desai N, Choudhary VP: Nutritional anemia in protein
energy malnutrition. Indian Pediatr 1993;30:1471-83.
Dubey AP: Megaloblastic anemia. PHO Review, IAP
1995;8:5-7.
Lokeshwar MR, Manglani M, Rao S, Patel S, Kulkarni
M: Iron deficiency anemia Clinical manifestations and
management. In: Mehta MN, Kulkarni M (Eds). Child
nutritionthe Indian Scene. Mumbai, 1990;269-95.
Madan S: Recommendations on Prevention and Control
of Iron Deficiency Anemia. In: Madan S, Mukherjee KL,
Khatua SP (Eds). Nutritional Anemia in Infancy and
Childhood. Publication of Indian Academy of Pediatrics
Subchapter on Nutrition, Calcutta, 1990.
Oski FA: Iron deficiency in infancy and childhood.
N Eng J Med 1993;329:190-93.
8.
Preventing iron deficiency in woman and children

technical consensus on key issues 79 October 1998.
UNICEF, UNU, WHO, MI. Technical Group International
Nutrition Foundation, USA 1998.
9. Sharma S, Prasad K, Rao KV. Identification of an
appropriate strategy to control anemia in adolescent girls
of poor communities. Indian Pediatr 2000;37:261-67.
785
10.
Technical consultation on Strategies for prevention and

control of iron deficiency anemia amongst under three
children in India. Indian Pediatr 2002;39:640-47.
11.
Zlotkin S: Current issues for the prevention and treatment

of iron deficiency anemia. Indian Pediatr 2002;39:
125-29.
15.5 Nutritional Anemias in Adolescence

Sushil Madan
INTRODUCTION
Anemia is the most common form of malnutrition mostly
due to iron deficiency amongst adolescents today. It is
of public health significance in our country, anemia
prevalence being > 30 percent. It is a pathological
condition where hemoglobin or hematocrit becomes
abnormally low because of low essential nutrients (like
iron, folic acid, protein, vitamin B12, C, and trace elements
like zinc) regardless of the cuase of these deficiencies.
Adolescents (10-19 years) constitute more than 20
percent of our population in India and > 50 percent suffer
from Iron Deficiency Anemia (IDA).
IRON DEFICIENCY ANEMIA IN ADOLESCENTS
Adolescence is the most vulnerable phase of life
associated with high iron requirements for growth and
development accompanied by expansion of blood
volume, muscle mass, natural loss of menstrual blood in
girls and increased demands with the onset of pregnancy.
WHO criterion is used for defining anemia by
hemoglobin (Hb) estimation in different age and sex
groups (Table 15.5.1).
Adolescents having Hb less than 12g percent are said
to be anemic and adolescent pregnant women (15-19 yrs)
should be having minimum Hb of 11g percent at the
onset of pregnancy, to prevent mental functions from
being affected due to irreversible brain damage to the
growing fetus.
Epidemiology
Global data-base by WHO (2000) on child growth and
malnutrition and National Family Health Survey-2 (2000)
in India, have suggested high prevalence of IDA (56%)
in school age children. The average prevalence rates

are: Asia (58.4%), Africa and Asia (>40%), Indonesia
(24-25%) and Bangladesh (98/94% for boys and girls
respectively). It primarily affects women, yet among
adolescents prevalence rates of anemia are closer for
males and females in some parts of the world (Table
15.5.2).
Recent regional surveys among adolescent girls of
urban, semi-urban and rural schools in India have found
anemia prevalence rate to be between 61.9-85.4 percent,
being highest among rural girls of low socioeconomic
status in the northern states of the country.3 Anemia and
iron deficiency was of higher order among rural as
compared to urban poor girls irrespective of their age
and menarchal status. This could be due to differences
in dietary habits, worm infestations, poor hygiene,
environmental sanitation and disposal of waste.4 Anemia
prevalence was more among girls of low weight, height
and BMI as compared to those who were heavier, tall
and having higher BMI.
TABLE 15.5.1: WHO criterion for diagnosis of anemia

Age/Sex group
Hb (g/dI)
Children 6 months6 yrs

Children 614 yrs
Adult males
Adult females (Non-pregnant)
Adult females (Pregnant)
<11
<12
<13
<12
<11
Mild anemia
Moderate anemia
Severe anemia
<1110
<107
<7
786

TABLE 15.5.2: Recent surveys prevalence of IDA-adolescent children
Country/Year
Profile of children
Sex (M/F)
Prevalence of anemia
Asia (Global data-base by WHO on child
Rural school children
Both
58.4%
Growth and Malnutrition 2000)

India (NFHS-2) 2000
Urban and rural (15-19 years)
56%
Bangladesh (Shahbuddin et at 2000)
Rural community
M/F (17-100%)
98/94%
East Java, Indonesia (Soitarjo DD 2001)
6486 students (12-15 years)
Prepubertal boys/girls,
Postpubertal boys
24/>25%
Africa and Asia (Partnership for

Child Development)
14000 Rural school children
Both
>40%
Pathophysiology
Iron balance in the body is achieved mainly by control
of absorption of iron rather than its excretion. Iron
absorption is physiologically regulated by1. Iron status
of subjects, more with decreased iron stores 2. Chemical
form of iron and balance between +/ factors of dietary
iron absorption. Fermentation, germination and malting
of food also increase iron absorption (Table 15.5.3).
A dietary intake of iron needed to replace basic losses
in stool, urine and skin, amount to 0.8 mg of iron per
day for and adolescent child. Iron needs peak sharply
TABLE 15.5.3
Factors influencing dietary iron absorption
Heme Iron Absorption
Amount of heme iron, especially as meat
Content of calcium in meal
Food preparation (time, temperature)
Non-Heme Iron Absorption
Iron status of subjects
Amount of potentially available non-heme iron
(adjustment for fortification iron and contamination iron)
Balance between factors
Plus-factors
Minus-factors
Ascorbic acid
Phytate
Meat/fish
Iron-binding polyphenols
The Sauerkraut factor
Calcium
(fermented foods)
Soy protein
Fermentation
Malting
Germination
Iron absorption is Physiologically
Regulated by
1. Iron status of subjects more with
Erythropoiesis
Iron stores
2. Chemical form of iron
3. Balance between factors
during growth spurt both in boys and girls wherein

additional 0.8 mg would be required per day. Girls who
have attained menarche, the median blood loss during
menstruation has been estimated to be between 2530
ml per month corresponding to an iron loss of 12.515
mg per month or 0.40.5 mg per day. With addition of
basal losses, the total iron requirement for menstruating
women is about (0.8 + 0.8 + 0.5) 2.3 mg per day. During
pregnancy, menstrual losses are reduced to nil, and
additional 1000 mg is required for the fetus, placenta and
increased maternal blood volume. Requirements during
first trimester are small, i.e. 0.8 mg per day but rise to 6.3
mg per day during second and third trimester of
pregnancy (Fig. 15.5.1).
ETIOLOGY
Adolescent child girl in particular is more vulnerable to
becoming anemic due to disturbed iron balance between
iron requirements and iron absorbed from diet.
Main causal factors are increasing physiological
demands by second spurt of growth, menstrual loss, and
early onset of pregnancy in absence of adequate iron
stores at birth and inadequate intakes of habitual diet
with green leafy vegetables and fruits containing iron
and vitamin C, eating junk food and skipping meals due
rising eostrogen levels cause fall in erythropoietin and
decreased bio availability of iron. Total calorie intake may
be as little as 1000 calories per day and iron intake in
girls 10-17 years is estimated to be 46 percent to 64 percent
of recommeded daily allowance. Total calorie intake may
be as little as 1000 calories per day as seen in rural areas
of Andhra Pradesh by National Institute of Nutrition
Surveys. Several dietary factors influence absorption and
bioavailability of dietary iron (refer to Table 15.5.3). Good
sources of heme iron (meat, fish, poultry), which help in
787
Figure 15.5.1: Iron needs peak sharply, during growth spurt
iron absorption as well, are often missing from Indian

diets. Anemia caused by iron losses due to malaria and
hookworm infection is quite common in our country due
to adolescents working in the fields. Malabsorption of
iron in cases with giardiasis, milk allergy and celiac
disease could lead to iron deficiency accompanied by that
of B12 and folic acid deficiency (Table 15.5.4).
Clinical Features
Iron deficiency is a systemic disorder involving multiple
systems rather than purely hematological condition
associated with anemia.
The peak incidence of iron deficiency occurs in
adolescents of 11 to 17 year age group. Occurrence of
various symptoms and signs and their severity depends
upon degree and severity of anemia, which are due to
diminished supply of oxygen to different tissues and
organs. Initial symptoms are fatigue and lassitude,
TABLE 15.5.4: Causal factorsIDA
Decreased iron stores at birth

Inadequate iron supply from inadequate diet
Poor bioavailability of iron
Increased physiological requirements
Abnormal iron losses
Malabsorption of iron
breathlessness on exertion, pallor of bulbar conjunctiva,

mucous membrane of tongue and palmar creases,
dizziness, giddiness, dimness of vision, headache and
anorexia. Nails show flatness, softness to feel and later
become spoon shaped. Findings of congestive heart
failure indicate severe anemia, Hb < 5 g percent.
Besides being a hemopoietic factor, iron deficiency
per se, without obvious anemia causes morphological and
biochemical changes at tissue level affecting:
1. Mental and Psychomotor Functions: Iron deficient
children are restless, disruptive, irritable, having poor
attention span, memory, concentration and academic
performance due to changes in brain iron content and
distribution. Cognition in particular is adversely affected
by anemia in both nourished and undernourished subject
due to poor synthesis and catabolism of neuro transmitters (dopamine, norepinephrine, serotonin) caused by
reduction in activity of monoaminooxidase and aldehyde
oxidase enzymes. A recent report on Rural Indian
children documented lower concentration and retention
even after the nutritional status was improved.
2. Growth Retardation: Apart from associated nutrient
deficiencies it can be attributed to anorexia, reduced
synthesis of nucleic acids and altered intestinal functions.
Rapid weight gain following iron therapy has been
reported.
788
3. Physical Work Capacity: There is linear relationship

between work capacity and iron deficiency. Heart rates
increase even with less level of work. Aerobic capacity
diminishes, anaerobic metabolism increases with
accumulation of lactic acid leading to fatigue. The adverse
effects of anemia are compounded due to overall under
nutrition. A significantly lower Rapid Fitness Index (RFI)
calculated from total exercise time and pulse rate 1 to 1.5
minutes after the exercise was observed among anemic
subjects against non anemics.
4. Immune Response: Iron deficiency state affects the
immmune system even before causing anemia. Defects
in cell mediated immunity and reduced capacity of
leucocytes to kill bacteria have been well documented.
Hence there is increased susceptibility to infections.
5. Gastro Intestinal Tract: Iron deficiency may lead to
stomatitis and atrophic gastritis with decreased gastric
acid production causing dyspepsia. There is greater
susceptibility to mucocutaneous candidiasis and
intestinal infections.
6. Heavy Metal Absorption: Iron deficient children have
an increased absorption of iron and other divalent metals
such as lead and cadmium. There is an increased risk of
lead poisoning on exposure to lead paints from toys and
environment.
7. Iron Deficiency and Pregnancy Outcome: There is
increased maternal mortality due to severe anemia
causing hemorrhage in last trimester of pregnancy/
during labor and also due to unwanted pregnancy and
abortions. Iron deficiency along with deficiencies of folate
and vitamin B12 result in poor fetal growth, higher
percent of still births and lower birth weight babies. There
is also increased neonatal, infant and under 5 mortality
as compared to those for mothers between 20-29 years
as shown by NFHS 2.
A recent report on Rural Indian Children documented

lower concentration and retention even after the nutritional
status was improved.
Diagnosis
IDA develops sequentially as observed by:
1. First Stagedepletion of stored iron, i.e. fall in serum
ferritin < 15 g/ml, absence of stainable iron in bone
marrow during spurt of growth and increase in red
cell diameter width (RDW > 15%) (Table 15.5.5).
2. Second Stagepreanemic or latent iron deficiency
decrease in serum iron <75 mg/dl, increase TIBC >350
ug/dl and decrease in transferrin saturation within
14 percent.
3. Third Stage Significant fall in serum iron <30 mg/
dl, increase in erythrocyte protoporphyrin, fall in
MCV, MCH, MCHC, hypochromic, microcytic
anemia accompanied by fall in Hb, Hct, red cell count.
SCREENING TESTS
Red cell count, Hb, Hct, are all decreased in IDA. MCV,
MCH and MCHC are also decreased. The peripheral
blood film shows hypochromic microcytic anemia with
poikilocytosis and target cells. There may be a dimorphic
picture with hypochromic, microcytic red cells along with
macrocytosis in children with iron deficiency associated
with Vitamin B12 or folate deficiency.
Reticulocyte count is normal unless child has had
recent blood loss or received hematinics in which case it
may be increased. Leucoyte count is usually normal.
Hypersegmented neutrophils may be seen due to
concomitant B12 or folate deficiency or due to interference
with folate utilization.
Low MCV and MCH with anemia favor the diagnosis
of IDA however specific reference standard may be used
for comparison. MCV is much more sensitive than MCH
TABLE 15.5.5: Stages in the development of iron deficiency and available confirmatory tests
Investigations
Normal
Pre-latent
Latent
Iron deficiency anaemia
Bone marrow iron
Normal
Reduced
Absent
Absent
Serum ferritin (SF)
do
< 15 ng
< 15
< 12
Transferrin saturation (TF)
do
Normal
< 16%
< 16%
Free erythrocyte prophyrin (EP)
do
do
Increased
Markedly increased
Haemoglobin
do
do
Normal
Progressive reduction
Mean corpuscular volume
do
do
do
Reduced
in iron deficiency, however, microcytosis may also be
seen in conditions like abnormal hemoglobinopathies,
anemia of chronic infection and inflammation, lead
poisoning and rarely sideroblastic anemia and chronic
renal diseases.
Red cell size distribution width (RDW) reveals
elevated levels in IDA as compared to normal levels in
anemia of chronic diseases or beta thalessemia trait.
Free erythrocyte protoporhyrin accumulates in the
red blood cells when it does not get sufficient iron to
combine with to form Hb. More than 70 microgram/dl
of RBC protoporphyrin above the age of 4 years is of
significant value to detect IDA. FEP over Hb ratio
increases when iron reserve is exhausted and returns to
normal only after majority of cells containing FEP are
formed during iron therapy.
Confirmatory Tests for IDA
Serum iron is reduced (N=50-180 mg/dl), TIBC is
increased (N=250-450 mg/dl). Transferrin saturation is
low (less than 16 percent suggestive and less than
7 percent diagnostic of severe iron deficiency anemia).
Serum ferritin is less than 10-12 ng/ml but it is usually
higher (however less than 50-60 ng/ml), with infection
or inflammatory diseases like rheumatoid arthritis,
collagen disorders, liver disorders, chronic renal disease
or malignancy. The test still lacks sensitivity and normal
value does not reliably exclude iron deficiency. In
addition serum transferrin receptor (sTfR) can be done
in places where infection is common for individual
screening (Table 15.5.5).
More often iron deficiency as a steady state develops
very gradually and is almost in equilibrium due to
conditions like chronic energy deficiency lasting for
months or years. The laboratory values for serum ferritin
and transferrin saturation are in normal limits but
patients respond to iron therapy by showing rise in
reticulocyte count by more than 2 percent, Hb and Hct
(by 1.0 gm/dl or by 3%) in 4-8 weeks time indicating
IDA. In such a situation with high prevalence of anemia
a. Clinical assessment
b. Hb estimation
c. Peripheral smear for microcytic hypochromic anemia
and malaria parasites
d. Stool examination for helminths, and
e. Response to iron supplementation may suffice.
789
Management
It involves (1) Treatment of underlyling cause and
correction of anemia in an individual patient.
(2) Prevention and control of IDA as Public Health
Program. The therapeutic approach must rely on
medicinal iron especially when anemia is moderate to
severe (Hb < 7 gm%) and treatment of cause. Ferrous
compounds are better absorbed than ferric iron, of these
ferrous sulphate, gluconate and fumerate are the
compounds most commonly used. Though somewhat
expensive, it is better to use slow release preparations,
which give higher absorption rates and minimal
gastrointestinal side effects with higher compliance. It is
better to use preparation containing folic acid like IFA
tablet because inadequate dietary intake may give rise
to folic acid deficiency for the demands of increased red
cell formation and also cause neural tube defects to fetus
with onset of pregnancy. Although iron absorption is
proportional to degree of anemia, the dose recommended
is 100 mg of elemental iron with 500 g of folic acid once
daily for mild anemia (Hb < 1012 g) and twice daily for
moderately severe anemia (Hb < 710 g) along with 25
50 mg of vitamin C which helps in iron absorption. The
desired Hb is usually reached in 2 months, but therapy
should continue for another 2 months to build up iron
stores showing ferritin level of 30 g/L.
Adolescent girls (1519 years) with Hb between
5 to 8 g/dl form 10 to 20 percent of all pregnant women.
They should be first screened for systemic or obstetric
problems and infections. In the absence of any
complications, IFA tablets can be administered at the
maximum tolerated dose and Hb can be repeated a
month later. Those who do not show any improvement
may be put on parenteral medication.
Failure to oral iron therapy may be due to
(1) Inadequate doses (2) Noncompliance (3) Continued/
Intermittent occult blood loss (4) Hypochromic
microcytic anemia due to thalassemia minor/lead
poisoning/chronic infections and (5) nutritional megaloblastic anemia. All should be appropriately ruled out.
Noncompliance is probably due to poor counselling and
lack of motivation and not due to side effects, once
considered a major reason for failure of iron therapy. The
tablets may be given with meals and in divided doses to
improve compliance. The adolescent must be given
proper nutritional counselling diet should contain fruits
and GLV (green leafy vegetables). Absorption inhibitors
790
should be avoided with principal meals. In cases with

hookworm infection, deworming is essential otherwise
anemia is likely to return once iron therapy is stopped.
Consistent improvement of hematological status is also
dependent on the treatment and improvement of the
underlying infection such as pulmonary tuberculosis and
urinary tract infection.
Parenteral iron therapyit is indicated in cases having
severe side effects with oral iron therapy, noncompliance
or gastrointestinal bleeding, which is aggravated by oral
iron therapy. Patients must be hospitalized for total dose
infusion by intravenous route, as severe anaphylactic
reaction can take place. Usually 100 mg of elemental iron
(iron dextran complex 50 mg/ml in 2 ml of saline) is given
intramuscularly every day till calculated dose [Iron (mg)=
wt in kg Hb deficit (g/dl) 4] is administered. It has
been found to be safe and effective method of treatment
of anemia in pregnancy and may result in better fetal
iron stores in comparison to oral route.
Blood transfusionmay be needed in most severe cases
of IDA with Hb within 3 to 4 g/dl. Packed or sedimented
red cells should be slowly administered, preferably 2 to
3 ml/kg at one time. A modified exchange transfusion
may be considered in presence of congestive heart failure
along with diuretic, digitalis and antiallergic drugs.
Prevention and control of IDAAdolescence is a crucial
stage for intervention because of high prevalence of
anemia and fact that 29 percent of urban and 45 percent
of rural girls get married before the age of 19. Adolescent
pregnancies contribute to 19 percent of total fertility
causing highest maternal mortality rates in our country
upto 4 times as likely as in women older than 20 years of
age from pregnancy related causes. Besides, both boys
and girls suffer from basic morbidity such as
malnutrition, communicable diseases, accidents, etc.
Girls also experience discrimination at home from before
and after birth leading to malnutrition with anemia and
vicious cycle of being small girl adolescent pregnancy
low birth weight baby small girl (Fig. 15.5.2).
Basic approaches for prevention and control of IDA
are: (1) Oral supplementation with medicinal iron (2)
Dietary modifications (3) Fortification of staple food with
iron. This should be accompanied with (4) control of
infections and improvement of socioeconomic status of
community and sanitary measures (especially proper
disposal of excreta and construction of latrines).
Oral iron Supplementation WHO has recommended
oral iron supplementation even in absence of overt
Figure 15.5.2: Urgent sustained effort to control IDA
anemia where prevalence rate is more than 30 percent

and facilities for Hb estimation are lacking. It is the most
rapid method of improving the iron status of an
adolescent child. This is a captive audience and can be
reached by health workers in schools, clubs, textile
industry besides pediatric clinics in hospitals, PHC and
MCH centers. Since diet alone cannot meet requirement
of iron during pregnancy in girls, dietary iron absorption
is also reduced during first trimester of pregnancy, hence
it is better to start oral iron supplementation from early
adolescence. It will also prevent irreversible abnormalities in cognitive functions and neural tube defects
due to iron and folic acid deficiency early in fetal life.
Dose recommended by National Nutritional Anemia
Control Program as NNACP is 1 IFA tablet (100 mg
elemental iron + 500 g of folic acid) for 100 days in a
year. Intervention studies have shown that intermittent
oral iron administration once or twice weekly of same
dosage has shown equally good results. Pregnant
adolescent girls should be given same dose after the first
trimester of pregnancy for a minimum period of 100 days.
Severely anemic children (Hb < 7 g/dl) should be given
two IFA tablets daily for a minimum period of 100 days.
Further they should be referred to the Primary Health
Center for diagnosis of the causative factors and
treatment. Adolescent girls during lactation should be
given same dose all through lactation and this is being
carried through ICDS and CSSM Family Welfare
Program of the country (Table 15.5.6).
Dietary modification/diversificationthis seeks to change
adolescents consumption behavior and their nutritional
status by comprehensive nutritional education as part
of family life education in schools. Horticultural
intervention, improved public distribution system and
791
TABLE 15.5.6: Basic Approach: Oral iron supplementation dosage

Risk Group
Tablet strength
Dosage
Period
Adolescent
100 mg elemental iron

+ 500 mg folate + 25 mg Vit C
-do-
I daily/once or twice weekly
100 days in a year/short

courses
100 days
-do-
One a day
-do-
One a day
Adolescent with
clinical anemia
Pregnant
adolescent girls
Adolescent girls
with lactation
Twice a day
From 2nd trimester of

Pregnancy till end
All through lactation
kitchen gardens could help in procurement of fruits and

vegetables. The idea is to (1) increase dietary iron intake
by increased intake of habitual foods (2) to increase iron
intake by promotion of iron rich foods (palak, sarson,
methi, cholai saag) (3) enhance bioavailability of ingested
iron with consumption of vitamin C rich foods like
lemons, tomatoes, amla, guava, sprouted dals, citrus
fruits (4) discourage intake of tea, milk, egg yolk soon
after meals (5) encourage cooking in iron utensils and
(6) promote intake of germinated and fermented foods.
With diet modification the relative bioavailability of iron
can be increased from as low as (5%) to intermediate
(10%) and as high as (>15%). Intervention studies by
Nutrition Education and Dietary Modification have
shown marked improvement by rise in Hb and/or
ferritin levels without iron supplementation (Fig. 15.5.3).
Fortification of foods with ironIt is the most effective
way of preventing IDA as iron being part of food;
compliance of population is not involved. Once
established, it is cost effective and long-term sustainable
measure. Fortification technology is already available.
Common salt fortified with Iron Orthophosphate and
Sodium Hydrogen Sulphate with Ascorbic acid has had
field trials in India and is found to be stable. Double
fortified salt has been available containing iron 1 mg/
g+ iodine 40 g/g. Daily intake of 15 g of salt can provide
15 mg of iron and will suffice as a supplement.
Home fortification with iron and zinc sprinkless or
iron alone successfully treats anemia in infants and
children. Fortified food with iron is still not available for
public health program by Government of India. Hence,
it is essential that NNACP is implemented more
effectively.
Strategies for prevention of IDADespite the magnitude
of the problem, hardly any strategies exist in Indian Public
Health program to tackle IDA among adolescents
especially girls. The main focus of IDA reduction programs
Figure 15.5.3: The effects of dietary composition of the relative bioavailability of iron. Diets of low (5%), intermediate (10%),
and high (> 15%) are shown.
India mixed cereal diet
Women, children (adolescent girls) 5%, Adultmen adolescent boys 3%, Pregnant women 8%.
has been on young children and women of reproductive

age. National Nutritional Anemia Prophylaxis Program
(NNAPP) was started in 1970 for pregnant women and
children of 1 to 11 years of age. IFA tablet containing 60
mg of elemental iron +500 g folic acid was administered
to pregnant women during last trimester of pregnancy
for minimum period of 100 days through the rural-based
ICDS and CSSM program. But after 20 years of
implementation, 20 to 38 percent of pregnant women were
still anemic at the end of pregnancy in spite of having had
IFA tablets for 100 days. Following this, in 1991, focus was
made on control of anemia by treating existing anemic
women and children in addition to prophylaxis dose as
recommended under NNAPP and the new program was
called National Nutritional Anemia Control Program
792
(NNACP). This aims at significantly decreasing the

prevalence and significance of anemia amongst women
of reproductive age and pre-school children. However,
we still remain far behind our goals in achieving reduction
of IDA as desired.
India became a signatory to World Summit for
Children in 1990. Following this, India developed
National Plan of Action for Childrena Commitment
to the child in 1993. National Nutrition Policy was revised
to see reduction of IDA in women by 1/3rd by year 2000
by oral iron supplementation, dietary diversification and
food fortification. Since these programs run vertically,
independent of each other, we are far behind achieving
our goals. At this stage (1993) it was planned to introduce
additional scheme for adolescent girls, Kishore Shakti
Yojna, as a part of ICDS Program. Herein, economically
disadvantaged girls would be given oral iron
supplementation by Anganwadi workers by home visits.
In addition, nutrition education sessions for promotion
of regular consumption of iron and vitamin C rich food
during pregnancy and adolescence would be provided
through ICDS, UBS, DWCRA, NLP and School Health
programs. This Program has neither been implemented
in all the districts and states of the country nor has it
shown significant impact by reduction in IDA till date

(Flow Chart 15.5.1).
Issues before us(1) High magnitude of problem in
adolescent children as shown by NFHS 2, (2) present
focus is narrow through rural-based ICDS, CSSMP and
RCH, who view adolescents as future parents only,
(3) Adolescent scheme is not being implemented in many
districts of the country, (4) very little impact among urban
poor due to lack of infrastructure, i.e. urban health
planning (5) Health care and support services for the
development (education, life skill programs) are lacking
both in urban and rural areas of the country.
Existing strategy (NNACP) and proposed improvements
National Nutrition Mission under the Chairmanship of
the Prime Minister desires to reduce severe anemia and
malnutrition in children by 50 percent by year 2010 as
per 10th National Plan. Hence emphasis should be on
Nationwide and Statewide implementation of the
following: (1) Intersectoral approach is the first
requirement for National Nutritional Policy by
coordination between Ministry of Health Family welfare,
DWCD, Education, Food, Social and Human Resources.
(2) Focus on adolescents (community/ household/
Flow Chart 15.5.1: Reduction of IDA
Individual level) in urban slums, rural and tribal areas
and at their schools and working places. (3) Integrate
Health and Social Sector Investment (4) Enforce Child
Marriage Restraint Act with community and adolescent
participation to prevent marriage before the age of 18
for girls and 21 years for boys. (5) Salt fortification
program to be hastened (6) Medical colleges to include
curriculum on adolescents health, nutritional status,
anemia, development at undergraduate and postgraduate level. (7) Involve a trained Pediatrician for (a)
Sarva Shiksha Abhiyan (6-14 years group) (b) RCH 2
Programme 2005 (c) Adolescent Friendly Health Services
at Hospitals, Primary Health Centers, Schools and
Welfare Centers. (8) School curriculum to include
Nutrition Health Education (NHF) for primary level and
NHE and FLE from secondary level. (9) Ensure access to
Quality Health Care System and improve utilization and
impact by working closely with NGOs (10) Provide good
working conditions and remuneration to working staff
(11) Streamline activities for ANM, AWW, CDBMO to
see convergence of 3 basic approaches and update them
with refresher courses/CME. (12) Holistic approach as
shown by MAMTA, CDC and CDCPO will improve their
nutrition iron status, development and prevent
unwanted pregnancy, maternal deaths and low birth
weight outcome (Flow Chart 15.5.2).
Flow Chart 15.5.2: IAP state task force for adolescent care
793
NUTRITIONAL MEGALOBLASTIC ANEMIAS

Megaloblastic anemia is caused by deficiency of either
folate or vitamin B12 or both. Folic Acid in its active
tetrahydrofolate form is involved in the synthesis of
purines, pyrimidines and amino acids especially serine
and methionine. Vitamin B 12 acts as coenzyme and
transfers methyl group from homocysteine to form
methionine. Vitamin B12 deficiency results in decreased
utilization of tetrahydrofolate, decreasing synthesis of
thymine leading to defective DNA synthesis. High folic
acid dependency for DNA synthesis and lower folic acid
dependency for RNA synthesis lead to prolonged protein
synthesis, decreased mitosis and consequently large cells.
These are reflected as megaloblasts in bone marrow,
macrocytes and giant hypersegmented polymorph
nuclear cells in peripheral blood smears. Decreased
mitosis leads to anemia, leukopenia, thrombocytopenia,
glossitis, and cervical dysplasia.
Unlike iron deficiency, hardly any epidemiological
studies are available on the incidence of folic acid or
vitamin B deficiency in the populations. However,
despite normal Hb about 60 percent of Indian women
are folate deficient due to increased demands, decreased
absorption, accelerated breakdown of folate to
paraminobenzoylglutamate, increased urinary loss and
fetal transfer during adolescent pregnancy as indicated
by low serum and RBC folic acid levels. In moderately
severe anemia (Hb 8.5 g%) 60 percent of bone marrow
shows megaloblastic reaction and RBC folate levels are
below 80 ng per ml (normal). No stainable iron is seen in
bone marrow in such subjects. Folate is given in dose of
5 mg per day for 2 to 3 weeks and then continued as
prophylaxis dose as IFA tablets. However, some studies
recommend use of multivitamin tablet (MRC vitamin
study) including 0.4 to 0.8 mg of folic acid in
periconceptual period to prevent neural tube defects.
Vitamin C present in multivitamin would prevent
oxidation of tetrahydrofolate and help to keep the folate
metabolic pool optimal. Low status of zinc in women of
childbearing age especially poor adolescents would also
improve, since folic acid conjugase is a zincmetalloenzyme which would help in the absorption of
folic acid by the intestine.
794
Nutritional vitamin B12 deficiency is not common in

adolescence. Rarely, it occurs as juvenile pernicious
anemia due to genetic absence of intrinsic factor. Vitamin
B12 deficiency may result in neurological manifestations
as peripheral neuritis, mental apathy and psychosis.
Infants solely breastfed for long time develop anemia.
The clinical picture gets improved by administering
single oral dose of 100 g of vitamin B12 to the mother or
to the infant.
BIBLIOGRAPHY
1.
Agarwal KN. Iron and the Brain. Neurotransmitter

Receptors and Magnetic Resonance Spectroscopy. British
J Nutr 2001;85,2:147-50.
2. Agarwal R Bharat; Approach to a child with Anemia.
The Child and Newborn, 2004;8:84-95.
3. Dwivedi Archana and Schultink Werner; Reducing
Anemia among Indian Adolescent Girls thru Once
Weekly Supplementation with Iron and Folic Acid. Dr
Panna Choudhury, Dr A P Dubey (Eds); Nutri Search,
Buletin of IAP Sub Speciality Chapter of Nutrition
2006;13,No.2.
4. Hota P. National Rural Health Mission. Indian J Pediatr
2006;73:193-95.
5.
Indian Council of Medical Research, National Workshop

on Micronutrients. Background documents Toteja GS,
Singh P. Micronutrient Profile of Indian Population. New
Delhi, Nov. 2003.
6. International Institute for Population Sciences (IIPS) and
ORC Macro, 2000. National Family Health Survey
(NFHS-2), 1998-99; India. Mumbai:IIPS.
7. Kanani S, Poojara R Supplementation with Iron Folic
Acid enhance Growth in Adolescent Indian Girls. J Nutr
2000;130:452-555.
8. Kaur S, Deshmukh PR and Garg B S. Epidemiological
Correlates of Nutritional Anemia in Adolescent Girls of
Rural Wardha. Indian Journal of Community Medicine
2006;4:Vol 31.
9. NMMB, Diet and Nutritional Status of Rural Population.
National Institute of Nutrition, 2002.
10. Park K. Parks Textbook of Preventive and Social
Medicine, Jabalpur: Banarsidas Bhanot Publishers,
2002;381.
11. Sen A and Kamani SJ. Deleterious Functional Impact of
Anemia on Young Adolescent School Girls. Indian
Pediatr 2006;43:219-26.
12. Zlotkin S, Arthur P, Shaver C, Antwi KY, et al. Home
fortification with Iron and Zinc Sprinkles or Iron
Sprinkles Alone Successfully Treats Anemia in Infants
and Young Children. J Nutr 2003;133:1075-80.
15.6 Thalassemia
MR Lokeshwar, Nitin Shah,
Swati Kanakia, Mamta Manglani
Thalassemia is an autosomal recessive, heterogynous
group of single gene disorder, seen in certain parts of
the world and represents a major health burden world wide. It is caused by defect in the globin chain synthesis
of hemoglobin (Hb) due to various mutations of genes
which code for globin chain of hemoglobin, leading to
reduced or absent synthesis of globin chain.
The thalassemia refers to group of blood diseases
characterized by decreased synthesis of one of the
polypeptide chains ( or ) that form normal adult
hemoglobin molecule (Hb.A-22). In Thalassemia,
chain synthesis is affected. In Thalassemia, chain is
involved.
If chain is absent, it is termed as 0 Thalassemia, if
partially produced then + Thalassemia.
Clinically Important Hemoglobinopathies prevalent
in India include
Thalassemia,
Thalassemia,
Hemoglobin S,
Hemoglobin D,
Hemoglobin E,
Double Heterozygous Disorders.
Several other hemoglobin (Hb) variants have been
reported from India but their frequency is relatively
low.
Classification of -Thalassemia Syndromes

The -Thalassemias are classified into 4 different
categories depending upon the number of genes affected.
Since the gene of -globin is duplicated on chromosome
16, each diploid human cell contains four copies of the
-globin gene. The four -Thalassemia syndromes with
increasing clinical severity include
Silent carrier,
-Thalassemia trait,
Hb. H disease and
Hydrops fetalis
795
TABLE 15.6.1: The -globin genes are represented one on each chromosome 11
Syndrome
Clinical Features
Hemoglobin pattern
Genes affected
-globin
Silent carrier
No anemia, normal
red cells at birth
1-2% Hb Barts (4)
Thalassemia trait
Mild anemia,
Hypochromic
Microcytic red cells
at birth
5-10% Hb. Barts (4)
HbH disease
Moderate anemia,
Hypochromic,
microcytic red cells
5-30% HbH (4)
Hydrops fetalis
Death in utero caused

By severe anemia
Mainly Hb. Barts, small

amounts of Hb Hs
and are, due to 1, 2, 3 and 4 gene defects respectively.

The -thalassemia genes are represented one on each
chromosome 11.
The -Thalassemias also include four clinical
syndromes of increasing severity (Table 15.6.1).
Silent carrier,
Thalassemia trait,
Thalassemia intermedia,
Thalassemia major.
Epidemiology
Although reliable data are still lacking for many regions
of the world, recent data indicate that about 7% of the
world population is carrier of hemoglobin disorder and
that 300,000-500,000 children are born each year with
severe homozygous state of these diseases.
Though first described in 1925 by Thomas Cooley
and Lee, now world over, there are more than 250 million
carriers (Heterozygous)of -Thalassemia gene (1.5% of
world population), and in South East Asia 40 million
(50% in India alone i.e. 20 million).
First case reported in India is by Dr. Mukherjee from
Calcutta (India) in 1938.
About 100,000 children are born every year world
over with the homozygous state for thalassemia. With
the birth rate of 22.8 per 1000, it is estimated that, 8-10,000
children born in India. There are around 65,000 - 67,000
thalassemia patients in our country.
-gene represented on chromosome no. 11 and 16.
In India prevalence of this gene varies, 1-17 % (3.3%).
If you draw a line between Mumbai and Kolkata on map
of India, region above the line the incidence of
Figure 15.6.1: Prevalence of thalassemia
thalassemia minor is around 3-17 %, whereas region

below the line the incidence is around 1-3% or less.
A higher frequency is noted in certain communities such
as in
North IndiaSindhis, Punjabis,
Migrants from Pakistan- Khatris and Khukrajas,
GujaratBhanushalis, Lohanas,
Baniyas, and Kuchies,
Maharashtra Neo-Buddhists, Mahars,
Kolis, Agris,
Karnataka
Goudas and Lingayats,
etc.
GoaGoud Saraswats also
From Certain Muslim and Christian communities
796
Pathophysiology
Hb. consists of two pairs of amino acid chains and .
Imbalance in the production of these peptide chains of

globin ( and ) leads to abnormal hemoglobinopathies.
Excessive unpaired peptide chain in hemoglobin is

precipitated on red cell membrane and damages it
leading to premature destruction of RBC (Hemolysis) in
bone-marrow and in peripheral circulation particularly
in reticulo-endothelial system of spleen. (Ineffective
Erythropoiesis)
Gamma chain synthesis persists after fetal life
Increased fetal hemoglobin with its high affinity for

oxygen, leads to tissue hypoxia, which, in turn, stimulates
erythropoietin secretion, leading to both medullary and
extramedullary Erythropoiesis
This resulting in expansion of bone marrow space- with

characteristic hemolytic faces with frontal, parietal and
occipital bossing, malar prominence and mal-occlusion
of teeth, and complications that include-distortion of ribs,

vertebrae, and pathological fracture of long bones,
splenomegaly, and its complications-hypersplenism,
hepatomegaly, gallstones, and chronic leg ulcers.
PATHOPHYSIOLOGY OF -THALASSEMIA
(SEE FIG 15.6.2)
Molecular Genetics
More than 200 mutations are described all over the world.
Common mutations responsible for more than 90% of
thalassemia mutations in our country include 619 bp deletion,
IVS 1 - 5 (G - C),
IVS 1 - 1 (G - T),
FS 8/9 (+ G),
FS 41/42 (- CTTT)
Recently, some rarer mutations have been described
include Codon 4/5 and 6 (ACT CCT GAG - ACA TCT
TAG), Codon 47/48 (+ ATCT), Codon 55 (+ A), IVS
2 - 837 (T - G), Codon 88 (+ T), Codon 5 (- CT)
IVS 1 110 (G - A), Codon 15 (TGG - TAG).
Figure 15.6.2: Pathophysiology of -Thalassemia
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Classification
Homozygous states Two types
Thalassemia Major
Thalassemia Intermedia
Thalassemia Major Children are clinically severe type
and are dependent on regular blood transfusion for their
survival (Fig. 15.6.3).
Thalassemia Intermedia Symptoms are milder and are
not dependent on blood transfusion for their survival.
Usually symptoms appear after the age of 2 years or more
(Fig. 15.6.4).
Heterozygous States
Two types
Thalassemia Minor
Silent carriers
Thalassemia MinorHeterozygous state and is
characterized by elevated HbA2 more than 3.4% and have
microcytic hypochromic red cells.
Silent Carriers
They are asymptomatic and have no hematological
findings and are diagnosed by chain synthesis. Suspected
when one of the parents of thalassemia major does not
have increased HbA2.
Figure 15.6.3: Thalassemia Major
Figure 15.6.4: Thalassemia Intermedia
Clinical Manifestation and Diagnosis of

Thalassemia
When to suspect?
The spectrum of clinical manifestation of Beta
Thalassemia varies widely.
One end of the spectrum is the:
Serious homozygous form (Thalassemia Major)
that presents in early infancy (6-18 months) with
pallor, failure to thrive, irritability, intercurrent
infections and hepatosplenomegaly.
If undiagnosed and untreated, more than 90% do
not survive beyond 3 to 4 years of age.
Untreated or irregularly treated children develop
significant hemolytic faces including fronto-parietal
bossing with a hot-cross-bun appearance of the skull
(caput quadratum), depressed bridge of nose, malar
prominences and malocclusion of teeth with protrusion
of maxillary teeth (Fig. 15.6.5).
Usually these children are apparently born normal
and do not have any symptoms till the age of 2 to 6
months. Affected children initially grow well for initial
few months. The child becomes irritable with gradually
increasing pallor, not taking feeds well, recurrent
infection and develops mild hepato-splenomegaly. Often
798

of PBF and a reticulocyte count can help in suspecting
and identification of hemoglobinopathies.
Reticulocyte count ranges from 2 to 4%.
Red Cell Indices- Hb, RBC, MCV, MCH and
MCHC, RDW
The CBC in Thalassemia Trait
Marked reduction in mean cell volume (MCV) and
mean cell hemoglobin (MCH).
RDW is the coefficient of variation of red cell volume
distribution. RDW is the objective documentation of
subjective anisocytosis. (Normal range- 11.5% to
14.5%.). High red cell count, relative to hemoglobin
Concentration and hematocrit.
The red cell distribution width (RDW) is within
normal range.
Figure 15.6.5: Thalassemia major: hot cross-bun appearance of the skull (caput quadratum)
these children are treated initially with oral irontherapy

with the mistaken diagnosis of iron deficiency anemia.
Other end of the spectrum is the heterozygous form
(thalassemia minor) who can lead practically normal
life except for mild persistent anemia not responding
hematenics, and have normal life span and they can
pass on their genes to their siblings.
In between these two extremes, are forms with
varying degree of clinical manifestations of anemia,
spleno-heptomegaly, and bony changes, who,
maintain their life fairly comfortably and are not
dependent on blood transfusion for their survival and
are called as Thalassemia Intermedia and are
homozygous.
LABORATORY TECHNIQUES
Methods for investigation of Thalassemia
For, reliable detection of hemoglobinopathies and
thalassemia, it is advisable to correlate clinical profile and
ethnicity of the individuals, with the blood count, blood
film, and do further investigations to confirm the
diagnosis.
Complete Blood Count (CBC) with red cell indices and
Peripheral Blood Film (PBF) Examination and
reticulocyte count.
CBC is frequently sufficient to postulate the diagnosis
of thalassemia. A primary screen with CBC, examination
Iron deficiency anemia (IDA) is associated with

Low red cell count relative to hemoglobin
concentration and hematocrit.
With low mean corpuscular volume (MCV) and mean
cell hemoglobin (MCH).
The red cell distribution width (RDW) is markedly
increased.
The following Table gives the differences in
laboratory values between -thalassemia trait and mild
iron deficiency anemia (IDA).
Low MCV
Normal MCV
High MCV
RDW Normal Thalassemia Normal

Aplastic anemia
trait
RDW High
IDA
Chronic liver
Megaloblastic
disease
anemia
malignancies, Hemolytic
myelofibrosis
anemia
myelotoxic drugs
PS of Thalassemia Child
Peripheral blood smear is diagnostic with characteristic
bizarre picture of red cells, which are microcytic,
hypochromic, with poikilocytosis, polychromasia,
moderate basophilic stippling, and fragmented
erythrocytes, target cells, and large number of
normoblasts (Figs 15.6.6A to D).
Reticulocyte count ranges from 2-4%. Some abnormal
hemoglobin, like HbS; and HbC can be detected or
suspected on CBC values and PBF examination.
Normoblasts are increased on peripheral smear.
799
Figures 15.6.6A to D: (A) Basophilic stippling, (B) Normoblasts, (C) Reticulocytes, (D) PS of sickle cell disease
Naked-eye single-tube red-cell osmotic fragility test

(NESTROFT) (Fig. 15.6.7)
Many investigators have studied naked-eye singletube red-cell osmotic fragility test (NESTROFT) as a
screening modality in -Thalassemia trait.
The test has a high sensitivity of 95 percent and high
negative predictive value of around 98 % but its poor
precision, inter technician variability and low specificity
has precluded it from becoming a routine procedure,
particularly after the availability of better parameter on
cell counters.
Iron Status
In Thalassemia Major
Serum iron (SI) level increased depending upon iron
overload.
Total iron binding capacity (TIBC) decreased.
Transferrin saturation (T.S.) increased
S Ferritin increased in thalassemia and is
proportionate to iron overload.
Figure 15.6.7: Thalassemia minor Nestrof test
In Iron Deficiency Anemia (IDA)

Serum iron (SI) level decreased.
Transferrin saturation (TS) decreased.
Total iron binding capacity (TIBC) increased.
S FerritineDecreased.
Osmotic FragilityReveals Reduced Fragility.
Bone marrow examination though not required for
diagnoses, shows normoblastic erythroid hyperplasia
and iron staining of bone marrow shows increased
store of iron in the form of hemosiderin.
HbA2 meassurement by:
Demonstration of red cell inclusion bodies
DNA analysis
Hb Electrophoresis HbF, Hb A2 and other
abnormal Hb-Fetal hemoglobin increased in the
patient (Thalassemia major) and Hb A2 is > 3.4
percent in both parents (Thalassemia Minor).
Estimation of hemoglobin A2 by electrophoresis.
Quantitation of Hb A2 remains the Gold standard for
the diagnosis of thalassemia trait.
Till recently electrophoresis was considered the gold
standard for measurement of Hb A2. The technique is
however, laborious, time consuming and unsuitable for
mass screening.
Cellulose acetate electrophoresis pH 8.5 with elution
Citrate agar or acid agarose gel electrophoresis pH
6.2
Isoelectric focusing
Micro column chromatography
Automated high performance liquid chromatography. (HPLC)
Quantitation of HbF
Assessment of distribution of HbF
Tests for Hb S
Test for unstable Hb.
800
Measurement of Hb A2 by elution from electophoresis

on cellulose acetate
Hemoglobin Electrophoresis at 8.4-8.6
Hemolysate is separated into its components fraction,
on cellulose acetate membrane. The relative
proportion of separated fractions are quantitated by
spectrometry of the elute of the separated fraction
Satisfactory separation of Hbs C,S,F,A,J, is obtained.
In general Hbs, S, D and G migrate closely together
as do Hbs C, E and O Arab. Differentiation between
these Hb, can be obtained by using acid agarose gel,
citrate agar electrophoresis, HPLC, or IEF.
Isoelectric Focusing (IEF)
Hemoglobin is separated on a gel according to their
isoelectric point (PI), the point at which the molecule
has no net charge. Hb molecule migrates through the
gel until they reach the point at which their individual
PIs equal the corresponding pH on the gel. At this
point, the charge on the Hb is neutral, and migration
ceases. The pH gradient counteracts diffusion, and
Hb variant forms a discrete narrow band. The
advantage of IEF is that the bands are sharper than
cellulose acetate and Hb D\G are separated from S.
Its disadvantages include precision of quantifying
hemoglobin at low concentration and needs expertise
to interpret. Only reference laboratories use the test.
Micro column Chromatography
Micro column chromatography and HPLC are
becoming popular. Hb A2 value of > 9 percent
indicated the presence of a co-eluting abnormal Hb
such as Hb E, Hb D iron and Hb lepore. Micro column
chromatography is an ion exchange chromatography.
The hemolysate is poured into a column containing
ion exchange resin. The added buffer elutes the
hemoglobin The technique is accurate but suffers
from the disadvantage that other Hb variants cannot
be identified and their presence interferes with
accurate measurement of Hb A2.
High Performance Liquid Chromatography
Both anion- and cation- exchange HPLC has been
applied to identify Hb variants. Cation- exchange has
become far more popular for routine use. Dedicated
instruments have been developed to identify and
quantify HbS by their retention times (the times at
which they elute) and computing the area under the
peak. BioRad Variant (Fig. 15.6.8) Hemoglobins are
Figure 15.6.8: Bio-Rad variant machine
Figure 15.6.9: Graphical representation of various types of

hemoglobin
separated graphically and quantified by spectrophotometer utilizing sophisticated computer software

(Fig. 15.6.9). Prior to sample application, the
instrument has to be primed and calibrated followed
by use of controls to check reproducibility, HPLC has
great advantage over other techniques of accurately
quantifying all normal and abnormal HbS seen in the
chromatogram.
Other Investigations that Help in Diagnosis of Thalassemia
Radiological Findings
X- ray skull and long bones Radiological findings include
widening of medulla due to bone marrow hyperplasia,
thinning of cortex and trabeculation in the long bone and
metacarpal and metatarsals.
Skull X-ray shows hair-on-end appearance, thinning
of cortex and trabeculation in the long bones and
metacarpal and metatarsal bones (Figs 15.6.10A to D).
Various other tests are indicated as and and when the
disease progresses and involves other organs. Such as
Liver Function Tests (LFT)Serum Billirubin, SGOT,
SGPT, GGT.
Glucose tolerance curve to rule out diabetes.
Endocrinal studies such as pituitary glands -Growth
hormone, and thyroid gland functions such as T3, T4,
and TSH, Parathyroid- Serum calcium, phosphorus,
paratharmone, and panaceas-fasting blood sugar and
glucose tollerance test and other endocrinal studies
as required.
Clinical Consequences of Iron Overload
Most of the complications of -thalassemia are attributable
to iron overload. Excess iron is toxic to the heart, liver,
and various endocrine glands.
The commonly affected endocrine glands include
Pituitary gland, thyroid gland, parathyroid gland,
pancreas, gonads
Clinically they may not be evident initially, and hence,
investigations are required for early detection, and
should be done in all thalassemia children from time
to time and treat them appropriately.
Diabetes may be seen as early as five years of age
and particularly seen in adolescent children, whereas
short stature is commonly noted after 10-11 years of
age.
Dysfunction of thyroid and parathyroid gland may
be sub-clinical initially. Hence a glucose tolerance test,
thyroid functions particularly T3, T4 and TSH, Sr.
calcium, phosphorus should be done frequently if
possible every year, beginning at the age of 5 years.
801
Affection of the liver is seen in thalassemia children

due to various causes including
Repeated plasma borne infection,
Iron overload,
Hence it is necessary to do the liver function test like
serum bilirubin, SGPT, SGOT, GGT, alkaline phosphatase and hepatitis markers particularly HBSAg and HCV
antibodies every six months to a year and so also look
for HIV infection by doing HIV test.
It is required to evaluate and monitor the organ
functions regularly particularly- heart, endocrine glands,
growth failure, and complications due to repeated blood
transfusions. Evaluation of weight and height velocity
should be done 10 years age onwards.
Growth failure is seen in 30% of patients in the
western world and nearly all patients in our country,
with few exceptions, these children grow normally in
the first decade particularly when treated efficiently and
growth failure usually becomes evident in the second
decade of life and later.
The mean age of attainment of different stages of
sexual maturity in thalassemic subject is delayed. The
cause of short stature in the iron overloaded patient is
not fully understood.
Various causes attributed for Growth retardation
Poor compliance to regular transfusion therapy and
poor maintenance of Hb level above 10-11 gm%
Inadequate chelation therapy.
Growth hormone deficiency secondary to pituitary
hemosiderosis.
Defective hepatic biosynthesis of somatomedins
(Insulin like growth factor I-IGF1) and sex steroid
deficiency.
Chronic hypoxia secondary to anemia is a
contributory factor for growth retardation. Patients
receiving frequent transfusions to maintain Hb level
above 10-11 gm% along with adequate iron chelation
therapy are physically indistinguishable from their
nonthalassemic peers.
Toxic effect of high doses of deferioxamine on skeletal
growth.
Figures 15.6.10A to D: (A and B) "Hir-on-end"appearance , (C and D) Osteopenia and thinning of cortext
802
Chronic hypoxia secondary to anemia is a

contributory factor for growth retardation. Patients
receiving frequent transfusions to maintain Hb level
above 10-11 gm% along with adequate iron chelation
therapy are physically indistinguishable from their
non-thalassemic peers.
Evaluation of Cardiac Complications
In -thalassemia, 70% of deaths are due to cardiac
complications.
Cardiac failure, and arrhythmias are the main cause
of mortality in thalassemic children.
Iron overload leads to deposition of iron in various
parts of the heart including ventricular walls and the
conduction system. When iron accumulates in the
cardiac tissue, free iron damages the cells of the layers
of the heart, due to lipid peroxidation and lysosomal
rupture.
Early detection of cardiac involvement can be done
by evaluation of ferritine level regularly and then
doing the various tests to evaluate the cardiac
functions like ECG, 2D Echocardiogram, stress test,
Holter monitoring. Ejection fraction is decreased and
abnormality in ECG may be present. Cardiac
complication seen in thalassemic children are
evidence of overt cardiomyopathy, abnormalities
such as left atrial dilatation, aortic root dilatation,
reduced left ventricular internal dimension in systole
and diastole. All these assist in evaluation, but do not
quantitate cardiac function. T2 weighted Cardiac MRI
is the only method of assessing severity of cardiac
iron overload.
Bone Disease in Thalassemia Major-Osteopenia
and Osteoporosis
Osteopenia and osteoporosis are major causes of
morbidity in aging thalassemic population, more in
women.
Osteoporosis as defined by WHO, a progressive
systemic skeletal disease is characterized by low bone
mass and micro architectural deterioration of bone
tissue, with consequent increase in bone fragility and
susceptibility for bone fracture osteopenia.
Hence monitoring for bone disease in thalassemia
children is essential particularly in adolescents and
older children.
This can be done by:

Estimation of Serum Ca/ P/Alk. PO4ase is a poor
indicator.
DEXA Scan for bone density is ideal.
A simple, cheap, reliable screening test may be the
estimation of Urine Ca/Cr ratio (> 0.2) and Urine
P/Cr ratio (> 0.6).
This will help in early detection and prompt
management of bone diseases in thalassemic children.
WHO Criteria for Osteoporosis
CATEGORY
Normal
Osteopenia
Osteoporosis
Established
Z SCORE
at or below - one SD
between -1 and -2.5 SD
at or below -2.5 SD (without
fractures)
at or below -2.5 SD (with
osteoporosis fragility
fractures)
Bone Mineral Density Study DEXA Scan

(See Figs 15.6.11 and 15.6.12).
TREATMENT OF OSTEOPENIA/OSTEOPOROSIS
Hormone replacement therapy- In females estrogen,
in males-HCG
Calcitonin-inhibitor of osteoclasts
Hydroxyurea, biphosphonates and IV pamidronateother modalitiess
Moderate and high impact activitieswalking, ballet
dancing, aerobics jogging, etc.
Diet, rich in calcium and vitamin D
Hormone replacement therapy for endocrine
abnormalities.
In Summary
During the approach of a case with thalassemia, it is not
only necessary to suspect thalassemia by doing simpler
tests like, evaluation of hematological parameter like CBC
along with various Red Cell Indices, NESTROF test
and confirm the diagnosis by estimating HbF and HbA2
and other abnormal hemoglobin by doing various test
like hemoglobin electrophoresis, column chromatography, isoelectric focusing or micro-column
chromatography or high performance liquid chromatography using various instruments like Bio-Rad Variant
Figure 15.6.11: DEXA Scan for bone dentistry over the vertebra
Figure 15.6.12: DEXA scan for bone dentistry over the vertebra
803
804
but also it is important to anticipate complication due to

iron overload involving various organs and due to
transfusion complications and hence it is necessary to
evaluate time to time organ functions for early detection
and complications.
MANAGEMENT OF THALASSEMIA MAJOR
Comprehensive management includes the following:
Confirmation of the diagnosis
Correction of anemia Packed red cell transfusions
Removal of excess iron Chelation Therapy
Management of complications Endocrine and
Cardiac complications
Pharmacological methods to increase gamma chain
synthesis
Curative Treatment Stem Cell Transplantation
Future treatment Gene replacement therapy.
Prevention of disease by antenatal diagnosis and
genetic counseling
Management of thalassemia major should be
preferably done at a comprehensive thalassemia care
center with outdoor transfusion facilities.
A team approach includes:
Pediatric hematologist,
Pediatrician,
Blood transfusion specialist
Endocrinologist,
Psychologist and
Social worker, etc
This not only helps patients and the family to face
various medical and psychological problems but also
helps in early detection and management of complications.
TRANSFUSION THERAPY IN THALASSEMIA
Transfusion therapy in thalassemia has two goals:
To prevent anemia
To suppress endogenous erythropoiesis to avoid
ineffective erythropoisis
Regular Blood Transfusions are Presently
the Mainstay of Treatment of Thalassemia Major
Palliative Pretransfusion - Hb level is around
< 7 gm% and mean Hb maintained is < 8.5 gm/dl.
Hyper Transfusion Pretransfusion Hb level is

around > 10gm% and mean Hb. Maintained is
> 12 gm%.
Super Transfusion Pretransfusion Hb level is
around > 12gm% and mean Hb. Maintained is
>14gm%.
Moderate Transfusion-Pretransfusion- Hb level is
around 9-10.5 gm% and mean Hb. Maintained is
>12gm %
Current recommendation is to maintain the mean
post transfusion Hb. level of 12 gm/dl and transfuse
the child at level of 9 to 10.5 gm/L (Moderate
Transfusion). PostTransfusion level of Hb should
not rise above 15 to 16 gm/dl.
Type of Transfusion
Leukoreduced packed red cell transfusion is desired
type of blood for thalassemic children.
Reduction of leukocytes to 5 106 is considered
adequate. Leukoreduction helps in reducing unwanted
reactions associated with leukocytes. It helps in
prevention of transfusion reactions and is achieved by
centrifugation;/saline washing/filtration.
It is ideal to use leukodepleted red cells done in the
blood bank. However, wherever, this is not feasible.
Methods for leukodepletion
Centrifugation Packed red cell transfusions can
remove 70% of leukocytes from 1 unit of blood.
Saline-cell washing (Triple Saline Washed)
(Fig. 15.6.13) or Deglycerolizedred cells can remove
90-95% of contaminated white cells. Saline washed
packed cells (triple saline washed) reduces blood
transfusion complications.
Deglycerolizedred cells. (Frozen cells) are useful to
patients with rare RBC antigens for whom it is
difficult to crossmatch the donors blood. Very
expensive and advanced technology is involved and
is useful for rare blood groups. Frozen blood with
absence of these antibodies, can be stored as long as
7 years or more.
Third generation leucocyte filters can remove 99.9%
of white cells. However, filters do not remove
cytokines. Bedside, filters are available commercially
which are highly expensive (Rs. 650 at discounted
rate). They are meant for single use only, and are
Figure 15.6.13: Cold centrifuse
disposable and hence are not affordable to most of

our patients (Fig. 15.6.14).
Irradiated blood cells should be given to patients
who have received BMT or candidates waiting for
bone marrow transplantation.
Thalassemic Children Live on Borrowed Blood
This obviates anemia
Improves tissue oxygenation, and prevents chronic
hypoxia
Improves normal growth and development
Prevents erythropoiesis thus avoiding expansion of
the bone marrow and extra medullarys erythropoiesis
Reduces hemolytic facies
Reduces hepatosplenomegalyand cardiomyopathy
Reduces gastro-intestinal absorption of iron.
Blood Transfusion is Mandatory for
All children with thalassemia major
Children with thalassemia intermedia who cannot
maintain Hb above 7g/dl, or
Those who show evidence of growth retardation and
severe bony changes
Post-transfusion level of Hb should not rise above 15
to 16 g/dl.
805
Figure 15.6.14: Leucocyte filter
WHEN TO START THE TRANSFUSION

Blood transfusion is started as soon as diagnosis
firmly established (Except in children > 18 months of
age).
If age is > 18 months, these children are observed to
r/o Thalassemia Intermedia and if Hb drops < 7
gms%, regular transfusion started.
If facilities are available it is worthwhile having DNA
analysis done prior to transfusion therapy. This will
help in prenatal diagnosis of future children.
It is equally important to know complete Genotype
of RBC to prevent red cell alloimmunization
following repeated blood transfusion. As this facility
is not available in our country, Combs crossmatching
is strongly recommended. To avoid alloimmunization, patients red cell antigen particularly ABO,
Rhesus, Kell, Kidd, Duffy system should be typed
before institution of trasfusion therapy which is not
done in our country due to lack of facilities.
WHAT TYPE OF TRANSFUSIONS
Ideal transfusion therapy includes:
The most ideal way to transfuse thalassemics is using
group and type specific saline washed packed red
cells (HCT - 65 to 75%) that are compatible by direct
antiglobulin test (Coombs crossmatched).
806
RATE AND FREQUENCY OF TRANSFUSIONS

10-15 ml/kg of saline washed packed red cells every
3 to 4 weeks.
Rate not more than 5 ml/kg/hr, however, in patients
with cardiac dysfunction not more than 2-3
ml/kg/hr should be given.
Shorter intervals of 2 to 3 weeks are more physiological.
10 ml /kg rises Hb level by about 3.5 gm /dl this is
adequate to maintain pretransfusion desired base line
Hb level of 10-11 gm /dl. when given 10 ml/kg every
third week.
Average time taken is 3-4 hours.
These red cells should be transfused at the rate of 3
to 4 ml/kg/hour.
Advances in Transfusion Therapy
Neocyte transfusions and Neocyte-Geriocyte exchange
transfusions.
Neocyte transfusions, to improve the survival of red
cells after transfusion, have been tried but with limited
success. In a unit of blood, red cells have a survival of
60 days. Proper et al in 1980 introduced the concept of
transfusing thalassemic children with young red cells,
the mean age being around 12 days. IBM 2991 Cold
centrifuge is used for both washing the red cells as well
as for dividing them into population of different age
group by differential centrifugation techniques. They
survive in the recipient for about 90 days, thus reducing
the amount of blood required and prolonging the interval
between two transfusions. They are experimental and
are not of practical use as there are greater risks of
alloimmunization, greater risk of viral infections and as
its high cost/sophisticated technique involved.
Amount and Rate of Transfusions
Approximately 180 ml/kg of red cells are required
to be transfused per year in non-splenectomized, nonsensitized patients to maintain the hemoglobin above
10 gms%, whereas splenectomized patients require
133 ml/kg per year.
Even without hypersplenism, the requirement is 30%
higher in non-splenectomized patients.
Efficacy of Transfusion Regimen
Rate of fall of Hb. should not exceed 1gm/dl/week in
splenectomised patients, and not more than 1.5 gm/dl/
week in non splenectomised patients. If Hb fall is greater

then investigate further for.
Alloimmunization of RBCs.
Hypersplenism (Blood transfusion requirement
increase more than 200c.c/kg./Yr.).
Drug induced, like aspirin, ribaverin, bleeding,
infection like malaria.
If transfusion requirement is >200c.c/kg/yr, explore
the cause of high transfusion requirement.
OUTDOOR CENTRE FOR THALASSEMIA
(PROGRESS IN TRANSFUSION THERAPY)
In the past, thalassemic children had to be admitted for
blood transfusion alongside other sick children of the
ward.
Prolonged hospital stay, cross infections, increased
cost, both to the parents and the institution as well as
psychological trauma was the brunt of such therapy.
With the advent of outdoor transfusion centers
(Figs 15.6.15 and 15.6.16), transfusion can be well
planned causing minimal psychological trauma to the
child and parents as transfusion is given in a cordial
compliant surrounding with other thalassemic
children.
There are fewout door transfusion centers in our
countries.
Blood bank support crucial to sustain regular
transfusion. Organizing camps possible with the help
of NGOs support.
There are more than 25 outdoor transfusion centers
all over the country. Outdoor center LTMG hospital
Bombay started in 1988.
Advantages of Outdoor Thalassemia Centers
Transfusions are given on OPD basis and hence no
hospitalization required.
Children are more comfortable.
It has made the therapy more convenient and
compliant as it can be planned on school holidays
and on the day convenient. There is less school
absenteeism and Parents lose less workday.
When child is admitted in the ward of the Hospital,
expenditure-indoor is around Rs.790/pt/day and
when treated on outdoor basis the expenditure is
around - 180/pt/day. This has reduced cost to parents
as well as to the institution.
Group therapy as a part of the intervention program
has an important role and direct beneficial impact on
outcomes.
It can be used as a platform to spread information,
current knowledge and for genetic counseling.
807
use of filters and for training parents about the use of

desferal pumps, etc.
This change in environment has made transfusion
therapy a great success.
Adequacy of Transfusions
It is important to check the adequacy of transfusions to
achieve best results and manage thalassemics ideally.
In the first decade of life, normal growth confirms
adequate transfusions.
Also the number of normoblasts should be <5/100
WBCs in well-transfused children. This may be an
indicator in older children (However, this is not
applicable to those children who have not been
initiated on therapy early and adequately in early
life).
COMPLICATIONS OF TRANSFUSION
Figure 15.6.15: Outdoor transfusion center
NHFTR (Non hemolytic febrile transfusion reaction)

Alloimmunizaton.
Plasma borne infections -Transfusion transmitted
infections
Iron overload.
PREVENTION OF INFECTIONS
Figure 15.6.16: Outdoor transfusion center services at

LTMG Hospital Sion, Mumbai
There is no threat of contacting infections from other

patients in the wards.
There is great psychological support.
Identification with the staff helps better compliance.
Parents exchange and share their experiences and
feelings.
Trained nurse/doctor in charge plans the transfusion
therapy well in advance giving sufficient time for
proper testing.
Trained nurse is responsible for maintaining the vein
- the lifeline of thalassemic children, for the proper
Other major problems encountered due to repeated

blood transfusion are transfusion transmitted
infections
Hepatitis B-5 - 30.6% of cases, and Hepatitis C-3039% of cases.
HIV infection can be tested for p24 antigen and DNA
PCR to detect HIV infection in the window period
and are expensive and impractical for our nation at
present. Incidence of HIV ranges from 0%
Chaudhary, et al to 70%-by Currymbhoy et al (1997)
and 10% by Manglani et al. Therefore it is mandatory
to screen blood for HIV, HBV, HCV by sensitive tests.
Other infections seen are CMV, Yersinia spp, and
malaria, etc.
Steps to Prevent These Infections Include
Stringent Donor Selection,
All thalassemic children who are negative for the
hepatitis B surface antigen and antibody, should
receive hepatitis B vaccine in 4 doses at 0, 1,2 and 12
months intramuscularly, Booster dose may be given
after 5 years.
808
Other infections include malariaIt is not possible to

screen the donors or blood bag in endemic countries
like ours for malaria, and hence the policy is to treat
the child whenever indicated.
Leukodepletion can minimize CMV infection.
Now screening for HbC antibodies are made
compulsory thus reducing the incidence. Interferon,
Pegylated interferon, Ribaverin are commonly used
in treatment of these children is highly expensive.
Yersinia Spp. Infection is more common in
thalassemic children receiving Inj desferal. Stop
desferal and initiate co-trimoxazole or aminoglycoside.
Iron Overload and Chelation Therapy
One of the other major problems encountered in the
management of thalassemia is iron overload.
Iron Overload Occurs in Thalassemic
Patients due to
Treatment with multiple transfusionsOne bottle of
blood transfusion given adds 200-250mg of iron to
the body store
Ineffective erythropoiesis
Excessive dietary absorption of iron from gut, to
compensate the large turnover of red cell mass
(especially in inadequately transfused children) [2-5
gm/year in thalassemic children compared to 0.0015
g/year in normal individuals]
Lack of physiologic excretory mechanism for the
excess iron.
The goal of iron chelation is to reduce the iron store
and subsequently maintain at low level (less than 1000
ng/ml).
Drugs Used Presently
Desferrioxamine (Injectable)
Deferiprone (Oral)
Deferasirox (Oral)
A major problem encountered in the management of
thalassemia is iron overload.
Regular red cell transfusions to maintain hemoglobin,
as well as increased iron absorption from GI tract due to
ineffective erythropoiesis, and consequent low
hemoglobin in irregularly transfused children is
responsible for iron overload.
As a general rule, patients with Thalassemia Major

should begin chelation therapy once they have had
10-20 transfusions or when ferritin leval rises above
1000/ug/liter.
Though several hundred compounds have been
developed and tried desferrioxamine (DFO) is gold
standard therapy and found to be most effective and
safe iron chelator.
It is reported that 2000 to 4000 patients die due to
iron overload every year.
Desferrioxamine (Desferal) (DFO)
The dose is 30 to 40 mg/kg/day given subcutaneously
over 8 to 10 hrs for 6 nights a week with the help of
subcutaneous desferal infusion pump (Fig. 15.6.17). The
dose is adjusted according to body wt. and extent of iron
over-load.
In recent times, methods of administration have
improved with better, more convenient smaller, lighter
infusion pumps with LCD display.
Figure 15.6.17: Subcutaneous deferral infusion pump
Balloon pumps, pre-filled syringes of desferal are

available though they are prohibitively costly.
Intravenous desferal can be given particularly in those
with very high iron overload through port-a-caths
(central line). It is not easy to maintain the central
catheter and infections are common.
However, high dose desferal (3 to 9 g/day) can be
given intravenously in severe hemosiderosis to
prevent/reverse cardiac toxicity of iron overload.
It is useful adjunct to subcutaneous infusion.
However, close monitoring for adverse reaction is
required.
Depot Desferal (desferrioxamine) (DFO) is the
newer modification in chelation therapy. With depot
preparation of desferal there is slow release of
desferrioxamine leading to substantial plasma level
of desferrioxamine in the blood for longer period and
hence urinary iron excretion is sustained for longer
period. This is more effective than the conventional
subcutaneous infusion.
Though, desferrioxamine is the gold standard in the
management of iron overload in thalassemia major, it
has not become popular particularly in the developing
countries and is being used in only 10 to 15% of
thalassemics in our country. This is mainly due to its high
cost and the need for continuous subcutaneous injection
over 6 to 8 hours. Poor compliance particularly seen in
the adolescent groups who often revolt against the use
of this pump. This has resulted in delay and irregularity
of its use. Hence, many of the thalassemic children
develop complications related to iron overload and may
require to be given high dose intravenous desferal
through the port or central line. This again is beyond the
reach of many children in developing countries.
809
Role of Vitamin C
Ascorbic acid deficiency increases insoluble iron
(hemosiderin). Vitamin C helps in conversion of
hemosiderin into ferritin, from which iron can be
chelated. High doses of vitamin C can lead to increased
free radical liberation and lipid peroxidation, resulting
in tissue damage and rapid cardiac decompensation and
even death. Addition of 100 mg of vitamin C daily, prior
to DFO therapy increases iron excretion.
Sixty percent of DFO chelated iron is excreted in urine
and 40 percent in stool.
Other Chelating Agents
Over the last 20 years, more than 500 oral chelating
compounds have been tried all over the world in search
of an ideal chelating agent which can be effective, cheap,
safe and can be given orally. Among the various drugs
under trial, few have completed animals studies, a few
are being tried in human volunteers and very few have
been marketed.
Toxicity of Desferal (desferrioxamine) (DFO)

Minimal
No tachyphylaxis has been observed
When given parenterally there may be liberation of
histamine leading to bradycardia, hypo/hypertension, rigors, headache, photophobia, feeling cold
and hot, etc.
When given subcutaneously local pain, indurations,
irritability and redness may occur.
Visual abnormality may occur in 4 to 10 percent of
patients and includes decreased acuity of vision,
peripheral field vision defects, defective dark
adaptation, thinning of retinal vessels, retinal
stippling and abnormal visual evoked responses and
cataract.
High frequency sensory-neural hearing loss has been
reported in 4 to 38 percent of patients.
As the auditory and visual toxicities are reversible,
yearly slit-lamp examination and audiometry are
mandatory to detect them early and if found, desferal
should be stopped.
Delayed linear growth has also been reported in
children below three years of age with desferal. These
may be accompanied by mild skeletal abnormalities
such as short trunk, sternal protrusion and genu
valgum
Deferiprone
One of the drugs which has been approved in some
countries across the world is dimethyl-hydroxy pyridone
(1,2 dimethyl-3-hydroxy pyrid-4-one (L1), developed in
Hiders laboratory-London, now generically named as
Deferiprone and available in India under the brand
name of Kelfer.
It mobilizes iron from transferrin, ferritin, and hemosiderin.
It has undergone extensive trials in USA, UK, Canada,
India and various other centers.
Dose: 75 to 100 mg/kg body weight/day in three to
four divided doses.
Results show that it is 70 to 100 percent as effective
as desferrioxamine and leads to effective reduction
in both serum ferritin and tissue iron overload.
Twenty to thirty percent children develop arthropathy, which is reversible after reducing the dose or
on stopping it. However, if the drug is not
discontinued in time or its dosage not reduced, it may
lead to swelling of the joint, synovial thickening,
synovial effusion, chondromalacia, mild flexion
deformity of the knee, painful external rotation of the
hip and vague generalized backache,destruction of
joint cartilage and irreversible damage to the joint.
810
Physical examination of the joints and complete blood

count including platelet count must be done regularly
when child is on deferiprone (L1) therapy.
ANA, anti ds-DNA, antihistone antibodies have been
reported positive in a few cases, suggesting a druginduced lupus.
Absolute neutropena and thrombocytopenia also
have been reported in occasional cases.
There has been no evidence of ear or eye toxicity.
Urinary excretion of Ca, Cu, Mn, Mg does not get
affected.
Kidney and liver parameters did not show any
alteration.
Some children can have GI symptoms like nausea,
vomiting, pain in abdomen and diarrhea.
To bring down the cost, to improve the compliance
and efficacy of the chelation therapy and reduce the side
effects, combination therapies have been tried.
Oral Deferiprone (L1) 75 mg/kg/day for 4 to 5 days in
a week and DFO 30 to 40 mg/kg day subcutaneously
with the help of subcutaneous infusion pump over 6-8
hours on weekends (2 days) have been shown to be more
efficacious in reducing both liver and heart iron. This is
based on the principle of shuttle hypothesis of one
chelator mobilizing the iron from stores in tissues and
the other helping in excretion from the blood stream.
With recent advances in chelation therapy especially
with the availability of oral chelating drugs like
deferiprone (L1) compliance has remarkably improved.
The cost of therapy has reduced considerably and hence
even in the developing countries many children are able
to get chelation therapy.
Deferasirox (Oral)- ICL 670 (Exzade)
A novel chelating agent belongs to tridentate tiazole,
with high affinity to iron as Fe+++ and chelates at a
ratio of 2:1 (Deferasirox: Iron).
Deferasirox-is a new, oral iron chelator for treatment
of iron overload associated with chronic blood
transfusion. As half-life of the drug is 11-16 hrs and
hence can be given once a day.
Given orally in the dose of 20 mg to 40 mg once daily.
It should be given approximately same time each day
on an empty stomach 30 minutes prior to food. Tablet
should be dispersed in water/orange /apple juice.
It is available as 250/500 mg tablet for oral suspension
dispersible tablets.
Dosage adjustment should depend upon patients

response, S. Ferritin, serum creatinine levels.
Five times as effective as subcutaneous DFO and 10
times more potent than deriprone in animal study.
Iron excretion is predominantly fecal. It excretes iron
from both reticuloendothelial cells as well as
paranchymal cells of various organs and chelated iron
excreted by liver through the bile.
Only side effects reported include mild abdominal
pain, gastrointestinal discomfort, constipation,
diarrhea, skin rash. No changes in auditory, visual
(ocular) or cardiac functions were observed.
It also has the ability to prevent myocardial cell iron
uptake, remove the iron directly from myocardial
cells and exchange the iron with DFO.
RFT/LFT/CBC should be monitored particularly in
patients who are increased risk of complications, have
pre-existing renal conditions, have associated comorbid conditions.
Co-administration of ICL 670 (Deferasirox) with Inj
DFO has synergic effect and helps in reducing dose
of both the drugs thus improving the compliance and
cost of the treatment as is done with oral chelation
therapy with deriprone and inj. desferal. Shuttle effect
also seen with this combination, as ICL 670Deferasirox acts as intracellular chelator and DFO as
extracellular. Other advantage is, it does not chelate
zinc or copper.
Bidentate (L1) chelator mobilizes tissue iron into
blood stream.
Hexadentate (DFO) binds irreversibly and excretes
iron.
Combination therapy is more effective.
HBED and L1 and ICL670A and DFO also have been
successfully tried.
Future Perspectives
Newer drugs like PIH (pyridoxal-isonicotynoyl
hydrozone) HBED- and diamethyl HBED though
looked promising, as they were relatively non-toxic
and effective. However, as they are non-patentable,
industry has none or limited interest
Pharmacologic manipulation of HbFdrugs like
hydroxyurea, butyrates, 5-azacytidine,
Erythropoietin has been tried to induce HbF
production with varying success.
Pharmacologic gene manipulations have been tried
in order to increase the production of HbF and to
811
prevent the precipitation of unpaired Hb chains.

Drugs used are 5-azacytidine, hydroxyurea, butyrate
derivatives. Though some of the studies have shown
Hb increment following butyrate therapy, majority
of workers have not found it to be useful. Hydroxyurea has been found useful particularly in thalassemia
Intermedia and double heterozygotes and Sickle cell
disease.
Management of Complications
GallstonesMore commonly seen in children not
receiving regular treatment. If asymptomatic may not
need any specific treatment.
Prophylactic cholecystectomy, may be done along
with spleenectomy
Leg Ulcers Seen more commonly in Thalassemia
intermedia and in Thalassemia Minor. Bed rest,
regular transfusion, wound care, local tissue factors G-CSF (1 vial diluted in normal saline) have been
found to be useful.
HYPERSPLENISM AND SPLENECTOMY
Causes of Hypersplenism
Inadequate transfusions
Alloimmunization
Chronic liver disease
Auto immune hemolytic disease
Splenectomy
Indications for Splenectomy In Thalassemia:
and Post Splenectomy Care
An increase in the yearly requirement of packed cells
more than double the basal requirement, i.e. packed
cell 230 to 250 cc per kg.
Decreased platelet counts are a relatively late
manifestation of hypersplenism.
With the advent of hyper and super-transfusion
therapy, splenomegaly and hypersplenism have
become a rarity. Hence splenectomy is usually not
needed in these patients.
All children needing splenectomy should receive
pneumococcal vaccine, H. influenza type b vaccine,
and meningococcal vaccine 6 to 8 weeks prior to
surgery. In endemic areas, prophylactic antimalarial
treatment may be given to prevent malaria
Avoid Spleenectomy before the age of 5 yr.
Figure 15.6.18: Splenectomized thalassemic child
If the child has already developed splenomegaly

and signs of hyper-splenism are present, and is above
5 years of age, splenectomy should be considered
(Fig. 15.6.18).
STEM CELL TRANSPLANTATION
This is only the curative therapy available today.
Sources
Bone Marrow,
Peripheral Blood,
Cord Blood,
Fetal Liver.
Though expensive, it is cost effective as compared to
yearly cost of regular blood transfusion and chelation
therapy.
Bone Marrow Transplantation
A ray of hope for permanent cure and better future for
children with genetic disorders has emerged with the
rapid advancement in the techniques and the success of
bone marrow transplantation.
The credit of first bone marrow transplantation in
thalassemia major goes to E. Donald Thomas who
performed this procedure in an 18 months old
thalassemic child in 1982, using HLA matched older
sister as donor. This child was cured of thalassemia. The
first BMT in india in thalassemia was successfully done
by Dr M Chandy and his group at Christian Medical
College, Vellore.
812
The Principles of Bone Marrow

Transplantation in Thalassemia
To destroy and prevent regeneration of defective stem
cells.
Sufficient immune suppression for good engraftment
of normal marrow.
To infuse stem cells with normal gene for -globin
chains.
To prevent GVHD with high dose therapy of
busulphan, cyclophosphamide, total body irradiation
and other modalities.
All over the world, more than 1000 transplantations
for thalassemia major have been done, with a 70 to 80
percent cure rate.
For those in Class I, the success rate is around 93 %

and with all three factors present, the success rate drops
to as low as 60%.
Bone marrow transplantation is most successful in
patients who are young, properly transfused, and wellchelated and in clinically well preserved without
hepatomegaly. The cost of BMT in India is around
Rs. 5-8 lacks and is being done at Christian Medical
College, Vellore, Tata Memorial Hospital, Parel, Mumbai,
Jaslok Hospital, Mumbai, and AIIMS in Delhi and many
other centers in the country (Fig. 15.6.19).
STEM CELLS
Also can be obtained from the cord of unaffected fetus
at delivery. Umbilical cord stem cells have good results
in most centers even with 0-2 HLA mismatched stem
cells. Lower GVHD and longer engraftment have been
reported. However, some have found higher early
morbidity.
BMT in-utero at 16 to 18 weeks of gestation is
underway. There would be no rejection as immune
system is not developed at that time. Mothers purified
stem cells can be used. Success and practical application
is awaited.
Endocrine Evaluation and Growth Monitoring
Figure 15.6.19: Bone marrow transplantation donor is

elder brother
The Three Most Important Adverse Prognostic

Factors for Survival and Event-free Survival are
(Lucarelli et al)
Presence of hepatomegaly (liver more than 2 cm
below costal margin)
Portal fibrosis
Irregular chelation.
Patients are Classified as Different Classes as
Below to Prognosticate the Outcome of Bone
Marrow Transplantation
Class I : None of the above factors
Class II : One or two factors
Class III :All of the above
Iron overload is responsible for dysfunction of many of

endocrine glands like thyroid, parathyroid pituitary
gland, gonads and pancreas leading to hypothyroidism,
altered calcium metabolism, stunted growth, delayed
puberty and diabetes. Clinically they may not manifest
initially and hence, regular evaluation is necessary.
Glucose tolerance test, thyroid function tests, serum
calcium and phosphorus should be evaluated from 5
years age onwards annually.
Ten years onwards, one must monitor the height and
weight velocity, perform the investigations for cardiac
complications (2D-ECHO), consider pertinent
hormone assays and do a DEXA scan for bone
density.
This helps in early detection and better management.
PREVENTION OF BIRTH OF THALASSEMIC CHILD
The treatment of thalassemia-major is very expensive,
painful and psychologically disturbing. Emphasis must
therefore, shift from treatment to prevention.
Fortunately, thalassemia major is a preventable disease.
As we know, thalassemia minor or carrier state can
be easily detected in a person by doing simple blood test
HbA2 by hemoglobin electro-phoresis or variant machine
or column chromatography.
Prevention includes population education, mass
screening, genetic counseling and antenatal diagnosis
and therapeutic abortion of affected pregnancy.
Not even 5-10% of thalassemic children born in India
receive optimal treatment.
Cost of treatment of 4-year-old thalassemic child is
around Rs.90-100,000 annually.
Bone marrow transplantation as a curative treatment
is out of reach for majority of children.
Need of the day
Population education.
Mass screening of target population.
Genetic counseling of minor couples.
Prenatal diagnosis.
Population Education
Population education is done through various mass
media, awareness campaigns in colleges and communities, posters, banners, etc. In a large population such
as in India, it may be more cost-effective to involve highrisk communities to begin with.
Mass Screening
Various methods of screening blood for thalassemia
minor are available which include peripheral smear
examination, RBC indices, Meintzers fraction,
Discriminant functions, NESTROFT (Naked Eye Single
Tube Red cell Osmotic Fragility Test), etc. However, none
of them are confirmatory. The only confirmatory test is
HbA2 estimation. To conduct an effective mass screening
program, the targeted population should belong to the
premarital and newly married groups, i.e. before they
have begun their families.
Genetic Counseling
If a person is a thalassemia minor, he/she should avoid
marrying another minor, but it is not a must. Because if
two minors marry, they can be given the option of
prenatal diagnosis. Genetic counseling is offered to all
who test minor. If only one of the partners is a minor,
there is no chance of them having a thalassemia major
child, but 50 percent chance during each pregnancy of
813
having a thalassemia minor child. But if both partners

are carriers or thalassemia minor, there is a 25 percent
chance of having a thalassemia major child, 50 percent
chance of having a thalassemia minor child and 25
percent chance of a normal child, during each pregnancy.
These are the people who should be convinced to
undergo prenatal/antenatal diagnosis.
Prenatal/Antenatal Diagnosis
When both partners, who are thalassemia minors, plan
to have their baby, they are told to report to their
hematologist as soon as possible after pregnancy is
confirmed. There are many centers for prenatal diagnosis
in Mumbai, Delhi, Chennai, Hyderabad, etc. The couple
is referred to one of them before 8th week of pregnancy
so as to enable the center to give an appointment for the
test between 9th and 11th week of pregnancy. This is the
ideal time for testing. This test is known as chorionic
villous sampling (CVS) and is done generally without
anesthesia.
The risk of fetal losses is below 1 percent in expert
hands, the risk of misdiagnosis also being below 1
percent.
Reasons for Misdiagnosis
Failure to amplify target DNA fragment

Maternal contamination
Sample exchange
Mispaternity.
The diagnosis is available within a week of test and is

given as:
i. Affected which means the fetus has thalassemia
major, or
ii. Unaffected meaning that the fetus is either
thalassemia minor or normal.
Affected fetuses are advised to be terminated and
unaffected fetuses to be continued.
If the couple misses to report before 8 weeks of
pregnancy, there is still a possibility for prenatal
diagnosis by 16 to 18 weeks of pregnancy. The tests done
include amniocentesis or cordocentesis. The results are
given as affected or unaffected with this test too.
Medical termination of affected fetuses is advised.
Since, couple with thalassemia minor has a 75 percent
chance of having an unaffected fetus during each
814
pregnancy, they can have children. But if they do not

wish to terminate the affected fetuses, they can opt for
adoption or no children or artificial methods using donor
sperms/ova.
Genetic Engineering
Aim is addition of a normal copy of the gene along with
key regulatory sequences. Insertion of normal gene in
the stem cells of recipient remains known challenging
goal of future therapy. There are two main approaches
to gene therapy:
Somatic gene therapy in which non-germ line cells
are involved.
Transgenic approach in which transfused gene can
be expressed in subsequent generations. This therapy
is still in experimental stage and likely to be therapy
of future in management of thalassemia. This
approach, however, has been impeded by difficulty
of attaining high-titer vectors for sustained
expression. Lenti Viral vector derived from Human
Immunodeficiency Virus, where a large fragment of
human beta gene and its locus control region, have
been introduced, though experimental, more effective
therapies will become available near future to cure
the disease.
PRE-IMPLANTATION DIAGNOSIS
Biopsy of blastula: By washing uterine cavity after in
vivo fertilization.
Analysis of a single blastomere from an eight cell
embryo after in-vitro fertilization.
PRE-CONCEPTION DIAGNOSIS
Analysis of the first polar body of an unfertilized egg
Distinguish between eggs which carry the defective/
normal gene.
In-vitro fertilization of normal egg.
Replace in mothers uterus-successful pregnancies are
reported.
Useful for couples against MTP.
Technically demanding, difficult to organize, high
cost.
CONCLUSION
Until last few decades thalassemia was regarded as
uniformly fatal disease and death was expected during
the second decade of life before adulthood. Till 1960s

and1970s particularly in developing countries like
INDIAmany children died even before diagnosis.1980s
and 1990s-regular transfusion-hyper transfusion therapy,
desferal therapy in western world and not in developing
world, markedly improved growth and development.
However. in future with progress in the understanding
molecular biology and pathophysiology of thalassemia,
advances in the transfusion therapy, organized quality
care and effective chelation therapy, thalassemics can
become fully active members of the society with proper
physical, mental and sexual growth without any disfiguration and are able to profit from their opportunities and
enjoy positions they are entitled to in the society. With
the free availability of oral chelators in near future, and
establishment of more and more outdoor transfusion
centers and thalassemia societies, the management of
thalassemia major will become easier and economically
feasible. With the advent of BMT, cure is possible and
gene therapy still remains hope for the future. In
developed countries where all these facilities are already
available, more and more thalassemic children are
leading a normal healthy life and even achieving
parenthood. Prenatal screening and antenatal diagnosis
as well as modern management of thalassemia are
technologically complex and expensive, and thus their
benefits remain limited only to the industrialized
developed world and in certain centers in India.
Unfortunately, developing countries like ours still have
a long way to go. Management of the disease has brought
brighter prospects of survival extending in to 3rd and
4th decades of life provided they receive the latest
treatment with good compliance, and have
metamorphosed thalassemia major from a fatal to a
preventable, manageable as well as a curable disease.
Thalassemia hence should no longer be seen as a
disease of childhood since patients now have prospects
of survival beyond adolescence particularly in countries
where health services are able to supply adequate
treatment. Hence todays expectations of thalassemic
adolescents are:
To reach the age of puberty, with normal growth and
development.
Expect same attainments as those of their healthy
peersin education, employment and a welladjusted
social and sexual life.
Growth failure and pubertal delay and fertility
represent major obstacles to the fulfillment of these
hopes.
This has opened a new chapter in the management
of thalassemia beyond blood transfusion and chelation
therapy. Problems of adolescence, growth and puberty,
bone mineralization, proper sexual development,
sexuality, ability to have proper education, to find
suitable employment, marriage and parenthood are
concerns that today require attention.
12.
BIBLIOGRAPHY
16.
1. Agarwal MB. Thyroid function in multi-transfused iron

loaded thalassemic patients. Ind Pediatr 1992;29:9971002.
2. Ashraf T, Saliman, et al. Thyroid function in thalassemia
major. J Tropical Pediatr Dec. 1999.
3. Borgna Pignatti C, DeStefan OP, Zonta L, et al. Growth
and sexual maturation in thalassemia major. J Pediatr
1985;106:150-55.
4. Colah RB, Mohanty D, Beeta Thalassemia: Expression,
Molecular mechanism and mutation in Indians.
Ind.J.Pediatr.1998;65:815-23.
5. Costin G, Kogurt MD, Hymen CG, Orleger JA. Endocrine
abnormalities in thalassemia major. Am J Dis Child
1979;133:497-502.
6. De Sanctis V, Katz M, Vullo C, et al. Effect of different
treatment regimes on linear growth and final height in
B-thalassemia major. Clin Endocrinol 1994;40:791-98.
7. De Virgillis S, Congia M, Frau F, et al. Desferrioxamine
induced growth retardation in patient with thalassemia
major. J Pediatr 1988;113:661-69.
8. DM Flynn, Angela F, et al. Hormonal changes in
thalassemia major. Arch Dis Child 1976;51:828-34.
9. F deluca, R Melluso, G Sobor, et al. Thyroid function in
thalassemia major. Arch Dis child 1980;55:389-92.
10. Gulati R, Bhatia V, Agarwal SS. Early onset of endocrine
abnormalities in B-thalassemia major in developing
country. J Ped Endocrinol Metabol 2000, 13: 651-656. Dr.
Rakesh Malhotra. Thesis submitted to University of
Bombay for D.M. (Endocrinology) Exam. July 2002, Dept.
of Endocrinology, KEM Hospital and GS Medical
College, Mumbai.
11. Kattamis C, Liakopoulou T, Kattamis A. Growth and
development in children with thalassemia major. Acta
Pediatr Scand 1990, (suppl) 366: 111-17.
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815
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children with thalassemia effect of different transfusion
regimes. Arch Dis Child 1970;450:502-09.
Lokeshwar MR, Manglani M, Rao S, et al. Current trends
in Thalassemia therapy. Proceedings of international
symposium cum workshop on Anemia in children
1991;14-21.
Nadkarni A, Goraskar AC, Krishnamoorthy R, et al.
Molecular pathogenesis and clinical variability of Beeta
thalassemia syndrome among Indians. Am. J. Hematol
2001;68(2):75-80.
Neil Mcintosh. Endocrinopathy in thalassemia major.
Arch Dis Child 1976;51:185-200.
Pintor C, Cella SG, Mansol. Impaired growth hormone
(GH) response to GH releasing hormone in thalassemia
major. J Clin Endocrinol Metab 1986;62:263-67.
Rodda CP, Reid ED, Johnson S, et al. Short stature in
homozygous B-thalassemia is due to disproportionate
trunk shortening. Clin Endocrinol 1995;42:587-92.
Theodoridis C, Ladis V, Papatheodoron A, et al. Growth
and management of short stature in thalassemia major. J
Pediatr Endocrinol Metab. 1998;11:835-46.
Vanna Saeng S, Fucharoen S, Pootrakful P, et al. Pituitary
function in thalassemic patients and the effect of chelation
therapy. Acta Endocrinol 1991;124:23-30.
Verma IC, Bijarnia S. The burden of genetic disorder in
India and a frame work for community controle. Commu.
Genet. 200ask 2;5:192-96.
Verma IC, Choudhury VP, Jain PK. Prevention of
thalassemia a necessity in India. Ind J Pediatr 1982;59:
649-54.
Vishwas Khajanchi. Thesis on Endocrine Dysfunctions
in Thalassemic Children, dissertation submitted at the
D.M. (Endocrinology) Examination, University of
Mumbai, July 2002, for FCPS (Pediatrics) Examination,
held by College of Physicians and Surgeons, Bombay,
Dr. E. Moses Road, Parel, Mumbai.
Weatherall DJ, Clegg JB, The Thalassemia Syndromes
4th Ed. Oxford, Blackwell Scientific Publications 2001.
Wolman TJ. Tranfsusion therapy in Cooleys anemia
growth and health as related to long range hemoglobin
level: A progress report. Am NY Acad Sci 1964;119:
736-47.
World Bank 2006, report of a joint WHO March of dime
meeting 2006-Quoted, Guidelines for the clinical
management of thalassemia. 2nd edition Thalassemia
International Federation Nicosia Cyprus. 2007;9.
Zamboni G, Marrati P, Talgiaro F, et al. Parathyroid
hormone, calcitonin and Vit. D metabolism in thalassemia major. Eur J Pediatr 1986;145:133-36.
816
15.7 Sickle Cell Disease

VS Dani
Sickle cell disease is a term used for a group of genetic
disorders characterised by production of hemoglobin
(Hb) S. It is the result of single base pair change, thymine
for adenine, at 6th position on -globin gene on
chromosome number 11 replacing valine for glutamic
acid. The substitution of single amino acid is responsible
for profound change in molecular stability and solubility
of hemoglobin S. Minor variations in non-coding
nucleotide sequence of gene are also seen. The
polymorphic variations are called haplotypes. Four such
haplotype have been found. Arab-Indian haplotype (No.
31) is found in Eastern Saudi Arabia and Indian
subcontinent. Benin haplotype (No. 19), Bantu haplotype
(No. 20) is prevalent in Africa, Mediterranean countries,
Northern and Southern American countries. Senegal
haplotype Africa. The term SCD includes several distinct
genotypes. More commonly seen are homozygous sickle
cell anemia (SS), heterozygous form (AS), sickle thalassemia (S0), less commonly seen forms are SD Punjab
disease, SO Arab disease.
Epidemiology
Sickle cell anemia is particularly common among people
whose ancestors came from sub-Saharan Africa, India,
Saudi Arabia and Mediterranean countries. Nearly 20
million people are affected in India. In broad term, the
prevalence of the sickle cell trait (healthy carrier who
have inherited the mutant gene from one person only)
ranges between 10-40% across equatorial Africa, in west
African countries such as Ghana and Nigeria the
frequency of trait is 15-20%.
Prevalence rate in India north east India 0-18%,
central India 22-44%, west India 0-33% and south India
0-40%.
Pathophysiology
Hemoglobin is normally present in the soluble form in
the red blood corpuscle. The Sol form of Hb changes to
gel form when Hb S is polymerized on deoxygenation.
In gel form Hb is crystallized to small rigid boat shaped
object known as tactoids. These tactoids polymerise
forming insoluble fiber like structures, deforming RBC
to sickle shape. The polymerization is facilitated by

hypoxia, hyperthermia, decreased pH, 2-3 DPG
concentration and carbon monoxide concentration.
On reoxygenation the red cell initially resume normal
configuration, but membrane damage is pronounced
with repeated cycle of sickling and unsickling resulting
in the fixation of membrane in sickle configuration
leading to irreversible sickle cell formation and
hemolysis. The hemolysis is responsible for anemia in
sickle cell disease.
In SCD the red cells have increased adherence to
endothelium. The red cells assume sickle shape after
deoxygenation and damage the endothelial cells leading
to sub-endothelial infiltration and narrowing of vessels.
Platelets aggregate over the adherent red cell damaged
endothelium causing blockage ischemia of tissue.
Clinical manifestations of sickle cell disease are extremely
varied. Some patients are entirely asymptomatic whereas
other patients are constantly troubled by painful
episodes. The clinical picture in most patients falls
between these two extremes.
Sickle Cell Crisis
The term sickle cell crisis was defined by Diggs as any
new syndrome that develops rapidly in patients with
sickle disease due to inherited abnormality. There are
three categories of sickle crisispainful crisis,
sequestration crisis, vaso occlusive crisis and aplastic
crisis.
Vaso-occlusive Sickle Cell Crisis
Vasoocclusive crises are acute painful episodes due to
intravascular sickling and tissue infarction. Vasoocclusive episodes are major clinical manifestation of
sickle cell disease and occur most commonly in bones,
lungs, liver, spleen, brain, and penis.
Acute Painful Event
The most common vaso occlusive crisis. There are
typically rapid onset deep throbbing pain, usually
without any abnormal physical or laboratory finding but
sometimes accompanied by local tenderness, erythema,
warmth and swelling. The underlying pathologic cause
is bone marrow ischemia, sometimes leading to frank
infarction with acute inflammatory infiltrate.
Lumbosacral spine, knee, shoulder, elbow and femur are
most commonly involved. In children younger than 5
years of age small bones of hands and feet are often
affected. This painful Hand foot syndrome is typically
the first clinical manifestation of sickle cell disease. Hand
and foot syndrome disappears when bone marrow from
small bones of hands and feet stops erythropoetic activity.
The age at which a child experiences the hand foot
syndrome is strong predictor of overall severity by 10
years of age. Avascular necrosis of bone occurs secondary
to vaso occlusion of nutrient artery. Femoral head,
humerus, upper part of tibia can be affected but weight
bearing makes femoral head necrosis more likely to cause
severe disability. Painful abdominal crisis occurs due to
localized areas of bowel dysfunction due to vaso
occlusion. Its exact cause is unknown, although
mesenteric sickling and vertebral diseases with nerve root
compression have been suggested. There is severe
abdominal pain and signs of peritonitis. The management includes bowel rest and maintenance of hydration.
If patients condition deteriorates despites these
measures, surgical exploration may be necessary.
Acute right upper quadrant pain with liver enlargement, tenderness, hyperbilirubinemia and abnormal liver
enzymes concentration may be as a result of intrahepatic
sickling.
Acute Splenic Sequestration Crisis
The event is characterised by sudden trapping of large
amount of blood in spleen or less commonly liver and
sudden, rapid, massive, enlargement of spleen with
trapping of considerable portion of red cell mass patients
suddenly become weak, dyspneic with rapidly enlarging
spleen, anemia and shock. The hematocrit becomes half
the patients usual value and associated with brisk
reticulocytosis with increased nucleated RBCs and
moderate to severe thrombocytopenia.
Splenic dysfunction occurs due to obstruction of
sinusoidal blood flow, causing diversion of blood
through intrasplenic shunts, bypassing phagocytic
reticuloendothelial element of the spleen. Sequestration
may recur within 4 months of initial episode. To eliminate
817
recurrence, elective spleenectomy after first episode is

recommended.
Aplastic Crisis
This event associated with temporary cessation of bone
marrow activity due to suppression by intercurrent viral
or bacterial infection parvovirus B19 is most commonly
associated organism. The child present with anemia
without compensatory reticulocytosis. Any child of sickle
cell disease with reticulocytopenia should be considered
as having parvovirus B-19 infection until proven
otherwise. Treatment requires packed red blood cell
transfusion.
Infection
Infection is the most common cause of morbidity and
mortality in children with sickle cell disease. The major
risk factor for increased vulnerability to infection is
splenic dysfunction. This leads to appearance of RBCs
with Howell Jolly bodies and irregular surface
characteristics (pits). When percentage of pitted RBCs
exceed 3.5%, the spleen is generally non-functional. Other
risk factors are defective alternative pathway for
complement mediated lysis due to deficient levels of
serum opsonin and abnormal production of antibodies.
In young children, risk of pneumococcal sepsis is
approximately 400 times that of normal children and
H. influenzae sepsis appears to be 2-4 times as commonly.
Capsulated organisms most commonly involved are,
streptococcus pneumonae H. Influenza. Osteomyelitis is
most often caused by salmonella.
Acute Central Nervous System Event
Among children with sickle cell anemia approximately
11% and 20% will have either overt or silent stroke
respectively before 18 yrs of age. Incidence is estimated
to be 0.7% per year during first 20 yrs of life, with highest
rate in children 5-10 yrs of age. This complication may
occur in isolated but also appears in setting of
pneumonia, aplastic crisis viral illness, painful crisis,
priapism or dehydration. The most common underlying
lesion is internal carotid stenosis or obstruction but
proximal MCA and ACA are also involved.
Pathologically acute sickling may simply be the last
straw causing acute infarction in chronically damaged
due to endothelium, already injured by sickle cells.
Symptoms and signs are hemiparesis, speech defect,
seizures, gait dysfunction.
818
Diagnosis: Best initial diagnostic test is CT scan. But it is

limited by not able to pick up in first 4 to 6 hours where
MRI can be the investigation of choice.
Treatment: Oxygen to maintain SPO2 above 96%. Simple
blood transfusion within 1 hr of presentation with goal
of increasing Hb to maximum of 11 gm/dl. Standard
approach in exchange transfusion reduces at least<50%
if not 30%. The maintenance of blood transfusion
programme for secondary prevention of stroke should
be considered. This results in 85% reduction in the rate
of overt strokes.
Intracranial hemorrhage is also category of sickle cell
related events. Many of these episodes are subarachnoid
hemorrhage from small bleeding aneurysm that probably
arises from internal damage.
Acute Chest Syndrome
These are episodes of acute lung injury with radiographic
evidence of infiltrate and usually accompanied by chest
pain, fever, cough tachypnea and hypoxia. This is leading
cause of morbidity and mortality in children and occurs
more commonly in children than adults.
Management: All patients with ACS must be treated in
hospital. PO2 of <75 mm Hg indicates poor prognosis.
Oxygen therapy is important in hypoxic patient.
Transfusion is critical for patient with persistent hypoxia.
Exchange transfusion is indicated if hematocrit is high.
Preliminary evidence inhaled nitric oxide may be of
benefit in severe hypoxia.
Priapism
Priapism is persistent painful penile erection. Highest
incidence is in children between 2-4 yrs. Recurrent
priapism manifests with episode lasting for few minutes
to several hours. It most commonly occurs around 4 am
during sleep or soon after waking. It usually subsides
spontaneously. If pain, engorgement persists for 24-48
hours, blood transfusion is indicated. Impotency may be
a sequelae.
Cardiovascular System
Abnormal cardiac findings in most patients with sickle
cell anemia are primarily due to chronic anemia and
compensatory increased cardiac output. Cardiomegaly

is found in most of the patient. Pulmonary hypertension
is the most severe cardio-vascular complication.
Renal System
Sickle cell nephropathy includes gross hematuria,
papillary necrosis, nephritic syndrome, renal infarction,
hyposthenuria, pyelonephritis and renal medullary
carcinoma. Hepatobiliary complication includes
cholelithiasis, hepatic infarction and transfusion related
hepatitis.
Eyes
Tortuosity and loculation of conjunctival vessel are seen.
Sickle cell retinopathy includes proliferative and nonproliferative retinopathy which can lead to vitreous
hemorrhage and retinal detachment.
Others
Gallstones are common complication. Only symptomatic
gallstones should be subjected to surgery.
Somatic and sexual growth is delayed in SCD. Age
of menarch is delayed by 2.5 years. Zinc deficiency has
been suggested as a cause for poor growth in our study.
We have observed that zinc supplementation augments
sexual growth but does not affect somatic growth.
Diagnosis
All newborns from high risk population should be
screened for SCD. Blood obtained from umbilical cord
or heel prick. Dried samples on filter paper may be sent
to central laboratory. The diagnosis can be done by Hb
electrophoresis, isoelectric focusing, high performance
liquid chromatography, globin DNA analysis, etc.
Diagnosis should be confirmed after 3 months.
Intrauterine diagnosis can be made by detection of
alteration of a site of specific restriction enzyme by
hemoglobin synthetic oligoneucleotides which detect
single base substitution and polymerase chain reaction
(PCR) amplification of DNA. Chorionic villous biopsy
or amniocentesis can be carried out for obtaining fetal
cells at 8-10 weeks and 14-16 week respectively.
In older children diagnosis is usually done on Hb
electrophoresis on cellulose acetate agar at pH 8.6.
Management
Patient with sickle cell disease should be followed on
routine basis. Patient and his family should be educated
about the nature, course, treatment and its complications
of the disease. Genetic counseling should be done of all
parents with disease and trait preferably in first 1-2
months of pregnancy. All patient of sickle cell disease
should receive pneumococcal, H. influenza, typhoid and
hepatitis B vaccines, in addition to routine immunization.
Protein conjugated pneumococcal vaccine to children less
than 2 yrs is given which should be followed by
polysaccharide (23 valent) vaccines after years.
Prophylactic penicillin should be given to all children
younger than 5 years. (125 mg BD until the age of 3 years
and after 3 years, 250 mg BD). Folic acid 1 mg/day can
be given to prevent megaloblastic anemia.
Transcranial Doppler ultrasonography is used to
screen children for risk of strokes. Children with ICA
flow of 200 cm/sec or higher should receive prophylactic
maintenance transfusion.
Painful events are usually treated with adequate
hydration and analgesics mostly NSAIDS Ibuprofen,
Diclofenac and rarely-opiate drugs can be used.
Blood Transfusion
Patients with SCD tolerate chronic anemia well and
require transfusion under following circumstances:
Sequestration crisis, CNS infarction, Aplastic Crisis,
preoperative, and hypoxia with acute chest syndrome.
In sequestration crisis and aplastic crisis, a standard
simple transfusion is necessary while in all other
situations exchange transfusion is preferable.
Other Approaches to Anti-sickling Therapy
1. Replacement of defective gene by bone morrow
transplantation or more specific gene therapy.
819
2. Stimulation of HbF production by 5 Azacytidine,

sodium butyrate and hydroxyurea.
BIBLIOGRAPHY
1. AL Hajeri A, Serjeant GR, Fedorowicz Z. Inhaled nitric
oxide for acute chest syndrome in people with sickle cell
diease (Review). Cochrane Database of Systematic
Reviews 2008.
2. C Hirst, WC Wang. Blood transfusion for preventing
stroke in people with sickle cell disease. Cochrane
Database of Systematic Reviews 2008 Issue 2.
3. Drover G J and Platt OS. Sickle cell disease, in Nathan
and Oskis Hematology of infancy and Childhood, 6th
edition Vol.12003, Sounders Company: 790-841.
4. Dayana VP Di Nuzzo, Silvana F Fonseca. Sickle cell
disease and infection. I Pediatr (Rio de J) Porto Algre
2004;80:5-15. Serjeant GR. Sickle Cell Disease, 3rd edition
2004 Oxford Medical Publication
5. Driscoll MC, Hurler A, Styles, et al. Stroke risk in sibling
with sickle cell anemia blood, 2003:101:2401-04.
6. Gladwin, MT, Sachdev V, Jison ML, et al. pulmonary
hypertension as risk factor for death in sickle cell anemia,
NEJM 04,350:886-95.
7. Jones AP, Davies SC, Olujohungbe A. Hydroxyurea for
sickle cell disease.
8. Kizito, ME, Mworozi E Nduguia C: Bacteremia in
homozygous sickle cell disease in Africa: Is
pneumococcal prophylaxis justified? Arch dis child
2007;92:21-24.
9. Paul S. Frenette and George F. Atweh. Sickle cell disease:
old discoveries, new concepts, and future promise. J Clin
Invest 2007;117(4):850-58.
10. Sickle cell anemia: Report by Secretariat, Fifty-ninth
world health assembly, Provisions Agenda item 11.4:
World Health Organization, A59/9, 24 April 2006.
11. Singh PC, Ballas SK. Drugs for preventing red blood cell
dehydration in people with sickle cell disease. Cochrane
Datatbase of systematic Reviews 2007, Issue 4.
12. The management of sickle cell disease. National Institute
of Health National Heart, Lung and Blood Institute.
Fourth edition 2002.
820
15.8 Red Cell Membrane Disorders

Rashmi Dalvi, Bharat Agarwal, R Agarwal
Hereditary or acquired defects in the structural components of the red cell membrane can result in decreased
survival or increased destruction of RBCs, giving rise to
a variable degree of anemia.
Hereditary Spherocytosis (HS)
This is the commonest of the red cell membranopathies
and is inherited mainly as an autosomal dominant trait,
resulting in a deficiency of the membrane proteins,
spectrin, ankyrin, or protein 4.2. The membranes of these
RBCs are rigid and therefore get sequestered in the
spleen. In the process they undergo various metabolic
changes, nutrient loss, and lose other membrane
components. The resultant net loss of surface area gives
the rigid spherocytic shape to the RBCs making them
susceptible to destruction by splenic macrophages.
Clinical features: A typical HS patient is relatively
asymptomatic. There may be a history of mild jaundice,
anemia may be mild or absent, but splenomegaly is
almost always present. More severe forms may present
in the newborn period with severe hyperbilirubinemia,
necessitating exchange transfusion.
As in other chronic hemolytic anemias they are prone
to aplastic crisis following parvovirus infection or
deficiency of folic acid. Some patients may develop, or
rarely even present for the first time with symptomatic
gallstones. Rarely leg ulcers and growth retardation may
complicate the course.
Laboratory features: The hemoglobin may be mildly
decreased or normal, however, there is marked reticulocytosis indicating compensatory erythroid hyperplasia.
The peripheral blood smear shows characteristic
spherocytes lacking the central pallor. The MCV is
normal but the MCHC is raised. These red cells show
increased osmotic fragility when incubated with
hypotonic NaCl solutions in vitro yielding a diagnostic
osmotic fragility curve (Figure 15.8.1).
Differential diagnosis: Spherocytes are also seen in other
states such as ABO incompatibility, other immune hemolytic anemias, burns and Clostridium perfringens sepsis.
Figure 15.8.1: PS showing micro-spherocytes
Management: Splenectomy is curative in typical forms of

HS, as it prolongs RBC survival to almost 80 percent of
normal and prevents the other complications. Because
of the higher risk of postsplenectomy sepsis in children,
it should be postponed at least up to 5 years of age.
Transfusions may be required during aplastic crisis or
in the first years if hemolysis is poorly compensated. For
pre- and post splenectomy care refer Page 811.
Other hereditary membrane disorders: Include hereditary
elliptocytosis, hereditary pyropoikilocytosis, hereditary
stomatocytosis and xerocytosis.
Acquired RBC membrane defects: These include acanthocytosis seen secondary to abetalipoproteinemia, or
vitamin E deficiency; paroxysmal nocturnal hemoglobinuria and membrane damage due to heavy metal
toxicity (Cu, Fe), hyperthermia and infection.
RED CELL ENZYMOPATHIES
Normal physiologic function and survival of mature
RBCs is critically dependent for their small but distinct
energy needs, on the glycolytic pathways (EmbdenMeyerhof and Hexose Monophosphate shunt) and
certain nucleotide salvage pathways. Defects in these
pathways could result in decreased survival of red cells.
Glucose-6-Phosphate Dehydrogenase Deficiency
(G6PD)
This is the commonest red cell enzyme defect, an
X-linked disorder seen in males, and very rarely in female
homozygotes. The clinically significant mutants identified are G-6-PD-Aminus (Afro-Americans), G-6-PDBminus, (Asia, Middle-East), G-6-PD-Mediterranean, and
G-6-PD-Canton.
G-6-PD is a vital enzyme in the HMP shunt pathway
which helps generate NADPH to counter oxidative stress.
Deficient individuals manifest a reduction in enzyme
activity and/or stability, and are, therefore, unable to
cope with increased oxidative stress and develop
hemolysis.
Clinical features: Clinical manifestations vary according
to the type of oxidant exposure and the G-6-PD variant.
a. Neonatal jaundice: Some cases may present in the
newborn period with acute hemolysis and hyperbilirubinemia necessitating exchange transfusion. Risk
factors for neonatal hemolysis include prematurity,
sepsis, drugs and maternal medication.
b. Acute hemolytic episodes: In these individuals
increased oxidative stresses as that occurring in fever,
infection, diabetic acidosis, exposure to certain drugs
and toxins can overwhelm the red cells antioxidant
capability and precipitate hemolytic anemia. In cases
of severe stress, intravascular hemolysis with hemoglobinuria may occur. Hemolysis is usually selflimited and the hematocrit stabilizes in 7 to 10 days.
Among many agents that provoke hemolysis in G-6PD deficient individuals, some commonly used ones
are prominent: antimalarial drugs (pamaquine,
primaquine), sulfonamides, urinary antibiotics (nalidixic acid, nitrofurantoin), acetanilide, phenylhydrazine, nephthalene (mothballs) and dyes. Other
agents which could cause hemolysis but are safe in
usual doses are: chloroquine, aspirin, acetaminophen,
vitamin C, quinidine, isoniazid, procainamide and
Vitamin K.
c. Chronic hemolytic anemia: These patients have
moderate to severe degree of chronic hemolysis,
exacerbated by exposure to oxidants. The syndrome
of favism characterized by profound hemolysis
following the ingestion of fava beans is seen in
individuals with the Mediterranean type of defect.
821
Diagnosis: Diagnosis is based on the clinical manifestations, of sudden pallor, jaundice, dark urine and mild
hepatosplenomegaly. The laboratory features seen
include anemia, reticulocytosis, hyperbilirubinemia and
hemoglobinuria. Estimation of enzyme activity is done
by qualitative screening tests, or more reliably by
quantitative assays. Table 15.8.1 shows common drugs
causing hemolysis in G-6-PD deficient subjects.
Therapy: Therapy is usually conservative. Exposure to
offending agents should clearly be avoided. Severe
hemolytic episodes may need packed red cell transfusion
and need to be monitored for complications such as renal
failure and DIC.
Pyruvate Kinase Deficiency
Pyruvate kinase deficiency results in a variable degree
of chronic hemolysis which can vary from the asymptomatic to severe life-threatening transfusion dependent
anemia. The latter may be seen in the newborn when
exchange transfusion may be required. Splenomegaly,
icterus, decreased heptoglobin, and reticulocytosis with
marrow erythroid hyperplasia may be seen in direct
proportion to the severity of disease. In severe cases
especially in young children splenectomy may ameliorate
the symptoms.
Other enzymes which may cause clinically significant anemia include Pyrimdine 5' nucleotidase, and
NADH and NADPH reductase.
TABLE 15.8.1: Common drugs causing hemolysis

in G6PD deficient subjects
Antimalarials
Chloroquine
Primaquine
Quinine
Antipyretics
Paracetamol
Aspirin
Phenacetin
Sulphonamides
Sulphadiazine
Sulphadimidine
Sulphanilamide
Sulphapyridine
Nitrofurans
Nitrofurantoin
Sulphones
Dapsone
Other drugs
Ascorbic acid
L-Dopa
Quinidine
GTN
Vitamin K
822
15.9 Autoimmune Hemolytic Anemia

Bharat Agarwal, Rashmi Dalvi
Acquired erythrocyte defects may have immune
(Coombs positive) or non-immune causes (Coombs
negative). Immune hemolytic anemia can be either
isoimmune or autoimmune. The commonest immune
cause is blood group incompatibility between the fetus
and the mother, e.g. Rh or ABO causing isoimmunization. This is discussed elsewhere.
TABLE 15.9.1: Causes of immune hemolytic anemia

A. Isoimmune
1. Hemolytic disease of the newborn
2. Incompatible blood transfusion
B. Autoimmune: IgG only; C3 only; mixed IgG and C3
1. Idiopathic
a. Warm antibody
b. Cold antibody
c. Cold-warm (Donath-Landsteiner antibody)
2. Secondary
a. Infection, viral
i. Infectious mononucleosis (Epstein-Barr virus
(EBV), cytomegalovirus (CMV), hepatitis, herpes
simplex, measles, varicella.
ii. Bacterial: Typhoid fever, septicemia
b. Drugs and chemicals: quinine, quinidine, phenacetin, p-aminosalicylic acid, sodium cephalothin
(Keflin), penicillin, tetracycline, rifampin, sulphonamides, chlorpromazine, pyramidon, dipyrone,
insulin, lead.
c. Hematologic disorders: leukemias, lymphomas,
lymphoproliferative syndrome, idiopathic thrombocytopenic purpura (Evans syndrome), paroxysmal
cold hemoglobinuria.
d. Immunopathic disorders: systemic lupus erythematosus, periarteritis nodosa, scleroderma,
dermatomyositis, rheumatoid arthritis, ulcerative
colitis.
e. Tumors: Ovarian teratomata, dermoids, thymoma,
carcinoma.
Warm Autoimmune Hemolytic Anemia (AIHA)

Red blood cell survival is shortened in AIHA due to
action of immunoglobulins (antibody) on the red cell
membrane (antigen). Antibodies of the IgG class are most
commonly responsible for AIHA in children. Rh
erythrocyte antigen is involved in more than 70 percent
of cases. Since the antibody has its maximum activity at
37C, the resultant hemolysis is called warm antibody
induced hemolytic anemia (Tables 15.9.1 and 15.9.2 and
Fig. 15.9.1).
Clinical Features
This is a severe life-threatening condition, the clinical features are: Sudden onset of pallor, jaundice and dark urine.
There may be splenomegaly. The laboratory findings
usually are: Very low Hb with marked reticulocytosis.
The peripheral smear may show spherocytes,
polychromasia, and autoagglutination (Fig. 15.9.2). Direct
Coombs test is usually positive. Other evidence of
hemolysis like hyperbilirubinemia, increased plasma Hb,
low heptaglobin level and hemoglobinuria should be
noted.
Management
Because of this being the life-threatening condition, the
Hb, reticulocyte count and spleen size should be
monitored very carefully. The modalities for treatment
of AIHA are:
1. Blood transfusion: Identification of compatible blood
may prove difficult. Since no totally compatible blood
can be found, washed packed red cells in small
volumes with high dose corticosteroid cover should
be employed.
2. Corticosteroid therapy: Hydrocortisone 8 to 40 mg/day
IV or prednisolone 2 to 10 mg/day PO is admini-
3.
4.
5.
6.
stered. Corticosteroids are given for several days and

slowly tapered off over a 3 to 4 weeks period. Lack of
response for 21 days should be considered as steroid
failure.
Intravenous gammaglobulin (IVIgG): In large doses may
be effective in steroid failures.
Plasmapheresis has been successful but the effect is
short-lived if antibody production is ongoing.
Splenectomy may be beneficial in some patients but
the results are unpredictable. It is indicated if the
hemolysis continues to be brisk despite above
measures for 3 to 4 weeks.
Cytotoxic agents, immunosuppressants (CyclosporineA) and hormonal treatment (Danazol) have been used
with variable success, but their use has not been
completely evaluated.
823
TABLE 15.9.2: Causes of non-immune

hemolytic anemia from RBCs
I. Membrane defects
A. Primary membrane defects with specific morphologic
abnormalities
1. Hereditary spherocytosis
2. Hereditary elliptocytosis
3. Hereditary stomatocytosis
4. Congenital hemolytic anemia with dehydrated red
cells
B. Altered phospholipid composition; increased lecithin
(phosphatidylcholine)
C. Hereditary ATPase deficiency
D. Secondary membrane defects: abetalipoproteinemia
II. Enzyme defects
A. Energy potential defects
(Embden-Meyerhof: anaerobic, ATP-producing pathway)
1. Hexokinase
2. Glucose phosphate isomerase
3. Phosphofructokinase
4. Triosephosphate isomerase
5. Phosphoglycerate kinase
6. 2,3-Diphosphoglyceromutase
7. Pyruvate kinase
B. Reduction potential defects
(hexose monophosphate: aerobic, NADPH-producing
pathway)
1. G-6-PD
2. 6-Phosphogluconate dehydrogenase (6-P-GD)
3. Glutathione reductase
4. Glutathione peroxidase
5. Glutathione synthetase
6. 2,3-Glutamyl-cysteine synthetase
C. Other defects
1. Ribose phosphate pyrophosphokinase
2. Adrenylate kinase
3. ATPase
III. Hemoglobin defects
A. Heme: congenital erythropoietic porphyria
B. Globin
1. Qualitative: hemoglobinopathies (Hb S, C, H, M)
2. Quantitative: alpha and beta thalassemia
IV. Congenital dyserythropoietic anemias
A. Type I
B. Type II
C. Type III
D. Type IV
Figure 15.9.1: Child with autoimmune hemolytic

anemia on steroid therapy
Figure 15.9.2: Blood film: autoagglutination
Cold Autoimmune Hemolytic Anemia

Cold hemaglutinin disease is almost always caused by
IgM antibody. But these are found less often in the pediatric age group. It usually occurs during Mycoplasma
pneumoniae infection. The hematologic features in cold
AIHA are similar to those in warm AIHA but are less
marked. Treatment consists of control of the underlying
disorder. Transfusions may be necessary.
824
15.10 Bone Marrow Failure Syndrome

Nitin Shah, MR Lokeshwar
Bone marrow failure syndrome results from failure of
production of mature red cells, granulocytes and platelets
leading to pancytopenia. It can lead to pancytopenia, (i.e.,
aplastic anemia) or mono or bicytopenia, (e.g. agranulocytosis).
Aplastic anemia is classified as acquired or inherited
in etiology. Inherited cases may or may not be present at
birth (congenital). The etiological classification of aplastic
anemia is shown in Table 15.10.1.
Acquired Aplastic Anemia
Severe aplastic anemia is defined as presence of two or
more of peripheral indicators like ANC < 500/cmm,
platelet count <20,000/cmm, corrected retic count < 1.0
percent, in addition to hypocellular bone marrow (< 30%
cellularity).
Epidemiology
Incidence is 2 to 6/million/year and is seen all over the
world. A small peak occurs at the age of 5 to 6 yrs due to
inherited causes of AA.
Thrombocytopenia will lead to bleeding manifestations
especially skin bleeds, mucosal bleeds, hematuria and
rarely intracranial hemorrhage. Neutropenia will lead
to infection and PUO, with or without localization of
infection. Anemia appears last and if severe will lead to
fatigue, breathlessness, puffiness, edema of feet and CCF.
One should look for evidence of etiological factors like
hepatitis, history of drug. Presence of hepatomegaly,
lymphadenopathy, bone pains, etc. usually rule out
aplastic anemia and suggest more sinister disease like
leukemia.
Etiology
1. Idiopathic
2. Secondary: (a) Drugs like chloromycetin, sulphonamides, NSAIDs, (b) Post-hepatitis, (c) Pregnancy,
(d) PNH, (e) Radiation and cytotoxic drugs, (f) Chemical
like benzene, (g) Infections like parvovirus, EB virus,
CMV, HIV, etc.
Pathophysiology Seed and Soil Theory
TABLE 15.10.1: Etiology of aplastic anemia

A. Acquired
a. Idiopathic
b. Secondary
i. Drugs, e.g. sulpha, or anticancer drugs, antiepileptics, chloromycetin, gold, etc.
ii. Radiation
iii. Chemicals, e.g. benzene
iv. Viruses, e.g. Hepatitis, EBV, Parvovirus, HIV, etc.
v. Pregnancy
vi. Paroxysmal nocturnal hemoglobinuria (PNH)
vii. Miscellaneous: Thymoma, eosinophilic fascitis,
Hypogammaglobinemia, Preleukemic syndromes,
etc.
B. Inherited
a. Fanconis anemia
b. Dyskeratosis congenita
c. Reticular dysgenesis
d. ShwachmanDiamond syndrome
e. Miscellaneouse.g. Familial aplastic anemias,
Monosomy 7, Downs syndrome, Dubowitz syndrome,
Amegakaryoctic thrombocytopenic purpura, etc.
a. Seed theory: It contemplates that AA is caused due

to lack of pluripotent stem cells/progenitor cells.
b. Soil therapy: Lack of surrounding microenvironment/stroma of bone marrow. Success of BM
transplant favors seed theory whereas success of
immunotherapy proves that in some patients it is the
soil which is at fault. Probably there are different
mechanisms of damage in different patients.
1. Peripheral blood: There will be anemia with normal
RDW with normocytic, normochromic RBCs,
occasional macrocytosis. Iron study may show iron
overload. There is presence of leukopenia with
decreased ANC, as also a decreased platelet count
with normal MPV. Stressed erythropoiesis is evident
in form of raised HbF and i-antigen in some patients.
2. Bone marrow: It is mandatory to do bone marrow
trephine biopsy as well as aspiration to diagnose AA.
It shows hypocellular marrow with empty spicules,
increased fats spaces, and increased lymphocytes/
plasma cells, etc (Figs 15.10.1 and 15.10.2).
3. Chromosomal studies: It should be done to rule out
Fanconis anemia which will show chromosomal
breaks.
4. Tests to find out etiological factors like LFT HbSAg,
etc.
Treatment
Supportive Care
It is the mainstay of therapy in all the cases and includes:
(1) Blood transfusion/packed cell transfusion should be
given to maintain Hb above 8 to 10 gm percent. Avoid
blood from relatives if BMT is contemplated. Iron
chelation may be necessary after 40 to 50 transfusion so
as to keep serum ferritin level less than 1000 ng/ml.
825
Bleeding: Platelet packs are given if patient has acute

mucosal bleeds or severe internal bleeding especially
with platelet count < 5 to 10,000/cmm. General measures
like local pressure, dental care, avoiding use of NSAIDs,
also help prevent bleeding.
Infections
Whenever the patient of AA has fever, one must collect
blood for culture, urine culture and culture from obvious
sites of infections before starting empirical broad spectrum antibiotics. Modify the antibiotic after the culture
report especially if patient does not show response in 48
to 72 hrs. One may consider use of antifungals if culture
shows fungal growth or when patient does not improve
inspite of changing antibiotics in 7 to 10 days time.
Antifungals used are fluconazole or Amphotericin-B.
Androgenic Steroids
They stimulate erythropoiesis. Nandronolone enanthate
is used in a dose of 2 to 5 mg/kg/day of injectable form
once in 10 days and continued till response is evident.
Efficacy is around 20 to 30 percent and that too only in
moderate AA. Side effects are many, especially masculinization, stunted growth, hepatotoxicity, cancer liver,
etc.
Immunotherapy
Figure 15.10.1: Trephine biopsy in aplastic anemia
Some patients of AA have immune-mediated disease and

hence benefit by immunotherapy with drugs like
cyclosporine-A, ATG, ALG either used alone or in combination. Cyclosproine-A is given orally in a dose of 10 to
12 mg/kg/day for upto 6 months. Side effects like
electrolyte disturbance, renal toxicity, hirsutism, gingival hypertrophy, etc. can occur. ATG/ALG are animal
sera against human lymphocytes or T cells. They are used
in the dose of 10 to 40 mg/kg/day I.V. drip form for 5 to
10 days after test dose. Side effects include anaphylaxis,
serum sickness, thrombocytopenia and severe
leukopenia. The success rate is 60 to 70 percent.
Steroids
Figure 15.10.2: Bone marrow aspiration in aplastic anemia
Steroids stimulate erythropoiesis. It also stabilises

capillary membrane and decreases bleeding. They are
useful to counteract side effects of androgenic steroids
on growing epiphysis and the serum sickness of
immunotherapy. Oral prednisolone is used in the dose
826
of 0.5 to 1 mg/kg/day and tapered to a minimum

effective dose. IV methylprednisolone has been used in
dose of 15 to 20 mg/kg/day IV drip form and tapered
gradually over 15 to 21 days. It has been found to be
effective in 30 to 40 percent of cases. Side effects include
hypertension, fluid electrolyte imbalance, infections,
suppression of neuroendocrinalaxis, psychosis, avascular
necrosis of head of femur, etc.
Growth Factors
Hemopoietic growth factors like G-CSF and GM-CSF
have been used to counteract neutropenia in patients of
AA especially neutropenia following BMT. It helps
control infections. Combination treatment with ALG or
ATG with methyl prednisolone cyclosporin and GCSF
also have been tried with better success.
Bone Marrow Transplantation (BMT)
Cure can occur following BMT using HLA identical
sibling donor which is possible in 30 to 40 percent of cases.
The cure rate is 70 to 80 percent in severe aplastic anemia.
It is more useful in children. The problems are high cost,
GVHD acute and chronic, infection and graft failure, etc.
Nowadays these facilities are available at many centers
in India.
FANCONIS ANEMIA (FA) (FIG. 15.10.3)
Introduction
It is a type of inherited aplastic anemia. The basic defect
is in the poor DNA repairs leading to spontaneous or
induced breaks in chromosomes. In 1927 Fanconi
reported cases of three brothers who had pancytopenia
with typical physical changes. Since then more than 700
cases of FA have been reported worldwide. Now by
definition diagnosis of FA requires presence of
chromosomal changes, and both physical changes or
anemia need not be present. In fact, more and more FA
cases are diagnosed who do not have aplastic anemia or
typical physical changes by studying chromosomal
changes in family members of an index case of FA.
Epidemiology
Mean age at diagnosis is 7 to 8 years with 4 percent cases
< 1 year old and 10 percent cases > 16-year-old in age.
Male to female ratio is 1.06 : 1.0.
Figure 15.10.3: Fanconi's anemia with strunted growth with

mental subnormality, hyperpigmentation around the mouth and
knuckle and polydactyly
Mode of Inheritance
Family studies have shown autosomal recessive type of
inheritance with chances of FA occurring in siblings and
cousins with increased chances of parenteral
consanguinity.
Physical Changes
Patients with FA were originally identified by presence
of characteristic physical changes including generalized
or perioral hyperpigmentation, caf au lait spots, short
stature, microcephaly, mental retardation, skeletal
anomalies like absent or hypoplastic thumb, bifid or
triphalangeal thumb, absent radius, hypogonadism,
spinal anomalies, renal anomalies like ectopic kidney
(Fig. 15.10.4), eye anomalies, deafness, ear malformations, GI anomalies, cardiopulmonary anomalies, etc.
15 to 30 percent of patients with FA are physically normal
or have only short stature and or skin changes.
Investigations done in a case of suspected FA include
CBC, platelet count, red cell indices, retic count, HbF
827
THERAPY
Prognosis
Without therapy 80 percent FA patients die at mean age
of 16 years and 2 years following aplasia and most by 4
years following aplasia. Twenty-five percent survive
beyond third decade.
Androgens
Mean age of survival with androgen is 17 years or 7 years
following onset of aplasia which is little better than no
therapy. Fifty to seventy-five percent of FA patients
respond to androgens and it may take 6 to 12 months for
peak response to occur. One can add prednisolone to
androgens. The doses and follow-up are same as for
acquired aplastic anemia.
Bone Marrow Transplantation (BMT)
Figure 15.10.4: Ectopic kidney in Fanconi's anemia
estimation, bone marrow aspiration and biopsy,

chromosomal studies, skeleton X-rays, USG for KUB.
CBC: It will show progressive anemia, macrocytosis, low
retic count and changes of stressed erythropoiesis like
increased HbF levels and presence of i antigen.
Gradually patient will progress to pancytopenia once
aplasia of bone marrow sets in.
Bone marrow and trephine biopsy: It will show changes
typical of aplastic anemia.
Cytogenetics: FA patients will show chromosomal
changes like breaks, gaps, rearrangements, endoreduplication, exchanges, etc. Peripheral blood lymphocytes
induced by PHA are studied for these changes. These
changes can be spontaneous or following clastogenic
stress like with DEB, Nitrogen mustard, Nitromycin and
cyclophosphamide. Homozygotes will show 8 to 9 breaks
per cell following lymphocytes cultures with DEB as
compared to 0.06 in non-FA persons. Some FA patients
may show clonality. Spontaneous but not DEB induced
breaks are also seen in Blooms syndrome whereas some
FA patients may show chromosomal changes only
following clastogenic stress. Hence, chromosomal study
is done always with DEB to correctly diagnose FA.
The only hope of long-term survival is BMT for FA

patients. Due to inherent chromosomal instability, these
patients are sensitive to radiation and chemotherapy
used for conditioning. Accordingly low doses of
cyclophosphamide should be used for better outcome.
The success of BMT is 78 percent with conditioning
regimen using 20 mg/kg of cyclophosphamide over 4
days and 5 cGy of total abdominolymphoid radiation,
48 percent when cyclophosphamide is used in the dose
of 50 mg/kg over 4 days. One must screen the sibling
donor before BMT to rule out occult FA.
Other Treatment
As expected immunotherapy with ATG/ALG or IV pulse
methylprednisolone is helpful in less than 10 percent of
patients. This proves that it is the seed which is at fault
in FA and not soil.
Other measures like supportive care, use of blood
products, prevention of HLA sensitization, treatment of
infection, monitoring of toxicities of drugs used, etc.
should be as for acquired aplastic anemia.
Complications
FA patients are prone to develop malignancies later on.
It includes 15 to 20 percent chances of leukemia mainly
AML and liver cancers mainly due to androgens. Rare
cancers include preleukemia, gynecological tumors,
Wilms tumor, meduloblastoma, etc.
828
Pure Red Cell Aplasia

This could be either acquired or congenital.
Acquired
Acquired red cell aplasia leading to anemia associated
with reticulocytopenia have been described. The causes
in most of them are uncertain and may be associated with
thymoma and remission is followed removal of tumor of
thymus. Antibodies against erythropoietin, erythroblast
have been reported.
High doses of chloramphenicol have been reported to
inhibit erythropoiesis resulting in anemia, thrombocytopenia, erythroid hypoplasia with vacuolated
normoblasts in the marrow. Viral infection may also lead
to marked reticulocytopenia (less than 0.1%) and bone
marrow aspiration shows markedly reduced number of
erythroid precursors.
Viral infection like parvovirus may lead to selective
suppression of erythroid precursors suggesting aplastic
crisis in hemolytic anemia.
The acquired pure red cell anemia may respond to
corticosteroid therapy. In some cases immunosuppressive therapy with cyclophosphamide or azathioprine
have been found to be useful particularly if corticosteroids are ineffective.
Congenital
Diamond Blackfan syndrome or constitutional chronic
pure red cell aplasia is characterized by isolated erythroid
hypoplasia occurring in early childhood. It is an inherited

disorder autosomal dominant or recessive inheritance.
A variety of congenital abnormalities may be associated
such as stribismus, webbed neck, deformed thumb, bony
abnormalities of finger and ribs. Congenital anomalies
like double ureter with hydronephrosis have been reported. Investigations suggest normochromic,
macrocytic anemia with marked reticulocytopenia.
Marrow aspiration characteristically discloses cellular
marrow with profound erythroid hypoplasia with
markedly increased M. E. ratio. Serum iron level may be
high, fetal hemoglobin is elevated in most cases and also
antigen on the red cell surface. Hypogammaglobulinemia
may be associated. Erythrocytes adenosine deaminase
have been found to be elevated. Mainstay of treatment
is transfusion therapy and adrenal corticosteroid.
Hemosiderosis is unavoidable complication and may also
eventually lead to portal hypertension and hypersplenism and hence chelation therapy and splenectomy
may be required. Dose of steroid is 1 to 2 mg/kg of
prednisolone for 4 to 6 weeks and if unsuccessful, then
may be discontinued. Steroid therapy may have to be
maintained to the minimal required dose.
Methylprednisolone may be tried. Successful marrow
transplantation have been reported in patients with
refractory to therapy and having HLA identical sibling.
Intravenous gammaglobulin have been found to be
useful. In most of the patients carefully adjusted steroid
therapy has been found successful.
15.11 Physiology of Hemostasis:

Approach to a Bleeding Disorder
Renu Saxena
Blood is a fluid connective tissue in constant circulation
throughout the body. Vascular injury results in extravasation of blood. Nature has devised hemostasis system to
prevent bleeding. Hemostasis involves presence of intact
vascular component, platelet and coagulation factors.
Vascular Component
The initial response to a bleeding injury is vasoconstriction. This is a temporary attempt to reduce/arrest
bleeding immediately.
Platelets
Exposure of underlying collagen following endothelial
injury activates the platelets. Initial event is a change in
shape of platelets from discoid to appearance of multiple
pseudopod like projections on its surface leading to
adhesion and aggregation of platelets at the site of injury
(primary aggregation) forming a white plug. Activation
of platelets stimulates the arachidonic acid pathway
within the platelet releasing thrombaxane A2 and ADP
(from the dense granules of platelet). These substances
cause further aggregation of platelets (secondary
aggregation), thereby increasing the size of the white
plug. Activation of platelets also results in release of PF3
on the surface of platelets which further stimulates the
coagulation reactions. This platelet plug serves as a
temporary seal, while formation of clot is necessary to
repair the damaged vessel.
Coagulation
The most important step in coagulation is thrombin
generation. This requires presence of activated F X,
F V, PF3 and prothrombin (F II). It has been proposed
that activation of factor X to Xa is possible by two
different systems. The extrinsic system is activated by
release of tissue factor (TF), a transmembrane glycoprotein present on the surface of many cell types. Tissue
factor forms a complex with FVII forming activated F
VIIa which activates factor X (Fig. 15.11.1).
It was earlier believed that the intrinsic system gets
activated by the activation of F XII which in turn activates
factor XI, F IX respectively. F IXa in presence of F VIIIa
829
activates factor X to Xa. Currently it is believed that factor

XII and XI do not play an active role in triggering of the
coagulation cascade. It has been shown that TF-VIIa
complex also activates F IX to F IXa which in presence of
F VIIIa activates X.
Factor Xa, in the presence of F Va and phospholipid,
converts prothrombin to thrombin. Thrombin acts on
fibrinogen to produce fibrin monomers, which are acted
upon by F XIII to form Fibrin polymers. Coagulation
cascade is controlled by multiple positive and negative
controls as given below.
Positive Feedback Controls
These controls stimulate coagulation system by increasing the thrombin generation.
a. Thrombin itself activates platelets to make more PF3
available for activation of the coagulation cascade.
It also potentiates activation of F VIII and V.
b. F VII is activated by factor Xa and which is further
enhanced by presence of tissue factor.
Figure 15.11.1: Normal coagulation pathway
830

TABLE 15.11.1: Approach to a bleeding patient: Hemostatic defects
Vessel Wall
Platelet
Coagulation factor
Bleed
Localized
Generalized
Generalized
Duration
Since birth
Since birth : hereditary

< 6 mos: Acute ITP
> 6 mos: Chronic
Since birth : hereditary

Recent onset : Acquired
Specific
History
Associated
autoimmune
disease
Drug ingestion
Preceding illness
Umbilical cord
Stump bleeding : F-XIII
Delayed wound healing
Fibrinogen def.
Spontaneous severe trauma
Family
X-linked [F VIII, IX]

Autosomal recessive [XIII, X, II, I]
Onset
Immediate
Immediate
Delayed
Size
Point
petechiae
Petechiae
Ecchymotic patches
Mucosal bleed
Common
Common
(epistaxis, gum,
menorrhagia)
Less common
Hemarthrosis
Common
Deep muscle
bleed
Common
Intra-abdominal
bleed
Common
Negative Controls
Thrombin generation is regulated in vivo by presence of
naturally occurring proteins in blood. These include
antithrombin III, protein C, protein S and tissue factor
pathway inhibitor (TFPI). The first 3 are produced in the
liver and act as antithrombotics. Antithrombin III
combines with thrombin and inactivates it. Protein C
inactivates F VIIIa and Va. Protein S serves as a cofactor
to protein C. TFPI inhibits action of TF VIIa complex.
Fibrinolysis
Polymeric fibrin is degraded by plasmin (an enzyme in
blood) to monomers, releasing fibrin degradation products (FDP) which include D-dimers. Plasmin is formed
by activation of plasminogen by tissue plasminogen
activator (TPA). Tissue plasminogen activator inhibitor
inactivates the TPA.
Approach to a Bleeding Patient
Bleeding constitutes a prominent manifestation of
hemostatic disorders. It may be secondary to hereditary
defects in vascular wall, platelets or coagulation factors.
Based on the history, pattern and severity of bleeding,

the cause of bleeding can be identified in many children
(Table 15.11.1). Detailed clinical history is helpful for the
diagnosis of the underlying defect.
The preliminary screening tests in patients with
bleeding disorders include platelet count, bleeding time,
activated partial thromboplastin time (APTT), plasma
prothrombin time (PPT) and clot stability tests.
A platelet count of less than 1.5 lac is considered
thrombocytopenic. However, a count less than 40,000/
cmm is often associated with spontaneous bleeding. In
acute thrombocytopenia, especially in children, a
preceding history, upper respiratory tract infection is
often available. This usually regresses spontaneously
within 6 weeks. Persistence of thrombocytopenia for
more than 6 months is suggestive of chronic thrombocytopenia. Bone marrow may show increased/normal
megakaryocytes in chronic idiopathic thrombocytopenic
purpura. Such megakaryocytic thrombocytopenia also
occurs in megaloblastic anemia, myelodysplastic syndrome, autoimmune diseases, DIC, HUS, etc. Thrombocytopenia also occurs in systemic diseases like aplastic
anemia, leukemias, myelophthistic anemia, thyrotoxi-
cosis and HIV. Bleeding time measured by Ivys
technique is an indicator of platelet count, function and
vascular defect. It is prolonged in cases with
thrombocytopenia platelet function disorders and
vascular defects. When platelet count is normal, a
prolonged bleeding time is suggestive of platelet function
defect and requires measurement of PF3 availability
content of platelet and agonist induced platelet
aggregation.
Plasma prothrombin time (PPT) is an indicator of
extrinsic and common pathway of coagulation. Activated
partial thromboplastin time is an indicator of intrinsic
and common pathways of coagulation. Prolongation of
PPT alone is suggestive of F-VII deficiency and needs to
be confirmed by F-VII assay. Prolongation of APTT alone
occurs in F VIII, IX, XI, or XII deficiency. Mixing tests of
APTT performed with normal serum or aluminium
hydroxide Al (OH3) adsorbed plasma further help in
differentiating these deficiencies. Normal serum contains
factors IX, X, XI, XII whereas Al(OH3) absorbed plasma
contains FV, VIII, XI, XII. Correction of an isolated
prolonged APTT with normal serum but not with
absorbed plasma suggests F-IX deficiency. Its correction
with adsorbed plasma but not with normal serum
suggests F-VIII deficiency. Correction with both, i.e.
normal serum and adsorbed plasma occurs in F-XI and
F-XII deficiency. However, specific factor assays are
confirmatory. Prolongation of both APTT and PPT along
with thrombocytopenia may occur in acute DIC and
needs to be confirmed by doing thrombin time and
fibrinogen degradation products (FDP). Thrombin time
gets prolonged in DIC due to presence of
hypofibrinogenemia (fibrinogen < 100 mg/dl) or FDP.
831
Prolongation of APTT and PPT with normal platelet

count and thrombin time may occur in hereditary
deficiency of common pathway factors of coagulation or
combined deficiency of factors. The latter occurs usually
in liver damage vit K deficiency inhibiting synthesis of
factors II, VII, IX, X. In factor XIII deficiency, however,
platelet count, APTT, PPT and bleeding time remain
normal. Abnormal clot stability tested with 5 Molar urea
is the only abnormality observed and thus this test
constitutes an important preliminary screening test.
Based on above tests most patients with hereditary
hemostatic defects can be diagnosed. However in some
patients with bleeding, the above tests may be normal.
These may have hereditary defects of fibrinolytic pathway protein (tissue plasminogen activator, plasminogen
activator) inhibitor, vessel wall defects or mild platelet
dysfunction.
BIBLIOGRAPHY
1. Colman RW, Hirsh J, Marder VJ, Salzman EW: Hemostasis and thrombosis edited by RW Colman J Hirsh, VJ
Marder, EN Salzman Lippincott Philadelphia 1994.
2. Davie EW, Ratnoff OD: Waterfall sequence for intrinsic
blood clotting science 1964;145:1310.
3. Esmon CT: The regulation of natural antocoagulant
pathways. Science 1987;235:1348.
4. Lammle B, Griffin JH. Formation & Fibrin clot: the
balance of procoagulant and inhibitory factors. Clinics
in hematology1985;14:281.
5. Loscalzo J, Schafer AI: Thrombosis and Hemorrhage
edited by J Loscalzo, AI Schafer, Williams & Wilkins,
Baltimore, 1998.
6. Mac Farlane RG: An enzyme cascade in the blood clotting
mechanism and to function as a biological amplifier.
Nature 1964;202:498.
15.12 Platelet and Bleeding Disorders

VP Choudhry, Amit Upadhyay
Normal hemostasis requires an integrated vessel wall,
quantitative and qualitatively well functioning platelets
and availability of coagulation factors. Any defect in
above three can lead to bleeding. The defects can be
hereditary or acquired. Vessel wall injuries are usually
local events and platelet and coagulation abnormalities
are systemic events.
Approach to a Bleeding Child

A careful history, a family pedigree and detailed history
and physical examination can give us a fair idea about
the cause of bleeding. Cephalhematoma or prolonged
bleeding from umbilical cord may be earliest indicator
of defective coagulation pathway like vitamin K
deficiency or hemophilia. Spontaneous hemarthroses
832
and muscle hematomas suggest any of the hemophilias

while mucocutaneous bleeding suggests platelet
disorders. Excessive bleeding in response to circumcision
can be seen in hemophilia or in Glanzmanns
thrombosthenia and delayed bleeding in response to
circumcision suggests factor XIII deficiency. Organ
specific bleeding like hemoptysis or hemetemesis are
very rarely the presenting symptom of any systemic
bleeding disorder except for the presence of hematuria
in hemophilia and almost always suggest local causes.
Nutritional history and details of drugs intake are helpful
for diagnosis.
Careful examination of the skin and mucous
membrane is necessary for detecting petechial spots and
purpuras. Hematomas, ecchymosis and oozing at the

venepuncture or injection site should be actively looked.
Joints should be examined for any deformities.
Hyperelasticity of skin and hyper extensibility of joints
can be seen in Ehler-Danlos Syndrome. Gum swelling
with petechial spots around the hair follicle is typical of
scurvy. Presence of significant lymphadenopathy or liver
or spleenic enlargement may point towards underlying
hematolgic malignancies.
In any child with bleeding, an initial screening of PT,
APTT, platelet count and a peripheral blood film
examination are essential and serve as basic tests for
further tests like coagulation factor assays, platelet
function tests, or bone marrow examination.
Figure 15.12.1: Diagnostic approach to thrombocytopenia
Disorder of the Platelets
Platelet disorders can be classified as either quantitative
or qualitative defects. Most common platelet disorder in
pediatric practice is thrombocytopenia.
Causes of thrombocytopenia are multiple. It may
result from decreased production (aplastic anaemia) or
due to increased destruction of platelets. Idiopathic
thrombocytopenic purpura is the major cause of
thrombocytopenia. Approaches to the differential
diagnosis of thrombocytopenia along with its causes are
given in Figure 15.12.1.
Idiopathic Thrombocytopenic Purpura (ITP)
Term is still being used conventionally while the true
term should be immune thrombocytopenic purpura. It
has an incidence of 4.0-5.3 per 1 lac children.
Pathogensis (Fig. 15.12.2): Thrombocytopenia results
from the increased destruction of antibody coated
platelets by the reticulo endothelial system predo-
833
minantly in the spleen. The antibodies are directed

towards the platelet membrane antigens, usually
GP II b/III a, GP Ib/IX and GPIa -IIa. The antibodies are
usually IgG but may be IgM or IgA and are usually
polyclonal. The sources of the antibodies is not yet fully
clear. It is postulated that these antibodies are produced
by some fetal autoantibody clones which escape their
deletion during immune system maturation and may get
activated following any viral or unidentified immune
trigger leading to production of antibodies, which cross
reacts with the platelet membrane glycoprotein. When
these antibodycoated platelets come in contact with
cells of RE system, the Fc portion of the antibody binds
with the Fc receptor of the RE cell resulting in
phagocytosis of the platelet. Spleen is the major site of
platelet destruction. Other factors like decreased
production of platelets secondary to destruction of
megakaryocytes or intramedullary destruction of
platelets may also contribute to the thrombocytopenia
though this is much more common in adult ITP.
Figure 15.12.2: Pathogenesis of idiopathic thrombocytopenia purpura
834
Types Based on the natural course and clinical

presentation, three distinct patterns have been identified,
viz.
Acute ITP
It is associated with severe thrombocytopenia and is
preceded by viral infection in over 50 percent of the cases.
It has self limiting course and majority (80 to 90%) of
children have a natural remission within two months.
vaccine also rarely leads to ITP. Severe manifestation of

ITP includes hematuria, gastrointestinal bleeding, severe
epistaxis, menorrhagia in adolescent girls, etc.
Intracranial bleed may occur in 1 to 2 percent of children
and may prove fatal. Physical examination is essentially
normal except signs of hemorrhage in acute ITP. Spleen
may be palpable in 5 to 15 percent of children with
chronic ITP. Natural course of disease, clinical
presentation and the outcome in acute and chronic ITP
is summarized in Table 15.12.1.
Chronic ITP
Patients have insidious onset of symptoms with
moderate thrombocytopenia persisting for at least six
months. Children with chronic ITP have only 10-20
percent chance of natural remission.
Relapsing ITP
Onset is similar to acute ITP but children have relapses.
Relapses may get precipitated following viral infections.
Clinical Presentation (Figure 15.12.3)
Children with ITP have isolated thrombocytopenia and
often develop petechiae, ecchymosis, and easy bruising.
The peak age for acute ITP is between 3 to 5 years, while
infants below 1 year often develop chronic ITP. Boys and
girls are equally affected unlike in adults where it is 4 to
5 times more common in females. Acute ITP is often
preceded by febrile viral episodes while relapses may
occur with or without preceding viral illness. MMR
Laboratory Features
Isolated thrombocytopenia is the only abnormality found
in complete blood count. Platelets are variable in size
with predominantly young large platelets and mean
platelets volume is usually high. Giant platelets can also
be seen in PBF. Platelets distribution width is increased.
Coagulation studies are normal except for increased
bleeding time in the majority. Circulating anti platelet
antibodies can be demonstrated. Current Phase III assays
for detection of these antibodies are sufficiently specific
but not sensitive.
Bone marrow examination reveals normal or
increased number of megakaryocytes but is essential to
exclude the possibility of leukemia, aplastic anemia or
tumor cell infiltration. Bone marrow examination is not
essential in a typical case of ITP. However, bone marrow
examination is essential in children with: (a) chronic ITP,
(b) abnormalities of the total or differential white cell
counts, (c) moderate or severe anemia, (d) with atypical
history (e) failure to respond to previous steroid or other
therapies, and (f) before starting steroid therapy.
TABLE 15.12.1: Acute and chronic ITP
Figure 15.12.3: Child showing petechiae, purpura and ecchymosis
Features
Acute
Chronic
Peak age
Sex predilection
Antecedent infection
Onset
Hemorrhagic Bullae
(oral mucosa)
Eosinophilia/lymphocytosis
Platelet count
Duration
Natural course
Spontaneous remission
Associated immunological
states
2-6 yrs
None
Common
Acute
Common in
acute phase
Common
< 20 109/L
4-6 wks
80%
20-40 yrs
F:M 3:1
Unusual
Insidious
Rare
None
20%
Rare
30-80 109/L
> 6 months
Uncommon
Diagnosis of ITP is made by exclusion of other cuases of
thrombocytopenia by history, clinical examination and
laboratory investigations. Several conditions should be
excluded before making the diagnosis of ITP. Intake of
drugs such as qunidine, heparin, prolonged use of
analgesics, anticonvulsants, cephalosporins, sulfonamides, etc. should be excluded. Children with aplastic
anemia and leukemia have anemia which is out of
proportion to the blood loss along with abnormal blood
counts. The presence of lymph nodes, hepatosplenomegaly or sternal tenderness suggests the possibility of
leukemia. Abnormalities of the limb are characteristics
or TAR (Thrombocytopenia with absent radii) syndrome.
Children with Fanconis anemia usually have
dysmorphic physical features and isolated thrombocytopenia. Rarely thrombocytopenia may precede the
development of aplastic anemia.
Supportive Care
Supportive care includes restriction of physical activities
and avoidance of aspirin and related drugs. All
immunization should be avoided during the acute phase.
Children with severe thrombocytopenia (platelet count
< 20,000/cu mm), severe mucosal bleeds, hematuria,
gastrointestinal bleeding, girls with menorrhagia should
be admitted to control the bleeding episode. Oral anti
fibrinolytic drugs can be used for mild to moderate
bleeding episodes.
Treatment
The decision whether to treat or only close monitoring
depends on platelet count and presence and severity of
bleeding. Most of the children with ITP usually do not
require drugs. A non-bleeding child with a platelet count
835
of 10,000 or more can be observed because in 80-85% of

patients ITP resolves by itself within 4-6 weeks.
For a child with minor bleed, supportive treatment
alone is usually sufficient. For any platelet count of less
than 10,000 or patient with life threatening bleeding
treatment is required. The most commonly used drugs
are:
1. Corticosteroids
2. IV IgG
3. Anti D IgG (Table 15.12.2)
1. Corticosteroids: These are the most commonly used
drugs for ITP. The mechanism of actions is:
(a) decreased clearance of opsonised platelet
(b) decreased production of antiplatelet antibodies
(c) increased capillary stability.
There are many treatment regimes being used.
Prednisolone in doses of 0.5-2 mg/kg/day to form a
maximum of 3-4 weeks is the most commonly used
regime. Usually prednisolone is used (2mg/kg/day)
for 2-3 weeks subsequently in tapering doses for
another 2-3 weeks. For quick responses either high
dose oral prednisolone (4mg/kg/day 4 days) or IV
Methyl prednisolone (30 mg/kg/day 3 days) can
be used. Serious side effects of prolonged steroid
therapy include hypertension, growth retardation,
osteoporosis, pseudotumor cerebri, psychosis and
Cushings syndrome.
2. IV IgG: IV IgG forms the mainstay of treatment of
serious episodes. It is used in doses of 400 mg/kg/
day 5 days or 1 gm/kg/day 2 days with the latter
being preferred approach now a days. IV IgG block
the Fc receptors and thus prevents the platelet
phagocytosis. Majority of patients will have
prolonged remission with single dose. Headache and
vomiting are the usual side effects and can be seen
upto 1-2 days post therapy. These are very expensive
however and carry small risk of transmitting TTIs.
TABLE 15.12.2: Mechanism of action of corticosteroids IV IgG and anti-D

Effect
Corticosteroids
IV-IgG
Anti-D
Reticulo-endothelial blockade
Platelet antibody binding
Altered FcR binding
T-helper cell suppression
Improvement in capillary resistance
Cytokine production
Reduced
Reduced
Normal
Antibodies synthesis
Reduced
Reduced
Normal/Reduced
836
3. Anti D: Anti (Rh) D binds Rh positive RBCs and leads

to their destruction in spleen. Since this saturates
splenic Fc receptors, more platelets survive in the
circulation. A positive direct Coombs test, a
decreased haptoglobin level and mild and transient
hemolysis occur in all Rh positive patients after anti
D. Generally, anti D therapy does not require blood
transfusion, although serious hemolysis can occur
rarely. A single dose of 50-100 ug/kg is recommended, as IV infusion over 3-5 minutes which
usually increases platelet counts in 70-80 percent of
patients to > 50,000/ul. This therapy is not effective
in Rh negative and in splenectomised patients.
Platelet Transfusion
Because of ongoing destruction platelet transfusion is not
used to raise platelet count in ITP. Occasionally it can be
used to transiently increase platelet count in combination
with other drugs in life threatening bleeding episodes or
prior to surgery.
Recombinant Factor VII
This agent can be used in life threatening refractory
bleeding episodes. It is also effective in assertive bleeding
episode in patient with platelet function disorders.
Splenectomy
Children with uncontrolled bleeding or children without
any response to steroids or IVIgG therapy, or with
chronic ITP should be considered for splenectomy.
Majority of the patients (65-88%) achieve remission
immediately after splenectomy. Splenectomy results in
immediate rise of platelets as the antiplatelet antibodies
are synthesized in the spleen and secondly the
reticuloendothelial system of the spleen is responsible
for clearing of antibody coated platelets. Platelet count
rises immediately after splenectomy and the maximum
level is achieved within 10-15 days. Peak platelet count
of 5,00,000 / mm3 is associated with prolonged remission.
Some patients may relapse even after splenectomy.
Children after splenectomy are more susceptible to
develop postsplenectomy sepsis secondary to infection
by encapsulated organism such as meningococcus,
pneumococcus, H. Influenzae. These children present with
fever, chills and may progress to coma, DIC and death.
All children should receive meningococcal and
pneumococcus and H. influenzae vaccination prior to

surgery. Penicillin prophylaxis should be initiated after
splenectomy and should preferably be given for life-long.
Chronic ITP
The objectives of therapy is to decrease the risk of serious
hemorrhages than to achieve normalization of platelet
counts. Platelet count does not co-relate with severity of
bleeding episodes. Treatment to children with chronic
ITP needs to be individualized depending upon the
platelet count, degree of bleeding, age of child, duration
of thrombocytopenia and childs activity level. If platelet
remains in a hemostatically safe range (> 15-20,000/mm3)
patients are often observed and active treatment is
reserved for clear signs of bleeding like increased
bruising, menorrhagia, prolonged epistaxis, etc.
Corticosteroids, IVIg and anti D have been used on
either needed or on monthly basis either alone or in
combination with danazole or vinca alkaloids to maintain
platelet counts > 50,000/mm3. Alternatively, splenectomy is successful in 78-80 percent of pediatric patients.
Recently many newer drugs like dapsone, immunosuppressive drugs like cyclosporin, mycophenolate
mofetil, cytotoxic drugs like cyclophosphamide,
azathioprine, monoclonal antibodies like Rituxmab,
Campath, etc. are being used in refractory cases with
variable responses.
Vinca alkaloids: Both vincristine and Vinblastine
increase the platelet count in approximately 70 percent
of ITP patients with sustained response in about 10
percent. Recommended dose of vincristine is 0.02
mg/kg and of vinblastine is 0.1 mg/kg given as bolus
injections at weekly interval for a minimum of three
courses. Peripheral neuropathy and constipation are the
main side effects.
Cyclophosphamide has been used in refractory ITP
patients. It is given in dose of 1-2 mg/kg/day P.O. daily
or 20-30 mg/kg IV every month. It increases platelet
count in more than 60 percent of patients and 30-35
percent of patients remain in long remission after 3-4
months of therapy. The mechanism of action involves
immunosuppression. Alopecia, bone marrow suppression, hemorrhagic cystitis and risk of secondary
malignancy are the potential side effects.
Azathioprine: It is a purine analogue which gets
converted into 6-MP in body and acts as an immune
modulator. Recommended dose is 1-4 mg/kg/day
for at least 4-6 months. It produces good sustainable
response in around 40 percent of refractory patients.
Danazole: It is a semi synthetic androgen and postulated
to decrease the number of Fc receptors on phagocytic
cells by antagonizing the action of estrogens. It is used
in dose of 300-400 mg/m2/day in divided doses. Virilisation and liver dysfunction are the main side effects.
Monthly LFTs are recommended.
Rituxmab: This is monoclonal antibody against CD 20.
It leads to depletion of circulating CD 20 positive Pre-B
cells in the blood leading to decreased antibody production resulting in decreased destruction of platelets. It has
been shown to produce sustained response in more than
50 percent of refractory pediatric ITP patients. The
recommended dose is 375 mg/m2 weekly for 4 weeks.
Risk of anaphylaxis is present and it should be given
under supervision.
Immune Thrombocytopenia
Platelet isoantibodies can be acquired under three
circumstances:
1. Congential isoimmune thrombocytopenia in the
neonate may result from the placental transfer of
isoantibodies formed by the mother due to
incompatible fetal platelet antigens.
2. Placental transfer of platelet antibodies from the
meternal circulation of a mother with ITP.
3. Post-transfusion isoimmune thrombocytopenia
which transfused platelets from the blood or blood
products provoke the formation of autoantibodies.
Pathophysiology of congential isoimmune
thrombocytopenia is similar to erythroblastosis fetalis.
Immunization to the platelet isoantigens (namely
PLA-1) has been observed. Mothers platelets are
negative for PLA-1 antigen while the babys platelets are
positive. Fetal platelets cross the placenta and the mother
produces the antibodies which are responsible for the
neonatal thrombocytopenia. The bleeding is usually mild
and the purpura occurs in the second week of life which
subsides within 2 to 4 weeks. If bleeding is severe,
transfusion of washed meternal platelets are effective.
Corticosteroids and exchange transfusion are also
effective.
Neonatal thrombocytopenia can result from the
placental transfer of platelet antibodies from the maternal
837
circulation. Nearly half of infants, born to mothers with

ITP, develop thrombocytopenia. The neonate is at higher
risk of developing thrombocytopenia when the mother
is having acitve disease or high levels of platelet
associated antibodies. Neonates often develop pupuric
or ecchymotic spots at birth and first few days are critical.
Intracranial bleed is an important cause of death.
Neonates with severe bleeding manifestation should be
treated with intravenous immunoglobulins or steroids.
Exchange transfusion removes the antibodies and may
help in controlling the bleeding.
PLATELET FUNCTION DISORDERS
Hemostatic disorders are more often secondary to the
quantitative disorders of the platelets. However, the
process of adhesion, activation and aggregation are
essential for hemostasis. Hereditary disorders in any of
these processes also result in the bleeding disorders
(Table 15.12.3). These disorders are termed as platelet
functional disorders.
BernardSoulier Syndrome
This is an autosomal recessive disorder characterized by
a triad of large platelets, moderate thrombocytopenia and
prolonged bleeding time. There is reduced or abnormal
expression of platelet GP Ib/IX (receptor for vWF) on
the surface of platelet. Platelet aggregation studies show
normal response to all agonists except for ristocetin.
Abnormal RIPA (ristocetin induced platelet aggregation)
can be corrected by addition of normal platelets. Platelet
flow cytometry can be used to confirm the disorder.
TABLE 15.12.3: Causes of platelet function disorders
Hereditary diseases
Associated with thrombocytosis
Glanzamanns thrombasthenia
Thrombopathic thrombasthenia
Defects of release reaction
Storage pool disease
Cyclo-oxygenase
Gray platelet syndrome
Isolated PF3 release
Thrombopathy (Deficient PF3 content)
Von Willebrands disease
Associated with thrombocytopenia
Bernard-Soulier syndrome
Wiskott-Alrich syndrome
838
WiskottAldrich Syndrome
CLINICAL FEATURES
It is an X linked inherited disorder characterized by small

platelets, thrombocytopenia, recurrent infections and
eczema. Platelet aggregates are abnormal and bleeding
time is usually increased. Splenectomy is helpful in the
majority of patients.
In all these disorders children have mild to moderate

mucosal bleeding, petechiae, ecchymosis, etc.
Menorrhagia may be the predominant feature. Bleeding
time is prolonged and thrombocytopenia may be
associated with Bernard-Soulier and Wiskott-Aldrich
syndrome. Diagnosis of platelet functional disorders is
based upon the high index of suspicion, presence of
bleeding manifestation from early childhood along with
defects of platelet adhesion, aggregation or deficient
release reactions and positive family history.
Management is supportive. Drugs such as aspirin,
NSAIDs, etc. which impair the platelet functions, should
be avoided. Hormonal therapy may be used to control
menorrhagia. Platelet transfusion is indicated in the
presence of uncontrolled bleeding. DDAVP and
antifibrolytic agents can be helpful in selected cases in
mild to moderate bleeding episodes. Recombinant factor
VIIa has also been used successfully in few patients with
platelet function disorders to control bleeding.
Glanzmanns Thrombasthenia
It is an autosomal recessive inherited diorder
characterized by severely reduced or absent platelet
aggregation in response to multiple physiological
agonists because of qualitative or quantitative
abnormalities in platelet glycoproteins GP IIb (CD 41)
and GP IIIa (CD-61). Patients with this disorder have a
normal platelet count, but a markedly increased bleeding
time, decreased or absent clot retraction and abnormal
platelet aggregation to physiologic agonists. Antifibrinolytic agents and platelet transfusion are used to
control bleeding episodes.
Storage Pool Diseases
Platelets have two major types of granules dense (delta)
and alpha granules. Dense granules contain ATP, ADP,
calcium and serotonin while the alpha granules contain
bigger molecules like vWF, fibronection, fibrinogen,
PDGF, PF4, etc. Bleeding disorders arise either due to
decrease in number or by decreased release or their
contents. Defects in the dense granules, alpha granules
or both can be present. Dense granules defects can also
be associated with defective biogenesis of melanosomes
leading to associated oculocutaneous albinism, e.g.
ChediakHigashi syndrome or HermanskyPudlak
syndrome.
Defects in -granules leads to Gray Platelet
Syndrome, which is characterized by abnormalities of
platelet - granules, thrombocytopenia and fibrosis in
the bone marrow. Blood smear shows agranular platelets
that appear grey on wrights stain because of lack of these
(azurophilis) granules. Platelet functional studies show
defective aggregation in response to ADP and epinephrin
in case of dense granule disorder, while defective
aggregation in response to thrombin and collagen is seen
in cases of alpha granule disorder. Diagnosis can be
confirmed on electron microscopy.
Hereditary Coagulation Factors Deficiency

Hereditary disorders are common in children; however,
deficiency of the coagulation factors can also result from
acquired causes (Table 15.12.4). Among these disorders
hemophilia A, hemophilia B and von Willebrands
disease are common. Deficiencies of these factors result
in bleeding of varying severity except for factor XII which
is associated with thrombosis.
von Willebrands Disease
This is the most common inherited bleeding disorder
with prevalence as high as 1 percent of the general
population. von Willebrand Factor (vWF) is a central
component of hemostasis which serves a carrier for factor
VIII and acts as a link between platelet and the vessel
wall. It binds to platelet GP Ib (vWF receptor) on
adjoining platelets and subendothelium and helps them
making clump. Its deficiency leads to von Willebrands
disease. Several subtypes have been identified, and of
these types 1, 2 and 3 are most common. Deficiency may
be quantitative (type 1 and 3) or qualitative (type 2). Type
1 variant is the most common and the mild form in which
vWF is 10-50 percent of the normal. In type 2 vWF is
839
TABLE 15.12.4: Coagulation factor deficiency

Hereditary Disorder
Common diseases
Factor deficiency
Hemophilia-A
VIII
Hemophilia-B
IX
von-Willebrands disease
VIII and vascular factor
Uncommon Diseases
Hemophilia-C
XI
Parahemophilia
V
Factor X deficiency
X
Factors VII, V, XII, XIII
Acquired Disorders
Deficiency of vitamin K dependent factors
Hemorrhagic disease of the newborn
_ Liver disorders
_ Malabsorption
Disseminated intravascular coagulopathy
Inhibitors to coagulation factors (Fact. VIII/IX)
abnormal in structure or function. Type 3 is the most

severe form with very low or undetectable levels of vWF.
Type 1 is usually inherited as autosomal dominant while
type 3 is usually autosomal recessive. Patients usually
present with mucocutaneous bleeding but type 3 may
present with hemarthroses and muscle hematomas
simulating hemophilia. Bleeding time is markedly
prolonged. Ristocetin co-factor assays and vWF antigen
assays are diagnostic.
Factor VIII activity is reduced and in type 3 cases, it
can be 3-10 percent of normal. Mild to moderately severe
disease (type 1) may show good therapeutic response to
DDAVP while type 2 and 3 are usually not responsive.
Severe form requires treatment with factor replacement
in the form of plasma or factor VIII concentrates
containing large quantity of intact vWF molecules.
Hemophilia
Hemophilia A and B are inherited bleeding disorders
and account for 80 to 90 percent of inherited coagulation
disorders. They are inherited as sex linked recessive
disorder. Women are carriers of hemophilia defect but
are asymptomatic while their male offsprings suffer from
the disease. Sporadic mutation of the gene is common
and accounts for 20 to 30 percent of cases.
Pathophysiology
Factor VIII and IX are essential for the generation of
thrombin. Activated factor IX forms a complex with
factor VIIa, calcium, membrane phospolipid to generate
Inheritance
X-linked recessive
X-linked recessive
Autosomal dominant
Autosomal recessive
-do-do-do-
Xa for the continuation of coagulation pathway. Factor

VIII has two components, viz. factors VIII related antigen
(VIII-Ag) and factor VIII coagulant activity (VIII-C). Ratio
of factor VIII C to factor VIII-Ag is one. In patients of
hemophilia and carriers, factor VIII-coagulant activity is
reduced while antigenic component remains normal.
Based on the factor levels, hemophilia is classified as
severe (factor level < 1% of the normal), moderate (factor
level between 1 to 5% of the normal) and mild (factor
level > 5% of the normal). Factor VIII or IX gene has been
analyzed and the common mutational defects have been
identified such as deletions, point mutation, stop condon,
etc. Point mutations are usually the underlying mutations
in 70 percent of hemophilia A and in 90 percent of
hemophilia B patients. Inversion 22 is the most common
and accounts for about 45 percent of various mutations.
Hind III and other mutations can be identified in
additional 40 percent of cases. Molecular studies are
being used as a tool for the antenatal diagnosis and
control of hemophilia.
CLINICAL PICTURE (TABLE 15.12.5)
Manifestations of hemophilia are dependent upon the
severity of hemophilia. Patients with mild disease are
usually asymptomatic and may develop prolonged
bleeding following teeth extraction, severe trauma or
following surgery. While patients with severe hemophilia
develop spontaneous bleeds in the skin, subcutaneous
tissues, and in the musculoskeletal system. Nearly
one-third of children develop bleeding following
840

TABLE 15.12.5: Incidence and severity of clinical manifestation of Hemophilia
Severe
Moderate
Mild
70%
50%
15%
30%
15%
20%
Incidence
Hemophilia A
Hemophilia B
Bleeding Manifestation
Age of onset
Neonatal Hemorrhage
- Post Circumcision
- Intracranial
Muscle/joint bleed
< 1yr
1-2 yrs
2 yrs-Adult
Common
Occasionally
Spontaneous
Common
Rare
Following trauma
CNS bleed
Post Surgical Bleeding
Oral Bleeding
High risk
Common
Common
Moderate risk
Common
Common
None
Rare
Following
trauma
Rare
Rare
Rare
circumcision. Excessive bleeding may result from the

umbilical cord. One or two percent of neonates may
develop intracranial bleeds. Common manifestations in
children with severe hemophilia include easy bruising,
oral bleeds, especially from the frenulum, hemarthrosis,
(Fig. 15.12.4) and intramuscular hematomas. Intra
articular bleeding accounts for > 90 percent of all serious
bleeding events in hemophiliac and mostly involved
weight bearing joints such as knee, elbows and ankle.
Acute hemarthrosis is characterized by rapid joint
swelling with pain, redness, stiffness and restriction of
movements. Recurrent joint bleeding in the same joint
results in progressive joint damage and the development
of hemophilic arthropathy over prolonged periods. It is
characterized by synovial hypertrophy, cartilage
damage, loss of joint space and bony changes. Decreased
use of the affected joint leads to muscle atrophy and
ankylosis of the joint. Bleeding in the muscles causes
severe pain and disability. Retroperitoneal bleed results
in severe abdominal pain, anemia, and even shock.
Intracranial bleeds though uncommon but often causes
death. Its early recognition and prompt treatment is
essential to reduce the mortality. Hematuria is often
troublesome. Gastrointestinal bleeding is severe and may
be difficult to control.
Prenatal Diagnosis
This is possible by either chorionic villous sampling
(CVS) at 10-12 weeks of Gestation or by Amniocentesis
at 16-18 weeks of gestation. Both procedures yield fetal
cells for DNA analysis. Direct fetal blood sampling can
also be performed at 18-20 weeks of gestation for assay
of fetal factor VIII or IX. Complication rates are < 1
percent for CVS and 1-2 percent of amniocentesis. Prenatal diagnosis enables to prevent along with
identification of genetic mutation in the affected sibling
is essential to look for the same mutation in the fetus.
Partial thromboplastin time and clotting time are
prolonged while bleeding time and prothrombin time
are normal. Factor VIII or IX deficiency can be identified
either by the individual factor assays or by mixing studies
with normal plasma or with adsorbed plasma.
Figure 15.12.4: Hemophilic arthropathy right knee joint
DNA studies are essential only in presence of male fetus.
However, in presence of female fetus DNA studies can
help identifying the Inversion 22, Hind or other point
mutations by ARMS or by linkage analysis.
841
Once unit of factor VIII/kg raises factor level by 2 percent.

It is administered at 12 hours interval to maintain the
required blood levels as its half-life is 8 hours. Dose of
factor VIII for replacement therapy is given in Table
15.12.6.
Management
Comprehensive management of hemophilia is essential
and should include control of bleeding episodes besides
educational, vocational training, knowledge of early
detection, benefits of prophylaxis therapy and
rehabilitation. Comprehensive care can be possible by a
team of pediatric hematologist, orthopedic surgeon,
physical therapist, dentist, genetic counselor, etc.
Fresh Frozen Plasma
Replacement Therapy
Cryoprecipitates
Prompt replacement therapy is essential for the effective

treatment. It controls the bleeding and prevents the
development of musculoskeletal deformities. Common
indications for the treatment are acute hemarthroses,
intracranial bleed, moderate to severe muscular bleeds,
intra-abdominal bleed and severe mucosal bleeds.
Replacement of factors with cryoprecipitates or factor
VIII concentrates and rest to the affected part are
essential. Presently in India, FFP and cryoprecipitates are
economical while factor VIII concentrates are expensive.
It contains approximately 50 percent of the F VIII-C, von

Willebrands factor activity, fibrinogen and F XIII. Single
bag of cryoprecipitate contains nearly 100 units of F VIIIC. It is useful for management of hemophilia, vonWillebrands disease, severe hypofibrinogenemia or
afibrinogenemia. Cryoprecipitate is preferred as it is
prepared from single unit and has lesser risk of blood
transmitted infections. Its disadvantages include: (a)
storage at 20 to 30 C, (b) difficulty to reconstitute and
(c) factor VIII-C levels vary from bag to bag.
It is readily available and is useful for the management

of mild bleeding episodes. It cannot be used alone to
control intracranial bleeding, acute hemarthrosis or
muscular hemorrhage as its large volume administration
leads to cardiac overload. One ml of FFP contains one
unit of factor VIII and IX along with other plasma factors.
TABLE 15.12.6: Dosage schedule for factors VIII and IX administration

Site of bleed
Loading
Dosage (U/Kg) maintenance
Other therapy
Acute hemarthrosis
20
20 U 12 hourly 3 days
15 U 12 hourly 2 days
10 U 12 hourly
Rest to the affected part, Ice

packs
Elastic bandage, non-weight
bearing, Analgesics (not
aspirin), Rarely joint aspiration
Intramuscular bleed
20-30
Life-threatening bleeds
CNS bleeds
Major trauma
Retroperitoneal bleeding
Neck bleed with
impending airway
obstruction
Tongue and mouth
lacerations
50
20
20 U 12 hourly has to be continued

for several days for extensive bleeds
40 U 12 hourly 7 days or
continuous infusion 3-4 U/kg
hourly 7 days after initial
bolus of 50 U
then
II. 20-30 U 12 hourly 7 days
III. 15-20 U 12 hourly 7 days
20 U 12 hourly 5-7 days
Dental extraction
(permanent teeth)
30
20 U12 hourly 3 days
Nil orally,
Sedation,
EACA/tranexamic acid
EACA/tranexamic acid
24 hrs before and 7 days after
842
Commercially Prepared Factor VIII Concentrates

Factor concentrates form the mainstay of treatment in
the developed countries. These products are not freely
available in the developing countries. The main
advantages include: (a) ease of storage, (b) reconstitution
and infusion, (c) known level of F VIII-C concentration
and, (d) longer shelf-life. Factor VIII concentrates are heat
treated to decrease the hepatitis and AIDS virus load.
Porcine Factor VIII Concentrates
This product is prepared from pig and is highly purified
factor VIII concentrate and is useful for the management
of hemophilia with inhibitors.
Prothrombin Complex Concentrate (PCC)
hormone. DDAVP results in three fold increase of factor

VIII and plasminogen levels. It is useful for treatment of
patients with mild to moderate hemophilia.
Acute Hemarthrosis
Treatment should be initiated without any delay to
prevent the development of chronic debilitating arthritis.
Rest to the affected joints is essential during the acute
stage. Passive and active exercise should be initiated as
soon as pain subsides. Ice pack may provide relief of pain.
Chronic synovitis leads to proliferation of synovium, and
destruction of cartilage. Resorption of bone may lead to
cyst formation and joint instability.
Head Injury
These concentrates contain the vitamin K dependent

clotting factors like II, VII, IX, X and protein C. It is used
for the management of severe hemophilia B.
Head trauma in a hemophilic child is an emergency and

replacement therapy in larger doses should be started in
the emergency room or even at home on suspicion. CT
scan should be done repeatedly to monitor the therapy.
Activated Prothrombin
Complex Concentrates (APCC)
Surgical Procedure
The product is used for management of patients with

inhibitors as it stimulates the common pathway directly.
Recombinant Factor VIII
Recombinant DNA technology has been used to produce
coagulation factor VIII. It is safe as it is not produced
from blood but is expensive. It can also be used for
treatment of patients with inhibitors.
Activated factor VII (Novoseven)
It bypasses the stage one and directly activates factor X
to facilitate the progression of coagulation systems. It can
be safely used to control bleeding in patients of
hemophilia with inhibitors. It is an expensive product
and is beyond the reach of majority.
Epsilon Aminocaproic Acid (EACA)
EACA and tranexamic acid are antifibrinolytic agents
and act by inhibiting the plasminogen activity. These
agents are useful for the management of patients with
mucosal bleeds.
Desmopressin Acetate
I-deamino-8-d-arginine vasopressin (DDAVP) is a
synthetic analogue of naturally occurring antidiuretic
Surgical procedures in hemophiliacs are safe in presence

of adequate replacement therapy. These patients should
be screened for presence of inhibitors besides estimating
the factor levels. Replacement therapy should be initiated
prior to surgery with factor VIII in the dose of 40 to 50
units/kg as a bolus dose and the treatment should be on
same lines as in head injuries.
Hemophilia B
Principles of treatment of hemophilia B are identical to
hemophilia A. One unit/kg of factor IX raises the plasma
levels by one percent. Dose of factor IX for various
conditions is given in Table 15.12.6.
Inhibitors
Developments of inhibitors (IgG antibodies) have been
observed in 15 percent of patients with severe hemophilia
A and 1 to 2 percent of patients with hemophilia B.
Patients with inhibitors have been classified as high or
low responders depending upon the inhibitor levels.
Management is dependent upon: (a) patients inhibitor
levels, (b) nature and extent of bleeding, and (c)
availability of the products.
Inhibitor levels are measured commonly by Bethesda
units. Patients with low inhibitors (<5 Bethesda units)
can be managed easily by factor replacement and
supportive therapy. However, bleeding in patients with
high inhibitor levels (>5 BU) is difficult to control. It is
preferable to use FEIBA, APCC or activated factor VII
along with supportive care. All these agents bypass
stage1 of the coagulation pathway and stimulate the
common pathway directly. These patients should
preferably be treated at specialized centers. After
controlling the bleeding, these patients need to be treated
according to various protocols for desensitization so that
bleeding episodes in future in these patients can be
managed with conventional therapy.
BIBLIOGRAPHY
1. Chang BH, Ho SJ. Automimmune Thrombocytopenia J
Thromb Hemost 2005;3:1763-72.
2. Chaurumrit A. Treatmetn of hemophilia in the
developing countries. Haemophilia 2003;9:387-90.
3. Diane J Nugent. Immune thrombocytopenic purpura of
childhood in American society of hematology educational
program book Hematology 2006;97-103.
843
4. Guidelines for investigation and management of

Idiopathic thrombocytopenic purpura in adults, children
and pregnancy. Brit J Hematol 2003;120:574-96.
5. Haya S, A Moret, A R Cid, et al. Inhibitors in Hemophilia
A: Current management and issues. Haemophilia
2007;13:52-60.
6. Kashyap R and Choudhry VP. Management of
hemophilia in developing countries. Ind J Pediatr
2001;68:151-57.
7. Paula HB Bolton-Maggs, K John Passi. Hemophilia A and
B. Lancet 2003;361:1801-9.
8. Reyhan Diz, Francisca C Gushiken and Jose A Lopez.
Thrombocytopenia in Williams textbook of
Hematology. Ed. Marshall A Lichtman, Ernest Beutler,
Kipps TJ, et al. 7th edition McGraw Hill Medical
2005;1749-84.
9. Saxena R, Ahmed RPH. Carrier detection in Hemophilia
A. Recent Advances in Hematology. Editors Choudhry
VP, Saxena R, Pati HP, J P Publications 2004;262-74.
10. Saxena R, Gupta PK, Mahapatra M, Choudhry VP. von
Willebrands disease, diagnosis and management. Ind J
Hemat Blood Transf. 2003;21:61-66.
15.13 Disseminated
Intravascular Coagulation (DIC)
Anupam Sachdeva, VP Choudhry
INTRODUCTION
DIC is a syndrome, secondary to an underlying disorder
and is characterized by a systemic activation of the blood
coagulation system, which results in the generation and
deposition of fibrin, leading to microvascular thrombin
in various organs and contributing to the development
of multiorgan failure. Consumption and subsequent
exhaustion of coagulation proteins and platelets, due to
activation of the coagulation system, may induce severe
bleeding complications. Derangement of the fibrinolytic
system further contributes to intravascular clot formation, but in some cases accelerated fibrinolysis (e.g. due
to consumption of 2-antiplasmin) may cause severe
bleeding. Hence, a patient with DIC can present with
simultaneous thrombotic and bleeding problem, which
obviously complicates treatment.
DIC is not a pathology in isolation. With possibly the
only exception of venom, DIC is a secondary response
to a pre-existing primary pathology, i.e., it is an

intermediary mechanism of disease.
The hallmark of normal hemostasis is the exquisite
regulation of a focused event, i.e., the formation of a
hemostatic plug, at the site of injury to a blood vessel.
The antithesis of this is what occurs in DIC. The events
are not confined to achieving hemostasis, i.e., they are
widely disseminated, albeit that this may be confined to
a local pathology, such as a hemangioma, or totally
systemic, as in gram-negative shock. The process is
initiated by a procoagulant event. The activation of the
fibrinolytic system is initially directed at clearing the
vasculature of unwanted deposits of fibrin, but it may
eventually compromise hemostasis.
Thus, DIC can be defined as an acquired syndrome
characterized by the activation of intravascular
coagulation upto intravascular fibrin formation. The
process may be accompanied by secondary fibrinolysis
844
or inhibited fibrinolysis. DIC involves consumption

coagulopathy although it is not always present in patients
with DIC, as microclot formation can occur without a
consumption coagulopathy.
The activation of fibrinolysis drastically intensifies the
bleeding tendency. Certainly, the activation of
fibrinolysis in the course of intravascular coagulation is
a secondary phenomenon.
Disseminated intravascular coagulation is an acquired
syndrome characterized by the activation of intravascular
coagulation up to intravascular fibrin formation. The process
may be accompanied by secondary fibrinolysis or inhibition of
fibrinolysis. This definition implies that microclot
formation and a consequent organ failure and/or a
hemorrhagic diathesis may occur.
Epidemiology
Precise numbers on the occurrence of DIC are not known.
In general, one can estimate, however, that of 1,000
patients admitted to a community hospital, only one
patient will develop DIC. The frequency of DIC should
be seen in relation to the underlying disease. The most
frequent disease states with which DIC may occur are
infections (systemic inflammatory response syndrome
SIRS).
Pathogenesis
The characteristic pathology is a procoagulant stimulus.
The generation of thrombin is the final expression with
the formation of gel fibrin and the activation of fibrinstabilizing factor. Thrombin not only activates platelets
inducing platelet aggregation and release but these also
provide specific binding sites for individual coagulation
factors as well as a coagulant active phospholipid surface.
With the help of these events thrombin promotes
dramatically its own generation following the initial
triggering of the coagulation cascade. Conversely,
thrombin generation activates potent mechanisms which
either down-regulate its generation or antagonize its
activity. In the presence of an endothelial cell co-factor
thrombomodulin activated protein C (APC), inactivates
the activated forms of factors V and VIII. In normal
hemostasis a balance exists between the coagulation and
fibrinolytic systems. The availability of tissue
plasminogen activator (tPA), required for conversion of
the inactive zymogen plasminogen to the active serine
protease plasmin, is also regulated by thrombin
promoting either directly or indirectly its release from

endothelial cell stores.There is profound increase in tPA
release and fibrinolysis following the generation of
thrombin. Although many issues relating to the interregulation of these events remain unresolved, we do
know that protein C and the tissue factor pathway
inhibitor (TFPI) play a major role.
Effects of Thrombin
Procoagulant
Converts fibrinogen to fibrin
Activates Factor XIII
Activates factors V and VIII
Activates platelets
Anticoagulant
Activates protein C
Stimulates fibrinolysis
Initiation of Coagulation
Thrombin generation occurs 3 to 5 hours after endotoxin
release or any trigger, and a pivotal role is played by
tissue factor/factor VIIa system in the initiation of
thrombin generation. Activation of coagulation in DIC
is tissue factor driven, whereas the intrinsic pathway of
coagulation does not appear to play an important role.
But it may play an important role in other systemic
inflammatory responses, such as the occurrence of
hypotension. The monocytes express the tissue factor on
their surface and this may play a pivotal role in DIC.
Extrinsic (Tissue Factor)
Pathway-dependent Stimulus
Tissue factor extracts, on entry in the circulation result
in acute DIC as can be seen in major brain trauma.
Leukocytes express the apoprotein. Monocytes from
individuals with neoplastic conditions process tissue
factor like activity as do promyelocytic leukemic cell lines.
Endothelial cells do not normally synthesize tissue factor
but this may become up-regulated. This is associated with
down-regulation of the expression of thrombomodulin,
the essential co-factor required for the activation of
protein C by thrombin. The tissue factor-dependent
extrinsic pathway of coagulation provides the
procoagulant stimulus in the development of DIC in
conditions such as obstetric accidents or trauma,
particularly head injuries. Alternatively, tissue factor
expression is up-regulated either due to stimulation of
cells competent in tissue factor synthesis or by the
availability of neoplastic cells where the generation of
such activity is unregulated.
Intrinsic Pathway-dependent Stimulus
The role of contact activation as an initiating mechanism
in normal hemostasis remains elusive. Activation of
factor XII occurs following exposure to natural materials,
or to artificial surfaces or injury to the endothelium,
induced by endotoxin exposure or burns. This provides
the initial trigger to thrombin generation, and promotes
the generation of bradykinin and thus contributes to the
vasodilatation and hypotension commonly found in
association with the coagulant or fibrin generating
characteristics of this syndrome. It has been shown to
directly promote plasminogen activation. Thus in DIC
we see decreased levels of factor XII, prekallikrein and
kallikrein inhibitors and an increase in levels of
bradykinin-inhibitor complexes in patients with
hypotensive septicemia.
Cellular Tissue Factor and its
Procoagulant Function
Tissue factor is a 47 kDa glycosylated protein, which is
expressed on the vascular adventitia and organ capsules,
and that is usually not in direct contact with the
circulating blood. Its function may be related to
intracellular signal pathways and cell activation. TF can
be expressed on the endothelial cells and mononuclear
leukocytes. Granulocytes may also express TF upon
stimulation with endotoxin.
In sepsis and DIC, TF is critical as a mediator of DIC
and septic shock. Intracellular infections, such as with
herpes viruses, may turn quiescent vascular endothelial
cells into TF-expressing procoagulant cells.
Induction of TF and Onset of DIC
The onset of DIC is dependent on TF, and its blockade
obtained by different means, including monoclonal
antibodies, and the tissue factor pathway inhibitor (TFPI)
diminishes DIC, it may have additional antiinflammatory effects, such as lowering of levels of
IL-6. At the same time, clinical studies with different
inhibitors of the coagulation cascade, including
845
(activated) protein C and antithrombin have suggested

that direct inhibition of coagulation can, indeed, be
beneficial in reducing morbidity or mortality.
Enhancement of TF-Mediated
Coagulation in DIC
The Level of Tissue Factor Expression: This means that
activation of TF-inducible cells in the circulation
determines the trigger of coagulation. In sepsis, cytokines
may induce circulating leukocytes to generate TF and
activate coagulation. In other conditions, the trigger may
be localized and the response systemic.
The Inhibitory Mechanisms: The progression of DIC
depends on the inhibitory potential of the blood.
Impaired synthesis of inhibitory proteins by the liver may
diminish their plasma concentration. Second, available
inhibitors may be depleted by saturation, with clotting
enzymes being continuously generated. Third, the partly
irreversible enzyme-inhibitor may be proteolytically
inactivated by proteases. The overall result is reduced
concentrations of free inhibitor proteins, such as
antithrombin and proteins C and S. The degree of
reduction of inhibitor proteins, particularly protein C, is
related to a poor clinical outcome in septic patients, and
repletion with supra-physiological concentrations of
these inhibitors may improve the outcome. There is an
important role for TFPI as a coagulation and, probably,
inflammation inhibitor, but its concentration is usually
not reduced in DIC. Other inhibitory mechanisms include
thrombomodulin and sulfated heparan proteoglycans,
which are located at the vascular endothelium.
The Amplification Mechanism: TF with factor VIIa causes
proteolytic conversion of factors IX and X. Generation of
factor Xa induces thrombin formation. Thrombin acts by
feedback activation of factors XI, VIII, and V, thereby
enhancing the thrombin generation rate. Thrombin also
activates platelets and converts fibrinogen to fibrin in a
reaction catalyzed by thrombin-activated factor XIII. The
fibrin clot becomes protected against lysis by thrombinmediated activation of a thrombin activable fibrinolytic
inhibitor (TAFI). Local thrombin concentrations and the
inhibitory systems will determine the progression of
fibrin in DIC.
The role of the contact system in the amplification
mechanisms is still uncertain. Activation of the contact
route leads to generation of factor XIa in children with
meningococcal sepsis. In sepsis, the factor XII system may
846
also play an important role in regulating vascular

permeability, as indicated by blocking antibodies and
their protective effect.
Factor XI, interposed between the contact system and
the intrinsic route of coagulation, is activated after
endotoxin infusion in humans.
Direct (non-physiological) Activation
of Coagulation
Factor X and prothrombin may in certain circumstances
be activated directly as occurs with mucin-producing
tumors leading to thromboembolic disease. A number
of venoms can directly activate prothrombin to thrombin.
Plasmin also activates and inactivates factor V and factor
VIII. Both neutrophil and pancreatic elastase activate and
subsequently inactivate factor V and probably factor VIII.
Increased Availability of
Coagulant Active Phospholipid
The phospholipids in the platelet provide a surface for
the assembly of enzymatically active complexes. Similar
phospholipids may be available from erythrocytes, which
are richly endowed with negatively charged
phospholipids on their inner leaflet but these would not
normally be externalized in contrast to the platelet which
undergoes flip-flop of its membrane to expose
negatively charged phospholipids following activation.
Hemolysis, e.g. during an incompatible blood transfusion
reaction, makes such lipids available and could lead to
DIC.
Inhibition of Coagulation: Inhibitors of coagulation can be
categorized into:
1. Inhibitors of thrombin generation.
2. Inhibitors of thrombin action.
Inhibitors of Thrombin Generation
The protein C/protein S system, because of its action on
the co-factors V and VIII may regulate the generation of
thrombin via the intrinsic/common pathways. Thus, the
protein C/S system clearly plays a pivotal role in
regulating thrombin generation resulting either from
increased tissue factor availability or contact activation.
1-antitryspin and 2-macroglobulin become more
prominent as overflow inhibitors. Their appearance in
patients with DIC appears to be associated with a poor
prognosis.
The tissue factor pathway inhibitor (TFPI) is another

example of an inhibitor whose activity is promoted by
the availability of the product of the pathway upon which
it acts.
Inhibitors of Thrombin Activity
Plasma levels of antithrombin III, the most important
inhibitor of thrombin, tend to be markedly reduced in
patients with sepsis due to consumption by ongoing
thrombin generation and impaired antithrombin III
synthesis. Low AT III levels in DIC are associated with
higher mortality. In fact, administration of ATIII
concentrates results in improvement of coagulation
abnormalities, amelioration of organ failure and in some
instances, reduction of mortality.
There is downregulation of thrombomodulin
resulting in diminished protein C activity, which
potentially enhances the procoagulant state. Treatment
with activated protein C reduces the coagulopathy. The
anticoagulant capacity of protein C is enhanced by the
free fraction of protein S. Increased plasma levels of
C4bBP, as a consequence of the acute phase reaction in
inflammatory diseases, may result in a relative protein S
deficiency, which contributes to a further procoagulant
state during sepsis.
Tissue factor, the trigger of coagulation is inhibited
by tissue factor pathway inhibitor (TFPI). Administration
of recombinant TFPI to healthy volunteers results in a
complete inhibition of endotoxin-induced thrombin
generation.
Thrombomodulin is involved in the process of protein
C activation. It is needed for thrombins procoagulant
effects on fibrin generation and platelet activation to an
anticoagulant effect mediated by protein C activation.
Reduced activity of the reticuloendothelial system (RES): The
reticuloendothelial cell system in general and the liver
in particular is involved in the clearance of activated
clotting factors from the circulation. The conditions
associated with relative RES blockade may exist in a
number of the clinical situations associated with the
development of DIC.
Fibrinolysis: The progression of fibrin formation to the
formation of occlusive fibrin plugs is also determined
by the fibrinolytic system. In DIC, the fibrinolytic protein,
plasminogen, and the tissue and urokinase plasminogen
activators (t-PA and u-PA, respectively) may become
depleted, thereby impairing the potential to form
plasmin. Concentrations of plasminogen activator
inhibitor-1 (PAI-1) may, in contrast, be elevated in septic
patients and related with poor clinical outcome, which
may be partly due to impaired fibrinolytic function.
Cytokines: All systemic inflammatory responses lead to
high levels of cytokines in the circulation. TNF becomes
detectable, and there is an increase in circulating levels
of IL-6 and IL-1.
IL-1 is a potent agonist of tissue factor expression.
TNF exerts potent procoagulant effect and is the first
cytokine to appear in circulation.
IL-6 is now being implicated in the above role and it
has been proved that injection of IL-6 causes generation
of thrombin.
TNF seems to be a principal mediator in the
depression of the protein C system in DIC. It is also
responsible for the PAI-1 induced depression of the
fibrinolytic system.
Anti-inflammatory cytokines, e.g. IL-10 may
modulate the activation of coagulation.
The activation of coagulation seems to be mediated
by IL-6, whereas TNF appears to play a pivotal role in
depression of anti-coagulation mechanism and impaired
fibrinolysis.
It is very clear that, in the majority of cases and
irrespective of the source of the procoagulant stimulus,
the fibrinolytic system is activated in response to the
procoagulant stimulus leading successively to thrombin
generation and fibrin desposition in the intravascular
space. It would seem to be the exception rather than the
rule that hemorrhagic manifestations of this syndrome
occur as a result of primary fibrinolysis. The management
approach is weighed in favor of regulating the
procoagulant activity rather than the fibrinolytic
response. If the clinical situation dictates that the latter
approach should be adopted, this should never be
instituted without concurrent therapy directed at
inhibiting either thrombin generation or activity.
Pathophysiology of DIC and
its Clinical Significance
In most cases of DIC, bleeding is the presenting clinical
symptom, and only limited evidence exists for a direct
relationship between fibrin formation and multiorgan
failure in patients with DIC. Protective effects of
anticoagulant agents, including heparin and hirudin also
847
support this beneficial effect of coagulation inhibition.

The crosstalk between coagulation and inflammation may form the hallmark of the clinical picture of
DIC and is responsible for the occurrence of multiorgan
failure.
The presenting bleeding complications in the course
of DIC can be explained by the combination of
thrombocytopenia, reduced coagulation reserve, and
vascular permeability, while hyperfibrinolysis may
contribute or be a predominant feature, such as in
promyelocytic leukemia. In fact, although bleeding is the
most prominent characteristic of DIC, knowledge of the
basis of this hemorrhagic syndrome is speculative at best.
Systemic and Local Derangement of Coagulation and
Fibrinolysis: It is well known that local effects on
coagulation and fibrinolysis may play an important role
in the occurrence of fibrin deposition and organ failure.
The fibrin deposition in kidneys and adrenals is most
dependent on a decrease in urokinasetype plasminogen activator expression.
In the lungs the tissue factor dependent thrombin
generation is insufficiently counter balanced by a reduced
urokinasedependent bronchoalveolar fibrinolysis
activity, mainly due to high levels of PAI -2.
DIC in the Neonate: Neonatal DIC may be triggered by
infection or hypoxia as an in utero event. The fetus may
be exposed to endotoxins from the mother or the placenta
or to thromboplastin and FDP generated in the placental
circulation or from the maternal circulation or may be
precipitated by hypoxia or hypotension.
Reticuloendothelial system of the spleen and liver
removes the coagulation products. FDP are inhibitors of
both plasma and platelets and they also require the RE
system for their removal. There is evidence that the
neonate is functionally hyposplenic, which delays the
clearance of activators and fibrinogen degradation
products. In addition blood flow is responsible for
transportation of these products from the site of
generation to the RE system and the fibrin inhibits flow
of blood. This is further complicated by the presence of
polycythemia and shock.
AT-III is the main inhibitor of thrombin and the levels
of AT-III in term babies are 30-50 percent of the adults.
But these are in concert with the levels of thrombin in
these children but in sick infants these may be woefully
inadequate.
848
Heparin cofactor II, which is responsible for

neutralization of nearly 30 percent of the thrombin
produced and its levels are also low as compared to the
adults.
2 macroglobulin is another inhibitor of thrombin and
its levels are at the adult level in the newborn and remain
elevated throughout infancy.
Protein C neutralizes activated Factor V and VIII and
it develops very late in the fetus and one may see levels
as low as 0.1 U/mL in the preterm babies and these levels
may be inadequate for neutralization of activated factors
V and VIII. The levels of protein C inhibitor are at the
adult levels in the newborn at term.
Protein S bound to platelet or endothelial cell
membrane is able to accelerate the APC-mediated
neutralization of Factor Va and VIIIa to the tune of 10,000
times. This protein S is bound in the plasma to binding
protein of the C4b and is unable to participate in the
above reaction but in the neonate almost all the protein
S is in the free form as compared to the adults where
nearly 60 percent are bound, and this is because of the
extremely low levels of C4b-p.
The neutralization of the coagulation proteases occurs
primarily on the endothelial surfaces. The complex of
AT-III with thrombin is catalysed by heparin like
substances, on the other hand the complex of heparin
cofactor-II with thrombin is promoted by dermatin
sulfate. Thrombomodulin accelerates the activation of
protein C by 20,000 times. Placenta is a rich source of
thrombomodulin. Prostacyclin produced by the
endothelial cells inhibits the platelets. Nothing much is
known about the role played by endothelial cells in the
neonates.
In the neonates the levels of plasminogen are about
50 percent of the adult levels and in the preterm baby
they are 30 percent of the adult levels. The protein which
binds the plasminogen is low in the neonate and thus
almost all the plasminogen is in the active form 2
macroglobulin is at the adult levels and remains so
throughout. Plasminogen activator inhibitor type 1
(PAI-1) are elevated in the cord blood.
Clinical conditions associated with DIC In the neonate:
Bacterial infection esp. septicemia is the most common
entity associated with DIC. Clinically, DIC occurs in
settings of severe hypoxia and acidosis with inadequate
perfusion and tissue necrosis.
Obstetric complications
Abruptio placentae
Placenta accreta
Chorioamnionitis
Fetal demise of one twin
Pre-eclampsia
Ac. fatty liver of pregnancy
Neonatal Viral Infections
Rubella
Herpes
Cytomegalovirus
Enterovirus
Systemic Candidiasis
Gram negative organisms
Hypoxia and hypoperfusion
Shock with poor perfusion and lactic acidosis
Preterm babies with RDS
Massive thrombosis
Babies with severe liver disease
Kasabach-Merritt syndrome
Placental chorioangiomatous malformations
Massive hemolysis
Nonimmune hydrops fetalis
Severe cold stress
Infections: It represents the single largest at-risk group,

presents as the most florid manifestation of the condition
and is responsible for the high mortality of these
conditions. The Waterhouse-Friderichsen syndrome,
with bleed in the adrenal is one of the most feared
outcomes of this condition, resulting in acute circulatory
collapse. Gram-negative bacteria are more frequently
associated with this complication than gram-positive.
DIC occurs in patients with infections due to specific
cell membrane components of the microorganisms
(lipopolysaccharide or endotoxin) and bacterial exotoxin
(e.g. staphylococcal toxins). All these components result
in a generalized inflammatory response characterized by
the systemic release of cytokines.
The mortality associated with DIC complicating
infection remains high, and its management remains
controversial. It is sobering that although one of the
fundamental principles of treating DIC is to address and
control the primary condition, despite the enormous
advances with regard to the availability of potent and
specific antibodies, the mortality remains high and does
not appear to have shown substantial improvement over
the years.
Trauma: Severe trauma leading to release of tissue
material into the circulation (fat and phospholipids),
hemolysis and endothelial damage may lead to systemic
activation of coagulation leading to DIC.
Tumors: Factors expressed on the surface of the tumor
cells may be responsible for DIC in cases of both solid
and hematologic malignancies, e.g. in APML there is a
severe hyperfibrinolytic state in addition to an activated
coagulation system.
Obstetric Accidents: The presentation may vary from the
acute fulminating and devastating hemorrhage associated with amniotic fluid embolism to the more chronic
presentation associated with the dead fetus syndrome.
Placental abruption and amniotic fluid embolic may also cause
DIC: Vascular disorders like aortic aneurysms or giant
hemangiomas (Kasabach-Merritt syndrome) or chorioangiomatous malformations may result in local activation
of coagulation. Activated coagulation factors can
ultimately overflow into the systemic circulation and
cause DIC, but more commonly, systemic coagulation
factors and platelets become depleted as a result of local
consumption.
Incidence and Clinical Relevance of DIC Frequency: In the
US: Approximately 18,000 cases of DIC occurred in 1994.
DIC may occur in 30 to 50 percent of patients with sepsis.
Mortality/Morbidity: Morbidity and mortality depend on
both the underlying disease and the severity of coagulopathy. Assigning a numerical figure for DIC-specific
morbidity and mortality is difficult. Following are
examples of mortality rates in diseases complicated by
DIC:
Idiopathic purpura fulminans associated with DIC
has a mortality rate of 18 percent.
Septic abortion with clostridial infection and shock
associated with severe DIC has a mortality rate of 50
percent.
In the setting of major trauma, the presence of DIC
approximately doubles the mortality rate.
Due to the ambiguity of the definition and the lack of
clear-cut diagnostic criteria the incidence of DIC cannot
be evaluated. In virtually all patients with gram-negative
septicemia diffuse activation of coagulation is detectable
with sensitive assays of coagulation factor activation
clinically, overt, DIC, however with a decrease in platelet
count, consumption of coagulation factors detectable
soluble fibrin and fibrin degradation products can be
found in 30 to 50 percent of consecutive series of patients.
In fact, clinically overt DIC is as common in Gram
849
septicemia as in Gram negative septicemia.

Severe trauma with inflammatory response was
associated with DIC in 50 to 70 percent of cases. This is
closely related to the disease severity scores.
Giant hemangiomas are associated with clinically
significant DIC in upto 25 percent cases.
The findings in DIC are dependent on the rate and
amount of thrombin generated as well as the bodys
capacity to remove the activated products of coagulation,
the capacity of the inhibitory proteins to neutralize
coagulation enzymes, the activation of fibrinolysis to
remove the intravascular fibrin strands and the rate of
production of the platelets and clotting factors.
The clinical importance of severe depletion of
platelets and coagulation factors in patients with diffuse,
widespread bleeding or in patients who need to undergo
an invasive procedure is indisputable, but to what extent,
intravascular deposition of fibrin, due to systemic
activation of coagulation, contributes to organ failure and
mortality is not certain.
CLINICAL PRESENTATION
Disseminated intravascular coagulation is an intermediary mechanism of disease an epiphenomenon and
as such the signs and symptoms will also depend on the
antecedent disease. There is a strong association with
infection which accounts for 70 percent of the cases
diagnosed in the neonates. The clinical presentation may
vary in relationship to the primary condition.
Physical
Circulation
Signs of spontaneous and life-threatening
hemorrhage
Signs of subacute bleeding
Signs of diffuse or localized thrombosis
Nonspecific altered consciousness/stupor
Focal deficits not usually present
Cardiovascular system
Hypotension
Tachycardia
Circulatory collapse
Respiratory system
Pleural friction rub
Signs of adult respiratory distress syndrome
(ARDS)
850
Gastrointestinal system
Hematemesis
Hematochezia
Genitourinary system
Signs of azotemia and renal failure
Hematuria
Oliguria
Metrorrhagia
Uterine hemorrhage
Dermatologic system
Petechiae
Purpura
Hemorrhagic bullae
Acral cyanosis
Skin necrosis of lower limbs (purpura fulminans)
Localized infarction and gangrene
Wound bleeding and deep subcutaneous
hematomas
Thrombosis (Fig. 15.13.1)
General Considerations
In evaluating a patient with clinical and laboratory
evidence of DIC, a judgment must be made as to whether
the condition is:
1. Acute or chronic
2. Systemic or localized
3. The fibrinolytic activity is a primary or secondary
manifestation of the condition.
The importance of defining the condition as acute
versus chronic relates to the urgency of management
decision-making and is usually a priority in the patient
presenting with laboratory rather than clinical evidence
of the condition. Although a significant number of
patients with sub-clinical acute DIC will show
spontaneous reversal, it is individuals in this group who
may show the most gratifying response to rapid
confirmation of the diagnosis and urgent institution of
DIC may be localized to an organ such as the kidney.
Although laboratory testing may provide systemic
evidence of the condition, the pathological effects may
be confined locally and the therapeutic approach may
be optimally directed to this, e.g. aortic aneurysm and
cavernous hemangiomas. The systemic effects may be
profound and some individuals may develop major
evidence of consumption of platelets and coagulation
factors and develop life-threatening hemorrhage.
Activation of the fibrinolytic system occurs leading
to the appearance of split products.
No single laboratory test or combination of tests is
available that is sensitive or specific enough to allow a
definite diagnosis. However, the diagnosis can reliably
be made without ambiguity by taking into consideration
the underlying disease in combination with the
laboratory findings.
Because DIC is a continuously progressing process,
it can be subdivided into three phases that might be
helpful in making the diagnosis and in treating the
patient.
Phase I: Compensated Activation of the
Hemostatic System
Figure 15.13.1: Child with DIC
During this phase, no clinical findings are observed, but

the underlying disease may raise suspicion for the
occurrence of DIC. Under these circumstances, tests
should be performed to demonstrate the activation of
coagulation (Table 15.13.1).
Phase II: Decompensated Activation of the
Hemostatic System
In contrast to phase I, the prothrombin time (PT) and the
activated partial thromboplastin time (aPTT) are
prolonged. Under these circumstances, the thrombin
time may still be normal, as the fibrinogen levels are still
adequate and the level of fibrinogen degradation
products (FDPs) is not very high. In this phase, frequent
analyses are necessary to demonstrate the dynamics of
the intravascular coagulation process. In phase II,
repeated determinations will demonstrate a continuous
drop in platelet count and in fibrinogen concentration
and coagulation factor activities, especially factor V
activity (Table 15.13.1).
851
Phase III: Full-Blown DIC

Full-blown DIC is characterized by an extremely
prolonged, or even unclottable, PT and aPTT. Frequently,
the thrombin time is significantly prolonged or also
unclottable. During this phase, the platelet count is very
low, and the coagulation factor activities are less than 50
percent of normal. The continuous transition from phase
I to phase II or even to phase III is typical for DIC. If, in
the course of DIC, hemolysis and/or schistocytes are
observed, this indicates that microclot formation is
causing red blood cell damage.
For the laboratory evaluation of DIC, it is important
to discriminate between an approach directed at:
TABLE 15.13.1: Phases and laboratory data of acute DIC

Phases
Phase I: Compensated Activation of the Hemostatic System
Clinical findings:
No symptoms
Laboratory analysis:
No measurable consumption of hemostasis components
Increased levels of activation markers
Increased levels of enzyme-inhibitor complexes
Phase II: Decompensated Activation of the Hemostatic System
Clinical findings:
Bleedings from injuries and venous puncture sites, as well as
decreased organ function (e.g. kidneys, lung, liver).
Continuous decrease in platelet count and coagulation factors
Continuous increase in activation markers
Continuous increase in enzyme-inhibitor complexes
Phase III: Full-blow DIC

Clinical findings:
Skin bleedings of different sizes, as well as multi-organ failure
Clearly expressed consumption of hemostasis components
PT: Prothrombin time

APTT: Activated partial thromboplastin time
F1+2: Prothrombin fragment F1+2
Laboratory data
PT, APTT, thrombin time: Within normal limits

Platelet count: Within normal limits; F1+2, TAT: Elevat
Antithrombin: Slightly decreased; Soluble fibrin; +
PT, aPTT: Prolonged or increasing prolongation,

respectively
Thrombin time: Mostly within normal limits,
but sometimes prolonged
Platelet count, fibrinogen concentration, coagulation
factor activities, antithrombin: Decreased or continuously
decreasing; F 1+2, TAT, FDPs: Clearly increased; Soluble
fibrin: Increased fibrin degradation products
PT, aPTT: Extremely prolonged or unclottable

Thrombin time: Very pronounced prolongation or
unclottable. Platelet count: Very diminished (<40% of the
initial value) fibrinogen, antithrombin, and coagulation
factor activities: Very decreased (<50% of the initial values)
F1+2, TAT, FDPs: Clearly increased; soluble fibrin: Increased
TAT: Thrombin-antithrombin complex
FDPs: Fibrin degradation products (including D-dimer)
852
1. Formation of a data base that confirms or improves

our understanding of the pathogenetic factors
involved in DIC.
2. Forming the diagnosis of DIC in an individual patient
with particular reference to the source of the
procoagulant stimulus in a given primary condition.
3. Monitoring the progress/severity of the condition
with particular reference to the response to
The best approach is to rely on the classical screening
tests, i.e., the activated partial thromboplastin time
(APTT), the prothrombin time (PT), the thrombin time
(TT), platelet count, FDP or D-Dimer and peripheral
blood smear examination. The one stage PTT is a sensitive
indicator of clotting factor deficiency. Thrombocytopenia
is a primary feature of the vast majority of patients with
DIC and in approximately 50 percent the count will be
less than 50 109/liter. Given the accuracy and facility
of modern particle counters, this test is one of the most
useful screening tests available except in those patients
with conditions such as leukemia where other factors
may be involved. Classically, the microangiopathic blood
picture and the associated anemia have been considered
hallmarks of the condition. It should be realized,
however, that this is a relatively non-specific finding that
is frequently seen in the primary conditions associated
with the risk of developing DIC, e.g. Kasabach-Merritt
syndrome, vascular protheses, etc. without DIC actually
being present.
It should be emphasized that normal findings do not
exlude a significant consumptive process. For example,
in pregnancy, a normal PTT and TT does not exclude
significant consumption of clotting factors such as factor
VIII and fibrinogen due to the substantial elevation of
these factors during the final stages of normal pregnancy.
Fibrinogen and Fibrinogen
Degradation Products
If the first laboratory analysis is done in phase II of the
disease, fibrinogen concentration, as well as FDP
concentration, should always be determined, in addition
to the screening tests mentioned here. This is important
because elevated FDP titers in combination with
thrombocytopenia and a decrease in clotting factor
activities allow the diagnosis of DIC (Table 15.13.2). An
increased FDP level is almost always seen from the
beginning of DIC when fibrinolysis is activated, whereas
in the advanced course of DIC fibrinolysis may be
exhausted or even inhibited. If, in the beginning of

suspected DIC, FDPs are not elevated, one can reliably
exclude DIC because experience has taught that
activation of fibrinolysis is almost always present in
patients with DIC.
Single Factor Determinations
Plasma Factor Activities, Antithrombin, and Plasminogen
Activity: If, in addition to pathologic screening test results,
the activities of these factors and inhibitors are below 50
percent of normal, acute or high-grade DIC can be
assumed. On examining the relationship between
outcome of DIC patients and hemostasis parameters,
antithrombin activity, protein C levels, plasminogen
activity PAP complexes, and PAI-I activity were related
to outcome.
Indicators of Activation of Coagulation
Activation markers: FPA, F1+2, soluble fibrin, and
thrombin
Anti-thrombin Complexes
The dynamics of DIC can be judged by measuring the
activation markers, such as fibrinopeptide A (FPA),
prothrombin fragment F1+2, and soluble fibrin, although
these tests may not be immediately available in the
routine laboratories. These three markers indicate the
generation of thrombin and the effect of thrombin on
coagulation factors. Because coagulation can take place
extravascularly, such as in pneumonia or periotonitis,
FPA and F1+2 are not specific parameters for the
diagnosis of DIC. In contrast, soluble fibrin in plasma
can only be generated intravascularly and, thus, it
represents a specific test for the diagnosis of
hypercoagulability. A drawback may be that useful FPA,
F1+2 and soluble fibrin measurements are very much
dependent on optimal venous puncture. Relatively easy
to perform is the determination of thrombinantithrombin (TAT) complexes which, similarly to the
mentioned activation markers indicate thrombin
generation.
Indicators of Fibrinolysis Activation
Fibrinogen Degradation Products, D-dimer, 2-antiplasmin,
and Plasmin-Antiplasmin Complexes
FDP is an important parameter to be determined for
making the diagnosis in combination with other assays.
In recent years, it has been shown that D-dimer tests are
more sensitive than the FDP assays and that normal Ddimer levels have a high negative predictive value for
the presence of intravascular fibrin degradation. Since
fibrinogen is also degraded extravascularly, an elevated
FDP or D-dimer level does not prove intravascular
fibrinolysis. Because FDPs are metabolized by the liver
and secreted by the kidneys. FDP levels are influenced
by liver and kidney function. Different FDP assays,
including D-dimer tests, are commercially available and
measure different subpopulations of FDPs. These assays
are not specific for a certain type of FDP because the
different FDP populations form complexes with each
other and even with soluble fibrin. As extreme hyperfibrinolysis does not occur until circulating 2-antiplasmin has been depleted, the determination of 2antiplasmin is helpful for judging the dynamics of
fibrinolysis.
The Disseminated Intravascular
Coagulation Score
A relatively precise, but somewhat tedious, DIC score
was proposed by the Japanese Working Party on DIC in
1988 and published as a modification in 1995. The score
is a compilation of varied points given to changes of the
PT ratio, fibrinogen concentration, FDP concentration,
platelet count and symptoms of bleeding and organ
failure due to microthrombosis.
MANAGEMENT
Acute Disseminated Intravascular Coagulation
As DIC usually complicates other pathologies, it is
important to recognize and institute appropriate
therapeutic measures directed at the primary disease as
well as basic life support consideration such as find and
electrolyte balance, adequate oxygenation, etc.
Fundamental to the management of the complicating
DIC is the implementation of aggressive therapy directed
at forestalling or eradicating the primary pathology as
the source of the procoagulant stimulus. For example,
institution of appropriate antibiotic therapy in specific
infections may bring about a spontaneous reversal of the
DIC process without additional therapy directed at DIC
itself.
Removal of the products of conception in obsteric
accidents. In those patients where the primary pathology
is not so amenable to correction or where DIC continues
853
despite therapeutic measures directed at the DIC itself

will be required. The overall approach is to restrain and
eventually eliminate thrombin generation and replace
blood components whose deficiency might either
promote the hemorrhagic tendency or diminish the
physiological anticoagulant response in endogenously
regulating thrombin generation.
Replacement of factors V and VIII and fibrinogen
using fresh frozen plasma or cryoprecipitate is
clearly essential in the acutely bleeding patient with
evidence of major consumption of these factors but this
may stoke the fire inferring that the hypocoagulable
state induced by DIC protects the individual from further
thrombin generation but this view is untenable.
Currently, opinion rests between either replacement as
the primary approach or replacement after initiating
anticoagulant therapy. In the latter, anticoagulation is
instituted only in those patients where replacement alone
may be predictably inadequate or proves to be so as the
condition progresses. This may occur in association with
any of the known primary disease conditions where the
severity and rate of consumption is so great that it
becomes physically impossible to keep pace with
replacement, e.g. amniotic fluid embolism are classic
examples of this situation. Thus, heparinization is
reserved for selected patients esp. in those conditions where the thrombotic tendency appears to
predominate, such as purpura fulminans, the use of
heparin may be life-saving. This observation together
with the association of this condition with homozygous
deficiency of protein C system and suggests that the use
of protein C concentrates may assume a significant role
in the management of these conditions in the future.
Moreover, although optimal replacement would not be
achieved with the use of fresh frozen plasma alone, some
degree of replacement would be achieved which could
explain why, supplementation of replacement therapy
by heparin is not always necessary despite theoretical
predictions to the contrary.
The overall goal of therapy is to remove the source of
the procoagulant stimulus. There is potential for
controlling the coagulant response by the use of
therapeutic concentrates of physiological inhibitors such
as protein C and tissue factors pathway inhibitor (TFPI).
Furthermore, as our knowledge of the basic mechanisms
of hemostasis improves and with better supportive care
occurring in the intensive care setting, infection control,
etc. more and more patients are likely to be saved.
854
Unfortunately, the comments that the letters DIC could

be taken as standing for Death Is Coming is not an
unreasonable reminder of the progress that remains to
be made in our understanding and management of this
not uncommon condition.
Drotrecogin alfa (Activated Protein C) has been used
in adults with a marked reduction in mortality. The dose
used is 24 microgms/kg/hr for 96 hr continuous
intravenous infusion and is provided as 5 mg and 20 mg
vials and concentration should be 100 to 200 mg/mL.
Chronic Disseminated Intravascular Coagulation
and Primary Fibrinolysis
This condition is rarely if ever seen in the neonatal and
the pediatric period.
CONCLUSIONS
Disseminated intravascular coagulation (DIC) is not a
clinical entity in itself. Instead, it always occurs secondary
to a broad spectrum of various diseases. DIC may be
defined as an acquired syndrome characterized by the
activation of intravascular coagulation up to
intravascular fibrin formation. The generation of soluble
fibrin in plasma is the prerequisite for microclot
formation, which contributes to multiple organ failure.
The massive and ongoing activation of coagulation may

result in the depletion of platelets and coagulation factors.
Activation of the fibrinolytic system may cause
proteolysis of plasmatic coagulation factors, as well as
generation of FDPs inhibiting fibrin polymerization and
platelet aggregation. Thus, intravascular coagulation, as
well as hyperfibrinolysis, result in a hemorrhagic
diathesis (consumption coagulopathy).
The diagnosis of DIC is based on the presence of an
underlying disease and a combination of laboratory tests
that indicate activation of the coagulation system, soluble
fibrin formation, and consumption of platelets and
coagulation factors. At present, no single laboratory test
is available to definitively assess the presence or absence
of DIC, but the combination of clinical findings and
laboratory analysis allows one to make the diagnosis and
differentiate three phases of DIC:
Phase II-decompensated activation of the hemostatic
system;
Phase III-full-blown DIC. There is a need to have a
test available which specifically and quantitatively
measures soluble fibrin, as the demonstration of soluble
fibrin in plasma early in the disease process would allow
prophylactic treatment of the patients in order to prevent
microclot formation and bleeding complications.
15.14 Bleeding Disorders in the Newborn

Jayashree A Mondkar,
Mamta Manglani, Armida Fernandez
Bleeding is a frequently encountered medical emergency
in the newborn. Newborn babies, especially those who
are low birth weight or premature are particularly at risk
for bleeding due to immaturity of a number of
components of the hemostatic system.
Causes of Bleeding in the Newborn
I. Deficiency of vitamin K dependent clotting factors
A. Hemorrhagic disease of the newborn (HDN) now
more appropriately termed "vitamin K deficiency
bleeding (VKDB)" occurs due to a transient
deficiency of the vitamin K dependent factors II,
VII, IX, X. Vitamin K is necessary for conferring
biological coagulant activity on these factors.

Though colostrum contains adequate amount of
vitamin K, lesser colonization by bacterial flora
of the gut of exclusively breastfed infants that are
necessary for synthesizing vitamin K, contributes
to a lower plasma level of vitamin K. Lower
concentration of vitamin K in breast milk also
further contributes to VKDB. Bleeding classically
occurs between day 2-7, in a well baby. Presenting
features include hematemesis, hemtochezia,
hematuria or hematoma at the site of trauma.
B. Early onset (<24 hours) and late onset VKDB>2
weeks) are also known to occur in certain
predisposed babies.
Maternal anticonvulsant therapy with phenytoin or
phenobarbitone, anticoagulant therapy with warfarin can
aggravate VKDB and can cause an early onset of
bleeding, an entity known as early VKDB or early HDN.
A rare late form also occurs in breastfed infants after
the 1st 2 weeks of life, especially if prolonged antibiotics
have been used. It is also seen in babies with prolonged/
recurrent diarrhea.
II. Inherited factor deficiencies
Afibrinogenemia, hypofibrinogenemia, factor VIII, IX
and von Willebrand's disease, factor XIII deficiency and
factor II (prothrombin) deficiency may present in the
neonatal period.
III. Thrombocytopenia
In normal neonates, the platelet count usually is 1.5 to 4
lac/cu.mm. Thrombocytopenia can be confirmed when
platelet count is less than 1 lac/cu.mm, although
spontaneous bleeding seldom occurs until the count
drops to <40,000 cells/cu.mm, unless there are other
confounding factors such as prematurity, sepsis, etc.
A. Neonatal alloimmune thrombocytopenia (NAIT):
This condition is similar to hemolytic disease of
the newborn and results from transplacental
passage of maternal specific IgG antiplatelet
antibodies from a platelet antigen negative,
sensitized mother. Petechiae, GI bleeds, hematuria
and occasionally intracranial hemorrhage (ICH)
may be the presenting features.
B. Autoimmune neonatal thrombocytopenia occurs
in babies due to passive transfer of IgG platelet
autoantibodies from mothers who have idiopathic
thrombocytopenic purpura, systemic lupus
erythematosus, etc.
C. Infections: Congenial viral infection especially
cytomegalovirus and rebella may cause
thrombocytopenia. Spirochetal infections,
toxoplasmosis, bacterial infections especially gram
negative septicemia also produce bleeding due to
thrombocytopenia.
D. Maternal drugs such as anticonvulsants,
antihistaminics, tolbutamide, etc. also cause
thrombocytopenia.
E. Bone marrow infiltration by leukemia, histiocytosis X and metastatic neuroblastomas can also
produce thrombocytopenia.
855
F. Thrombocytopenia is also associated with

syndromes like thrombocytopenia with absent
radii (TAR).
IV. Platelet functional disorders with normal count can
also cause hemorrhage in the newborn.
A. Glanzmann's thrombasthenia, Storage Pool
Disease and Bernard Soulier Syndrome are some
of the common inherited platelet functional
disorders. These are diagnosed if a direct (non
EDTA) peripheral blood smear shows absence of
platelet clumps with near normal counts. In
Bernard Soulier syndrome, large sized (giant)
platelets are seen on peripheral blood smear.
B. Salicytes, NSAIDs and thiazine diuretics affect
platelet function. Drugs like aspirin, indomethacin, and carbenicillin can also cause
acquired platelet dysfunction.
V. Disseminated Intravascular Coagulation
Due to hypoxia, acidosis or placental causes
(chorioangioma), dead twin, abruption placentae, gram
negative sepsis, severe asphyxia, shock renal vein
thrombosis may also present with bleeding in a neonate.
Approach to Diagnosis
Diagnosis can be reached as per the clinical approach in
a bleeding neonate as elucidated in Table 15.14.1A,
followed by specific investigations and their interpretation as shown in Table 15.14.1B.
Investigations
Apt.test : It is carried out to distinguish swallowed
maternal blood from neonatal gastrointestinal bleed.
1 part of vomitus is centrifuged with 5 parts of water for
1 minute at 2000 rpm. 1 ml of 1% NaOH is then added to
4 ml of the supernatant. Resistant pink color of the
solution indicates the presence of fetal blood.
Other Routine Tests
Every neonate who presents with bleeding should
undergo the following tests: platelet count, prothrombin
time (PT), activated partial thromboplastin time (aPTT).
Tests such as bleeding time and clotting time are not
sensitive and do not help in reaching a diagnosis.
856

TABLE 15.14.1A: Clinical approach in a bleeding neonate
Condition
I.
II.
III.
III.
Interpretation
Maternal History
1. Antenatal infections (TORCHES & HIV)
2. Drug ingestion: Phenytoin,
Phenobarbitone, aspirin, warfarin
3. H/O bleeding in mother: ITP, SLE
Family History
Bleeding in other sibling
Present History
1. Birth History
Birth asphyxia, acidosis, shock
Day 1 bleeding
Thrombocytopenia
Early onset of VKDB
Thrombocytopenia
Inherited coagulation, platelet disorder
DIC
Early VKDB Afibrinogenemia,
Hypofibrinogenemia
Factor XIII deficiency, DIC
Classic VKDB
Day 2- Day 6 bleed

GI bleed, LBW baby.
Not received Vit K
At brith. Exclusive breastfeeding
Site of Bleeding
GIT
Mucosa, Skin
Umbilicus
Postsurgery, from wound site
Swallowed maternal blood, VKBD

Thrombocytopenia, trauma, DIC
Factor I, XIII deficiency
Inherited clotting factor disorder
TABLE 15.14.1B: Differential diagnosis of bleeding in neonate: Laboratory profile
Sick neonate
Well neonate
Platelet count
PT
aPTT
Diagnosis
Decreased
Decreased
Prolonged
Normal
Prolonged
Normal
DIC
Platelet consumption, hypoxia, sepsis,
necrotizing enterocolitis, renal vein thrombosis
Normal
Normal
Normal
Prolonged
Prolonged
Normal
Prolonged
Prolonged
Prolonged
Liver disorder
HDN
Herditary clotting factor VIII, IX, XI, XII deficiency
Normal
Decreased
Normal
Prolonged
Normal
Normal
Normal
Normal
Normal
F VII deficiency
Immune thrombocytopenia, occult infection
Bleeding due to local factors trauma, anatomic
abnormalities, qualitative platelet abnormality,
factor XIII deficiency
Other Specific Tests
Management
I. Fibrin spilt products with values greater than the

kit specific cut-off indicate DIC. However, D-dimers
are more specific and available today.
II. Qualitative function tests for platelets: Aggregation
with various agonists test the function of platelets.
III. Specific factor assays.
Appropriate management of an infant with a

hemorrhagic disorder is dependent on the correct
identification of the hemostatic defect and replacement
of the component found to be deficient. Platelet
transfusions, coagulation factors in the form of specific
factor concentrates, fresh frozen plasma (FFP), crypreci-
857
TABLE 15.14.2: Therapy for acquired hemostatic defects in the newborn

Indications
Product
Dosage
Thrombocytopenia
Platelet
Concentrate
1 pack/5kg will raise platelet

count by 75-100 x 103/cu.mm
Coagulopathy
Fresh Frozen
10-15 ml/kg will raise factor
(DIC, Liver disease)
Plasma
level by 10-15 units/kg.
Severe fibrinogen deficiency
Cryoprecipitate
1 pack/3 kg will raise

fibrinogen level to > 60 mg/dl
pitate, etc. are used depending upon the diagnosis. Table

15.14.2 summarizes the therapies needed in the
management of these disorders.
platelet counts in fetal blood are less than 50,000/

cu.mm.
VKDB: Parenteral vitamin K in the dose of 1 mg is given

initially IV or SC. Intra-muscular route is avoided as
hematomas may form. This dose can be repeated after
6-8 hours, if bleeding continues. Fresh frozen plasma
10-15 cc/kg may be given if severe bleeding occurs. This
may be repeated 12 hourly if necessary. If Hb is less than
13 gm/dl, packed red cells need to be Given. VKDB can
be prevented by administering 1 mg vit K, IM to every
newborn in the labor room.
Bleeding due to inherited deficiency of factor VIII or
IX, is managed by use of factor concentrates. For severe
von Willebrand's disease, vWF containing factor VIII
concentrates should be used. Cryoprecipitate is the best
concentrated source of fibrinogen or factor XIII. For other
factor deficiencies, FFP will transiently raise the factor
levels.
Post Natal Management of Neonatal Thrombocytopenia
DIC: Treat the underlying cause, i.e. appropriate

antibiotics in sepsis, correction of acidosis, hypoxia.
Replacement therapy may be given with fresh frozen
plasma (FFP) 10-15 cc/kg every 12 hourly. Platelet transfusions may be required if counts are less than 40,000/
cu.mm.
Thrombocytopenia due to Maternal ITP
Antenatal Management
I. High dose immunoglobulins may be of some use as
they cross the placenta after 32 weeks gestation.
(Prednisolone: 10-20 mg/day, two weeks prior to
delivery may be given.
II. Intrapartum fetal platelet count from scalp vein may
be done and delivery by cesarean section is done if
Platlet counts are monitored and infant is treated with

intravenous immunoglobulins. Corticosterioids
may need to be considered if there is poor response to
IVIG.
Isoimmune Thrombocytopenia
Maternal steroids are not helpful. Elective cesarean
section is indicated if fetal scalp platelet counts are less
than 50,000/cu.mm. Intravenous immunoglobulins have
been tried. In severe cases, with platelet count below
30,000, washed and preferably irradiated maternal
platelets or platelets from other known specific platelet
antigen negative donors is indicated. In infants with
platelet counts between 30,000 to 50,000/cu. mm,
intravenous IgG in a dose of 1 gm/kg/day for two
consecutive days may be used.
BIBLIOGRAPHY
1. Al Mofada S M, Osman M, Kides E, et al. Risk of thrombocytopenia in the infants of mothers with idiopathic
thrombocytopenia. Am Perinatol 1994;11:423-26.
2. Ballin A, Andrew M, Ling E, et al. High-dose intravenous
gammaglobulin therapy for neonatal autoimmune
thrombocytopenia. J Pediatr 1988;112:789-92.
3. Bauer K. Rare hereditary coagulation factor abnormalities. In: Nathan DG, Orkin SH, Ginsburg D, Eds.
Hematology of infancy and childhood. WB Saunders,
2003;1577-96.
4. Blanchette VS, Johnson J, Rand M. the management of
alloimmune neonatal thrombocytopenia. Baillieres Best
Pract Res Clin Haematol 2000;13:365-90.
5. Bussel JB: Alloimmune thrombocytopenia in the fetus
and newborn. Semin
858
6. Montgomery RR, Gill JC, Scott JP. Hemophilia and von

Willebrands disease. In: Nathan DG, Orkin SH,
Ginsburg D, Eds. Hematology of infancy and childhood.
Philadelphia: Hematology of infancy and childhood
Philadelphia: WB Saunders, 2003;1547-76.
7.
8.
9.
Poncz M. Inherited platelet disorders. In: Nathan DG,

Orkin SH, Ginsburg D, Eds. Hematology of infancy and
childhood. Philadelphia: WB Saunders, 2003;1527-46.
Thromb Hemost 2001;27:245-52.
Turner T. Treatment of premature infants with abnormal
clothing parameters, Br J Hematol 1981;47:65.
15.15 Hematopoietic Growth Factors

Purvish M Parikh, MR Lokeshwar
Hematopoiesis is a complex process with a simple

underlying concept. A finite population of self-renewing
pleuripotent stem cells in the bone marrow generate the
entire spectrum of mature blood cells [erythrocytes,
platelets, granulocytes (neurophils, eosinophils, basophils), monocytes/macrophages and lymphocytes]. This
production of 3.5 1011 cells/day under the control of a
variety of hematopoietic growth factors which intricately
regulate the process of hematopoiesis.
Hematopoietic growth factors are glycoproteins that
promote growth and differentiation of blood cells by
activating specific receptors expressed on the surface of
blood progenitor cells (Fig. 15.15.1).
HEMATOPOIETIC FACTOR STIMULATING
RBC PRODUCTION
Erythropoietin
Erythropoietin, a glycoprotein produced primarily by the
kidney regulates production of red blood cells. It acts
through EPO receptor (EPO-R). The gene for EPO is on
chromosome 7(pter-q-22) and the gene for EPO-R is on
chromosome 19(p). EPO stimulates proliferation of
mature brust-forming units erythroid (BFU-E) and
colony forming units erythroid (CFU-E). EPO leads to
increase in DNA synthesis in BFU-E and increase in Hb
synthesis in CFU-E. EPO also maintains viability of CFUE and allows them to bypass apoptosis. The normal
human serum erythropoietin level is 5 to 32 m U/ml.
Recombinant human erythropoietin (rHuEPO) for
clinical use is available as erythropoietin alpha (epoetin
alpha) and erythropoietin beta (epoetin beta).
Figure 15.15.1: Hematopoietic growth factors and

cell lineages
Darbepoietin alfa (anaresp; also called novel

erythropoiesis stimulating protein) is a new long-acting
erythropoietin, with a half-life 3 times longer than the
old epoetins. Its recommended dose is 0.25 to 1.5
microgram/kg once a week (suggested conversion index:
weekly erythropoietin dose/200 = weekly darbepoietin
dose) making it a very convenient administration
schedule. Hypertension is the only major side effect
reported.
Use of Erythropoietin
1. Chronic renal insufficiency: The anemia of chronic
renal failure is caused primarily by a deficiency of
EPO. 50 to 150 units/kg subcutaneously three times
a week is the recommended dosage. Iron stores must
be adequate for optimal response. Shunt thrombosis
2.
3.
4.
5.
6.
7.
8.
9.
and exacerbation of hypertension are important side

effects of rHuEPO in this patient population.
Zidovudine-induced anemia: Zidovudine (AZT)
causes direct bone marrow suppression and also
inhibits heme synthesis. The recommended dose is
100 U/kg thrice in a week for 8 weeks.
Anemia in cancer patients receiving chemotherapy:
HuEPO is useful in reducing transfusion requirements and maintaining hematocrit in patients with
multiple myeloma and those treated with cisplatin.
Anemia of prematurity: This is due to inadequate
EPO production by immature kidneys. rHuEPO (with
iron supplementation to all patients) in 241 such
patients showed that EPO group required less
transfusion (0.87 vs 0.25; p = 0.013). No transfusions
were required in 27.4% cases as compared to 4.1
percent of control group (p = 0.008). However, it may
take as much as 10 to 12 days before the Hb levels
start increasing. Hence high risk premature neonates
must be started on EPO as soon as possible.
Bone marrow transplantation: rHuEPO has been
shown to be of help in reducing transfusion requirements in autologous marrow transplantation.
Preoperative autologous donation: rHuEPO has been
used to stimulate hematopoiesis and increase the
volume of blood collected during autologous
donations. In the preoperative period its uses include
(i) in patients who are anemic and alloimmunized
where we might be unable to meet anticipated needs
(ii) to correct anemia in patients who refuse blood
transfusion (for religious reasons) and also to prevent
anemia in bone marrow donors who should not be
exposed to the risk of sensitization by allogenic blood.
Sickle cell anemia and thalassemia: Recombinant
human erythropoietin has been shown to increase the
production of fetal hemoglobin (HbF). This may be
of benefit in reducing sickling attacks and crises. In
thalassemia intermedia, increase in Hb has been
documented.
Myelodysplastic syndromes.
Other disorders: Anemia of chronic disease (like in
rheumatoid arthritis) has been successfully treated
with rHuEPO since these patients have elevated levels
of various cytokine (IFN gamma, TNF alpha, Il-1) that
prevent increase in EPO following hypoxic
stimulation.
859
HEMATOPOIETIC FACTORS STIMULATING

GRANULOCYTE PRODUCTION
GM-CSF and G-CSF
The gene for GM-CSF is located on the long-arm of
chromosome 5(5q21-32). Genes for IL-3, IL-4, IL-5,
macrophage CSF (M-CSF), C-fms (M-CSF receptor) and
an early growth response gene EGR-1 are also localized
to the long arm of chromosome 5. The GM-CSF gene
codes for a protein of 127 amino acids. The molecular
weight of the purified native human GM-CSF is 18,00022,000 daltons. The molecular weight of the recombinant
protein varies from 18,000 to 30,000 daltons. These
differences are due to glycosylation. The gene for G-CSF
is located on chromosome 17(q21-22). The native protein
contains 174 amino acids and has molecular weight of
18 to 22 kilodaltons depending on the extent of
glycosylation.
USES
1. Cancer chemotherapy induced myelosuppression:
They are established agent to hasten neutrophil
recovery post-chemotherapy and also to reduce
potential hematopoietic toxicity after more dose
intensive regimen.
2. Bone marrow transplantation: It is done for acceleration of myeloid recovery in autologous bone
marrow transplantation and for treatment of graft
failure.
3. Bone marrow failure syndrome: They have a limited
role in aplastic anemia, myelodysplastic syndromes
and congenital, cyclical, autoimmune and idiopathic
neutropenias.
4. Harvesting normal granulocytes for transfusions.
5. Kostmanns syndrome: It is a disease characterized
by decreased number of peripheral blood neutrophils
and arrested maturation of myeloid progenitor cells
due to a nonsense mutation in the gene for G-CSF
receptor.
6. Collection of peripheral blood progenitor cells.
7. Ex-vivo expansion of progenitor cells.
8. Infectious diseases.
Stimulation of neutrophil production can enhance the
inflammatory response and lead to a better outcome of
infection community acquired pneumonia, sepsis
syndrome and high risk preterm neonates.
860
The American society of clinical oncology has brought

out guidelines for optimal use of hematopoietic growth
factors (G-CSF). One important indication that is
understated is the potential lifesaving benefit of the use
of G-CSF in neonatal sepsis and premature neonates.
AdministrationDose and Route of
Administration, Side Effects
At the recommended doses of 5 to 10 microgram/kg (or
250 microgram/sq.M) both G-CSF and GM-CSF are well
tolerated. The commonest side effect is bone pain. Others
include skin rashes, lethargy and myalgia. A syndrome
of flushing, hypotension, tachycardia, dyspnea, nausea
and vomiting with arterial oxygen desaturation has been
described after the first injection and was found to be
reversed by oxygen and intravenous fluids. At doses >
20 g/kg per day. GM-CSF has been associated with
pleural and pericardial effusions, venous thrombosis and
pulmonary embolism.
Hematopoietic Factors Stimulating
Platelet Production
Thrombopoietin is a glycoprotein consisting of 353 amino
acids with a molecular weight of 30 KD. Its gene is located
on chromosome 3q27. Structurally, it has 46 percent
sequence similarity with human erythropoietin. It is
produced in the liver following a fall in the platelet count
the thrombopoietin levels rising maximally by 8 hours
and peaks at 24 hours. Circulating levels of
thrombopoietin are inversely related to platelet mass.
Platelets contain an avid thrombopoietin receptor that
efficiently binds and removes thrombopoietin from
circulation. Thus normal or elevated levels of platelets
inhibit the action of TPO on bone marrow by binding to
circulating TPO. It is important to remember that:
1. Platelet transfusions may blunt the recovery of
megakaryocytes
2. Other cytokines or disorders may modify the
constitutive hepatic production of thrombopoietin,
similar to reduced erythropoietin levels in renal
disease
3. Small molecules could be developed to decrease the
platelets clearance of thrombopoietin and in turn
stimulate platelet production
4. Disease related abnormalities in the platelets ability
to clear thrombopoietin may alter thrombopoietin
levels. For example, diminished clearance of
thrombopoietin by abnormal platelets may account

for the elevated platelet counts seen in myeloproliferative syndromes such as essential
thrombocythemia.
5. In conditions associated with marrow failure (e.g.
aplastic anemia), thrombopoietin levels are high
whereas in ITP thrombopoietin levels are low. Thus
TPO levels may be used for the differentiation of
thrombocytopenia due to bone marrow failure or
increased destruction.
Among the various hematopoietic growth factors,
thrombopoietin has got the longest half-life, i.e. 30 hours.
The platelet count begins to increase 3 to 5 days after
starting therapy. This is because thrombopoietin acts by
stimulating the production and maturation of
megakaryocytes.
Potential Clinical Uses of Thrombopoietin
1. Chemotherapy of solid tumors: Both rhTPO and
MDGF are effective in attenuating both the degree
and duration of thrombocytopenia.
2. Bone marrow transplantation:
3. Chemotherapy of acute leukemias: As severe
thrombocytopenia is routinely observed after
induction therapy of AML, TPO might be beneficial
in this setting.
4. Radiation therapy
5. Aplastic anemia and other bone marrow failure states
6. ITP and thrombocytopenia of HIV
7. Harvesting peripheral blood progenitor cells
8. Platelet apheresis (with a single dose of 3 g per
kilogram of body weight, the circulating platelet
count and yield increases by two to three times).
In addition to thrombopoietin, several other
recombinant cytokines (including interleukin-1, interleukin-3, interleukin-6, interleukin-11, granulocytemacrophage colony-stimulating factor, steel factor (SCF),
PIXY-321 and promegapoietin (interleukin-3thrombopoietin fusion protein) have some stimulatory
effects megakaryocytic cells. However, majority of these
cytokines have not had beneficial effects on platelet
recovery after myelosuppressive therapy or have had
serious side effects. Only interleukin-11 is approved by
FDA for chemotherapy induced thrombocytopenia. IL11(oprelvekin) is available as Neumega and its dose is
50 mg/kg/day for 10-14 days.
BIBLIOGRAPHY
1. Allen RC, Stevens PR, Price TH, Chatta GS, Dale DC. In
vivo effects of recombinant human granulocyte colonystimulating factor on neutrophil oxidative functions in
normal human volunteers. J Infect Dis 1997;175:1184-92.
2. Auerbach M, Ballard H, Trout JR, McIlwain M, Ackerman
A, Bahrain H, et al. Intravenous iron optimizes the
response to recombinant human erythropoietin in cancer
patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial. J Clin Oncol.
2004;22(7):1301-7.
3. Chatta GS, Price TH, Allen RC, Dale DC. Effects of in
vivo recombinant methionyl human granulocyte colonystimulating factor on the neutrophil response and
peripheral blood colony-forming cells in healthy young
and elderly adult volunteers. Blood 1994;84:2823-29.
4. Dale DC, Liles WC, Llewellyn C, Price TH. Effects of
granulocyte-macrophage colony-stimulating factor
(GM-CSF) on neutrophil kinetics and functions in normal
human volunteers. Am J Hematol 1998;57:7-15.
5. De Palo T, Giordano M, Palumbo F, Bellantuono R,
Messina G, Colella V, et al. Clinical experience with
darbepoietin alfa (NESP) in children undergoing
hemodialysis. Pediatr Nephrol. 2004;19(3):337-40.
6. Garcia-Carbonero, Mayordomo JI, Tornamira MV, et al.
Granulocyte colony-stimulating factor in the treatment
of high-risk febrile neutropenia: A multicenter randomized trial. Journal of the National Cancer Institute
2001;93:31-38.
7. Johnston E, Crawford J, Blackwell S, et al. Randomized,
dose-escalation study of SD/01 compared with daily
filgrastim in patients receiving chemotherapy. Journal
of Clinical Oncology 2000;18:2522-28.
861
8. Kaushansky K. Thrombopoietin. N Engl J Med 1998;339:

746-54.
9. Macdougall LC. Novel erythropoiesis stimulating
protein. Seminars in Nephrology 2000;20:375-81.
10. Molineaux G, Kinstler O, Briddell B, Harelty C, et al. A
new form of filgrastim with sustained duration in vivo
and enhanced ability to mobilize PBPC in both mice and
humans. Exp Hematol 1999;27:1724-34.
11. Ozer H, Armitage JO, Bennett CL, Crawford J, Demetri
GD, Pizzo PA, et al. Update of recommendations for the
use of hematopoietic colony-stimulating factors:
Evidence-based, clinical practice guidelines. J Clin Oncol
2000;18:3558-85.
12. Price TH, Chatta GS, Dale DC. Effect of recombinant
granulocyte colony-stimulating factor on neutrophil
kinetics in normal young and elderly humans. Blood
1996;88:335-40.
13. Quirt I, Micucci S, Moran LA, et al. Erythropoietin in the
management of cancer patients with non-hematologic
malignancies receiving chemotherapy (Practice
Guideline No. 12-1).
14. Rusthoven J, Bramwell V, Stephenson B, et al. Use of
granulocyte colony-stimulating factor (G-CSF) in patients
receiving myelosuppressive chemotherapy for the treatment of cancer. Cancer Prevention and Control
1998;2:179-190.
15. Turner KJ, Neben S, Weich N, Schaub RG, Goldman SJ.
The role of recombinant interleukin 11 in megakaryocytopoiesis. Stem Cells. 1996;14(Suppl)1:53-61.
16. Welte K, Gabrilove J, Bronchud MH, Platzer E, Morstyn
G. Filgrastim (r-metHuG-CSF): the first 10 years. Blood
1996;88:1907-29.
15.16 Transfusion Medicine and Component

Therapy in Pediatrics
RK Marwaha, Sudeshna Mitra, Deepak Bansal
Blood transfusions can be life saving. It is a precious
commodity in India, where the demand frequently
exceeds the amount that is collected. Blood transfusions
are not without risks and should be administered
judiciously, when genuine benefits are expected.
Advances in transfusion therapy have enabled
separation of whole blood into its component parts,
which can be transfused selectively depending on the
need of an individual patient and the underlying
condition. Thus blood component therapy meets specific
requirements and minimizes the risk of transfusion

related complications. The principles of preparations and
use of blood component derivatives are enunciated in
this chapter.
Blood components are prepared from single donations by
conventional blood bank methods (e.g. centrifugation
where blood components are separated due to differences in their relative densities). They require stringent
storage systems. Blood group compatibility between the
components and the patient is important. In contrast,
862
blood derivatives (e.g. factor concentrates) are prepared

from large pools of donor plasma by fractionation and
purification. They have more lenient storage requirements and are administered without regard to ABO
compatibility. More and more blood banks are now able
to provide small volume transfusion products for
children and neonates (e.g. pentavalent transfer bags)
with minimal wastage of blood inventory.
Blood Components and their Preparation
Whole blood is made up of cellular elements and plasma
which is further composed of protein, salts and water.
The cells are separated out from whole blood and from
one another by centrifugation techniques as depicted in
Figure 15.16.1.
Apheresis is a specialized procedure which removes
whole blood from the donor and separates it into
component parts by centrifugation (Figure 15.16.2). The
desired component is harvested and remainder returned
to the donor. The procedure allows selective collection
of platelets or granulocytes in sufficient amounts from a
single matched and ABO compatible donor.
Whole blood
Whole blood should be used when a patient requires
replacement of both circulatory volume and an increase
in oxygen carrying capacity. The specific indications for
transfusion of whole blood are enumerated in Table
15.16.1.
Previously whole blood was prescribed instead of a
specific blood component, a practice which did not serve
the purpose in most situations. Blood stored for >24 hours
at 2-6 C has few viable platelets and granulocytes. Labile
coagulation factors also decreased with time. Almost 90%
platelets and 40% factor VIII activity are lost within 24
hours at this temperature. This is in addition to the
complications associated with whole blood transfusions
especially after prolonged storage and when massive
transfusions are required. Stored blood contains citrate,
TABLE 15.16.1: Indications for transfusion of whole blood
Acute massive blood loss (>10ml/kg body weight in <24 hrs.

Exchange transfusion in neonates (<72 hrs old blood)
Cardiovascular bypass surgery
Hyperleucocytosis in leukemia
Figure 15.16.1: Component separation techniques
863
Preparation
Figure 15.16.2: Cell separator used for collection of specific

components from whole blood and/or plasmapheresis
TABLE 15.16.2: Complication of massive whole blood

transfusion
Platelet depletion
Coagulation factor depletion
Hypocalcemia; Hyperkalemia
Hypothermia secondary to transfusion of cold blood
Acidosis
Hyperglycemia
Respiratory distress syndrome
adenine and increasing levels of potassium. Correcting

the hypovolemia with crystalloids/colloids and attaining
the restoration of hemoglobin with packed red cells, is a
more judicious transfusion policy. The potential
problems after massive transfusions are enlisted in Table
15.16.2.
To prevent these complications, it is essential to
replenish labile clotting factors by fresh frozen plasma
(1 unit for each 3 to 5 units of whole blood) and platelets
(6 units of platelet concentrates for each 10 units of whole
blood). During exchange transfusion in neonates and
rarely in older children, whole blood transfusions may
lead to hypocalcemia due to citrate toxicity, which can
be prevented by intravenous administration of calcium
gluconate.
Packed Red Blood Cells
RBCs, the most frequently transfused blood component,
are given to increase the oxygen carrying capacity of the
blood in anemic patients who do not require restoration
of blood volume.
Packed RBCs are obtained from whole blood by

sedimentation or by heavy spin (i.e. centrifugation at
4000 g for 5 min) at 4C from 1 unit of blood (450 ml)
after expression of about 225- 250 ml of plasma, 1 unit of
packed RBC is obtained with a PCV of approximately
70%. It should be stored at 2-6C and has the same shelf
life as whole blood, provided PCV does not exceed 80%.
Removal of plasma decreases the amount of electrolytes
and ammonia, which is beneficial in patients with
incipient CHF, renal failure and hepatic failure.
Moreover, chances of allergic/ anaphylactic reactions
are minimized.
Each 8 ml/ kg of body weight of packed RBCs in
children and 3ml/ kg of body weight in infants is
expected to raise Hb by 1gm/dl and PCV by 3%.
Indications
Factors, other than the hemoglobin concentration that
must be considered in the decision to transfuse RBCs
include:
a. Signs, symptoms and functional cardiac capacity.
b. Manifest cardiorespiratory disease.
c. Cause and the anticipated course of the underlying
anemia.
d. Alternative therapies such as iron and recombinant
human erythropoietin (EPO). EPO reduces the need
for RBC transfusion and improves the overall
condition of children with chronic renal failure.
Packed Red Cell Transfusion in Neonates and
Young Infants
Guidelines for transfusing RBCs to neonates are
controversial, and practices vary. Generally, RBC
transfusions are given to maintain hemoglobin at an
optimal level, which would be decided on a case to case
basis. The quantum of RBC transfusion will depend on
the specific neonatal disorder.
Packed Red Cell Transfusion would be Indicated in
Neonates in the Following Situations
a. Hemoglobin <13.0g/dl in neonates <24 hours old.
b. Hemoglobin <13.0g/dl in neonates with severe
respiratory disease.
c. Hemoglobin <13.0g/dl in infants with congenital
heart disease severe enough to cause cyanosis or
congestive heart failure.
864
d. Hemoglobin <10.0g/dl in infants facing major

surgery.
e. Hemoglobin <8.0g/dl in clinically stable neonates
with clinical manifestations of anemia (poor weight
gain, tachycardia, tachypnea, recurrent apnoea).
f. Replacement of phlebotomy blood losses, milliliter
for milliliter not of proven benefit. RBC transfusion
recommended to maintain hemoglobin at a level
deemed appropriate for the clinical condition.
Packed Red Blood Cells In Older Children
Guidelines for RBC transfusions in older children and
adolescents are similar to those for adults. But
transfusions may be given more stringently to children
because normal haemoglobin levels are lower in healthy
children than in adults. Moreover, children have greater
ability to compensate for anemia and may be transfused
at lower hemoglobin or hematocrit levels. The most
frequent indications for packed RBC transfusion include
hematologic disorders like thalassemia, leukemia and
aplastic anemia.
1. In hemolytic anemia (e.g. thalassemia) life-long
transfusions are required. RBC transfusions are
initiated when Hb drops to <7g/dl. A hypertransfusion regimen, wherein Hb is maintained at
levels in excess of 9-10g/dl is widely practiced.
Leukocyte poor RBCs are recommended to minimize
transfusion reactions and can be attained by using
commercially available filters or by washing RBCs in
normal saline. A leukocyte filter used for
leukodepletion in multiply transfused patients is
shown in Figure 15.16.3.
2. Bone marrow failure syndrome: RBC transfusions are
recommended when Hb is <7 g/dl. They must be
sparingly used in case a bone marrow transplantation
is a feasible therapeutic option.
3. Malignancies: There is agreement that transfusions
are necessary when Hb is <7g/dl. Children with mild
anemia (Hb 9-12 g/dl) with no associated symptoms,
when recovery of counts is imminent, do not require
transfusion support. Transfusion should be given,
even in the absence of symptoms, during or following
an intensive cycle of chemotherapy or during
radiation therapy. Myelosuppression is predictable
in these situations.
4. In nutritional deficiency anemia the decision to
transfuse or not is made on a case to case basis. If the
diagnosis is correct, an increase in reticulocyte and
Hb level is observed within days of therapy. Children

with severe nutritional anemia with incipient or overt
manifestations of congestive cardiac failure need RBC
transfusion.
5. Significant preoperative anemia individual approach
is necessary; most children who do not have
cardiorespiratory disease, do not require Hb levels
of greater than 10g/dl before, during or after surgery.
6. Postoperative Hb <8g/dl with symptoms or signs of
anemia. Most children can quickly restore normal Hb
if given oral iron therapy and there should be a
compelling reason to administer a postoperative RBC
transfusion to a pediatric patient.
7. Hb <13g/dl in patients with severe pulmonary
disease, requiring assisted ventilation.
Children with high counts (>100 10 9 /L) and
superior mediastinal syndrome should not be transfused
till the general condition is stable.
Amount of Transfusion
The standard transfusion volume is 10 ml/kg. The
maximum that can be safely administered in one
Figure 15.16.3: Bedside leukocyte filter used for leukodepletion

in multiply transfused patients to minimize transfusion reactions
transfusion is 15 ml/kg and this too only if the patient is
hemodynamically stable. In severe anemia (hemoglobin
<5 gm/dl), child should receive multiple small
transfusions of 3-5 ml/kg over 3 hours separated by few
hours. The advantage of partial exchange transfusion is
that anemia is corrected rapidly and isovolemically. This
method is advisable when there is CHF.
Leukocyte-poor RBCs
Patients requiring multiple transfusions, (e.g.
thalassemics) are prone to develop antibodies against
antigens on leucocytes and platelets leading to nonhemolytic febrile reactions. Transfusion of leukocytepoor RBCs is recommended to minimize the risk of
transfusion reactions. The various techniques employed
to remove WBCs are as follows:
i. Kentrifugation (at 5000 g for 7 min) followed by
removal of plasma and buffy coat: (approximately
80% WBCs are removed).
ii. Filtration using microaggregate, cotton wool or
polyester filters at the time of transfusion or just
prior to issue from blood bank: (>99% WBCs are
removed).
iii. Washing RBCs in normal saline removes 85% WBCs.
It can be used with at least 5 washings in patients
with anti-IgA antibodies.
iv. Deglycerolizing frozen, thawed RBCs (98% WBCs
are removed). The procedure is, however, more
expensive.
PLATELET TRANSFUSIONS
Preparation
Platelet rich plasma (PRP) must be separated from whole
blood by light spin (2000 g for 3 minutes) at 20-24oC
within 6 hours of collection. The supernatant PRP is
expressed into a transfer bag to be used as such or for
processing to platelet concentrates (PC). PCs are made
by further centrifuging PRP at 5000 g for 5 minutes at
20-24 oC. The supernatant platelet poor plasma is
expressed. About 50 ml of plasma is left with the platelet
button to ensure a pH of >6.2. An alternative approach
involves the collection of single donor platelets by
apheresis using a cell separator. Unlike red blood cells,
platelets are stored at 20-24C, under constant gentle
agitation to avoid aggregation. Storage is recommended
only for 3-5 days because of risk of bacterial
contamination. Platelet concentrates (PC) are stored at
20- 24 C under constant agitation and have a shelf-life
865
of 3 to 5 days. Concentrates stored at 2-6C do not require

agitation but have a shelf-life of less than 24 hours and
are hemostatically less effective.
One unit PC prepared from 450 ml whole blood
contains at least 5.5 1010 platelets in 50 ml plasma.
Indications
The indications for platelet transfusion in children with
quantitative and qualitative platelet disorders are similar
to those for adults, but neonates and infants < 4 months
form a special group and may need platelet support at
even higher platelet counts than indicated for children
and adults.
Besides the absolute platelet count, the underlying
condition giving rise to thrombocytopenia is an
important factor determining the need for platelet
transfusion. Patients with marrow failure (leukemia and
aplastic anemia) require frequent platelet support while
patients with immune thrombocytopenias are never
transfused except in the event of life threatening bleeds
or prior to splenectomy. More vigorous transfusions are
also needed during certain phases of chemotherapy and
during therapy with ATG.
One unit PC prepared from 450 ml whole blood
contains at least 5.5 1010 platelets in 50 ml plasma. One
unit PRP has the same amount in 250 ml plasma. One
unit PC harvested by apheresis is equivalent to 5-6 units
prepared manually. This is particularly useful when HLA
matched platelets are required. The guidelines for platelet
transfusions in pediatric practice are outlined in Table
15.16.3.
Studies in patients with thrombocytopenia caused by
poor marrow production indicate that spontaneous
bleeding increases markedly when platelet levels fall to
< 20 109 /L, particularly in patients who are ill with
infection, anemia or dysfunction of liver. These
observations form the basis of the 20 109 /L cut off
platelet count for patients with bone marrow failure. This
threshold has been challenged by adult studies, and some
favour a platelet transfusion trigger of 5 to 10 109 /L
for patients with uncomplicated conditions. However,
in practice, severe thrombocytopenia commonly occurs
in association with fever, antimicrobial therapy, active
bleeding, an invasive procedure, DIC and other
coagulation defects. Platelet counts in oncology and
transplant patients are frequently maintained at 20 109
/L or higher. However, prophylactic platelet transfusions
are difficult to implement as the demand for blood
components exceeds the patient requirements.
866
TABLE 15.16.3: Guidelines for pediatric platelet transfusion

Children and Adolescents(platelet count (x109/L)
PLTs <50 and bleeding
PLTs <50 and invasive procedure
PLTs <20 and marrow failure with hemorrhagic risk factors
PLTs <10 and marrow failure without hemorrhagic risk factors
PLTs at any count, but with platelet dysfunction plus bleeding
or invasive procedure
Infants within first 4 months of life
PLTs <100 and bleeding
PLTs <50 and invasive procedure
PLTs <20 and clinically stable
PLTs <100 and clinically unstable
PLTs at any count, but with platelet dysfunction plus bleeding
or invasive procedure
Indications
Qualitative Platelet Disorders (Abnormal platelet
functions)
Qualitative platelet disorders may be inherited or
acquired. The acquired conditions are either reversible
(drugs, uremia, DIC, scurvy) or irreversible
(myelofibrosis/leukemia). In these disorders, minor
bleeds are managed by local measures. Treatment of the
underlying disease usually corrects the bleeding
diathesis. Platelet transfusions may be required before
invasive procedures.
Inherited disorders with platelet dysfunction include:
von Willebrands disease, Glanzmann thrombasthenia,
Bernard Soulier disease, Wiskott Aldrich syndrome etc.
Since platelet dysfunction is a long term problem and
repeated transfusions may lead to alloimmunisation and
refractoriness, platelets should be transfused only in
extreme need (if significant bleeding actually occurs).
Prophylactic transfusions are rarely justified, unless an
invasive procedure is planned. In such situations, a
bleeding time twice the upper limit of laboratory normal
may be taken as a rough guide but is poorly predictive
of hemorrhagic risk or need to transfuse platelets. In these
patients, alternative therapies, including desmopressin
acetate, should be considered to avoid platelet
transfusion.
Recommendations for Platelet
Transfusion During Infancy
Multiple pathogenic mechanisms are operative in high
risk neonates including (i) accelerated platelet destruction
due to shortened platelet survival time (ii) increased
platelet associated immunoglobulin G (iii) inadequate

increment of platelet values after PLT transfusion, and
(iv) diminished platelet production, as evidenced by
decreased number of megakaryocyte progenitors and
relatively low levels of thrombopoietin in response to
thrombocytopenia.
Preterm infants, in particular ,exhibit thrombocytopenia commonly. Two firm indications for neonatal
PLT transfusions are to treat hemorrhage that has already
occurred and to prevent hemorrhage from complicating
an invasive procedure. Most neonatologists use a PLT
count <50 109 / L as a transfusion trigger in these
circumstances,while some choose to transfuse when
platelet count falls below 100 x 109/L.
The majority agree that it is reasonable to give
platelets to any neonate whose platelet count is <20
109 L. However, there is no documented benefit to
transfusing prophylactic platelets to maintain a
completely normal platelet count even in neonates.
Currently, there are no alternatives to platelet
transfusion to treat thrombocytopenia in neonates.
Recombinant thrombopoietin and Interleukin 11 are
promising agents. However, neither is recommended for
use during infancy and both have potential toxicities. The
present use is only under experimental settings.
It is best to use the ABO and Rh group compatible
platelets. In an emergency situation, platelet concentrates
may be given without regard to the ABO group. This
usually causes no problems unless the platelets are
grossly contaminated with red cells. When long term
platelet support is likely, platelets obtained by apheresis
procedure from HLA compatible donors are
recommended. In such patients use of leucofiltered
platelets reduces the frequency of alloimmunization.
Infusion of one unit of platelet concentrate raises the
platelet count, one hour after transfusion, by 5 - 10 109/
L/sqm body surface area. The usual dose of platelets in
a child is 3 to 4 units when the count is < 20 109/ L. PCs
are administered with a standard infusion set with 170
200 microfilter and are usually given as rapidly as
possible.
Granulocyte Transfusions
Several advances, in particular, the use of recombinant
granulocyte colony stimulating factor (G-CSF) to
stimulate donors have made it possible to collect
excessively large number of normal neutrophils for
transfusion into neutropenic patients who have life
threatening infections.
Preparation
Granulocyte concentrates can be prepared manually by
harvesting the buffy coat layer from a single unit of blood
or by leucopheresis. As the specific gravity of
granulocytes is very similar to RBCs, separation by
centrifugation is not satisfactory. This yields 0.5 0.6
109 granulocytes per unit of whole blood. One such unit
prepared by apheresis contains 1 1010 granulocytes, i.e.
an equivalent of 18-20 units of buffy coat. Granulocyte
concentrates can be stored at 20 24C for 24 hrs. The
product must be ABO compatible with the recipient
because they are frequently contaminated with
significant amounts of red blood cells.
Indications
The use of granulocyte transfusion has remained limited
in clinical practice, largely due to the availability of newer
antibiotics and use of agents like IVIg, G-CSF, other
recombinant cytokines and immune modulating agents.
Infected neutropenic patients usually respond to
antibiotics alone, provided bone marrow function
recovers early in infection.Because children with newly
diagnosed leukemia respond rapidly to induction
chemotherapy, only rarely are they candidates for GTX.In
contrast ,infected children with sustained bone marrow
failure (e.g. malignant neoplasms resistant to treatment,
aplastic anaemia,bone marrow transplantation)may
benefit from the addition of GTX to antibiotic therapy.
The use of GTX for bacterial sepsis that is
unresponsive to antibiotics in patients with severe
neuropenia (<0.5 109 / L is supported by most of the
controlled studies).
Guidelines for Transfusing Neutrophils in Children
Blood neutrophils <0.5 109/L and bacterial infection
unresponsive to antibiotics
Blood neutrophils <0.5 109/L and yeast or fungal
infection progressing or appearing during treatment
with antimicrobials.
Neutrophil dysfunction with bacterial, yeast, fungal
infection unresponsive to antimicrobials.
Guidelines for Transfusing Neutrophils in
Infants <4 months
Blood neutrophils <3 109/L. and fulminant sepsis
during the first week of life
867
Blood neutrophils <1 109 /L and fulminant sepsis

after first week of life
Plasma Components
Fresh frozen plasma
Preparation
Plasma is separated from single units of whole blood by
heavy spin at 2-6C or derived from plasmapheresis. If
frozen within 6-8 hours of collection, it yields fresh frozen
plasma (FPP). The volume from a single donation is about
200 ml.
FFP contains factors II, V,VII,VIII,IX,X and fibrinogen.
It should be thawed in a water bath at 37C and
administered within half-an hour after thawing as the
activity of factors V and VIII are rapidly lost. FFP has a
shelf life of 1 year if kept at 30C or below.
Indications
FFP transfusions are indicated in the following situations:
i. Replacement of coagulation factors in liver disease,
deficiency of vitamin K dependent factors (II, VII,
IX, X), DIC, overdose of oral anticoagulants,
cardiopulmonary bypass, massive blood transfusions; ii) Specific deficiencies of factors V, XIII, XI.
iii) Replacement of hemostatic factors when specific
concentrate preparations are not available, e.g.
hemophilia A and B; deficiencies of VII, X,
fibrinogen and prothrombin; von Willebrands
disease; antithrombin III deficiencies; and iv) in
sitiuations where certain plasma constituents are
lacking e.g. fibronectin in septicemia, C1 esterase in
hereditary angioneurotic edema, and PGI2 inducing
activity in thrombotic thrombocytopenic purpura.
The volume and frequency of FFP transfusions
would depend upon the indication and the
assessment of an individual patient. Usually a dose
of 10-15 ml/kg body weight is recommended at a
flow rate not exceeding 10 ml/min.
TABLE 15.16.4: Patients at risk of transfusion induced GVHD
Bone marrow transplant recipients
Recipients of cellular blood products from 1st degree
relatives
Neonatal exchange transfusion, especially after intrauterine
transfusion
Children with immunodeficiency
868
Cryoprecipitate
Preparation
Cryoprecipitate is prepared by rapid low temperature
freezing at -70C of freshly separated plasma (within 6-8
hours of collection) with subsequent rapid thawing at
2-6C and centrifugation using heavy spin for 7 minutes.
10-15 ml plasma is left with the cryoprecipitate in the
primary bag. Cryo-poor plasma is expressed in the
second satellite bag. Cryoprecipitate is stored at -30C or
lower for 12 months. It contains factors V, VIII,
fibrinogen, XIII and fibronectin. One unit of
cryoprecipitate of 10- 20 ml usually contains 80 120 IU
of factor VIII and 250 to 300 mg of fibrinogen.
Indications
Cryoprecpitate is used in moderate and severe
hemophilia A in the absence of factor VIII concentrates
and is the product of choice in : i) von Willebrands
disease and mild hemophilia A; ii) Dysfibrinogenemia,
hypofibrinogenemia and consumptive coagulopathies;
iii) Intractable bleeding in uremia and platelet storage
pool disease and iv) Congenital factor XIII deficiency. It
may also be of benefit in patients with septicemia or burns
because of the fibronectin content. Occasionally, it is used
for correcting factor VIII deficiency caused by massive
transfusion.
Cryopoor Plasma, Liquid Plasma,
Single Donor Plasma
Preparation
FFP from which cryoprecipitate has been removed is
called cryopoor plasma. Plasma in a unit of whole blood
can be separated at any time during storage upto 5 days
after the expiration date of whole blood. If this plasma is
stored at < 18oC it is called single donor plasma and
can be stored upto 5 years after date of collection. If not
frozen, it is called liquid plasma which is stored at 2-6oC
and can be transfused upto 5 days after expiration date.
FFP which has exceeded a shelf-life of one year is
subsequently called single donor plasma.
Indications
These products have normal amounts of factors II, VII,
IX and X and can be used in patients requiring warfarin
reversal or liver disease. In resource constrained
situations, where patients cannot afford albumin
concentrates, these products can be given.
Specific Factor Concentrates

Specific factor concentrates include antihemophilic factor
concentrate (AHF, factor VIII) and prothrombin complex.
Both are prepared by fractionation of large pools of
plasma. They can be stored at 6-8 C for 2 years.
Intermediate purity factor VIII concentrates contain
15-20 IU/ ml. It is the product of choice for moderate
and severe hemophilia A.
Prothrombin complex when reconstituted contains
30-100 IU/ml of all factors in it. Heparin and/or ATIII
are added to some products to prevent coagulant activity.
It is recommended for replacement therapy in
hemophilia B (factor IX deficiency) but may also be used
for congenital or acquired deficiency of factors II, VII or
X, and bleeding in hemophiliacs with antibodies against
factor VIII. The dose and frequency of administration of
these products would need to be tailored to the severity
of bleeding manifestations in an individual patient.
Concentrates of fibrinogen, XIII and XI have been
used in the past but are no longer recommended because
of the safety, availability and efficacy of cryoprecipitate
and FFP.
Antithrombin III concentrates are used for treating
thrombotic episodes in patients with congenital AT III
deficiency in a dose of 50 units/kg body weight. Antiinhibitor complexes have been designed for use in
patients with inhibitors to factor VIII. These activated
procoagulant and coagulant mixtures bypass
requirement of factor VIII in patients who have
developed inhibitors to the same.
In addition to plasma derived factor concentrates,
high purity FVIII concentrates prepared by recombinant
technology are available, though these are more
expensive as compared to the former.
Albumin
Albumin preparations are available in concentrations of
5% (called plasma protein fraction or PPF) and 20% PPF
has 90% albumin, the rest being and - globulins.
It may be used to replace plasma proteins in : i) Burns;
ii) Extensive surgery; and iii) Hemorrhagic shock while
awaiting blood (crystalloid solutions are as effective). The
main indication for use of 20% albumin solution is severe
hypoproteinemia in nephrotic syndrome associated with
massive anasarca, the dose being 0.5 to 1g/kg.
Diuretics are essential when edema is present because
every 10 ml of 20% albumin draws 35 ml of extravascular
fluid into the circulation within 15 minutes of
administration.
869
Normal and Specific Immunoglobulins (Ig)
Autologous Blood Transfusion
Normal Immunoglobulins (Ig) are obtained by

fractionation of plasma whilst specific Ig are separated
from plasma from donors who possess a high titre of
specific antibodies. The indications for use are:
i) Prevention and treatment of diseases such as hepatitis,
rubella, varicella-zoster, tetanus, measles, rabies, etc;
ii) Replacement therapy, antibody deficiency syndrome;
iii) Treatment of immune disorders such as immune
thrombocytopenic purpura; iv) Prevention of
sensitization in Rh (D) Negative women by administering
anti-D immunoglobulin; v) Prophylaxis and treatment
of neonatal sepsis and vi) Kawasaki disease.
It is the transfusion of blood into its own donor. Such

transfusions are used primarily in patients undergoing
elective surgical procedures. Blood is collected by
bleeding the patient on several occasions pre-operatively.
The Hb should be >11 gm/dl before collection of each
unit and the patient is administered iron supplements.
Units of blood thus obtained are stored and used in the
donor when required. Advantage gained is the avoidance
of blood of any other person, thus eliminating risk of
transmission of infections. In children volume of blood
and anticoagulant is to be adjusted to body weight.
Hazards of Blood Transfusion
Irradiated Blood Components

Cellular blood components need to be irradiated to
prevent transfusion-associated graft vs host disease in
immunocompromised patients (Table 15.16.4). The
recommended dose of gamma radiation is 25 Gy to the
central portion of the unit and at least 15 Gy at the
periphery. Irradiation destroys viable lymphocytes. The
shelf-life of platelets remains unchanged, but red cells
expire 28 days after irradiation or at the end of storage
period, whichever is earlier. Irradiated blood is
recommended for intrauterine transfusions and for
patients undergoing hematopoietic stem cell
transplantation or those receiving donor units from first
degree relatives.
Adverse reactions to blood transfusion can be subdivided

according to whether they are immediate or delayed and
whether they are immunologically mediated. Table
15.16.5 outlines the adverse effects of transfusion. Acute
hemolytic reaction is the dreaded complication of blood
transfusion, one of the common causes being clerical
errors of mislabeling, resulting in the infusion of the
wrong patients blood. Signs and symptoms include fever
with chills, back and chest pain, flushing, nausea and
dark urine due to hemoglobinuria. These can progress
to shock with acute renal failure. Management of acute
hemolytic transfusion reaction is outlined in Table
15.16.6.
TABLE 15.16.5: Adverse effects of transfusion

Types of reactions
Usual cause
Immunologic
Hemolysis with symptoms
Anaphylaxis
Febrile, nonhemolytic
Urticaria
Noncardiogenic pulmonary edema
Graft versus host disease
Red cell incompatibility

Antibody to IgA in donor
Antibody to donor leukocyte antigens
Antibody to donor plasma proteins
Donor antibody to leukocytes of patient
Functional lymphocytes in blood
Non-immunologic
Fever with shock
Hypothermia
Hemolysis without symptoms
Air embolus
Hyperkalemia
Hypocalcemia
Disease transmission
Iron overload
Volume overload
Bacterial contamination
Rapid infusion of cold blood
Physical or chemical destruction of blood (e.g. freezing)
Air infusion in line
Rapid infusion of multiple units of stored blood
Massive transfusion of citrated blood
HIV, Hepatitis C, B,cytomegalovirus, malaria, syphilis
Multiple transfusions in chronically anemic patients without blood loss
870
Future Perspectives in Transfusion Medicine:

Blood Substitutes
Red cell substitutes that have been in the process of
development since almost three decades are still in
clinical trial phases. Hemoglobin derived oxygen carriers
and perfluorocarbons are being tried as oxygen delivery
agents. However, their short half-life (<24 hours) and
inability to replicate oxygen delivery of the intact RBCs
have limited their clinical utility. Platelet substitutes are
largely platelet derived and include frozen platelets, cold
stored liquid platelets and platelet derived
microparticles. The non-platelet derived substitutes
include red cells coated with fibrinogen, fibrinogen
coated albumin microcapsules and liposome based
platelet glycoproteins and activated coagulation factors.
However, there is still a long way to go before these
products become licensed for clinical use.
Recently enzymatic removal of A and B antigens by
bacterial glycosidases has raised the hope of converting
red cells to the universal O type of red cells. These discoveries are at present laboratory achievements, but their
translation to patient bedside may still be a long journey.
In addition in-vitro erythropoiesis has been induced from
hematopoietic stem cells under specific conditions.
of transmission during the window period cannot be

completely eliminated. Moreover, emerging diseases
pose new threats. Specific blood component therapy
suited to the requirements of an individual patient must
be recommended whenever possible. It is advisable to
take informed consent of the parent(s) or guardian
because of the inherent immunological and infectious
risks of transfusions.
TABLE 15.16.7: Indications for use of blood components
Component
Indications
Whole blood
Acute massive blood loss

Exchange transfusion
Packed red cells
Thalassemia
Aplastic anemia
Nutritional anemia
Childhood cancers
Platelets
Thrombocytopenia
- with decreased production
- with increased/normal
production
Abnormal platelet function
- Acquired
- Congenital
Granulocytes
Severe neutropenia
Septicemia not controlled with
antibiotics
Fresh frozen plasma
Liver disease
Cardiopulmonary bypass
Massive blood transfusions
Specific clotting factor
deficiencies if factor
concentrate is not available
Cryoprecipitate
von Willebrands disease

Hypofibrinogenemia
Factor XIII deficiency
Hemophilia A if factor
concentrate is not available
Summary
Blood and blood products should be transfused only
when there are clear and specific therapeutic indications
(Table 15.16.7). The risks of transfusion reactions and
transfusion related infections deserve careful consideration. Although blood units are screened for transfusion
transmitted diseases by sensitive technologies, the risk
TABLE 15.16.6: Management of acute
hemolytic transfusion reaction
Discontinue blood transfusion but maintain IV access

Alert blood bank and send back unit of blood
Draw clotted and anticoagulated blood specimens from a vein
other than the one being used for transfusion. Requisition the
following tests: DCT, plasma Hb, full blood counts, blood urea,
serum creatinine, serum bilirubin, serum electrolytes
Collect urine sample for urinary hemoglobin
Investigate for disseminated intravascular coagulation; blood
culture if fever is a prominent feature
Monitor urine output
Treatment is largely supportive: infusion of normal saline to
maintain adequate urine output, furosemide and dopamine to
enhance renal cortical perfusion. Dialysis may be required if
acute tubular necrosis develops.
Factor VIII concentrate
Hemophilia A
Prothrombin complex
Hemophilia B
Albumin
Burns
Shock
Severe edema in neophrotic
syndrome
Before exchange transfusion
Immunoglobulins
Prevention and treatment of

some disease, e.g. hepatitis
Antibody deficiency syndrome
Immune disorders, e.g. ITP
Neonatal sepsis
Kawasaki disease
BIBLIOGRAPHY
1. Brecker ME. American Association of Blood Banks.
Technical Manual 15th Edition, 2005. Chapter 8
Collection, Preparation, storage and distribution of
components from whole blood donations, 175-202.
2. Brozovic B. Brozovic M. Manual of Clinical Blood
Transfusion. 1st edn. Edinburgh, Churchill Livingstone,
1986;20-79.
3. Blajchman MA. Substitutes and alternatives to platelet
transfusions in thrombocytopenic patients. J Thrombosis
Haemostasis 2003;1:1637-41.
4. Liv QP, Sulzenbacher G, Yuan H, et al. Bacterial
glycosidases for the production of universal red blood
cells. Nature Biotechnology 2007; published online 1
April 2007 doi: 10.1038/nbt1298.
5.
6.
7.
8.
9.
10.
871
Napler JAF. Blood transfusion therapy. A problem

oriented approach, New York, John Wiley and Sons,
1987;54-135.
Petz LD, Swisher SN, Clinical Practice of Transfusion
Medicine, 2nd Edn. New York, Churchill Livingstone,
1989;239-69.
Pizzo PA, Poplack DG. Principles and Practice of
Pediatric Oncology. 2nd Edn., Philadelphia. JB. Lippincot
company 1989;943-75.
Rutman RC, Miller WV. Transfusion therapy. Principles
and procedures, 2nd Edn, Maryland. Aspen System
Corporation, 1985;29-46.
Saran RK. Transfusion Medicine Technical Manual.
Directorate General of Health Services.Ministry of Health
and Family Welfare, Govt. of India.2003;193-243.
Stowell CP. Whatever happened to blood substitutes.
Transfusion 2004;44:1403-4.
16.1 Malignancies in Children: Purna A Kurkure ......................................................................................................................................... 874

16.2 Acute Leukemia: Anupama Borker, SH Advani .................................................................................................................................... 874
16.3 Hodgkins Disease: Purna A Kurkure, Brijesh Arora, Roshni Bhagwat ................................................................................................ 880
16.4 Non-Hodgkins Lymphoma: Purna A Kurkure, Brijesh Arora, Roshni Bhagwat .................................................................................. 883
16.5 Wilms Tumor: Purna A Kurkure, Brijesh Arora, Shailesh Kanvinde ..................................................................................................... 887
16.6 Neuroblastoma: Purna A Kurkure, Brijesh Arora, Shailesh Kanvinde .................................................................................................. 890
16.7 Soft Tissue Sarcoma: Sajid Qureshi, Purna A Kurkure ........................................................................................................................ 895
16.8 Retinoblastoma: Sripad Banavali .......................................................................................................................................................... 901
16.9 Bone Marrow Transplantation: Brijesh Arora, Purvish M Parikh, MR Lokeshwar .............................................................................. 903
874
16.1 Malignancies in Children

Purna A Kurkure
The recent understanding and advances in the total
management of pediatric cancers forms one of the most
exciting chapters in the entire field of oncology. With
increasing control of infectious disease, eradication of
malnutrition and the rapid strides of the pediatric
surgeons in correcting benign surgical problems, more
children are now going to be affected by cancer. In U.S.
cancer is second to accidents as a cause of mortality in
children beyond first year of life. There is paucity of
accurate vital statistics in our country. Children constitute
approximately 40% of Indias population which is more
than 1 billion. Annual incidence rates of cancer are about
75 and 80 per 105 men and women respectively or around
8 lacs new cancers per year. Approximately 5% of these
are in pediatric age group as estimated by population
based cancer registries. Thus 40,000 new pediatric cancers
are estimated to be diagnosed annually. Leukemias and
Lymphomas comprise nearly half of pediatric cancers
followed by tumors of the CNS, sympathetic nervous
system, soft tissues, kidney, bone, eye liver and germ
cells. Child is not a miniature adult. The types of
childhood cancers and response to therapy totally differ
from those in adults.
The hallmark of success in pediatric oncology is
multidisciplinary approach executed through carefully
orchestrated combine modality team comprising of a
pediatric oncologist, a pediatric surgeon, a radiation
oncologist, diagnostic specialists and supportive care
services. Burchenal succinctly characterised the basic
tenet of multidisciplinary approach by stating that the
pride of discipline must be put aside. All the experts
should work together, keeping well being of the child as
the central issue. First chance is the best chance and
giving optimum treatment at outset is the most important
factor in deciding the outcome. Any advances in health

care is only as valuable as it is available and accessible to
those who need it. It has been well documented that
organised and co-ordinated treatment programme
carried out by experienced pediatric oncologist in well
staffed and well equipped Pediatric cancer unit is
effective. But at the same time early referral for prompt
diagnosis and for ensuring efficient follow-up, the
community pediatricians role is crucial. The National
Training Project In Practical Pediatric Oncology has
been initiated under the auspices of Pediatric
Hematology Oncology chapter of IAP in collaboration
with the International Society of Pediatric Oncology
(SIOP) since 1998 with an aim to train educate and
encourage pediatricians to participate in shared care of
childhood cancer patients.
Advances in the treatment of childhood cancers have
dramatically increased survival rates to around 70% in
developed countries. It has been estimated that by the
year 2010, approximately 1 in 250 young adults will be
survivor of childhood cancer in U.S.A. Although this
constitutes a remarkable medical achievement, the late
morbidity in this growing survivor population has
become an area for concern. The need to predict the
future impact of current therapeutic strategies is a major
challenge for the pediatric oncologist. A balance of
reassurance to the survivor and vigilance in monitoring
for relapse, second malignancies and other sequelae is
required. Recent concept of a truly Cured child in
pediatric oncology envisages not only a biological cure
of the disease but a child on par with peers in growth
and development physically and in achievements and
aspirations, both mentally and emotionally.
16.2 Acute Leukemia

Anupama Borker, SH Advani
INTRODUCTION
Acute leukemia is a malignancy arising due to the clonal
proliferation of abnormal hematopoietic cells leading to
the disruption of normal marrow function.
Acute leukemias account for about 40% of childhood

cancers. Acute lymphoblastic leukemia (ALL) comprises
about 70- 80% and acute myeloid leukemia (AML) about
10-15 % of childhood leukemias. The remaining subset
Pediatric Oncology
consists of the uncommon childhood leukemias viz.
chronic myeloid leukemia (CML) and juvenile myelomonocytic leukemia (JMML).
TABLE 16.2.1: Co-relation of ALL subtypes with

surface markers
Pre B-cell
CD10+, CD19+, CD20+,

CD21+, HLA DR+
Mature
B-cell
CD19+, CD20+, CD21+,

sIg+
T-cell
CD3+, CD5+, CD7+
Etiology
Although the etiology of acute leukemia is unknown,
several genetic conditions and environmental agents are
known to be associated with childhood leukemia. Certain
inherited conditions like Downs Syndrome (trisomy 21),
Fanconi syndrome, Bloom syndrome, Schwachman
syndrome, Klienfelter syndrome, Turner syndrome
(45,XO), neurofibromatosis, ataxia telangiectasia, severe
combined immunodeficiency and Li Fraumeni syndrome
(p53 deletion) are known to predispose to leukemia.
Ionizing radiation, exposure to benzene and certain drugs
like alkylating agents, nitrosureas and epipodophyllotoxins have been incriminated in the pathogenesis
of acute leukemias.
875
Presence of CD10
(Common ALL antigen
- CALLA) connotes a
favourable prognosis
Corelates with L3
leukemiaBurkitts
leukemia, needs
intensified therapy
Associated with older
age, high initial WBC
count, mediastinal
mass and higher risk
of CNS disease
TABLE 16.2.2: Common chromosomal abnormalities

associated with childhood ALL
Translocation
Affected genes
Comments
Classification
T (1,19)
PBX1 E2A
High risk
The classification of ALL has evolved from one, which

was based predominantly on morphology to one, which
is based on immunophenotyping, karyotyping and
molecular biology techniques. For ALL, the results of
immunophenotyping are used to classify the leukemia
as either B-cell derived or T-cell derived. The morphologic classification (FAB classification - French American
British classification) is still used by many centres, due
to its ease and familiarity. It classifies the blasts as L1, L2
and L3 depending on the cell size, amount of cytoplasm
and the presence of nucleoli and vacuoles. Progenitor Bcell derived ALL constitutes 80-85% of childhood ALL.
Fifteen percent are derived from T-cells and 1-2 % from
mature B-cells. (Table 16.2.1) Certain chromosomal
abnormalities are associated with a favourable prognosis
viz. t (12; 21) and simultaneous presence of trisomy 4
and 10. Others like t (4; 11) and the Philadelphia
chromosome t (9; 22) connote a poor prognosis. The
presence of t (8, 14) is associated with Burkitt leukemia
where short duration intensive chemotherapy gives high
cure rates (Table 16.2.2). In general, patients with
hyperdiploidy (DNA index > 1.16) fare better than those
with hypodiploidy.
For AML, the FAB classification is widely used.
However, the new WHO classification is now gaining
acceptance. According to this classification, presence of
more than 20% blasts in the bone marrow is diagnostic
of acute leukemia (Table 16.2.3).
T (4,11)
MLL
Associated with infantile

leukemia, high risk
T(9,22)
BCR ABL
Philadelphia chromosome,
high risk
T (12,21)
TEL AML1
Good prognosis
T (8,14)
MYC IgL
Burkitts leukemia, Needs

short duration intensive
therapy
The changes are easily summarized: the leukemias

with consistent cytogenetic abnormalitites and those that
are MDS related were taken into separate groups; the
rest of the old FAB classification was put under the AML
not otherwise categorized entry.
The presence of t (8; 21), trisomy 8, inv (16) and t (15;
17) is associated with favourable prognosis whereas Del
(7) and t (4; 11) are poor prognostic chromosomonal
abnormalities.
Clinical Features
Clinical features of acute leukemia are related to the
decrease in the normal cells in the bone marrow viz. Red
blood cells (RBCs), white blood cells (WBCs) and
platelets, as well as the leukemic cell infiltration of
various organs. The average duration of symptoms
before diagnosis varies from 1-2 weeks to 1-2 months.
876

TABLE 16.2.3: FAB and WHO classification of acute myeloid leukemias (AML)
AML classification
FAB
M0: minimally differentiated

M1: myeloblastic leukemia without maturation
M2: myeloblastic leukemia with maturation
M3: hypergranular promyelocytic leukemia
M4: myelomonocytic leukemia
M4Eo: variant, increase in marrow eosinophils
M5: monocytic leukemia
M6: erythroleukemia (DiGuglielmos disease)
M7: megakaryoblastic leukemia
WHO
AML with recurrent cytogenetic translocations
AML with t(8;21)(q22;q22) AML1/CBFalpha/ETO
Acute promyelocytic leukemia: AML with
t(15;17)(q22;q12) and variants PML/RARalpha
AML with abnormal bone marrow eosinophils
inv(16)(p13;q22) t(16;16)(p13;q22) CBFbeta/MYH1
AML with 11q23 MLL abnormalities
AML with multilineage dysplasia
With prior MDS
Without prior MDS
AML with myelodysplastic syndrome, therapy related
Alkylating agent related
Epipodophyllotoxin related
Other types
AML not otherwise categorized
AML minimally differentiated
AML without maturation
AML with maturation
Acute myelomonocytic leukemia
Acute monocytic leukemia
Acute erythroid leukemia
Acute megakaryocytic leukemia
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis
Initial symptoms may be vague like anorexia,

fatigability and low-grade fever.
Bleeding tendencies like easy bruising, gum bleeding,
epistaxis or petechiae and ecchymosis are common. Fever
may be due to an infection like otitis media, pneumonitis
or an abscess, or due to leukemia itself. Oral ulcers or
thrush may be present at diagnosis. Bone and joint pains
and occasionally joint swelling are common symptoms.
Patients are usually pale with evidence of petechiae,
purpura or ecchymosis. Generalized lymphadenopathy
and hepatosplenomegaly is present in patients with high
tumor burden. Tachypnea and respiratory distress may
be present secondary to severe anemia leading to
congestive cardiac failure or secondary to the presence
of a mediastinal mass leading to tracheal compression.
A large mediastinal mass may also cause superior vena
cava syndrome with facial edema and plethora,
throbbing headache, conjunctival congestion and dilated
neck veins.
Patients with high tumor burden can occasionally
present in tumor lysis syndrome with decreased urine
output and azotemia secondary to uric acid nephropathy.
About 5-10% patients have central nervous system

(CNS) involvement at diagnosis and present with
headaches or cranial nerve palsies. It may be associated
with papilledema and other signs of raised intracranial
pressure. Testicular involvement at diagnosis is
extremely rare but can be present, usually with painless
testicular enlargement.
Patients with acute myeloid leukemia are more likely
to present with bleeding manifestations. Acute promyelocytic leukemia (APML ie AML-M3) can present with
disseminated intravascular coagulation due to the release
of thromboplastin from the promyelocytic granules. Gum
hypertrophy and skin deposits (leukemia cutis) are
characteristic of AML M4/M5. Rarely patients may
present with a soft tissue mass (granulocytic sarcoma)
which is an extramedullary myeloid cell tumor and this
may precede the leukemia in the bone marrow by several
weeks.
Laboratory Features
The complete blood count at diagnosis usually shows
decreased hemoglobin level and low platelet count. The
Pediatric Oncology
877
WBC count may be elevated or depressed, in either case

it is characterised by neutropenia. Blasts may or may
not be present in the peripheral blood or may be reported
as atypical lymphocytes.
Bone marrow aspiration smears confirm the diagnosis
when more than 30% blasts are present (>20 % for AML
by the WHO classification).
Morphology along with cytochemistry can accurately
diagnose about 80% acute leukemias. Immunophenotyping is useful for further subtyping according to the
lineage and for tailoring treatment and for prognostication. Rarely a bone marrow biopsy is necessary for
adequate tissue to rule out other causes.
Cerebrospinal fluid (CSF) analysis, including cytology
is necessary for staging. The presence of elevated CSF
leucocyte count and the presence of blasts in the CSF
indicate CNS leukemia and connote a poorer prognosis.
Biochemical evaluation including liver and renal
function tests, serum lactate dehydrogenase (LDH), uric
acid, electrolytes and calcium, phosphorus and magnesium levels should be performed to establish baseline
organ function and to rule out tumor lysis syndrome.
Serology for human immunodeficiency virus (HIV),
hepatitis B and C and Epstein Barr virus (EBV) and
cytomegalovirus (CMV) should be performed at
diagnosis. Coagulation profile with prothrombin time
(PT), partial thromboplastin time (PTT), fibrinogen level
and fibrinogen degradation products (FDP) should be
done to rule out disseminated intravascular coagulation
(DIC).
Myelodysplastic syndromes, constitutional bone

marrow failure syndromes and hypoplastic or aplastic
anemia also present with pancytopenia and need to be
differentiated from acute leukemia.
Consolidation Chemotherapy
The differential diagnosis of acute leukemia includes

several benign and malignant conditions. The commonest cause for transient pancytopenia is viral infection
induced myelosuppression. Drug induced cytopenia can
be ruled out by careful history. Immune mediated
thrombocytopenia (ITP) can be differentiated from acute
leukemia by the presence of acute onset isolated
thrombocytopenia in an otherwise well child. In case of
doubt a bone marrow aspiration is required to rule out
leukemia. Other hematologic malignancies like chronic
myeloid leukemia, juvenile myelomonocytic leukemia,
and chronic myeloid leukemia in blast crisis or
lymphoma evolving to leukemic phase and bone marrow
failure secondary to marrow infiltration by metastatic
deposits in neuroblastoma, rhabdomyosarcoma and
Ewings sarcoma can occasionally mimic acute leukemia.
Consolidation chemotherapy decreases the leukemic

burden further. Drugs used include vincristine,
cyclophosphamide, and daunorubicin and cytosine
arabinoside.
Management
The management of acute leukemia is intense and
prolonged. It needs the combined efforts of the pediatric
oncologist, the radiation oncologist, the nursing team,
the dietician, the psychologist and the medical social
workers to treat these children with intent to cure.
Principles of Treatment of ALL
At diagnosis the leukemic tumor burden approximates
1012 cells. Chemotherapy given in phases reduces the
leukemia cells by log cell kill. After the initial 4-6 months
of intensive chemotherapy, oral maintenance chemotherapy is given for 18-24 months to prevent resurgence
of leukemia cells and to achieve a cure.
Induction Chemotherapy
Induction chemotherapy is the first few weeks of
intensive treatment given to produce remission. It
includes 3-4 drugs including vincristine, prednisone or
dexamethasone, L-Asparginase and daunorubicin.
Intrathecal chemotherapy includes methotrexate or
cytosine arabinoside. About 95% patients achieve a
morphologic remission at the end of induction chemotherapy.
CNS Directed Therapy

The concept of CNS preventive therapy is based on the
assumption that undetectable CNS leukemia is present
at diagnosis. Since systemic chemotherapy may not
achieve adequate drug levels across the blood brain
barrier, cranial irradiation with intrathecal chemotherapy
has been in use since the 1970s as CNS preventive
therapy. This is associated with neurocognitive dysfunction and secondary malignancies in some survivors. High
dose chemotherapy using methotrexate or cytosine
arabinoside achieves good CNS penetrance and newer
878
protocols reserve cranial irradiation for patients with

CNS disease at presentation and for those who are at
high risk for CNS relapse.
Maintenance Chemotherapy
Maintenance chemotherapy using oral mercaptopurine and
methotrexate is given for 18 to 24 months in order to
eradicate dormant leukemia cells.
Different institutes use different treatment protocols
for childhood ALL. Most European and American
protocols use aggressive chemotherapy regimens with 5
year survival rates over 80-85%. In India the multi-centric
protocol MCP841 has been used in three major centres
across the country with cure rates of 50%.
TABLE 16.2.4: Protocol MCP 841 for ALL

Cycle
Chemotherapy
Dose and Schedule
Induction 1 (I1)
Prednisone
Vincristine
Methotrexate*
L-Asparaginase
Daunorubicin
40 mg/m p.o.days 1-28

1.4 mg/m i.v.days 1,8,15 and 22
12 mg IT, days 1,8,15 and 22
6000 u/m i.m on alternate days 10 doses, days 2-20
30 mg/m .i.v days 8,15 and 29
Induction 2 (I2)
Mercaptopurine
Cyclophosphamide
Methotrexate*
Cranial Radiation
75 mg/m p.o. daily days 1-7 and days 15-21

750 mg/m i.v days 1 and 15
12 mg/m IT days 1,8,15and 22
180 cGy daily x 10 days ( total 1800 cGy)
Repeat induction (RI1)

Consolidation (C)
Same as I1
Cyclophosphamide
Vincristine
Mercaptopurine
Cytarabine
Doses and schedule as per I1

750 mg/m i.v day 1
1.4 mg/m i.v days 1 and day 15
75 mg/m p.o.daily days1-7 and days 15-21
100 mg/m sc every 12 hours 6 doses on
days 1-3 and days 15-17
30 mg/m i.v days 15
Daunorubicin
Maintenance
(M, six cycles)
Prednisone
Vincristine
Daunorubicin
L-Asparaginase
Methotrexate
Mercaptopurine
40 mg/m p.o.days 1-7

1.4 mg/m i.v on day 1
30 mg/m i.v on day 1
6000 u/m i.m days 1,3,5 and 7
15 mg/m p.o., once a week. Missing every
4th for a total of 12 weeks. Begin on day 15
75 mg/m p.o. daily, 3 weeks out of every 4
For total of 12 weeks. Begin on day 15
Each cycle subsequent to I1, began as soon as the neutrophil count is >/= 1000/m3 and the platelet count is >/= 100,000/mm
*Dose for patient >/=3 years: patients aged 2-3 years 10 mg: patients aged 1-2 years received 8 mg, and patients less than one year
received 6 mg
Treatment of AML
Induction chemotherapy for AML consists of aggressive
multiagent protocols. An anthracycline (daunorubicin
or Idarubicin) is used in combination with cytosine

arabinoside, given over 7-10 days with or without
etoposide. The resultant myelosuppression takes about
Pediatric Oncology
3-4 weeks to recover. About 70% patients achieve
remission at the end of induction chemotherapy. Post
remission treatment consists of 2 courses of high-dose
chemotherapy using cytosine arabinoside. There is no
definitive role of maintenance chemotherapy in
childhood AML.
Acute promyelocytic leukemia (APML) or AML M3
is characterised by the presence of t (15:17) involving the
retinoic acid receptor (RAR). The use of all transretinoic acid (ATRA) causes the differentiation of the
promyelocytes leading to their maturation with
resolution of the coagulopathy. Its use in combination
with chemotherapy like anthracycline leads to complete
remission. Maintenance therapy with ATRA improves
long-term disease free survival. Arsenic trioxide, alone
or in combination with ATRA has also produced
excellent response rates in APML patients.
Supportive Care
Supportive care is extremely important in the treatment
of acute leukemias. This includes blood component
therapy and aggressive management of infectious
complications. Packed red blood cell transfusions are
indicated to maintain hemoglobin over 8 gm/dl in well
children and over 10 gm/dl in patients with fever and
infection. Platelet transfusions are indicated if platelet
count is less than 10000/cmm or in the case of overt
bleeding, especially in patients with fever and infection.
Every episode of febrile neutropenia should be treated
aggressively with broad-spectrum antibiotics after
drawing blood cultures. All patients should receive
prophylaxis for Pneumocystis carinii pneumonia with
cotrimoxazole and for fungal infections with clotri-
879
mazole. Maintenance of oral and perianal hygiene

reduces the risk of infections to a significant extent. The
use of hematopoietic growth factors (GCSF and
GMCSF) reduces the period of neutropenia but are
expensive and do not improve the overall outcome of
the patients.
Bone Marrow Transplantation
The indications for bone marrow transplantation or stem
cell transplantation in ALL in first remission include
those patients who are at very high risk for relapse. These
include those patients with presence of t (9, 22), those
who continue to have minimal residual disease after first
few months of intensive chemotherapy or those who fail
to achieve remission at the end of induction. It is also
indicated for those patients who have an early relapse
i.e. while still on treatment. In AML it is indicated in first
remission in those who have adverse cytogenetic features
and for all patients who relapse.
Prognosis
Survival in ALL has improved from 1%in 1965 to 50% in
the mid-70s and up to 70% in the mid-90s. ALL is a
heterogeneous disease and prognosis depends on the
subtype, the tumor burden at presentation, the associated
cytogenetic abnormality, the ploidy, and most
importantly, the response to treatment. Early clearance
of blasts from the peripheral blood (day 7 absolute blast
count) after initiation of treatment and evidence of bone
marrow remission on day 14 of induction therapy has
been associated with a very good prognosis. Table 16.2.5
lists the prognostic factors in childhood ALL.
TABLE 16.2.5: Prognostic features in acute lymphoblastic leukemia

Feature
Standard risk
High risk
Age
Sex
Initial WBC count
Hepatosplenomegaly
Lymphadenopathy
Mediastinal mass
CNS leukemia
Phenotype
Ploidy
Cytogenetics
Response to treatment
2-10 years
Females
< 50000/cmm
Absent
Absent
Absent
Absent
Pre B (T-cell- intermediate)
Hyperdiploidy
T (12:21), trisomy 4 and 10
Good early response
< 1 year, >10 years

Males
>50000/cmm
Massive
Massive
Present
Present
Mature B-cell
Hypodiploidy
T (9:22), t (4,11),t (8:14)
Poor early response
880
BIBLIOGRAPHY
1. Advani SH. Treatment of ALL in India: An analysis of
risk factors and results at three major centers. Med Ped
Oncol 2002;39:259.
2. Advani SH, Pai SK, Venzon D, et al. ALL in India: An
analysis of prognostic factors using a single treatment
regimen. Ann Oncol 1999;10:167-76.
3. Arico M, Valsecch MG, Camitta B, et al. Outcome of
treatment in children with Ph chromosome positive ALL.
New Eng J Med 2000;342:998-1006.
4. Chessels JM. The management of high risk lymphoblastic
leukemia in children. Br J Hema 2000;108:204-16.
5. De Boton S, Coiteux V, Chevret S, Rayon C, Vilmer E, et
al. Outcome of childhood acute promyelocytic leukemia
with all-trans retinoic acid and chemotherapy. J Clin
Oncol 2004;15;22(8):1404-12.
6. Gaynon P S, Trigg ME, Heerma NA, et al. Childrens
Cancer Group trials in ALL from 1983-1995. Leukemia
2000;14:2223-33.
7. Golub TR, Arceci RJ. Acute myelogenous leukemia. In:
Pizzo PA, Poplack DG, editors. Principles and Practice
of Pediatric Oncology. Philadelphia: Lippincott-Williams
and Wilkins 2006;591-644.
8. Hill FG, Richards S, Gibson B, Hann I, Lilleyman J,
Kinsay S, et al. Successful treatment without cranial
irradiation of children receiving intensified chemotherapy for acute lymphoblastic leukemia: Results of a
risk stratified randomised central nervous system
treatment trial, MRC UKALL XI Br J Hematol 2004;
124(1):33-46.
9. Kanerva J, Saarinen PihkalaUM, Niini T, Riikonen P,

MottonenM, Makipernaa A, Salmi TT, Vettenraata K,
Knuutila S. Favourable outcome in 20 year follow-up of
children with very low risk ALL and minimal standard
therapy with special reference to TEL-AML1 fusion.
Pediatric Blood Cancer 2004;42(1):30-5.
10. Magrath I, Shantha V, Advani SH, Adde M, Arya LS,
Banavali SD, et al. Treatment of acute lymphoblastic
leukemia in countries with limited resources; lessons
learnt from a single protocol in India over a twenty year
period. Eur J Cancer 2005;41:1570-83.
11. Margolin JF, Steuber CP, Poplack DG. Acute lymphoblastic leukemia. In: Pizzo PA, Poplack DG, editors.
Principles and Practice of Pediatric Oncology.
Philadelphia: Lippincott-Williams and Wilkin 2006;
538-90.
12. Pui CH, Evans W. Treatment of acute lymphoblastic
leukemia. N Engl J Med 2006;364:166-78.
13. Schrappe M, Reiter A, Ludwig WD, et al. Improved
outcome in childhood ALL despite reduced use of
anthracyclins and cranial RTResults of trial. ALL- BFM
90 Blood 2000;95:3310-22.
14. Silverman LB, Sallan SE. Newly diagnosed childhood
ALL. An update on prognostic factors and treatment.
Current Opinoions Hematol 2003;10(4):290-96.
15. Woods W G, Neudorfs, Gold S, et al. A comparison of
allogenic bone marrow transplant, autologous bone
marrow transplant and aggressive chemotherapy in
children with AML in 1st remission. A report from the
CCG. Blood 2001;97:56-62.
16.3 Hodgkins Disease

INTRODUCTION
Hodgkins disease (HD) is a malignant disorder of
lymphoreticular system. Hodgkins disease occurs in 5
to 7 per 1,00,000 population. The incidence is highest in
late childhood and early adulthood (15-35 years). It is
very uncommon under 5 years of age and almost never
seen under 2 years of age. In asian population, HD is
common even at younger ages. The sex ratio progresses
from male preponderance of 10:1 under the age of 7 years
falling to 1.1:1 after the age of 12 years.
Etiology
Variation in the incidence of HD in different ethnic
groups and association with human leukocyte antigen
suggests that inherited susceptibility plays an important

role in the pathogenesis. Environmental factors such as
Epstein-Barr virus infection, familial clustering of cases
and higher incidence in twins may be some of the other
contributing factors.
Pathology (Table 16.3.1)
Hodgkin lymphoma can be dividea
Nodular Lymphocyte-Predominant
Hodgkin Lymphoma (NLPHL)
This pathologic class of Hodgkin lymphoma is characterized by large cells with multilobed nuclei, referred to
as popcorn cells. NLPHL is most common in males
Pediatric Oncology
younger than 10 years. Patients with NLPHL generally
present with localized, nonbulky disease. Almost all
patients are asymptomatic.
Classical Hodgkin Lymphoma
The hallmark of classic Hodgkin lymphoma is the R-S
cell. This is a binucleated or multinucleated giant cell
that is often characterized by a bilobed nucleus, with two
large nucleoli, giving an owls eye appearance to the cells.
The classical subtypes are defined according to the
number of Reed-Sternberg (R-S) cells, characteristics of
the inflammatory milieu, and the presence or absence of
fibrosis. A striking characteristic is the rarity (about 1%)
of the malignant R-S cell in specimens and the abundant
reactive cellular infiltrate of lymphocytes, macrophages,
granulocytes, and eosinophils. The histologic features
and clinical symptoms of Hodgkin lymphoma have been
attributed to the numerous cytokines secreted by the RS cells, which include interleukin-1, interleukin-6, and
tumor necrosis factor. Classical HD is divided into four
subtypes as detailed in the Table 16.3.1.
Staging (See Table 16.3.2)
A
B
No symptoms
Fever, night sweats, or weight loss of more
than 10% of body weight in the previous
6 months.
Bulky disease (greater than 10 cm in
maximum dimension; greater than 1/3rd of
the internal transverse diameter of the
thorax at the level T5/T6.
TABLE 16.3.2 : Modified Ann Arbor classification of

Hodgkins disease
Stage
Description
Involvement of single lymph node region (I) or of a

single extralymphatic or site (IE) by direct extention.
Involvement of two or more lymph node regions on
the same side of diaphragm or localized
involvement of an extra-lymphatic organ or site and
of one or more lymph node regions on the same
side of the diaphragm (IIE)
Involvement of lymph node regions on both sides
of the diaphragm Abdominal disease is limited to
the upper abdomen (i.e. spleen, splenic hilar
nodes, celiac nodes, porta hepatitis nodes)
Involvement of lymph node regions on both sides
of the diaphragm Abdominal disease includes paraaortic, mesenteric, and iliac involvement with or
without disease in the upper abdomen.
Disseminated involvement of one or more
extralymphatic organs or tissues with or without
associated lymph node disease.
II
III1
III2
IV
E
CS
PS
Limited involvement of a single extranodal site

Clinical stage: When based solely on
physical examination and imaging technique.
Pathologic stage: When based on biopsies
HD has an insidious onset. The most frequent presentation in up to 80% of patients is painless cervical
lymphadenopathy, of which 60% have asymptomatic
TABLE 16.3.1: Histopathologic classification of classical Hodgkins disease

Rye
1. Lymphocyte Rich (LR)
2. Nodular sclerosis (NS)
3. Mixed cellularity*
(MC)
4. Lymphocyte depletion (LD)
Distinctive features
Relative frequency (%)
Benign appearing lymphocytes with or without histiocytes.

Few Reed-Sternberg (R-S) cells
No fibrosis
Thickened capsule with proliferation of orderly collagenos
bands, that divide lymphoid tissue in nodules: Lacunar
variant of R-S cells.
5-15 R-S cells per high power field. Fine fibrosis in interstitium
Focal necrosis may be present
10-15
Abnormal cells with relative paucity of lymphocytes.

Fibrosis and necrosis common but diffuse
*Most common in developing countries and in children.
881
20-50
20-40
5-16
882
involvement of the mediastinum. Constitutional or class

B symptoms are more common with advanced disease
(stage I-5%, stage IV-81%) and are associated with a
poorer outcome. Uncommon extranodal sites are CNS,
bone, GIT and skin. A reduced cell mediated immunity
results in an increase susceptibility to infections.
Evaluation of a Patient
History and Physical examination
Complete blood count
Liver and renal function tests, Serum LDH, Serum
albumin
Lymph node biopsy
Bone marrow aspiration and biopsy: This is done in
advanced disease (III,IV), B-symptoms, bony
involvement or abnormal counts.
Radiological studies: Chest X-ray, CT Scan of neck,
chest and abdomen and pelvis, Imaging of other sites
as and when indicated
Positron emission tomography (PET) Scan of the
whole body:
PET scanning may identify more sites of initial disease
than conventional imaging and is more accurate in
detecting viable Hodgkin lymphoma in posttherapy
residual masses., PET scanning should be performed at
baseline and a minimum of 3 weeks post chemotherapy
completion and 8 to 12 weeks post radiation.
Prognostic Factors in Hodgkin Lymphoma
Several factors influence the success and choice of
therapy. Pretreatment factors associated with an adverse
outcome include advanced stage of disease, presence of
B symptoms, bulky disease, extranodal extension, male
sex, and elevated erythrocyte sedimentation rate. These
factors are interrelated in the sense that disease stage,
bulk, and biologic aggressiveness are frequently
codependent. There is some controversy as to whether
histology is an important prognostic factor. The rapidity
of response to initial cycles of chemotherapy based on
PET is also prognostically important and is being used
to determine subsequent therapy.
of children are gender-specific differences in chemotherapy-induced gonadal injury. The desire to cure young
children with minimal side effects has stimulated
attempts to reduce the intensity of chemotherapy
(particularly alkylating agents) and radiation dose or
volume. In general, the use of combined chemotherapy
with radiation broadens the spectrum of potential
toxicities, while reducing the severity of individual drugrelated or radiation-related toxicities. Current approaches
use chemotherapy alone with or without low-dose
involved-field radiation therapy (LD-IFRT). The volume
of radiation and the intensity/duration of chemotherapy
are determined by prognostic factors at presentation,
including presence of constitutional symptoms, disease
stage, and bulk.
All children generally receive combination chemotherapy as initial treatment. While regimens containing
alkylating agents are associated with an increased risk
for infertlity and therapy-related leukemia; in nonalkylator-containing regimens, doxorubicin is associated
with cardiac damage and bleomycin can produce
pulmonary fibrosis. Common regimens currently utilized
for treatment include non-alkylator-containing regimens
such as ABVD (doxorubicin [Adriamycin], bleomycin,
vinblastine, and dacarbazine), Hybrid regimens with
lower total cumulative doses of alkylators, doxorubicin,
and bleomycin such as COPP/ABV (cyclophosphamide,
vincristine, procarbazine, prednisone/doxorubicin,
bleomycin, and vinblastine), DBVE (doxorubicin,
bleomycin, vincristine, etoposide), BEACOPP
(bleomycin, etoposide, Adriamycin, cyclophosphamide,
vincristine (Oncovin), prednisone, procarbazine) and
VAMP (vincristine, doxorubicin, methotrexate, and
prednisone). The current therapeutic strategy and
outcome for children with HD is outlined in Table 16.3.3.
TABLE 16.3.3: Treatment modalities and results in
Hodgkins disease
Risk Group
Treatment modality
Survival DFS%
Low Risk
(Stage I, IIA,
no Bulk,
No B symptoms)
VAMP/DBVE/ABVD
96-98
2-4 cycles + Low-dose
field RT
High Risk
(IIB, III, IV,
bulky disease)
COPP-ABV/ DBVEPC/ABVD 6 cycles +

Involved field RT
Treatment
Treatment of HD in pediatric population is different in
certain respects from adults. Devising the ideal
therapeutic approach for children with HD is complicated by their increased risk for late adverse effects. In
particular, radiation therapy can cause profound
musculoskeletal growth retardation and increase the risk
for cardiovascular disease and secondary solid malignancies in children. Further complicating the treatment
RT = Radio therapy
70-75
Pediatric Oncology
Nodular Lymphocyte-Predominant Hodgkin
Lymphoma (NLPHL)
Children with NLPHL have a favorable outcome,
particularly when the disease is in early stage. Thus,
treatment for NLPHL focuses on reducing initial therapy
to reduce long-term treatment-related morbidity and
mortality. Although current standard therapy for
children with NLPHL is chemotherapy plus LD-IFRT,
patients have also been successfully treated with either
chemotherapy alone or complete resection of isolated
nodal disease.
Principles of Radiotherapy
Most newly diagnosed children are treated with riskadapted chemotherapy alone or in combination with LDIFRT. LD-IFRT involves the use of meticulous and
judiciously designed fields to achieve local control of
disease and to minimize damage to normal tissue. The
LDRT treatment volume includes the initially involved
lymph node region(s). In general, doses of 15 Gy to 25
Gy are used, with modifications based on patient age,
the presence of bulk or residual (postchemotherapy)
disease, and normal tissue concerns. Transposition of
ovaries to midline and midline pelvic block to protect
ovarian function and testicular shield or sperm banking
in male children is routinely considered.
883
avascular necrosis. Radiation therapy can lead to thyroid

dysfunction, increased risk for myocardial atherosclerotic
heart disease, and is associated with solid tumor
development in radiation fields. All these potential
complications mandate a close long-term follow-up after
completion of therapy.
CONCLUSIONS
Hodgkins disease is one of the most curable cancers in
children. Current use of appropriate staging techniques
and treatment protocols has resulted in an excellent
overall survival. The formidable challenge is to maintain
high cures and ameliorate treatment sequelae.
BIBLIOGRAPHY
1.
2.
3.
4.
Late Effects
5.
Survivors of Hodgkin lymphoma are at risk for numerous

late complications of treatment. Alkylating agents and
etoposide have been associated with acute myeloid
leukemia (AML) and myelodysplastic syndromes.
Doxorubicin can lead to cardiomyopathy and bleomycin
can cause pulmonary fibrosis. Steroid use can produce
6.
7.
AB Thomson, WHB. Wallace Treatment of Pediatric

Hodgkins Diseasea balance of risks European Journal
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G Schellong. The balance between cure and late effects
in childhood Hodgkins lymphoma: The experience of
the German-Austrian Study-Group since 1978. Annals
of Oncology 1996;7(Suppl 4):S67-S72.
H Van den Berg, J Zsiros, H Behrendt. Treatment of
childhood Hodgkins disease without radiotherapy
Annals of Oncology 1997;8(Suppl.1):S15-S17.
Karayalcin G, Behm FG, Gieser PW, et al. Lymphocyte
predominant Hodgkin disease: Clinico-pathologic
features and results of treatmentthe Pediatric Oncology
Group experience. Med Pediatr Oncol 1997;29(6):519-25.
Meany HJ, Gidvani VK, Minniti CP. Utility of PET scans
to predict disease relapse in pediatric patients with
Hodgkin lymphoma. Pediatr Blood Cancer 2007;
48(4):399-402.
R Potter. Pediatric Hodgkins Disease European Journal
of Cancer 1999;35(10):1466-74.
Schwartz CL. Special issues in pediatric Hodgkins
disease. Eur J Hematol Suppl 2005;(66):55-62.
16.4 Non-Hodgkins Lymphoma

INTRODUCTION
Non-Hodgkins Lymphoma (NHL) is neoplasm of a wide
range of cell types that comprise the immune system.
All lymphomas are generalized diseases from the outset
and have patterns of spread that mimic the migration

patterns of their normal cellular counterparts. Lymphoma (Hodgkin and non-Hodgkin) is the third most
common childhood malignancy, and NHL accounts for
approximately 7% of cancers in children younger than
884
20 years. NHL occurs most commonly in the second

decade of life, and occurs less frequently in children
younger than 3 years. Immunodeficiency, both congenital and acquired (HIV infection or posttransplant),
increases the risk of NHL. With current treatments, about
80% of children and adolescents with NHL will survive
at least 5 years.
Classification and Clinical Presentation
(Table 16.4.1)
In children, NHL is distinct from the more common
forms of lymphoma observed in adults. While lymphomas in adults are more commonly low or intermediate
grade, are dominantly nodal, have variable growth
fraction and poor long-term outcome; almost all NHL
that occurs in children is high grade, extranodal, has
higher growth fraction and good outcome. Classification
of NHL in childhood is based on clinical behavior,
response to treatment and immunophenotype.
NHL of childhood currently falls into three therapeutically relevant categories: (1) B-cell NHL (Burkitt
lymphoma/leukemia and diffuse large B-cell lymphoma); (2) lymphoblastic lymphoma (primarily precursor
T-cell lymphoma and, less frequently, precursor B-cell
lymphoma); and (3) anaplastic large cell lymphoma (T-
cell or null-cell lymphomas). Each type of childhood NHL

is associated with distinctive molecular biological
characteristics.
Clinical Features
Burkitt Lymphoma
Burkitt lymphoma accounts for about 50% of childhood
NHL and exhibits consistent, aggressive clinical
behavior. The malignant cells show a mature B-cell
phenotype. Burkitt lymphoma expresses a characteristic
chromosomal translocation, usually t(8;14) and more
rarely t(8;22) or t(2;8). Each of these translocations
juxtaposes the c-myc gene to immunoglobulin locus
regulatory elements, resulting in the inappropriate
expression of c-myc, the gene involved in cellular
proliferation.The two most common primary sites of
disease are the abdomen and head-neck region. Other
sites of involvement include testes, bone, peripheral
lymph nodes, skin, bone marrow, and central nervous
system (CNS).
Diffuse Large B-cell Lymphoma
DLBCL is a mature B-cell neoplasm that represents 10%
to 20% of pediatric NHL. DLBCL occurs more frequently
TABLE 16.4.1: Major histopathological categories as per WHO classification

NHL type
Immuno-phenotype
Chromosome Translocation
Genes Affected
Burkitt and
Burkitt-like
lymphomas
Mature B-cell
t(8;14)(q24; q32),
t(2;8) (p11;q24),
t(8;22)(q24; q11)
C-MYC, IGH, IGK, IGL
Diffuse large
B-cell
Mature B-cell
Intra-abdominal
(sporadic), head and
neck (non-jaw, sporadic),
jaw (endemic)
Nodal, abdomen,
bone, primary
CNS, mediastinal
Lymphoblastic
Pre-T-cell
lymphoma
(precursor
Pre-B-cell
T-cell or
precursor B-cell)
Mediastinal,
bone marrow
Skin, bone
Anaplastic large
cell lymphoma
(systemic)
Lymph node,
skin, bones,
visceral, soft tissues
CD30+
(Ki-1+)
T-cell or null cell
No consistent
cytogenetic
abnormality
identified
MTS1/
p16ink4a
deletion TAL1
t(1;14) (p34;
q11), t(11;14)
(p13;q11)
t(2;5) (p23;
q35)
TAL1, TCRAO, RHOMB1,

RHOMB1, HOX11
ALK-NPM
Pediatric Oncology
during the second decade of life than during the first.
Pediatric DLBCL may present clinically similar to Burkitt,
though it is more often localized and less often involves
the bone marrow or CNS. Outcomes for children with
DLBCL are more favorable than those observed in adults,
with overall 5-year event-free survival (EFS) rates of
approximately 90% in children.
About 20% of pediatric DLBCL present as primary
mediastinal disease (primary mediastinal B-cell lymphoma [PMBCL]). This presentation is more common in
older children and adolescents and is associated with an
inferior outcome compared with other pediatric DLBCL.
Lymphoblastic Lymphoma
Lymphoblastic lymphoma makes up approximately 20%
of childhood NHL. More than 75% of lymphoblastic
lymphomas have a T-cell immunophenotype and the
remainder have a precursor B-cell phenotype.
Nearly 75% of patients with lymphoblastic lymphoma present with anterior mediastinal mass, and
symptoms of dyspnea, wheezing, stridor, dysphagia, or
swelling of the head and neck. Pleural effusions may be
present, and the involvement of lymph nodes, usually
above the diaphragm, may be a prominent feature. There
may also be involvement of bone, skin, bone marrow,
CNS, abdominal organs (but rarely bowel), and
occasionally other sites such as lymphoid tissue of
Waldeyer ring and testes. Patients with more than 25%
marrow blasts are considered to have leukemia, and
those with fewer than 25% marrow blasts are considered
to have lymphoma.
885
Evaluation of Children with NHL

History and physical examination
Complete blood count, peripheral smear
Renal function, uric acid, liver function, serum
albumin, lactate dehydrogenase
Examination of cerebrospinal, peritoneal, pericardial
or pleural fluid-cytomorphology and immunophenotyping
Surgical biopsy
Chest radiograph or CT-scan of the chest
Ultrasonography/CT-Scan of the abdomen with
contrast
Bone marrow aspiration and Biopsy
Plain radiogram/ CT-scan of other affected sites
PET scan of whole body (optional)
Staging
The most widely used staging scheme for childhood nonHodgkin lymphoma (NHL) is that of the St. Jude
Childrens Research Hospital (Murphys Staging), which
is outlined in Table 16.4.2. In general, treatment for
childhood NHL depends on localized versus disseminated disease. Localized disease is usually defined as
stage I or II disease, while stage III or IV disease is
generally considered disseminated.
Management
Childhood NHL is an extremely chemosensitive disease.
Surgery plays a very limited role, mainly for arriving at
TABLE 16.4.2: St Judes staging system for childhood NHL
Anaplastic Large Cell Lymphoma
Low risk
(localized)
Stage Definition
I
High risk
(advanced)
Anaplastic large cell lymphoma (ALCL) accounts for

approximately 10% of childhood NHL. While the
predominant immunophenotype of ALCL is mature Tcell; null-cell disease (i.e. no T-cell, B-cell, or NK-cell
surface antigen expression) does occur. More than 90%
of ALCL cases have the translocation t(2;5)(p23;q35)
leading to the expression of the fusion protein NPM/
ALK. Clinically, ALCL has a broad range of presentations, including involvement of lymph nodes and a
variety of extranodal sites, particularly skin, bone,
gastrointestinal tract, lung, pleura, and muscle.
Involvement of the CNS and bone marrow is uncommon.
ALCL is often associated with systemic symptoms (e.g.
fever, weight loss) and a prolonged waxing and waning
course, making diagnosis difficult and often delayed.
III
II
IV
Single tumor (extranodal)Single anatomic area

(nodal) excluding mediastinum or abdomen
Single tumor (extranodal) with regional node
involvement. Primary gastrointenstinal tumor with
or without involvement of mesentric node.or
On same side of diaphragm:
a. Two or more nodal areas
b. Two single extranodal tumors with or without
regional node involvement
All primary intrathoracic tumors. All extensive
primary intra-abdominal disease. Two or more
nodal or extranodal areas on both sides of
diaphragm
Any of the above with CNS or bone marrow
involvement
886
a diagnosis. Radiation of primary sites is used very rarely

in emergency situations. Hence, multi-agent chemotherapy directed to the histologic subtype and stage of
the disease remains the cornerstone of therapy.
There are two potentially life-threatening clinical
situations that are often seen in children with NHL: (1)
superior vena cava syndrome (SVCS) often seen in
lymphoblastic lymphoma; and (2) tumor lysis syndrome,
most often seen in lymphoblastic and Burkitt NHL. These
emergent situations should be anticipated in children
with NHL and addressed immediately.
Patients with large mediastinal masses and SVCS are
at risk of cardiac or respiratory arrest during general
anesthesia or heavy sedation. Due to these risks, the least
invasive available procedure to establish the diagnosis
of lymphoma such as bone marrow examination,
thoracocentesis, a lymph node biopsy under local
anesthesia or a computed tomographyguided core
needle biopsy should be contemplated. Tumor lysis
syndrome results from the rapid breakdown of malignant
cells resulting in a number of metabolic abnormalities,
most notably hyperuricemia, hyperkalemia, and
hyperphosphatemia. Hyperhydration and allopurinol or
rasburicase (urate oxidase) are essential components of
therapy. Gastrointestinal bleeding, obstruction, and
(rarely) perforation may also occur in abdominal NHL.
Therapy of Pediatric NHL
Localized Non-Hodgkin Lymphoma in Children
Stage I and II patients with grossly resected (>90%)
disease regardless of histology have an excellent
prognosis, with 90% or better disease-free survival (DFS).
For localized B-NHL (Burkitts or DLBL), use of short,
intensive, pulsed chemotherapy for 2-3 months with
aggressive CNS-directed chemotherapy without cranial
radiation is standard. Common drugs used are
dexamethasone, cyclophosphamide, methotrexate,
cytarabine, prednisolone (IT), intrathecal methotrexate,
ifosfamide, etoposide and doxorubicin.
For localized lymphoblastic lymphoma (grossly
resected, i.e. >90% stage I/II disease), a leukemia like
approach with induction, consolidation, CNS-directed
therapy and maintenance for a total of 18-24 months leads
to more than 90% DFS.
For localized anaplastic large cell lymphoma (ALCL),
pulsed chemotherapy similar to B-NHL therapy is
preferred.
Disseminated Childhood B-cell Non-Hodgkin

Lymphoma
Patients with disseminated B-lineage NHL (Burkitt or
DLBCL) have an 80% to 90% long-term survival through
the use of short, intensive, pulsed chemotherapy with
aggressive CNS-directed chemotherapy without cranial
radiation. The use of high-dose methotrexate (>5 g/m2),
cytarabine, and etoposide have appeared to be helpful
in addition to the drugs mentioned above. Patients with
Burkitt leukemia should be treated with protocols
designed for Burkitt lymphoma. Rituximab is a mouse/
human chimeric monoclonal antibody targeting the
CD20 antigen and is routinely used against DLBCL in
adults. In children, rituximab in combination with the
intensive chemotherapy regimen is being evaluated.
Disseminated Childhood
Lymphoblastic Lymphoma
Patients with disseminated lymphoblastic lymphoma
have long-term survival rates higher than 80%. As
opposed to other pediatric NHL, lymphoblastic lymphoma responds much better to leukemia like therapy over
2 years than with shorter, intensive, pulsed chemotherapy regimens. Common drugs used are prednisone,
dexamethasone, vincristine, daunorubicin, doxorubicin,
L-asparaginase, cyclophosphamide, cytarabine, methotrexate, 6-mercaptopurine and 6-thioguanine. Cranial
radiation is currently used only for patients with CNS
disease at diagnosis.
Disseminated Childhood Anaplastic
Large Cell Lymphoma
Children and adolescents with disseminated anaplastic
large cell lymphoma (ALCL) have a disease-free survival
(DFS) of approximately 60% to 75%. Both short pulse
intensive as well as leukemia like strategies are effective
for the treatment of disseminated ALCL.
CONCLUSIONS
Intensive combination regimens with optimal supportive
care have been shown to be feasible and curative for most
children with NHL. The current focus is now on reducing
therapy for low risk disease and intensifying treatment
for high risk NHL for optimum long term survival.
Management of relapses continues to be a challenge and
warrants high dose chemotherapy with stem cell rescue
in selected cases.
Pediatric Oncology
BIBLIOGRAPHY
1.
Anderson JR, Jenkin DT, Wilson JF, et al. Long-term

follow-up of patient treated with COMP or LSAL2
therapy for childhood non Hodgkins lymphoma: report
of CCG 551 from the Childrens Cancer Group. J Clin
Oncol 1993;11:1024-32.
2. Magrath. The treatment of pediatric lymphomas:
Paradigms to plagiarize?Annals of Oncology 8 (Suppl 1):
S7-S14, 1997.
3. Patte C, Michon J, Frappaz D, et al. Short-pulse B Non
Hodgkins lymphoma type chemotherapy is efficacious
treatment for pediatric anaplastic large cell lymphoma:
887
a report of the Berlin-Frankfurt-Munster group trial NHL

BFM 90. Blood 2001;97:3699-3706.
4. Reiter A, Schrappe M, Parwaresch, et al. Non Hodgkins
lymphomas of childhood and adolescence: results of a
treatment stratified for biologic subtypes and stage - a
report of the Berlin-Frankfurt-Munster group. J Clin
Oncol 1995;13:359-372.
5. Reiter A, Schrappe M, Tiemann M, et al. Improved
treatment results in childhood B-cell neoplasms with
tailored intensification of therapy: a report of the BerlinFrankfurt-Munster group Trial NHL - BFM 90. Blood
1999;94:3294-3306.
16.5 Wilms Tumor

INTRODUCTION
Wilms tumor is the commonest childhood renal tumor
and is named after a German surgeon Max Wilms, who
described it first in 1899. Wilms tumor develops as a
result of abnormalities in the development of metanephric blastema. Wilms tumor is the model tumor for
multidisciplinary treatment approach in pediatric
malignant solid tumors.
Epidemiology
The median age at presentation is 4 years for unilateral
tumors and 2.5 years for bilateral tumors. Approximately
1.5 % cases of Wilms tumor are familial. It constitutes 6
% of all childhood cancers.
Wilms tumor normally develops in otherwise healthy
children; however, approximately 10% of patients with
Wilms tumor have recognizable phenotypic syndromes
which have been divided into overgrowth and nonovergrowth categories. Overgrowth syndromes result in
macroglossia, nephromegaly, and hemihypertrophy such
as Beckwith-Wiedemann syndrome ( BWS; 10% to 20%
of Wilms tumor incidence), isolated hemihypertrophy
(3% to 5% of Wilms tumor incidence), Perlman syndrome, and Sotos syndrome etc. Examples of nonovergrowth syndromes are isolated aniridia; Wilms
tumor, aniridia, ambiguous genitalia, and mental
retardation (WAGR) syndrome; Blooms syndrome, and
Denys-Drash syndrome (characterized by intersexual
disorders, nephropathy, and Wilms tumor). Children

with a predisposition to develop Wilms tumor (e.g.,
Beckwith-Wiedemann syndrome, WAGR, hemihypertrophy, or aniridia) should be screened with ultrasound
every 3 months until they reach age of 8 years.
Although most patients with Wilms tumor are
karyotypically normal, genomic studies have led to the
localisation and subsequent cloning of WT genes in two
regions - 11p13 and 11p15. The former is WT1 gene and
is associated with WAGR Syndrome and the latter is WT2
gene which is associated with Beckwith Wiedemann
Syndrome. Additional tumor-suppressor or tumorprogressive genes may lie on chromosomes 16q and 1p
as evidenced by LOH for these regions in 17% and 11%
of Wilms tumors, respectively. Patients classified by
tumor-specific loss of these loci have significantly worse
relapse-free and overall survival rates, and warrant more
aggressive therapy.
Pathology
Most Wilms tumors are unicentric, 11% are multicentric
but unilateral and 7% are bilateral. Histologically, Wilms
tumor mimics development of a normal kidney consisting of three-cell types (triphasic): blastemal, epithelial
(tubules), and stromal. Not all tumors are triphasic, and
monophasic patterns may present diagnostic difficulties.
There is no anaplasia in 90% of Wilms tumors.
Approximately 10% cases may have anaplastic histology
(extreme cellular pleomorphism and atypia), which may
888
be focal or diffuse. Focal anaplasia does not confer a poor

prognosis, while diffuse anaplasia does. Anaplasia is
associated with resistance to chemotherapy and may still
be detected after preoperative chemotherapy. Clear cell
sarcoma of the kidney, rhabdoid tumor of the kidney,
neuroepithelial tumor of the kidney, and cystic partiallydifferentiated nephroblastoma are childhood renal
tumors distinct from Wilms tumor.
Investigations
Investigation
1. Abdominal USG
and Doppler
2. CT-Scan
Clinical Features
Most commonly patients present with a palpable
abdominal mass accidentally noted by the parents or
during the course of a routine clinical examination.
However, about one third of patients present with
abdominal pain, anorexia, vomiting, malaise, or a
combination of these symptoms. Gross or microscopic
hematuria is found in 30% of patients. Hypertension is
present in about 25% and is attributed to increase in renin
activity. Occasional presentation in a subset of patient is
rapid enlargement of the abdomen associated with fever,
anemia and hypertension as a result of sudden subcapsular hemorrhage. In rare cases of renal vein or caval
extension of tumor, varicocele, hepatomegaly, ascites or
congestive heart failure may be present. Acquired von
Willebrands disease may occur in less than 10% of
patients. Features of congenital syndromes may be
present in 13-28% of patients.
3. Chest Xray/CT-Scan
4. Fine needle aspiration
cytology of mass
Purpose
Organ of origin
Identify contralateral
Kidney involvement
Presence/absence of
tumor thrombus in IVC
Further evaluation of
extent of tumor extension
into adjoining structures
such as liver, spleen and
colon.Visualisation and
function of contralateral
kidney
Pulmonary metastasis
Cytological confirmation
of diagnosis prior to
prenephrectomy
chemotherapy
Staging: Due to the different treatment approaches

adopted by the two large cooperative study groups, two
major staging systems are currently used: american early
surgery-based system developed by the National Wilms
Tumor Study group (NWTSG Table 16.5.1) and an
european delayed surgery-based system developed by
SIOP (International society of Pediatric Oncology).
TABLE 16.5.1: Staging system of the National Wilms Tumor Study (NWTS)
Stage I
Tumor limited to the kidney and completely excised

a. The tumor was not ruptured before or during removal
b. The vessels of the renal sinus are not involved beyond 2 mm
c. There is no residual tumor apparent beyond the margins of excision
Stage II
Tumor extends beyond the kidney but is completely excised

a. No residual tumor is apparent at or beyond the margins of excision
b. Tumor thrombus in vessels outside the kidney is stage II if the thrombus is removed en bloc with the tumor
Stage III
Residual tumor confined to the abdomen:

a. Lymph nodes in the renal hilum, the periaortic chains, or beyond are found to contain tumor
b. Diffuse peritoneal contamination or implants are found on the peritoneal surfaces
c. Tumors was biopsied before surgery (tru-cut, open or FNAC)
d. Tumor extends beyond the surgical margins either microscopically or grossly
e. Tumor is not completely resectable because of local infiltration into vital structures
Stage IV
Presence of hematogenous metastases or metastases to distant lymph nodes
Stage V
Bilateral renal involvement at the time of initial diagnosis
Pediatric Oncology
Although a direct comparison is not practical due to the
difference in surgical timing, both staging systems are
valuable in predicting outcomes.
889
required. The NWTS treatment approach and outcome

is illustrated in Figure 16.5.1.
Principles of Surgery
Prognostic Factors
The tumor stage at diagnosis, histological features
(favorable vs unfavorable, presence of diffuse anaplasia)
and patient age are the most important prognostic
determinants which impact on treatment selection and
outcome. Loss of heterozygosity at chromosome 1p and
16q are also considered for treatment plan in current
trials.
Treatment
WT can be considered a model for successful multidisciplinary management of cancer, with improvement
in survival from a mere 30% in 1930s to more than 85%
at present. The most important contributions have been
from NWTSG and SIOP. However, there is a philosophical difference in their treatment approach. The
NWTSG recommends primary surgery before administration of chemotherapy while SIOP advocates administration of 4 weeks of chemotherapy prior to surgery.
NWTS approach allows accurate documentation of
histology and tumor extent prior to chemotherapy. The
SIOP approach downstages the disease, makes surgery
easier and reduces the chances of spillage with
consequent reduction in abdominal and distant relapse
but carries a risk of non-WT histology being present in
the primary tumor. The NWTSG advocates preoperative
chemotherapy only in presence of WT in a solitary or
horseshoe kidney, bilateral tumors and venal caval
thrombus above hepatic veins. Since both these
approaches have yielded excellent results; individualization of treatment based on tumor size and extent,
general condition of patient and surgeons experience is
Surgical resection is the most important component in

the multimodal management of WT. Radical nephrectomy with lymph node sampling through the transperitoneal route is the standard of care. Tumor spillage
and intraperitoneal dissemination increases the risk of
intraabdominal relapse. Partial nephrectomy is only
recommended for patients with synchronous or
metachronous bilateral tumors, tumors in solitary
kidneys, renal insufficiency of any etiology and children
with risk of multiple neoplasms such as in BWS.
Chemotherapy
Chemotherapy plays a very important role in the
management of WT. The current first line drugs for WT
are vincristine, dactinomycin and doxorubicin. The
second line drugs for non-responsive or relapsed disease
are ifosfamide, etoposide, carboplatin and cyclophosphamide. The SIOP group has favored the use of
preoperative chemotherapy in attempt to down stage the
tumor, whereas the NWTS advocates upfront nephrectomy without preoperative therapy in order to precisely
identify the tumor stage.
Radiotherapy
Radiation to flank or abdominal irradiation is considered
for stage III favorable-histology (FH) tumors and stage
IIIII diffuse anaplastic WT. Radiotherapy should be
planned starting within 10 day of surgery. Whole lung
irradiation is administered for patients with pulmonary
metastases.
Figure 16.5.1: Algorithm for Management (Based on NWTS)

CPM = cyclophosphamide; DAM = dactinomycin ; DOX = doxorubicin;
VCR = vincristine; RT = radiotherapy; FH = favourable histology;
UH= unfavourable histology; wk = week; PI = pulse intensive.
NWTS National Wilms Tumour Study Group
890
NWTS Treatment and Results
CONCLUSION
Patients with stages I-II/FH or stage I/anaplastic Wilms

tumor are classified as low risk (LR) and those with stages
III-IV/FH Wilms tumor or stages I-IV/anaplasia are
classified as high risk (HR).
Since Wilms tumor is one of the most curable malignancies of childhood; current emphasis is on maximizing
cure, minimizing late effects and continued surveillance
for late effects of therapy.
BIBLIOGRAPHY
Risk Group Treatment
Stage
2 yrs OS (%)
Low risk
I-II ( FH)
I(anaplasia)
III-IV/FH
II-IV/UFH
More than
95%
85-95%
40-80%
Low-intensity
CT
High Risk High intensity
CT+ RT
OS - Overall survival , CT-Chemotherapy, RT- radiotherapy
Long Term Sequelae

Renal failure after surgical management of unilateral WT
is rare. Cardiac problems secondary to anthracycline
administration compounded by whole lung radiotherapy
as well as pulmonary complications secondary to whole
lung radiotherapy are real concerns in long-term and
need to be addressed. Gonadal dysfunction secondary
to chemo and or radiotherapy may occur. Children
treated for WT are also at an increased risk of second
malignancy, especially if they have received radiotherapy
in addition to chemotherapy.
1. DAngio GJ, Breslow N, Beckwith JB, et al. Treatment of

Wilms tumor. Results of the Third National Wilms
Tumor Study. Cancer 1989;64(2):349-60.
2. Green DM, Breslow NE, Beckwith JB, et al. Effect of duration
of treatment on treatment outcome and cost of treatment
for Wilms tumor: a report from the National Wilms Tumor
Study Group. J Clin Oncol 1998;16(12): 3744-51.
3. Grundy PE, Breslow N, Li S, et al. Loss of Heterozygosity
for Chromosomes 1p and 16q is an Adverse Prognostic
Factor in Favorable Histology Wilms Tumor. A Report
from the National Wilms Tumor Study Group. J Clin
Oncol 2005;23:7312-21.
4. J De Kraker. Commentary On Wilms Tumour. European
Journal of Cancer 1997;33(3):419-20.
5. Kalapurakal JA, Dome JS, Perlman EJ, et al. Management
of Wilmstumor: current practice and future goals. Lancet
Oncol 2004;5:37-46.
6. Reinhard H, Semler O, Burger D, et al. Results of the
SIOP 93-01/GPOH trial and study for the treatment of
patients with unilateral nonmetastatic Wilms Tumor.
Klin Padiatr 2004;216:132-140.
7. Tournade MF, Com-Nougue C, de Kraker J, et al. Optimal
duration of preoperative therapy in unilateral and
nonmetastatic Wilms tumor in children older than 6
months: results of the Ninth International Society of
Pediatric Oncology Wilms Tumor Trial and Study. J Clin
Oncol 2001;19:488-500.
16.6 Neuroblastoma
INTRODUCTION
Neuroblastoma is the most common extracranial solid
tumor in children and the most common tumor in
infancy. Neuroblastoma and related neoplasms arise
from those neural crest cells which differentiate in to cells
of the sympathetic ganglia and adrenal medulla. Hence,
Neuroblastoma originates in the adrenal medulla or
paraspinal sites where sympathetic nervous system
tissue is present (Fig. 16.6.1).
Epidemiology
Neuroblastoma is predominantly a tumor of early
childhood, with two thirds of the cases presenting in
children younger than 5 years. It accounts for 7-10% of

all childhood cancers. The etiology is unknown.
Occasionally, it is congenital or is discovered prenatally
by fetal ultrasonography.
Clinical Features
The most common presentation of neuroblastoma is an
abdominal mass. The most common symptoms are due
to a tumor mass or bone pain from metastases. Approximately 70% of patients with neuroblastoma have
metastatic disease at diagnosis. Proptosis and periorbital
ecchymosis are common in these patients and arise from
retrobulbar metastasis (Fig. 16.6.2) Extensive bone
Pediatric Oncology
891
found. On rare occasions, children may have severe,

watery diarrhea due to the secretion of vasoactive
intestinal peptide by the tumor. Children with neuroblastoma rarely present with paraneoplastic neurologic
findings, including cerebellar ataxia or opsoclonus/
myoclonus. The opsoclonus/myoclonus syndrome
appears to be caused by an immunologic mechanism that
is not yet fully defined.
Pathology
Figure 16.6.1: Location of sympathetic chain
Neuroblastoma is one of the small blue round cell tumors

of childhood (others are Non-Hodgkins lymphoma,
Ewings/Primitive neuroectodermal tumor and Rhabdomyosarcoma). The typical neuroblastoma is composed
of small, uniform cells with hyperchromatic nuclei and
scanty cytoplasm. The presence of neuritic processes
(neurophil) and Homer-Wright pseudorosettes helps to
distinguish neuroblastoma from other round cell tumors.
The fully differentiated, benign counterpart of neuroblastoma is the ganglioneuroma which is composed of
mature ganglion cells, neurophils and schwann cells.
Ganglioneuroblastoma has features intermediate
between the other two.
Evaluation of Patient (Figs 16.6.3 and 16.6.4)
Primary site
X-Ray, USG, CT-Scan/MRI scan
24 hr-Urinary VMA
131I MIBG scan
Metastatic disease
Bone marrow aspiration and trephine biopsy
Technetium Bone scan
131I MIBG scan
Figure 16.6.2: NeuroblastomaRaccoons sign with

bilateral proptosis
marrow metastasis may result in pancytopenia. Abdominal distention with respiratory compromise due to
massive liver metastases may occur in infants. Because
they originate in paraspinal ganglia, neuroblastomas may
invade through neural foramina and compress the spinal
cord extradurally, causing paralysis. Horner syndrome
may be caused by neuroblastoma in the stellate ganglion,
and children with Horner syndrome without apparent
cause should be examined for neuroblastoma and other
tumors. Fever, anemia, and hypertension are occasionally
Figure 16.6.3: Abdominal neuroblastoma with calcification
892
Figure 16.6.4: Posterior mediastinal mass in

thoracic neuroblastoma
Diagnostic Criteria
The gold standard for the diagnosis of neuroblastoma is
examination of tumor tissue by histopathology. Some
neuroblastomas cannot be differentiated, via conventional light microscopy, from other small round blue cell
tumors of childhood. In these cases, evidence for
sympathetic neuronal differentiation may be demonstrated by immunohistochemistry, electron microscopy
or by finding elevated levels of serum catecholamines
(e.g., dopamine and norepinephrine) or urine catecholamine metabolites, such as vanillylmandelic acid (VMA)
or homovanillic acid (HVA).
The International Neuroblastoma diagnostic criteria
(INDC) are:
1. An unequivocal pathological diagnosis made from
tumor tissue by light microscopy (with or without
immunohistochemistry and electron microscopy
and/or increased urine catecholamines or metabolites
Or
2. Bone marrow aspirate or biopsy containing unequivocal tumor cells, and increased urine catecholamines
or metabolites.
Staging of Neuroblastoma
Clinical staging as per Evans (CCSG) staging system is
done if surgery is not done upfront. International
neuroblastoma staging system (INSS) is used when
surgical details are available and is one of the most
important prognostic factors.
INSS
EVANS
Stage 1
Stage I
Localized tumor confined to

the area of origin; complete
gross excision with or
without microscopic residual
disease, ipsilateral and
contralateral lymphnodes
negative microscopically
Tumor limited to organ

or structure of origin
Stage 2 A
Unilateral tumor with
incomplete gross excision;
identifiable ipsilateral and
contralateral lymphnodes
Stage II
Tumor with regional
spread that does not
cross the midline;
ipsilateral lymphnode
may be involved
Stage 2 B
Unilateral tumor
with complete
or incomplete
gross excision;
with positive ipsilateral
lymph nodes, identifiable
contralateral nodes
Stage 3
Tumor with spread to
midline with or without the
involvement of regional
lymph node or unilateral
tumor with contralateral
regional lymph node
involvement or midline
tumor with bilateral regional
lymphnode involvement
Stage III
Regional tumor crossing
the midline; bilateral
lymph nodes may be
involved
Stage 4
Dissemination of tumor
to distant lymph nodes, bone,
bone marrow, liver and/or
other organs
Stage IV
Tumor with metastases
to distant sites
Stage 4-S
Localised primary tumor as
defined for Stage I or II
with dissemination limited
to liver, skin and/or bone
marrow
Stage IV-S
Localized primary tumor
and disseminated disease
limited to liver, skin
and/or bone marrow
To facilitate comparison of results obtained with

different treatment regimens, a radiology-based
international risk group staging system has been recently
Pediatric Oncology
developed. Here in, localized or metastatic disease is
determined by the absence or presence of image-defined
surgical risk factors.
RISK STRATIFICATION
Depends upon many factors.
Age and Stage
Children of any age with localized neuroblastoma and
infants younger than 1 year with advanced disease and
favorable biological characteristics have a high likelihood
of long-term, disease-free survival. Older children with
advanced-stage disease, however, have a significantly
decreased chance for cure, despite intensive therapy.
Pathology
The Shimadas pathologic classification appears to have
prognostic significance. it is based on histological features
such as presence or absence of stroma, degree of
differentiation and mitosis-karrhyorexis index.
Biological Factors
Treatment decisions are based on important factors such
as tumor cell chromosome number, amplification of the
MYCN oncogene within tumor tissue, unbalanced 11q
loss of heterozygosity (LOH), and LOH for chromosome
1p. An open biopsy is usually needed to obtain adequate
893
tissue for determination of these biological characteristics. Other biological prognostic factors that have
been extensively investigated include tumor cell telomere
length, telomerase activity, and RNA; urinary vanillylmandelic acid (VMA), homovanillic acid (HVA), and
their ratio; TrkA gene expression; neuron-specific enolase
level, serum lactic dehydrogenase level, and serum
ferritin level.
Treatment
Treatment strategies vary according to the risk groups
(See Table 16.6.1). The risk of progression of the tumor
causing morbidity and mortality is gauged based on the
stage of the tumor, the age of the child at diagnosis, and
tumor biology. The biological features considered are the
Shimada classification, amplification of the MYCN gene,
and the number of chromosomes in tumor cells. For
identical age, stage and NMYC status, presence of
unfavorable histology upgrades the patient to the next
risk category.
This risk-based neuroblastoma treatment plan assigns
each patient to a low-, intermediate-, or high-risk group.
(Risk groups are defined in the Table 16.6.1). In patients
without metastatic disease, initial surgery is performed
to establish the diagnosis, to resect as much of the
primary tumor as possible, to accurately stage disease
through sampling of regional lymph nodes that are not
adherent to the tumor, and to obtain adequate tissue for
biological studies.
TABLE 16.6.1: Treatment strategy based on risk categories of the patients

Risk category
Treatment
Risk
Stage
Age
(months)
NMYC
Low
1
2A/2B#
Any
Any
Any
Non-amp
4S*
<12
Non-amp
Intermediate
3#
4
4S**
Any
< 18
< 12
Non-amp
Non-amp
Non-amp
High
2A/2B
3
4S
4
> 12
Any
< 12
> 18
Amp
Amp
Amp
Any
Surgery
Surgery followed by low dose chemotherapy
(cyclophosphamide and doxorubicin)
Observation if asymptomatic, chemotherapy/RT
if symptomatic
Multiagent chemotherapy (cyclophosphamide,
cisplatin, etoposide, doxorubicin) +
2nd look surgery RT to tumor bed if gross
residual disease
Multiagent chemotherapy as induction followed by
surgery, high dose chemotherapy with autologous
BMT as consolidation and biological therapy (13 cisretinoic acid) as maintenance treatment for minimal
residual disease
*DNA index > 1, **DNA index = 1, # - stage 2/3 with favorable histology
Survival
90%
85-90%
75%
20-40%
894
INTERNATIONAL NEUROBLASTOMA
RISK GROUP SYSTEM
A new risk group system has been developed based on
13 prognostic factors including stage, age, histology,
grade, MYCN status, 11q or 1p status, DNA ploidy, LDH
etc. It classifies patients in to 4 groups; very low risk
(>85% event free survival), Low-risk (75-85% EFS),
intermediate risk (50-75% EFS) and high risk (< 50%
survival). It is likely to be internationally adopted soon
for treatment planning and prognostication in all new
cases.
Low Risk
Treatment for patients categorized as low risk is with
surgery alone, but surgery may be combined with 6 to
12 weeks of chemotherapy. Chemotherapy is reserved
for patients who are symptomatic, such as from spinal
cord compression or, in stage 4S, respiratory compromise
secondary to hepatic infiltration. The chemotherapy
agents include carboplatin, cyclophosphamide, doxorubicin, and etoposide. The cumulative dose of each
agent is kept low to minimize permanent injury from
the chemotherapy regimen.
Observation in Special Low-Risk Cases
Selected presumed neuroblastomas incidentally detected
in infants by screening or ultrasound with low urinary
VMA and HVA levels, no involvement of great vessels
or invasion into the spinal canal, and small tumor size
may safely be observed without obtaining a definitive
histologic diagnosis and without surgical intervention,
thus avoiding potential complications of surgery in the
newborn.
Intermediate Risk
Patients categorized as intermediate risk are treated with
surgery and 12 to 24 weeks of the same chemotherapy
regimen as in low-risk. Radiotherapy may be required
in selected cases.
High Risk
Patients categorized as high risk are generally treated
with aggressive multiagent chemotherapy consisting of
very high doses of carboplatin, cyclophosphamide,
doxorubicin, etoposide, ifosfamide and high-dose
cisplatin. After the induction chemotherapy, resection
of the primary tumor should be attempted, followed by

consolidation with myeloablative chemotherapy,
sometimes total-body irradiation, and autologous stem
cell transplantation. Radiation of residual tumor and
original sites of metastases is often performed before,
during or after myeloablative therapy. After recovery,
oral 13-cis-retinoic acid for 6 months is given for
treatment of minimal residual disease. Both myeloablative therapy and retinoic acid improve outcome in
patients categorized as high risk.
Newer Therapies
A slew of novel chemotherapeutic as well as biological
molecules are being evaluated in clinical trials. Many of
these including monoclonal antibody therapy with antiGD2 antibody, tandem myeloablation and stem cell
transplantation, 131I-MIBG therapy, and topotecan
might become part of frontline therapy in future.
CONCLUSIONS
Neuroblastoma represents one of the most enigmatic and
challenging malignancies for treatment decisions because
of its unusual biological behavior which includes
spontaneous regression at one end to treatment resistant
progression at other end of the spectrum. The main
achievements in the management of Neuroblastoma
during the last two decades have been the reduction of
chemotherapy in patients with low risk disease and the
intensification of chemotherapy in high risk disease.
BIBLIOGRAPHY
1. Brodeur GM, Pritchard J, Berthoid F, et al. Revisions of
the International criteria for Neuroblastoma diagnosis
staging and response to treatment. J Clin Oncol
1993;11(8):1466-77.
2. George RE, London WB, Cohn SL, et al. Hyperdiploidy
plus nonamplified MYCN confers a favorable prognosis
in children 12 to 18 months old with disseminated
neuroblastoma: a Pediatric Oncology Group study. J Clin
Oncol 2005;23(27):6466-73.
3. Katherine K. Matthay, Judith G. Villablanca, Robert C.
Seeger, et al. Treatment of high risk Neuroblastoma with
intensive chemotherapy, Radiotherapy, Autologous
Bone Marrow Transplantation, and 13-CIS-Retinoic Acid.
New England Journal of Medicine 1999;341(16):1165-73.
4. LC Bowman, ML Hancock, VM Santana, et al. Impact of
intensified therapy on clinical outcome in infants and
children with neuroblastoma: The St Jude Childrens
Research Hospital experience, 1962 to 1988 Journal of
Clinical Oncology 9:1599-1608.
Pediatric Oncology
5. Nickerson HJ, Matthay KK, Seeger RC, et al. Favorable
biology and outcome of stage IV-S neuroblastoma with
supportive care or minimal therapy: a Childrens Cancer
Group study. J Clin Oncol 2000;18(3):477-86.
6. Nishihira H, Toyoda Y, Tanaka Y, et al. Natural course
of neuroblastoma detected by mass screening: s 5-year
prospective study at a single institution. J Clin Oncol
2000;18(16):3012-7.
7. RP Castleberry, JJ Shuster, G Altshuler, et al. Infants with
neuroblastoma and regional lymph node metastases
have a favorable outlook after limited postoperative
895
chemotherapy: A Pediatric Oncology Group Study.

Journal of Clinical Oncology 10:1299-1304.
8. Schmidt ML, Lal A, Seeger RC, et al. Favorable prognosis
for patients 12 to 18 months of age with stage 4
nonamplified MYCN neuroblastoma: A Childrens
Cancer Group Study. J Clin Oncol 2005;23(27):6474-80.
9. Shimada H, Ambros IM, Dehner LP, et al. Terminology
and morphologic criteria of neuroblastic tumors:
recommendations by the International Neuroblastoma
Pathology Committee. Cancer 1999;86(2):349-63.
16.7 Soft Tissue Sarcoma

Sajid Qureshi, Purna A Kurkure
Soft tissue sarcomas in children are relatively rare. They
are conveniently divided into two broad categories
rhabdomyosarcoma (RMS) and nonrhabdomyosarcoma
soft tissue sarcomas (NRSTS). The incidence of these soft
tissue sarcomas is age dependent; RMS accounts for 60%
of cases in children younger than 5 years; in contrast,
more than three-fourths of all soft tissue sarcomas in
patients aged 15 to 19 years are NRSTS. Surgery is the
prime treatment modality for all pediatric soft tissue
sarcomas. Chemotherapy has a major role in the
treatment of RMS while its role in NRSTS is restricted
for high grade and large size tumors.
Rhabdomyosarcoma
RMS is the most common soft tissue sarcoma in children
and adolescents, accounting for approximately 5% of all
pediatric cancers and approximately half of all soft tissue
sarcomas. 1 The multidisciplinary approach for the
treatment of RMS led to the formation of the Intergroup
Rhabdomyosarcoma Study Group (IRSG) in 1972. The
IRSG (now the Soft Tissue Sarcoma Committee of the
Childrens Oncology Group) has completed four
consecutive cooperative group trials (IRS-I: 19721978;
IRS-II: 19781984; IRS-III: 19841991; IRS-IV: 19911997)
evaluating new drug combinations, chemotherapy
intensity, radiologic evaluation of tumors, radiotherapy
and tumor biology. 2 These studies and therapeutic trials
have lead to an increase in 5 years survival from 25% to
70% over the past 40 years (Fig. 16.7.1).
Most cases of RMS occur sporadically, but the disease
has been associated with familial syndromes, including
Figure 16.7.1: Chart showing study of rhabdomyosarcoma:

Increase in 5-year survival from 25% to 70%; over the past 40
years
Li Fraumeni (caused by germline mutation of p53) and

neurofibromatosis (caused by mutation in NF1).
Pathology
RMS belongs to the family of small, round, blue cell
tumors which also include neuroblastoma, lymphoma
and PNET. Three general pathologic types of RMS have
been described: embryonal, alveolar, and pleomorphic.
A rare primitive tumor, undifferentiated sarcoma, has
also been included in the IRSG. Subsets of embryonal
RMS include botryoid and spindle cells. The contemporary International Classification of RMS categorizes
(a) botryoid and spindle-cell RMS, as having a superior
prognosis; (b) embryonal RMS, with an intermediate
prognosis; (c) alveolar RMS and undifferentiated
sarcoma having a poorer prognosis.
896
Embryonal RMS is the most common histology seen

in children, comprising more than two-thirds of all RMS.
The head and neck and genitourinary tract RMS are
frequently embryonal type. Ten percent are botryoid, and
these tumors commonly arise in hollow organs like the
vagina, nasopharynx, biliary tract, and urinary bladder.
Spindle cell tumors are common in the paratesticular site.
Alveolar RMS is seen in approximately 20% of children
and is most frequently found in the extremities, trunk,
and perineum.
Molecular studies of embryonal RMS have shown loss
of heterozygosity at the 11p15 locus. Alveolar RMS are
associated with translocations of the FKHR gene on
chromosome 13 with PAX3 (chromosome 2) or PAX 7
(chromosome 1) in 55% and 22% respectively.
The clinical presentation of a child with rhabdomyosarcoma varies depending on the primary site. Approximately 40% of rhabdomyosarcoma occur in the head and
neck region; another 20% arise from the genitourinary
sites, 20% in the extremities, and 20% other locations.1
Head and Neck
Approximately 25% head and neck RMS arise in the orbit,
50% in other parameningeal sites, and 25% in nonorbital,
nonparameningeal locations, such as the scalp, face,
buccal mucosa, oropharynx, larynx, and neck. The
parameningeal sites include tumors arising from the
nasopharynx, nasal cavity, paranasal sinus, middle ear
mastoid region, infratemporal fossa, and pterygopalatine
fossa. These sites exhibit a propensity for bony erosion
and contiguous intracranial spread hence, they have the
worst prognosis.
Genitourinary
Tumors arising from the prostate or bladder are
frequently large, so that it may not be possible to
determine the specific site of origin. Paratesticular RMS
arises from mesenchymal elements of the spermatic cord,
epididymis, or tunics.
RMS of the vagina and vulva occur in young children
and present with a nodule or protrusion of grape-like
mass from the introitus. Uterine corpus and cervix RMS
are less common compared with vaginal tumors.
Extremity
Extremity RMS is characterized by a higher incidence of
regional lymph nodes involvement (1025%) which has
a negative impact on survival. Hence surgical evaluation
of lymph nodes, even when there are no clinically
involved nodes, is necessary to ensure accurate staging.
Other Locations
Paraspinal, abdominal wall, chest wall, perineum/
perianal, retroperitoneum/pelvis and biliary tract are
other sites for RMS.
Preoperative Workup
In addition to a complete history, physical examination
and standard investigations including complete blood
counts (CBC), electrolytes, and renal function tests, liver
function tests (LFTs) and urinalysis (UA) specific
investigations for evaluation of the primary tumor and
metastatic disease should be performed.
Computed tomography (CT) and magnetic resonance
imaging (MRI) of the primary site can help determine
the tumor size and extent as well as invasion to
surrounding structures. The draining lymph nodes are
also imaged to determine spread particularly in children
with extremity lesions or boys >10 years of age with
paratesticular RMS. CT is advantageous for the
evaluation of bone erosion and abdominal adenopathy.
MRI is preferable over CT for limb, pelvic, and paraspinal
lesions. Metastatic workup includes a bone marrow
aspirate and imaging of the chest and bones. For children
with parameningeal tumors, imaging of the neuraxis is
important to determine whether there is intracranial
extension and/or neuraxis spread; the cerebrospinal fluid
from a spinal tap is also analyzed for malignant cells as
parameningeal tumors can disseminate through this
route. Routine brain imaging for asymptomatic patients
with metastatic disease and non-head and neck primary
is not generally helpful.
Pretreatment Clinical Staging
Pretreatment clinical staging is based on physical
examination and preoperative imaging and determined
by the site, size, and invasiveness of the primary tumor,
nodal status, and distant spread (Table 16.7.1). Favorable
Pediatric Oncology
897
TABLE 16.7.1: IRS pretreatment staging

Stage
Sites
T*
Size
Orbit, head, and neck (excluding

parameningeal), GU-nonbladder/non-prostate, biliary
tract
Bladder/prostate, extremity,
parameningeal, other
(includes trunk,
retroperitoneum, etc.)
Bladder/prostate, extremity,
Parameningeal, other
(includes trunk,
retroperitoneum, etc.)
All
T1 or T2
a or b
N0 or N1 or Nx
M0
T1 or T2
N0 or Nx
M0
T1 or T2
a
b
N1
N0 or N1 or Nx
M0
M0
T1 or T2
a or b
N0 or N1
M1
*T, tumor; T1, confined to anatomic site of origin; T2, extension and/or fixation to surrounding tissue.
Size; a, < 5 cm; b, > 5 cm
N, regional nodes; NO, regional nodes not clinically involved; Nx, clinical status of regional nodes unknown; N1, regional nodes clinically
involved.
M, metastasis; M0, no distant metastasis; M1, distant metastasis present.
Biopsy incision should be planned in such a way that it

can be incorporated in future resection of the tumor.
Adequate tissue should be removed for pathologic and
biological studies. For deeper, less-accessible lesion core
needle biopsy is appropriate for diagnosis.
particularly applicable to extremity and trunk lesions,

but should be applied whenever feasible as it impacts
the failure-free survival and overall survival.
The goal of surgery is wide and complete resection
of the primary tumor with a surrounding envelope of
normal tissue without disfiguring or compromising the
function. For unresectable tumors at initial diagnosis
neoadjuvant chemotherapy with or without RT may be
able to shrink the tumor with possibility of surgery.
Adequate margins of 0.5 cm should be obtained
circumferentially which is more easily obtained in the
extremities or trunk compared to head and neck tumors.
All margins should be marked and oriented at the
operative field to enable precise evaluation of margins.
Any microscopic or gross tumor should be marked with
small titanium clips in the tumor bed to aid radiotherapy
simulation and subsequent re-excision.
Resection of the Mass
Lymph Node Sampling/Dissection
If the initial surgical procedure was performed prior to

the diagnosis of RMS, more often than not, gross residual
disease or contaminated margins could be anticipated.
Under these circumstances re-excision is advisable.
Pretreatment re-excision (PRE) is a wide re-excision of
the previous operative site, including an adequate
margin of normal tissue before adjuvant therapy. PRE is
Clinically and radiologically positive nodes should be

biopsied to confirm tumor involvement thus ensuring
correct assessment of disease risk and assignment of
optimal therapy. The surgical evaluation of nodes that
are clinically uninvolved are specifically required in
extremity tumors and for children older than 10 years of
age with paratesticular tumors. Lymph node evaluation
sites of location include the orbit, nonparameningeal

head and neck, paratesticular, gynecological and biliary
tract tumors, whereas unfavorable sites include the
parameningeal, extremity, bladder, prostate, trunk, and
retroperitoneal tumors. The presence of positive cytology
from the cerebrospinal fluid, pleural or abdominal fluids,
as well as implants on pleural or peritoneal surfaces is
considered distant metastasis.
Surgical Principles
Biopsy
898
should not include a fervent lymphadenectomy as the

intent is not therapeutic and studies have shown that
there is no benefit from formal nodal dissection especially
if metastasis of RMS from the tumor site has occurred.
The concept of sentinel node mapping offers promise for
selective identification of nodes with subclinical disease.
If regional nodes are positive then nodes distal to the
regional nodes, should be harvested for pathologic study
since any tumor identified in these nodes would be
considered metastatic disease and would affect therapy.
TABLE 16.7.2: Clinical grouping system

Group I
Group II
Clinical Group
After pathologic examination from the definitive
operation, patients are assigned to a Clinical Group based
on the completeness of tumor excision and the evidence
of tumor metastasis to the lymph nodes or distant organs.
(Table 16.7.2). The extent of the disease after resection is
one of the most important prognostic factors to predict
which patients are likely to be cured. Decisions regarding
use of radiotherapy (RT) are often based on the Group
as patients with group 2, 3, and 4 tumors require RT.
Chemotherapy
RMS is a systemic disease hence even localized RMS may
be associated with distant micro metastasis. The gold
standard for chemotherapy includes a combination of
vincristine, dactinomycin, and cyclophosphamide
(VAC). Current IRS treatment recommendations are
based on risk group classification (Table 16.7.3). Low risk
children have a greater than 90% 5-year survival,
intermediate risk ranging from 55% to 70% 5-year
survival, and high risk less than 50% 5-year survival.
Combinations of VA + RT remain the standard
treatment for patients with low risk disease. The standard
Group III
Group IV
Localized disease, completely resected

A. Confirmed to organ or muscle of origin
B. Infiltration outside organ or muscle of origin;
regional nodes not involved
Compromised or regional resection including
A. Grossly resected tumors with microscopic
residual tumor
B. Regional disease, completely resected, with
nodes involved and/or tumor extension into
an adjacent organ
C. Regional disease, with involved nodes,
grossly resected, but with evidence of
microscopic residual tumor
Incomplete resection or biopsy with gross
residual disease remaining
Distant metastases present at onset
chemotherapy in patients with high-risk disease is

combination of VAC and RT.
Radiotherapy
RT is an important treatment modality for RMS especially
in the setting of residual (microscopic) disease or when
surgery is not feasible or very morbid. Children with
group 1 embryonal disease may not need RT. All patients
with group II to IV tumors receive RT as well as all group
I alveolar tumors. Doses from 36 Gy to 50.4 Gy are
commonly used. For patients with group III disease or
those with gross disease, a dose of 50.4 Gy given in 28
fractions (1.8 Gy/day) is used for all sites, with the
exception of orbital tumors which can be treated with 45
Gy in 25 fractions (1.8 Gy/day). Patients who had their
tumors resected with positive margins of resection (IRS
group IIa) receive 36 Gy in 20 fractions (1.8 Gy/day) to
TABLE 16.7.3: Risk based therapy in IRS-IV

Risk
Stage
Group
Site
Histology
Low 1
1 or 2
1
1
3
I or II
III
III
I or II
Favorable or unfavorable
Orbit only
Favorable
Unfavorable
EMB
EMB
EMB
EMB
Intermediate
2 or 3
1-3
III
I-III
Unfavorable
EMB
ALV
High
4
4
IV
IV
EMB
ALV
Low 2
Definitions: Favorableorbit/eyelid, head and neck (excluding parameningeal), genitourinary (not bladder or prostate).
Unfavorablebladder, prostate, extremity, parameningeal, other (trunk, retroperitoneal, etc.).
EMBembryonal, botryoid, or spindle variants or ectomesenchymomas with embryonal features.
ALValveolar or undifferentiated sarcomas, or ectomesenchymomas with alveolar features
Pediatric Oncology
the tumor bed. Patients who had regional node
involvement but completely resected (group IIb) receive
41.4 Gy in 23 fractions (1.8 Gy/day).
The late effects of RT are an area of concern and newer
techniques of RT delivery are being used which are
intended to minimize local toxicities without affecting
outcome. These techniques include three-dimensional
RT, intensity-modulated RT, proton therapy, and
brachytherapy.
Prognosis
The prognosis of patients with RMS is dependent on
many factors. Favorable prognostic factors include
embryonal/botryoid histology, primary tumor sites in
the orbit and nonparameningeal head/neck region and
genitourinary nonbladder/prostate regions, a lack of
distant metastases at diagnosis, complete gross removal
of tumor at the time of diagnosis, tumor size less than or
equal to 5 cm, and age less than 10 years at the time of
diagnosis. Clinical grouping was identified as one of the
most important predictor of failed treatment and tumor
relapse.
Relapse
Approximately 30% of patients with rhabdomyosarcoma
will relapse. The median survival from first recurrence
is 0.8 years with an estimated 5-year survival rate of 17%.8
Children with Stage 1 or group 1 disease and embryonal
or botryoid histology with local or regional relapse have
the best prognosis.
Nonrhabdmyosarcoma Soft Tissue Sarcomas
Nonrhabdmyosarcoma soft tissue sarcomas (NRSTS) are
a heterogeneous group of tumors accounting for 35%
of all childhood malignancies and around 60% of all
sarcomas in children. The relative infrequency of the
different histopathological subtypes precludes performance of clinical trials on a single tumor type, and
consequently, NRSTS have to be analyzed as a group.
With contemporary treatment, more than 70% of
children and adolescents with surgically resected
nonmetastatic disease are expected to be cured. In
contrast, fewer than 10% of patients with metastatic
disease are expected to become long-term survivors.
Pathology
The NRSTS group encompasses several histological
variants, including synvovial sarcoma, malignant
peripheral nerve sheath tumor, alveolar soft part
sarcoma, angiosarcoma, clear cell sarcoma, fibrosarcoma,
899
ectomesenchymoma, epitheloid hemangioendothelioma,

GIST, hemangiopericytoma, myxoid chondrosarcoma,
spindle cell sarcoma, malignant fibrous histiocytoma
(MFH), leiomyosarcoma, epitheloid sarcoma, liposarcoma, dermatofibrosarcoma and poorly differentiated
or undifferentiated sarcoma, not otherwise specified.
Currently the WHO classification of soft tissue tumors:
intermediate (rarely metastasizing) and malignant
tumors, gives an exhaustive list of malignant NRSTS and
rhabdomyosarcoma.
With evolution of molecular studies, specific
chromosomal translocations have been identified in
certain sarcomas. Synovial sarcoma is associated with
t(x;18) (p11,q11) (SYT-SSX), alveolar soft parts sarcoma
associated with t(X;17) (p11;q25) (ASPLTFE3), and
myxoid liposarcoma with t(12;16) (q13;p11) (TLS-CHOP)
and t(12;22) (p13;q12) (EWS-CHOP). These chromosomal
translocations can be helpful in making the definitive
diagnosis and also for prognostication.
They are more common in children above 5 years of age
but may occur in any age groups. Commonest presentation includes mass lesions anywhere in the body. The
frequent anatomic sites are the extremities, most often
in the lower limbs, followed by the trunk, the thorax,
and the head/neck area. The lesions characteristically
impersonate a benign-looking, well-circumscribed
mass, which may mistakenly be observed or excised as a
shell-out procedure (Whoops procedure). The extent of
the disease at presentation is usually local (70%),
locoregional (9%), or metastatic (21%). Metastatic disease
is most commonly seen in the lungs, followed by the brain
and bone marrow.
Evaluation and Diagnosis
Magnetic resonance imaging (MRI) is considered the
imaging modality of choice for the evaluation of local
and regional disease as it provides superior soft tissue
resolution, multiplanar image acquisition, and does not
require iodinated contrast agents or ionizing radiation.
Malignant lesions are usually larger and display
inhomogenous signal intensity on T2-weighted images.
A contrast-enhanced CT scan is useful for evaluation of
abdominal tumors and pulmonary metastases. Although
PET scans have become customary for investigations of
many tumors, the role in NRSTS is yet to be clearly
defined.
The utility of a biopsy in achieving a diagnosis
surpasses any other investigation. The prime consi-
900
deration is to obtain adequate amount of tissue for

diagnosis with minimal disruption of tissue planes. Of
paramount importance is the correct placement of the
biopsy incision as an ill-conceived biopsy may adversely
affect the definitive surgical procedure. All incisions,
when possible, should be longitudinal on extremities,
parallel to the neurovascular structures, to allow easy
wide local excision. Fine-needle aspiration, trucut needle
biopsies or an open incisional biopsy are preferred
because they provide the least risk of local contamination.
Primary surgical resection is undertaken for small tumor
or when wide local resection can be done without risk or
functional deformity.
Treatment
high grade tumors, in tumors with positive margins of

resection or low grade unresectable tumor. Local control
with radiotherapy alone for unresected NRSTS has been
reported to be not higher than 2530%. The use of
neoadjuvant RT with or without chemotherapy is being
investigated for achieving significant shrinkage of
initially unresectable tumor for facilitating resection.
However, the disadvantages include delay in surgical
resection, wound healing and loss of information on
tumor extent and pathology. In view of the distinct late
effects of radiotherapy in very young children, it can be
avoided in patients less than 2 years of age. Newer
techniques of radiation delivery like intensity-modulated
radiation therapy and proton beam therapy may reduce
the toxicity of radiation.
Surgery
Surgery has remained the cornerstone of treatment as
many of the NRSTS are considered not very chemosensitive. Wide local resection is the main objective of
surgery for NRSTS. The exact margin of resection that is
required to achieve a favorable outcome is unclear.
Historically, the standard margin of resection accepted
in adults was 2 cm, with recurrence rates of 1015%. In
young children or adolescents with tumors in the head
and neck, mediastinum, or retroperitoneum, however, a
margin of 2 cm is not feasible as it would require
excessive mutilating surgical procedures. Previous
reports have recommended a tumor free margin or a
margin greater than 1 cm for adequate local control.11
Unplanned resections frequently (50%) have microscopic residual disease which is associated with a higher
rate of local recurrence. Hence a pretreatment re-excision
or PRE should be undertaken when the initial operation
was not a cancer operation or when malignancy was not
suspected preoperatively. The main aim of PRE is to
achieve microscopic radicality prior to other treatment
and to avoid irradiation of the tumor bed. It appears to
have a positive effect on recurrences and survival. But a
delay of up to 107 days (median 29 days) to complete
surgical resection has been shown to have no adverse
effects.
Pulmonary metastatectomy is advocated as an
adjunct to combine modality therapy in children with
NRSTS as it has been shown to increase disease control
in pediatric NRSTS.
Radiotherapy
NRSTS are less responsive to radiotherapy than RMS and
ES. Adjuvant radiotherapy has been recommended for
Chemotherapy
The role of adjuvant chemotherapy in the treatment of
pediatric NRSTS remains controversial. Chemotherapy
is recommended for initially unresectable or metastatic
disease. It is also been used in surgically-resected highgrade and tumors more than 5 cm. The frequently used
drugs were a combination of vincristine, ifosfamide and
doxorubicin. Synovial sarcoma had higher response rates
than other patients with the ifosfamide based regimen.
BIBLIOGRAPHY
1. Blakely ML, Spurbeck WW, Pappo AS, et al. The impact
of margin of resection on outcome in pediatric nonrhabdomyosarcoma soft tissue sarcoma. J Pediatr Surg
1999;34:672-5.
2. Chui CH, Spunt SL, Liu T, et al. Is reexcision in pediatric
nonrhabdomosarcoma soft tissue sarcoma necessary
after an initial unplanned resection? J Pediatr Surg
2002;37:1424-9.
3. Hays DM, Lawrence W Jr, Wharam M, et al. Primary
reexcision for patients with microscopic residual tumor
following initial excision of sarcomas of trunk and
extremity sites. J Pediatr Surg 1989;24:5-10.
4. Mandell L, Ghavimi F, LaQuaglia M, et al. Prognostic
significance of regional lymph node involvement in
childhood extremity rhabdomyosarcoma. Med Pediatr
Oncol 1990;18:466.
5. Meza JL, Anderson J, Pappo AS, Meyer WH. Analysis of
prognostic factors in patients with nonmetastatic
rhabdomyosarcoma treated on intergroup rhabdomyosarcoma studies III and IV: the Childrens Oncology
Group. J Clin Oncol 2006;24:3844-51.
6. Neville HL, Andrassy RJ, Lobe TE, et al. Preoperative
staging: prognostic factors and outcome for extremity
rhabdomyosarcoma: a preliminary report from the
Pediatric Oncology
Intergroup Rhabdomyosarcoma Study IV (1991-1997). J
Pediatr Surg 2000;35:317-21.
7. Pappo AS, Anderson JR, Crist WM, et al. Survival after
relapse in children and adolescents with rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study Group. J Clin Oncol 1999;17:
3487-93.
8. Pappo AS, Rao BN, Jenkins JJ, et al: Metastatic
nonrhabdomyosarcomatous soft-tissue sarcomas in
children and adolescents: The St Jude Childrens
Research Hospital experience. Med Pediatr Oncol
1999;33:76-82.
9. Paulino AC, Okcu MF. Rhabdomyosarcoma. Curr Probl
Cancer 2008;32:7-34.
901
10. Puri DR, Wexler LH, Meyers PA, et al. The challenging
role of radiation therapy for very young children with
rhabdomyosarcoma. International Journal of Radiation
Oncology Biology Physics 2006;65:1177-84.
11. Spunt SL, Poquette CA, Hurt YS, et al: Prognostic factors
for children and adolescents with surgically resected nonrhabdomyosarcoma soft tissue sarcoma: An analysis of
121 patients treated at St Jude Childrens Research
Hospital. J Clin Oncol 1999;17:3697-3705.
12. Wiener ES, Anderson JR, Ojimba JI, et al. Controversies
in the management of paratesticular rhabdomyosarcoma:
is staging retroperitoneal lymph node dissection
necessary for adolescents with resected paratesticular
rhabdomyosarcoma? Seminars in Pediatric Surgery
2001;10:146-52.
16.8 Retinoblastoma
Sripad Banavali
INTRODUCTION
Genetics and Molecular Biology
Retinoblastoma (RB), a malignant tumor of the embryonic neural retina, is the most common primary malignant
intraocular tumor of childhood. It occurs in approximately 1 in 18,000 infants. Hereditary and non-hereditary
patterns of transmission occur; there is no sex or race
predilection. The average age at diagnosis for bilateral
tumor is 12 months and for unilateral tumors it is 21
months. In trilateral RB syndrome, pineal tumors develop
in approximately 1 in 100 patients with bilateral ocular
disease. Characteristically, the diagnosis is made by
ophthalmoscopic, radiographic and ultrasonographic
appearance, without pathologic confirmation.
Retinoblastoma has served as the prototype and model

for understanding the heredity and genetics of childhood
cancer. In the 1970s' Knudson proposed that RB required
two mutations to develop the two hit theories. It occurs
either spontaneously or as an inherited disorder. RB
shows an autosomal dominant inheritance pattern with
high penetrance. Approximately 55% of tumor occur as
non-hereditary, unifocal, unilateral tumor. An additional
15% are unilateral, but are hereditary with a family
history. 30% occur as heritable bilateral unifocal or
multifocal tumors. The RB gene is a tumor suppressor
gene and RB tumors are homozygous for chromosome
13q 14 abnormalities with either deletions or alterations
of genetic material at that locus. Hereditary cases shows
a germ line abnormality in one gene at this locus. Some
affected children have other systemic features of the 13q
deletion syndrome.
Pathology
This tumor which usually arises from the posterior
portion of the retina, consists of small round closely
packed malignant cells with scanty cytoplasm. Tumor
may grossly appear crumbly and friable with gelatinous
areas of degradation, patches of calcification or
pigmented hemorrhage. It may appear as a single tumor
in the retina, but typically has multiple foci. The growth
may be endophytic (forward into the vitreous cavity) or
exophytic (into the subretinal space). The tumor
fragments may break off and float free in the vitreous to
seed other parts of retina. The most frequent
extraocular sites of involvement are the optic nerve, orbit
and periorbital tissues, cranial tissue, bone and bone
marrow.
Clinical Aspects
The most common sign of retinoblastoma is the white or
cat's eye reflex (leukokoria), the appearance of the yellowwhite tumor mass behind the lens. Other signs associated
with RB are visual impairment, strabismus, pseudohypophyon, hyphema and vitreous hemorrhage.
Proptosis, signs of increased intracranial pressure of bone
pain may occur with very advanced or metastatic disease.
The findings of leukokoria must be followed by careful
fundoscopic examination under anesthesia. Ideally, an
902
MRI scan of the orbit should be performed to evaluate

extent of tumor and to assess whether optic nerve, bony
structures or pineal gland are involved. Most intraocular
retinoblastomas show evidence of intratumoral calcification. Ultrasound may aid in the differential diagnosis,
which include other causes of leukokoria such as retinal
detachment or dysplasia, retinopathy of prematurity,
persistent hyperplastic vitreous, nematode endophthalmitis, cataract, coloboma of the choroid. Radionuclide
bone scan and examination of bone marrow and CSF for
tumor cells are necessary only if there is evidence of transscleral extension or extension beyond the cut end of optic
nerve. Second malignant neoplasms are a major concern
in RB survival. Approximately, 30% of individuals cured
of hereditary form of RB, will have a second malignancy
within 30-years. Osteosarcoma is the most frequent
second malignancy, although other tumors such as
rhabdomyosarcoma, melanoma, fibrosarcoma and
lymphoma have been reported.
Treatment
Although retinoblastoma is the most common primary
intraocular tumor in children, the treatment of this
disease is a complex topic. Therapeutic plans usually
require a multidisciplinary approach by a team consisting
of ocular oncologist, pediatric oncologist and radiation
oncologist. Treatment should be highly individualized.
Treatment strategies for retinoblastoma have gradually
evolved over the past few decades. The driving force
behind these new approaches is to avoid enucleation
and/or external beam radiation therapy and trend
towards focal conservative treatment. Every effort is
being made to save the childs life with preservation of
eye and sight, if possible. The first goal is survival, with
maintenance of vision and salvage of the globe as
important secondary goals.
Retinoblastoma leads to metastatic disease and death
in 50% of children worldwide but in less than 5% of
children in the United States and other developed nations
with advanced medical care. Over the past decade, there
has been a trend away from enucleation and external
beam radiotherapy and towards chemoreduction
followed by focal therapies. This is largely due to more
effective chemotherapeutic regimens, improved focal
treatment modalities, and the desire to avoid loss of globe
and/or exposure to radiotherapy. External beam
radiotherapy (EBRT) has been a standard treatment for
medium and large, or visually threatening, intraocular
RB, but it markedly increases the risk of cosmetic
deformities and secondary cancer in children with
germline RB mutations.
Chemotherapy may be useful in all three clinical

settings: in intra-ocular retinoblastoma, in cases of
micrometastatic spread, and when there are overt
extraocular metastases. Tumor shrinkage with chemoreduction may allow treatment with less invasive
measures such as cryotherapy, laser photocoagulation,
thermotherapy or plaque radiotherapy, thereby, avoiding
enucleation and EBRT.
While chemotherapeutic agents vary according to the
preference of the pediatric oncologist, most of the current
studies have relied on carboplatin with or without
Etoposide, vincristine and cyclophosphamide. To
circumvent the multidrug resistance, cyclosporine has
been added to chemotherapy at some centers. Intraarterial melphalan has been recently used for salvaging
eyes with large intra-ocular disease, which otherwise
were destined to be enucleated.
Prognosis
The prognosis for patients with RB is directly related to
the size and extension of the tumor. Most tumors that
are confined to the eye can be cured. Cures are infrequent
when extensive orbital or optic nerve extension has
occurred or patient has CNS or distant metastasis.
Reported mortality with tumor invasion to the lamina
cribrosa is 29%, posterior to the lamina cribrosa is 42%
and to the cut end of the optic nerve is 78%. Orbital
recurrence, 2.5% in one series carries 66 to 94% mortality
with a mean survival of 15 months. The prognosis of
patients with CNS metastasis is still very poor nearing
0% even with aggressive therapy. However with the
advent of high dose chemotherapy with stem cell
transplantation, more and more patients with other (bone
and bone marrow) metastatic disease are now surviving.
Overall 5 years disease free survival with enucleation
and external beam irradiation has been reported as 88%
to 94%. Subsequent 10-year survival decreases in bilateral
cases secondary to second tumors.
BIBLIOGRAPHY
1. Abramson DH, Dunkel IJ, Brodie SE, et al. A phase I/II
study of direct intra arterial (ophthalmic artery)
chemotherapy with melphalan used for intra ocular
retinoblastoma. Opthalmology, 2008.
2. Deegan WF. Emerging strategies for the treatment of
retinoblastoma. Curr Opin Ophthalmol 2003;14:291-5.
3. Shields CL, Shields JA. Diagnosis and management of
retinoblastoma. Cancer control 2004;11:317-27.
4. Yanagisawa T. Systemic chemotherapy as a new
conservative treatment for intraocular retinoblastoma.
Int J Clin Oncol 2004;9:13-24.
Pediatric Oncology
903
16.9 Bone Marrow Transplantation

Brijesh Arora, Purvish M Parikh, MR Lokeshwar
INTRODUCTION
Bone marrow transplantation (BMT) is now called blood
and marrow transplantation or hematopoietic stem cell
transplantation (HSCT). HSCT is the term used to
describe the collection and transplantation of hematopoietic stem cells from bone marrow, peripheral blood
or umbilical cord blood. HSCT is established therapy for
congenital or acquired disorders of the hematopoietic
system and for hematological malignancies. This chapter
will deal with the principles, terminology and basic
applications of this transplantation. The biological
properties of hematopoietic stem cells that facilitate
transplantation include their capacity to proliferate and
differentiate into the entire lymphohematopoietic system,
their ability to migrate to the bone marrow space
following intravenous injection, and their maintained
viability despite cryopreservation, prolonged storage and
thawing for re-infusion. The mechanism by which BMT
is supposed to cure malignancy is by the anticancer effect
of drugs as well as by the immunological reaction
between graft and cancer cells known as graft versus
tumor effect. This second mechanism is important for
eradication of minimal residual disease in most cancers.
More than 50,000 transplants are performed each year
worldwide. In the last two decades, the number of HSCT
procedures has increased markedly due to expanding
indications, easy availability of donors for allogeneic
transplantation (including an increase in volunteer
unrelated donors of bone marrow/peripheral blood to
> 7.5 million worldwide and the establishment of
umbilical cord blood banks) and greater safety, allowing
HSCT in older and sicker patients (e.g. use of reducedintensity conditioning, improved prophylaxis, diagnosis
and treatment of infectious complications.
BMT in India
In India, there are at least twelve centres offering this
facility (including Tata Memorial Hospital, Mumbai;
Christian Medical college, Vellore; Institute Rotary
Center Hospital, New Delhi; Apollo Hospital, Chennai;
Army Hospital (R and R), New Delhi; Army Hospital,
Pune; Gujrat Cancer Research Institute, Ahmedabad;

Jaslok Hospital, Mumbai; Apollo Hospital, Hyderabad;
Sahyadri Hospital, Pune; Tata Rural Cancer Center,
Barshi; Adiyar Cancer Center, Chennai). Tata Memorial
Hospital was the first to start BMT in India on 20th March
1983. VK was then a nine year-old-girl with acute
myeloid leukemia. She went on to complete her studies
and currently is enjoying a happy married life while
being gainfully employed. A perfect example of cancer
cure! Tata Memorial Hospital was also the first center to
do umbilical cord blood transplantation, haploidentical
transplant (with the father as the donor) and allogeneic
transplant for chronic granulomatous disease. So far,
more than 500 transplants have been done in our country.
The various indications for BMT in children are shown
in Table 16.9.1.
Types of Hematopoietic Stem Cell Transplantation
HSCT can be classified according to:
1. Donor type (autologous self, syngeneic identical
twin, allogeneic non-identical donor)
2. Relationship between donor and recipient (related or
unrelated)
3. Degree of HLA matching between donor and
recipient (matched or mismatched); haplo-identical
HSCT may now be performed, often from a parent
donor to a child recipient
4. Anatomical source of the stem cells( Bone marrow ,
Peripheral blood,Umbilical cord blood)
5. Type of transplant conditioning (standard (myeloablative) or reduced-intensity (non-myeloablative).
6. Type of graft manipulation (if any) (e.g. T-cell
depletion in allogeneic HSCT, tumor cell purging in
autologous HSCT)
Allogeneic HSCT occurs between a donor and a recipient
who are not immunogenically identical. It can lead to
graft-vs-host disease (GvHD immune cells from the
donor react against antigens on host cells) and graft
rejection (immunocompetent host cells destroy the donor
stem cells before the graft is established). The risk of these
complications is determined largely by the degree of
904
TABLE 16.9.1: Indications for hematopoietic stem cell

transplantation
A. Allogenic HSCT
Malignant disorders
Leukemias
1. High-risk acute lymphoblastic leukemia (ALL) in first
remission or relapsed ALL in second remission
2. Acute nonlymphoblastic leukemia (AML, ANLL) (after first
remission)
3. Chronic myelogenous leukemia
4. Juvenile chronic myeloid leukemia (JCML)
5. Juvenile myelomonocytic leukemia (JMML)
Lymphomas
1. Hodgkin
2. Non-Hodgkin
Myelodysplasia
Myelofibrosis
Familial hemophagocytic lymphohistiocytosis
Nonmalignant disorders
Congenital
1. Immunodeficiency syndromes
a. Severe combined immunodeficiency syndrome (SCID)
b. Congenital agammaglobulinemia (Bruton disease)
c. DiGeorge syndrome
d. WiskottAldrich syndrome
e. Chronic mucocutaneous candidiasis
2. Hematologic disorders
a. Hemoglobinopathies( Sickle cell anemia, Thalassemia)
b. Fanconi anemia (progressive)
c. ShwachmanDiamond syndrome
d. Kostmann agranulocytosis
e. DiamondBlackfan anemia
f. Dyskeratosis congenita
g. Thrombocytopenia absent radii syndrome (TAR)
h. Chronic granulomatous disease
i. ChdiakHigashi syndrome
3. Storage diseases (Gaucher disease)
4. Lysosomal diseases
5. Mucolipidosis
6. Mucopolysaccharidoses
7. Infantile osteopetrosis
Acquired
1. Severe aplastic anemia
2. Paroxysmal nocturnal hemoglobinuria
B. Autologous HSCT
Hematologic malignancies
1. Non-Hodgkin lymphoma
2. Hodgkin disease
3. Relapsed AML
4. CML (investigational)
Solid tumors
1. High-risk Neuroblastoma stage
2. Metastatic Ewing sarcoma
3. Metastatic Rhabdomyosarcoma
4. Germ cell tumor
5. Brain tumor
6. Testicular cancer
7. Wilms tumor
matching between donor and recipient for antigens

encoded by genes of the MHC complex on chromosome
6. The most important genes are those encoding the
human leukocyte antigen (HLA) molecules responsible
for binding antigenic proteins and presenting them to
T- cells. Survival is not markedly affected following
HSCT involving one mismatched antigen, but is
significantly reduced by two or more mismatches.
The risk of relapse of malignant disease is lower
following allogeneic HSCT than after syngeneic or
autologous HSCT, because of an immune-based graftvs-leukemia or graft-vs-tumor effect.
Autologous HSCT (ABMT) involves removal and
storage of the patients own stem cells, with subsequent
re-infusion following high-dose myeloablative therapy.
The advantage of autologous HSCT is that higher doses
of myeloablative chemotherapy can be administered than
would otherwise be possible. There is no risk of graft
rejection or GvHD, but there is also no graft-vs-leukemia
or graft-vs-tumor effect. In addition, there is a risk of
contamination of the autologous stem cell product by
tumor. Purging of the autologous cells by negative
selection aimed at destroying tumor cells or positive
selection of CD34+cells (CD34 is the surface antigen that
characterizes hematopoietic stem cells) has been shown
to reduce the number of contaminating tumour cells.
ABMT was initially restricted to solid tumors where
the bone marrow was free of disease. The autologous
reinfusion of hematopoietic cells helped in rescue from
the otherwise lethal myelosuppression by potentially
curative chemoradiotherapy given for the primary
tumor. ABMT has been successfully used in Neuroblastoma, Germ cell tumors, retinoblastoma and
medulloblastoma. Subsequently this concept was also
expanded to include the hematological malignancies as
well such as lymphomas. The aim is to give benefits of
allo-BMT to patients who cannot undergo the procedure
due to various reasons.
Peripheral blood HSCT: Presence of circulating CD34
+ve stem cells in humans has been known since 1971.
However their number is too small to be of clinical use
of transplantation (being less than 0.5%). With the advent
of recombinant human hematopoietic growth factors, we
now have a method to mobilize them from the marrow
into circulation in sufficient number for clinical use. It is
now well established that these circulating cells can
establish durable marrow engraftment. Most HSCT now
Pediatric Oncology
use peripheral blood rather than bone marrow as a source
of stem cells. The higher stem cell dose provides an
engraftment advantage. In the allogeneic setting,
peripheral blood HSCT is associated with a higher
incidence of chronic GvHD and fewer disease relapses.
Umbilical cord Transplantation: Cord blood banks are
another source of stem cells. The graft composition and
biological properties of umbilical cord stem cells and
immune effectors differ from those of adult bone marrow
and peripheral blood donations, offering enhanced
engraftment (despite a low CD34+ cell dose) and a
reduced incidence of GvHD, Even in the presence of two
or three HLA antigen mismatches. It is particularly useful
for transplantation in children.
Requirement and Limitations
The main requirement for performing allogenic BMT is
the availability of HLA matched sibling or unrelated
donor. HLA antigens mount response against the foreign
antigens. The HLA antigens are broadly divided into
three groups Class I (HLA -A, -B and C), class II (HLADR,-DP,-DQ) and class III group which include diverse
group of proteins (C2 and C4, TNF alpha and beta, etc.).
For allo BMT, typing of Class I and II group antigens is
mandatory. The HLA phenotype of an individual is
determined using monoclonal antibodies (serological
methods), homozygous typing of cells in mixed
lymphocyte culture (MLC) and T-cell clones. Recently
typing for HLA-DR, -DP and DQ loci is also done by
molecular methods like restriction fragment length
polymorphism (RFLP) and sequence specific oligonucleotide probes (SSOP). The discrepancy between host
and donor HLA type predisposes to development of
GvHD.
For any individual there is a 25% chance of having
such a sibling donor. The reduction in family size over
the years has further decreased these chances. Though
the establishment of voluntary bone marrow registries
has made it possible to get a HLA matched unrelated
donor, the high incidence of treatment related complications and mortality with unrelated BMT has limited
its utility. Age is also a limitation as allo BMT cannot be
done beyond the age of 55 years.
Methodology
Once a suitable patient is identified, he undergoes
investigations to establish a baseline organ function
905
status. The pretransplant evaluation includes cardiac,

pulmonary and renal function studies, hematological
studies including hemoglobin electrophoresis and tests
for hemolytic anemia, serology for hepatitis virus,
cytomegalovirus, HIV virus and toxoplasma, and
determination of blood groups, blood group antigens and
minor blood group antigens. Blood group mismatch
between patient and donor is not a contraindication for
transplant. Before the start of conditioning chemotherapy
secure venous access in established by using long-term
siliconized central venous catheters (Hickmans or
Groshong either single or multiple lumen). Patient
prophylactically receives oral antibiotics, antifungal
agents and Pneumocystis carinii prophylaxis depending
upon the institutional policy.
Stem Cell Collection
Traditionally, stem cell collection involves the aspiration
of 0.5-1.5 litres of bone marrow, mainly from the posterior
iliac crests, under general anesthesia. Hematopoietic stem
cells circulate in very low concentrations in the peripheral
blood, but increase markedly during recovery from
chemotherapy or with cytokines such as granulocyte
colony-stimulating factor (G-CSF). Adequate numbers
of stem cells for transplantation can be harvested from
donor peripheral blood after administration of G-CSF
for 4-5 days.
In the autologous setting, peripheral blood stem cells
can be harvested following chemotherapy and G-CSF.
Harvesting involves an automated pheresis procedure
and is generally well tolerated. Umbilical cord blood
contains a high concentration of hematopoietic
progenitors with high proliferative capacity. Unrelated
umbilical cord blood banks are now established.
Transplantation of Stem Cells
Before transplantation, conditioning therapy is given to
eradicate the underlying disease and, in the allogeneic
setting, immunosuppress the patient sufficiently to
prevent rejection of the transplant.
Choice of conditioning therapy depends on many
factors, including the underlying disease, patient age,
donorrecipient HLA matching and stem cell source.
Standard (myeloablative) conditioning usually involves
high-dose chemotherapy, often with total-body irradiation. TBI is most commonly combined with cyclophosphamide (Cy/TBI). Since, use of TBI is associated
with acute toxicity in the form of mucositis, enteritis,
906
anorexia, etc and delayed complications life growth

retardation, pulmonary dysfunction and cataracts, TBI
can be replaced by combining busulphan with cyclophosphamide or use of additional drugs like VP-16,
Cytosine arabinoside, Idarubicin , etc. The conditioning
treatment schedules used for ABMT have been more or
less similar to those used for allogeneic BMT. Anti-T cell
antibodies (e.g. antithymocyte globulin, alemtuzumab)
are often used in allogeneic HSCT to reduce the immune
complications of graft rejection and GvHD.
Following conditioning, stem cells are infused
through a large bore central venous catheter (e.g.
Hickman line) and migrate to the bone marrow. There is
a period of obligate neutropenia (usually about 23
weeks) before engraftment of mature, donor-derived
blood cells. During this time, the patient is nursed in an
isolation cubicle with air filtration to prevent inhalation
of fungal spores. Supportive care (e.g. anti-infection
drugs, blood and platelet transfusions) is important in
the early post-transplantation phase. Patients receiving
allogeneic HSCT receive cyclosporin A or tacrolimus for
the first few months to prevent GvHD.
Complications
mucocutaneous barriers. During this period bacterial

infections are common and after first 2 weeks incidence
of fungal infections is also high. During the phase of early
immune recovery which lasts for 3 to 4 months, the blood
counts are normal. This phase is modulated by development of acute GvHD which delays immune recovery and
the treatment of the condition especially with steroids
further causes immune suppression. At this time patient
is susceptible to get infection with CMV and also fungal
infections like Aspergillus and Candida. The phase of
late immune recovery starts from 6 months and may not
be complete for 1 to 2 years. Development of chronic
GvHD during this period significantly delays the
immune recovery. During this time reactivation of
varicella zoster, infection with capsulated bacteria like
S. pneumoniae, Neisseria, H. influenzae, mucocutaneous
candidiasis is commonly encountered. In order to reduce
the incidence of infections, prophylactic use of antibacterial, antifungal and antiviral agents has been tried.
Isolation of patient in HEPA filtered rooms with laminar
airflow and reverse barrier nursing helps in preventing
acquisition of new pathogens. Table 16.9.2 enlists the
infections seen during different phases after transplantation.
Early Complications
Conditioning related: These include nausea, vomiting,
alopecia, hemorrhagic cystitis (cyclophosphamide),
mucositis and interstitial pneumonitis. Major organ
toxicity (e.g. cardiomyopathy, veno-occlusive disease of
the liver) may also occur.Neurologic side effects
especially convulsions are common with TBI and
Busulfan. Prophylactic use of phenytoin during the
chemotherapy has been recommended for this complication.
Infections: These are the most important cause of
morbidity and mortality posttransplant. The patients are
susceptible to infections with bacteria, viruses, fungi as
well as parasites. This is because of the various factors,
i.e. myelosuppression, immunosuppression, tissue
damage, indwelling venous access devices and use of
parenteral nutrients, etc. Development of graft versus
host disease depresses the host immunity further and
increases the chances of infections. The post-BMT period
characterized by three phases viz. 1. Phase of aplasia 2.
Early immune recovery and 3. Late immune recovery.
The phase of bone marrow aplasia lasts for 3 to 4 weeks
and in addition is associated with disruption of
TABLE 16.9.2: Infections most frequently seen at different

times post-transplantation
I. Infections in first 30 days post-transplantation
A. Bacteremia
Gram-positive organisms: Staphylococcus epidermidis
Gram-negative aerobes and anaerobes
B. Invasive fungal infections: Aspergillus, Candida
C. Reactivation of herpes simplex I
II. Infections 30120 days post-transplantation
A. Protozoal infections
Pneumocystis carinii
Toxoplasma
B. Viral infections
Cytomegalovirus (CMV)
Adenovirus
EpsteinBarr virus (EBV)
Human herpesvirus 6 (HHV-6)
C. Fungal infections
Candida (C. albicans and C. tropicalis)
Aspergillus
Trichosporon
Fusarium
Candida krusei
III. Infections after 120 days post-transplantation
A. Sinopulmonary infections with encapsulated organisms
B. Viral infections (cutaneous herpes zoster)
Pediatric Oncology
Graft failure is rare in autologous HSCT, but can occur
following use of an inadequate stem cell dose. Causes of
graft failure following allogeneic HSCT include immune
rejection, infection with CMV, parvovirus or human
herpes virus 6, an inadequate stem cell dose, and use of
myelotoxic drugs in the post-transplantation period. A
second transplantation procedure may be required if
graft failure does not respond to appropriate measures
(e.g. treatment of viral infection, administration of GCSF).
GvHD occurs when allo-reactive T-cells from the donor
react with antigenic targets on host cells. Acute GvHD
develops within 3 months post-transplantation; chronic
GvHD develops or persists after this time.
Acute GvHD occurs in 30% of recipients of stem cells
from HLA-identical sibling donors and 5060% of
recipients from unrelated donors. It is characterized by
an erythematous maculopapular rash, diarrhoea, and
liver disease with increased bilirubin and transaminase
levels. More severe acute GvHD (grade IIIV) is
associated with reduced survival and requires immunosuppressive therapy with corticosteroids and second-line
agents such as cyclosporin, tacrolimus, mycophenolate
mofetil and ATG. Preventive measures are important and
involve either post-transplantation immunosuppression
(generally cyclosporin and methotrexate) or removal of
T-cells from the stem cell inoculum (usually by T-cell
antibodies given in vivo or in vitro).
Chronic GvHD develops in 1050% of transplant
recipients surviving beyond 6 months. It is characterized
by sicca syndrome, bile duct degeneration and cholestasis, bronchiolitis obliterans, mucocutaneous scleroderma and arthritis. Treatment of chronic GvHD is based
on prednisolone, immunosuppressive agents and
antibiotic prophylaxis, but is generally unsatisfactory.
Newer agents including thalidomide, antibodies to the
interleukin-2 receptor and tumor necrosis factor, and
extracorporeal photopheresis are also being increasingly
used.
Late complicationsThese include endocrine problems
(e.g. infertility, ovarian failure, osteoporosis, hypothyroidism, growth hormone deficiency),cataracts
(particularly after total-body irradiation) and secondary
malignancies (e.g. AML, myelodysplasia, solid-organ
tumors, skin cancers).
907
BMT FOR HEMATOPOIETIC DISORDERS

Hematopoietic Malignancies
For certain leukemias and myelodysplastic diseases (for
example, those identified by unfavorable genetic
markers), HSCT is the only curative option available and
is considered a primary treatment modality. Otherwise,
HSCT for hematopoietic malignancies is widely used as
a salvage therapy for patients who fail primary
chemotherapy.
Acute Myeloid Leukemia
Acute myeloid leukemia (AML) has poor outcome if
treated with conventional chemotherapy alone. Traditionally the treatment has been the combination of
cytosine arabinoside and anthracycline. VP-16 has also
been used. With the current treatment regimens, 70 to
90% children achieve complete remission. In patients
achieving remission after conventional chemotherapy,
relapse remains the most important risk with more than
70% patients developing the complication. The median
time to relapse has been 1 year. Hence, only 30 to 40%
patients are long-term survivors. Second remission can
be achieved in 40% patients but the duration of response
is short. Hence allogenic-BMT is recommended after first
remission as a curative modality for all patients except
ones with favourable cytogenetics and good risk group
which includes acute promyelocytic leukemia with translocation t(15;17), t(8;21) and inv(16), or with chemotherapy-sensitive disease defined by a low minimal
residual disease (MRD) after the first induction course.
The results of transplant are best if it is done during first
remission. Results from various studies have shown that
almost 50 percent patients can be cured of their disease
if the transplant is done during first remission. The results
of transplant done in first relapse or second remission
are same with 30 percent leukemia free survival and
relapse probability of 40 to 45%.
The results of ABMT are better than conventional
therapy for AML. In patients achieving second or
subsequent CR, the chances of cure are less than 5% with
conventional therapy. ABMT has shown consistently
better results in these patients with 3035% probability
of DFS and relapse risk of 50%.
908
Acute Lymphoblastic Leukemia

ALL in pediatric population has been a success story of
modern day combination chemotherapy. With current
regimens, it is possible to cure 70 to 80% children with
standard risk ALL and 60 to 70% with high- risk ALL.
Nevertheless there remain some ALL subtypes which
are not cured by conventional chemotherapy alone. These
include Ph positive, hypodiploid and t(4:11) positive
ALL, biphenotypic leukemia and patients with high
MRD (>1%) after induction. In these patients, BMT offers
a better chance of cure. BMT is considered for such high
risk ALL patients after its remission and as a salvage
procedure for resistant disease or after second and
subsequent remissions.
In children with high-risk ALL transplanted in first
remission, disease free survival in the range of 80% can
be obtained. Allo BMT can cure 35% of relapsed patients
in second remission, which is not possible with
conventional chemotherapy. In patients with induction
failures, it can achieve long-term disease free status in
almost 40% patients. Compared to AML, the role of
ABMT is unproven in ALL and is investigational.
MYELODYSPLASTIC SYNDROME
MDS in children must be distinguished from AML
presenting with a low blast count; the latter shows
minimal hematopoietic dysplasia and often manifests
cytogenetic abnormalities associated with AML.
Allogeneic HSCT remains the principal curative
modality. DFS rates between 36% and 87% have been
reported for children with primary MDS who are
undergoing allogeneic transplantation from matched
alternative donors. Because of higher relapse rates,
patients with JMML and refractory anemia with excess
blasts in transformation (RAEBt) generally fare worse
than patients with the other MDS types. However, more
recent trials have reported improved DFS up to 55% for
matched HSCT and 49% for unrelated donor HSCT in
these disorders.
CHRONIC MYELOGENOUS LEUKEMIA
CML is rare among children. Prior to the development
of the specific BCR/ABL tyrosine kinase inhibitor,
imatinib, HSCT was the only recognized curative
therapy. Although imatinib induces hematologic
remission in more than 90% patients and cytogenetic
remission in more than 70%, only a minority of patients

achieves a molecular remission. Currently, there is no
data to guide the duration of imatinib therapy and to
suggest that imatinib is curative. All of this has created
uncertainty regarding the role and timing for HSCT. At
present, the optimal management of newly diagnosed
CML is unclear. Matched-sibling HSCT for patients in
chronic phase of CML results in cure rates of 70% and
86%. For children with a donor, HSCT can be curative
and delay in HSCT beyond a year may diminish the
potential for cure. Current data do not indicate an adverse
influence of prior Imatinib therapy on HSCT. Up to 30%
of patients fail to achieve a satisfactory cytogenetic
response to imatinib. In this circumstance, HSCT should
be considered even if this requires HSCT from alternative
donors. There may be a role for imatinib as adjuvant
therapy to prevent disease relapse following HSCT and
along with donor lymphocyte infusions to control
reappearance or persistence of BCR/ABL cells after
HSCT.
HODGKINS DISEASE AND NON-HODGKINS
LYMPHOMA
Pediatric patients with lymphoma who do not enter
remission or who subsequently relapse are rarely cured
using therapy at conventional doses. These children
benefit with ABMT. Lymphoma patients with favorable
characteristics have a DFS of up to 60% after ABMT,
whereas fewer than 20% of poor-risk patients achieve
durable remissions. In NHL, progressive disease or lack
of response to salvage chemotherapy before ABMT is a
negative prognostic factor associated with DFS of less
than 10%. For patients with relapsed HD, bulky disease
and poor response to prior chemotherapy at the time of
ABMT adversely affects outcome.
TRANSPLANTATION FOR SOLID TUMORS
Brain Tumors
The prognosis is dismal for those children with brain
tumors failing surgery, radiation therapy, and/or
conventional chemotherapy. Several groups have
explored the use of autologous BMT. The results for
patients with primitive neuroectodermal tumor or
medulloblastoma and high-grade gliomas outside the
brainstem are closely correlated with tumor burden at
the time of HSCT, ranging from less than 10% in children
Pediatric Oncology
with bulky disease to 50% for those with minimal or no
disease. HSCT has also been used with encouraging
preliminary results in infants and young children to
avoid or reduce neuroaxis radiation. However, good
outcome depended on the ability of surgery or chemotherapy, or both, to produce a state of minimal disease
before HSCT.
Neuroblastoma
Conventional treatment of children with high-risk
neuroblastoma has generally resulted in a DFS of less
than 20%. Newly diagnosed high-risk patients treated
with regimens culminating in ABMT have been reported
to have a 3-year DFS of 43% after conditioning with
myeloablative chemotherapy and TBI. Purged BM is used
as the SC source in most studies. Post-HSCT therapy with
oral cis-retinoic acid, which decreases proliferation and
induces differentiation in neuroblastoma cells, further
improves survival in this cohort. Use of iodine-131
metaiodobenzylguanidine (131I-MIBG), a targeted
radiotherapeutic agent , monoclonal antibodies [e.g., antiganglioside G(D2)] as adjuvant therapy after autologous
SCT, use of genetically modified tumor vaccines, and the
use of autologous tumor-specific T-cell therapy after
transplant are novel strategies being used to further
improve the outcome for this poor prognosis disease.
Sarcomas and Other Solid Tumors
Results of autologous ABMT for children with high-risk
Ewings sarcoma and Rhabdomyosarcoma including
those with metastatic disease at presentation or those
with recurrent disease have been discouraging. This poor
response after autografting may be related to contamination of SC harvests with tumor cells, which appears
associated with relapse. An EFS of 21% at 5 years for
new patients with metastatic disease and 32% for those
transplanted in CR2 has been reported. Some children
with metastatic Wilms tumor have a poor likelihood of
cure with conventional therapy. Autologous HSCT leads
to EFSs ranging from 36% to 48.2% in this group, with
improved outcomes seen in patients who were in CR at
the time of HSCT. In conclusion, curing children with
recurrent or refractory solid tumors remains difficult and
can result in appreciable toxicity.
Non-Malignant Disorders
Congenital immunodeficiency disorders including
severe combined immunodeficiency, WiskottAldrich
909
syndrome and ChediakHigashi syndrome can generally

be cured with HSCT. Cure rates are 90% with HLAidentical sibling donors and 5070% with unrelated or
haplo-identical related donors.
Severe aplastic anemia HSCT is generally regarded
as the optimal treatment for patients less than 40-years
of age; cure rates of up to 90% are expected. Results are
less favourable in older patients and in those without an
HLA-identical donor, and a trial of immunosuppression
is often recommended.
Hemoglobinopathies HSCT from an HLA-identical
sibling donor achieves a cure in 7090% of patients with
conditions such as thalassemia and sickle cell anemia,
particularly if transplantation is undertaken before
development of end-organ disease.
Other non-malignant conditions HSCT has been used
successfully in storage disorders (Gauchers disease,
Hurlers syndrome, leucodystrophy), congenital
leucocyte disorders (Kostmanns syndrome, chronic
granulomatous disease) and congenital anemia
(BlackfanDiamond syndrome, Fanconis anemia), and
is under investigation in severe autoimmune disorders
such as scleroderma and rheumatoid arthritis.
Recent Developments and Future Advances
Reduced-intensity conditioning In reduced-intensity
conditioning allogeneic HSCT (mini-transplants), totalbody irradiation is avoided and conditioning comprises
of chemotherapy that is nonmyeloablative but immunosuppressive. Fludarabine is widely used with other
agents (e.g. melphalan, busulfan, cyclophosphamide),
and some protocols include T-cell antibodies (e.g.
alemtuzumab, ATG) given in vivo. Peripheral blood stem
cells are preferred over bone marrow to enhance
engraftment. This approach is particularly promising in
patients with lymphoma and myelodysplasia.
Alternative donor transplants Overall likelihood of
identifying an HLA-identical sibling donor is about 30%.
A suitable unrelated donor (matched or one antigen
mismatched) is found in 5080% of cases, depending on
the patients HLA type and ethnicity. Thus, many
patients have no allogeneic donor. Haplo-identical
transplantation (often a parent donor matched for only
one haplotype with a child patient) has recently become
possible. Engraftment is promoted by a high stem cell
dose and very immunosuppressive conditioning
regimens. GvHD is prevented by stringent T-cell
depletion of the infused graft.
910
Graft engineering Many groups are investigating the

possibility of selecting subpopulations of cells from
peripheral blood stem cell collections, for infusion at the
time of or following HSCT. Examples include T-cell
subset depletion to reduce GvHD, selection and culture
of virus-specific cytotoxic T-cells to induce enhanced
immune responses (e.g. to CMV and EBV), and a similar
approach involving leukemia-specific antigens (e.g. Bcr/
Abl in CML) to augment the graft-vs-leukemia effect.
CONCLUSION
HSCT is one of the most challenging and a promising
therapeutic modality for treatment of a wide variety of
disorders. Its results and applications are likely to expand
further with easier donor availability for unrelated
transplantation, use of alternative stem cell sources
including umbilical cord, reduced-intensity conditioning
and graft engineering. In the future, gene therapy and
stem cell research is further expected to dramatically
change the landscape of stem cell transplantation.
BIBLIOGRAPHY
1. Blume KG, Forman SF, Appelbaum F. Thomas hemopoietic cell transplantation book. Oxford: Blackwell, 2004.
2. Bodmer JG, Marsh SG, Albert ED, et al. Nomenclature

for factors of the HLA system,1998. Hum Immunol
1999;60(4):361-95.
3. Gluckman E. Umbilical cord blood hematopoietic stem
cells; biology and transplantation.Curr Opin Hematol
1995;2(6)413-16.
4. Gratwohl A, Baldomero H, Horisberger B, et al. Current
trends in hematopoietic stem cell transplantation in
Europe. Blood 2002;100:2374-86.
5. Gupta S, Kumar L, Raju GM, Kochupillai V, Shukla DK.
Autologous bone marrow/Stem cell transplantation;
initial experience at a north Indian referral center. Nat1
Med J India 2000;13(2):61-66.
6. Hongeng S, Krance RA, Bowman LC, et al. Outcomes of
transplantation with matched-sibling and unrelateddonor bone marrow in children with leukemia. Lancer
1997;350(9080):767-71.
7. Levine JE, Harris RE, Fausto R, et al. A comparison of
allogeneic and autologous bone marrow transplantation
for symptomatic lymphoma. Blood 2003;101(7):2476-82.
8. Matthay KK, Villablanca JG, Seeger RC, et al. Treatment
of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow
transplantation, and 13-cis-retinoic acid. Childrens
Cancer Group. N Engl J Med 1999;341(16):1165-73.
9. Morrison VA, Peterson BA. High-dose therapy and
transplantation in non- Hodgkins lymphoma. Semin
Oncol 1999;26(1):84-98.
17.1 Disorders of Growth: PSN Menon ....................................................................................................................................................... 912

17.2 Disorders of Pituitary: PSN Menon ..................................................................................................................................................... 919
17.3 Obesity: Anju Virmani ........................................................................................................................................................................... 925
17.4 Disorders of Thyroid Gland: Meena P Desai ..................................................................................................................................... 931
17.5 Disorders of Bone and Mineral Homeostasis: Vijayalakshmi Bhatia ............................................................................................... 935
17.6 Disorders of Puberty: Prisca Colaco ................................................................................................................................................... 941
17.7 Disorders of Sexual Differentiation: P Raghupathy .......................................................................................................................... 947
17.8 Disorders of Adrenocortical Biosynthesis: P Raghupathy .............................................................................................................. 951
17.9 Disorders of Adrenal Glands: PSN Menon ........................................................................................................................................ 955
17.10 Diabetes Mellitus: Vijayalakshmi Bhatia .............................................................................................................................................. 962
912
17.1 Disorders of Growth

PSN Menon
SHORT STATURE
Growth Charts
A child is diagnosed to have short stature when his or

her height is below the 3rd percentile or below 2 SD of
the mean height for that age and sex. Even when the
actual height measurements are within normal ranges,
the child should be regarded as short, if the height
velocity is less than the 25th percentile for age over 6 to
12 months of observation or the child is very short for
midparental or target height.
The growth pattern of child should be recorded both

numerically as well as graphically using appropriate
growth charts.
Rationale of Clinical Evaluation

Measurement of Growth
Supine length is measured by an infantometer in infants
and children less than 2 years and standing height by a
stadiometer in older children. The techniques for
measuring height are detailed in Chapter 2. In addition
to height, measurements of weight, midarm
circumference, skin fold thickness and head
circumference are often helpful in diagnosis. The height
and weight can be expressed as standard deviation scores
(SDS or Z score). Z score is calculated using the formula:
(The childs height mean height for age from a reference
chart) 1 SD of height for that age in the reference data.
Height Velocity
Estimation of height velocity is essential for optimal
decision making. On an average most infants measure
50 cm in length at birth, and gain approximately 25 cm
in the first year of life, 12.5 cm in the second year, 6-7 cm
each in the third and fourth years, and subsequently 5
cm every year until pubertal growth spurt. The peak
height velocity during adolescence is about 9-11 cm per
year for boys and about 7-9 cm per year for girls.
Retardation of height is very significant if height velocity
is low or decreasing. On the other hand, if the child has
a normal height velocity and is growing along his
percentiles, the parents can be reassured. Height velocity
can also be expressed in Z scores.
Predicting Adult Height

A crude way to assess the genetic potential is to plot the
heights of the parents on the adult equivalent (e.g. at 1820 years) on a standard growth chart. The target height
or midparental height (MPH) is calculated by the formula
for boys: average of fathers height and mothers height
+ 6.5 cm; for girls: average of mothers and fathers
heights 6.5 cm. MPH should be plotted on the adult
equivalent on the growth chart. It provides the target
height for the child and the percentile he/she is likely to
follow (Fig. 17.1.1).
Body Proportions
The body proportions employed in clinical decision
making are upper:lower segment ratio (US:LS ratio) and
arm span:height ratio. They vary with age. The US:LS
ratio is approximately 1.7 at birth, 1.3 at 3 years, 1.1 by 6
years and 1 by 10 years. Arm span is less than length at
birth by 2.5 cm and equals height at about 11 years and
thereafter it is greater than height. An abnormal US:LS
ratio or arm span:height ratio indicates disproportionate
short stature. Children with achondroplasia have a
normal sized trunk with short limbs, while
spondyloepiphyseal dysplasia gives rise to short trunk
and normal limbs.
Pubertal Assessment
Pubertal assessment has an important role in the
diagnosis and prognosis of short stature. Onset of puberty
is associated with the height spurt seen during
adolescence. Delayed or precocious puberty thus has an
important role in stature. The stage of puberty is assessed
by the Tanners method of sexual maturity rating.
Testicular volume is measured by comparing testis with
an orchidometer.
Endocrinology
913
Figure 17.1.1: Growth chart showing how to record a child's height. The actual height of a 9 years old girl is recorded as 120 cm
as 'measured height'. The father's height, mother's height and the target or midparental height is recorded at 20 years on the
growth chart. She is expected to follow the 25th centile according to the target height but is short for her target height for age. The
mean height for the age is recorded at the 50th centile. Bone age, recorded as a triangle is further behind her chronological age,
but equal to her 'height age', the point where the actual height crosses the 50th centile
914
Bone Age Assessment

An essential investigative tool for evaluating short stature
is bone age measurement. This is conventionally done
from X-rays of wrist and elbow. The bone age is
computed from the appearance of epiphyseal centers and
fusion of epiphysis with metaphysis using Greulich-Pyle
atlas or Tanner-Whitehouse method. A child with
delayed bone age has a better prognosis for future height
gain than those with appropriate or advanced bone age.
Children with familial genetic short stature have bone
age appropriate for chronologic age, whereas those with
an endocrine cause for such as growth hormone
deficiency or hypothyroidism have delayed bone age.
Adult height can be predicted by computing chronologic
age and bone age using the Bayley-Pinneau charts.
Etiology of Short Stature
Short stature may be due to a variety of disorders (Table
17.1.1). Endocrine causes include hypothyroidism,
hypopituitarism, diabetes mellitus, Cushing syndrome,
pseudohypoparathyroidism and hypogonadism. A
significant number of children who turn-up for
evaluation of short stature have no pathological cause.
Most have a physiological cause for their short stature.
Clinical and Laboratory Evaluation
An algorithmic approach to diagnosis of short stature is
given in Figure 17.1.2.
Clinical History
The time of onset of short stature has great relevance in
the differential diagnosis. Hence antenatal and birth
history (including maternal illness during pregnancy,
birth weight, length, gestational age, signs of congenital
anomalies), development, puberty, psychosocial
behavior and nutrition are essential. Details of
consanguinity, family history of short stature and
pubertal development are indispensable.
Short stature with normal height velocity with growth
curve following a line parallel to 3rd centile and positive
family history suggest familial short stature (FSS). Children
with constitutional delay in growth and puberty (CDGP)
have growth failure from the age of 2-3 years with
delayed onset of puberty, positive family history in
parents or siblings. When the growth failure is noted
postnatally, environmental causes such as malnutrition,
chronic infections, and emotional disturbances in family
should be probed. Social history is important to detect

psychosocial short stature. All systems including
endocrine, renal and gastrointestinal, should be reviewed
carefully to identify the likely cause for deceleration of
growth.
The presence of characteristic physical signs of an
endocrine disease or dysmorphic syndrome greatly
facilitates the diagnostic work-up. Children with
endocrine disorders generally have a weight percentile
better than that of height, whereas those with systemic
disorders usually lose weight first and are thin by the
time they are short. Disproportions of body are seen in
skeletal dysplasia, rickets, hypothyroidism and some
dysmorphic syndromes. Pallor and signs of vitamin
deficiencies are frequent in many nutritional disorders,
TABLE 17.1.1: Differential diagnosis of short stature
A. Normal variants
1. Familial genetic short stature
2. Constitutional delay in growth and puberty
B. Disproportionate short stature
1. Skeletal dysplasias: Achondroplasia, hypochondroplasia,
spondyloepiphyseal dysplasia
2. Rickets: Nutritional, metabolic
3. Untreated hypothyroidism
C. Proportionate short stature of prenatal onset
1. Intrauterine growth retardation
Placental insufficiency disorders: Maternal toxemia,
diabetes mellitus
Intrauterine infections: TORCH complex
Teratogens: Alcohol, nicotine, drugs
2. Dysmorphic syndromes: Russell-Silver syndrome, Seckel
syndrome
3. Chromosomal anomalies: Down syndrome, Turners
syndrome
D. Proportionate short stature of postnatal onset
1. Nutritional disorders: Malnutrition
2. Chronic infections: Tuberculosis
3. Gastrointestinal disorders: Celiac disease, chronic
diarrhea, malabsorption syndromes, chronic liver disease
4. Hematological disorders: Hemolytic anemia
5. Renal disorders: Chronic renal failure, tubular disorders
6. Cardiac disorders: Congenital cyanotic heart disease,
chronic congestive failure
7. Pulmonary disorders: Cystic fibrosis, chronic asthma
8. Endocrine disorders: Hypothyroidism, growth hormone
deficiency and insensitivity, Cushing syndrome,
hypogonadism, pseudohypoparathyroidism, diabetes
mellitus
9. Psychosocial short stature
Endocrinology
Figure 17.1.2: An algorithmic approach to diagnosis of short stature.

LFT Liver function tests, RFT Renal function tests
915
916
malabsorption, chronic anemia, hypothyroidism and

renal failure. It is also important to evaluate the genitalia
and grade the pubertal development.
Constitutional delay in growth and puberty (CDGP) is
defined as a delay of growth and puberty in an otherwise
healthy child, usually an adolescent, with a standing
height below the expected for chronological age, but not
for his bone age. It tends to affect more boys than girls. It
should be a diagnosis of exclusion. The final adult height
will be within the normal range. These children are short
from around 2-3 years of age. Growth is just below but
parallel to 3rd centile initially with a further deviation
as the adolescent pubertal spurt is delayed. Bone age is
delayed. There is a familial tendency for short stature
and delayed catch up. The spine length may be relatively
short compared to limb length.
Children with familial short stature are short with a
height appropriate for the parents height with normal
height velocity. The growth curve is below but parallel
to the 3rd centile. Body proportions are normal and
pubertal development is appropriate for age. Bone age
is appropriate for his/her age. Again this is a diagnosis
of exclusion.
Children with congenital growth hormone deficiency
(GHD) are short with a cherubic appearance, doll-like
face and microphallus. Presence of midline anomalies
such as cleft lip, cleft palate or single central incisor tooth,
suggests the possibility of hypopituitarism. Visual field
defects, optic atrophy, optic nerve hypoplasia and
papilledema are often associated with septo-optic
dysplasia and tumors of the pituitary-hypothalamic
region.
Acquired hypothyroidism often manifests as short
stature. Coarse facies, myxedema, dry rough skin,
macroglossia and developmental retardation with
delayed relaxation of deep tendon reflexes characterize
hypothyroidism. Growth retardation may sometimes be
the only presenting feature of Cushing syndrome in
childhood. Pseudohypoparathyroidism manifests with short
stature, round facies, central obesity, short fourth
metacarpals and mental subnormality, hypocalcemic
tetany or seizures, cataract and calcification in the basal
ganglia.
Turner syndrome may present in girls with short
stature alone. It is characterized by the presence of short
webbed neck, shield chest, widely placed nipples with
characteristic cardiac, renal and skeletal defects. Down
syndrome, a common cause of mental retardation, has
short stature with characteristic facies with mongoloid

slant of eyes. Russell-Silver syndrome is characterized by
IUGR, small triangular facies, hemihypertrophy,
clinodactyly, occasionally a large penis and precocious
puberty, and sometimes GH deficiency.
Investigations
If the clinical work up suggests a cause for short stature,
the appropriate confirmatory test should be performed.
Many a time children with short stature present with no
other abnormality on history and examination. Thus in
all cases of significant short stature with a low growth
velocity and/or delayed bone age, it is advisable to
perform screening investigations to diagnose some of the
important causes (Table 17.1.2).
Estimation of bone age is the first vital step in the
diagnosis of short stature. Most children with CDGP,
nutritional disorders, chronic diseases have mild delay
and endocrinopathies such as GH deficiency and
hypothyroidism have significantly delayed bone age.
Cushing syndrome and precocious puberty cause an
advancement of bone age. If the screening tests are
normal, tests to exclude relatively silent causes of short
stature should be performed. These include tests to
exclude hypothyroidism, GH deficiency, renal tubular
acidosis, Turner syndrome, and celiac disease. It is a
policy in some pediatric endocrine centers to do thyroid
function in all children and chromosome studies (for
Turner syndrome) in all girls referred for short stature.
Elevated gonadotropins, especially FSH, also point
towards the diagnosis of Turner syndrome. Those with
TABLE 17.1.2: Laboratory evaluation for short stature
A. Radiology: X-ray for bone age
B. Hematological tests: Hemoglobin, hematocrit, total and
differential leukocyte counts, blood cell morphology, ESR
C. Urinalysis: pH, specific gravity, osmolality, microscopy,
protein, glucose estimations
D. Stool examination: Microscopy for parasitic infections, fat
for malabsorption, glucose
E. Blood chemistry: fasting blood sugar, urea, creatinine,
sodium, potassium, calcium, phosphate, alkaline phosphatase,
cholesterol, albumin and transaminases, venous CO2
F. Special tests: Tuberculin test and chest X-ray, thyroid
hormones (T4 and TSH), tests for celiac disease (antiendomysial and transglutaminase antibodies), FSH and
karyotype (Turner syndrome)
G. Tests for hypothalamic-pituitary axis: IGF-I, IGFBP-3 and
GH stimulation tests, X-ray skull for suprasellar calcification,
MRI brain.
Endocrinology
disproportionate short stature require skeletal survey,
and evaluation for hypothyroidism and RTA. Low
bicarbonate levels suggest RTA.
A measurement of insulin like growth factorI (IGF
I) is useful when the cause of short stature is uncertain.
In some centers IGF binding protein, IGFBP3 is also
estimated as a screening tool. Low levels (below 2 SD of
the mean) of IGF-1 and IGFBP-3 suggest the probability
of growth hormone deficiency. Measurement of GH in a
random blood sample is not a reliable test for GH
deficiency, as GH levels are usually low during day and
spontaneous peaks are brief and unpredictable. The most
practical method is a pharmacological GH stimulation
test using clonidine, insulin or other agents. A GH level
less than 10 g/ml following stimulation indicates
impaired pituitary secretion. Details of GH deficiency
and insufficiency are given in Chapter 17.2.
Management
After the initial visit, the family should be advised
regarding the need for a balanced diet with adequate
calories and proteins, coupled with regular physical
exercises. Supplemental hematinics may be prescribed
if indicated. Height and weight should be recorded and
height gain assessed regularly. Counseling of the child
and the family is essential in conditions such as familial
short stature, CDGP, skeletal dysplasia and IUGR. The
importance of regular follow-up and monitoring of
therapy should be stressed.
Treatment of short stature essentially depends on the
cause. There is no specific treatment for familial short
stature and most cases of IUGR. CDGP can cause
enormous anxiety, and peer-group pressure may lead to
psychological distress. They may benefit from a short
course of low dose testosterone (50 mg testosterone
intramuscularly every 3-4 weeks) or estrogen (2.5 g of
ethinyl estradiol daily) given for 3-6 months. This will
trigger the secondary sexual characteristics and the
pubertal growth spurt.
Hypothyroidism should be managed with
replacement by levothyroxine. Low dose estrogens are
useful in girls with Turners syndrome and delayed
puberty. Anabolic steroids (oxandrolone) have been tried
with some success in Turner syndrome and a few
children with CDGP. They act by increasing GH
secretion. A low-dose daily regimen will induce growth
spurt, which continues even after the steroids are
stopped. Specific therapy for chronic systemic disorders,
917
e.g. renal tubular acidosis and celiac disease is associated

with good catch-up growth. For most skeletal dysplasias,
there is no medical treatment, even though GH has been
shown to benefit some selected groups. Limb lengthening
surgery is an option for some skeletal dysplasias.
Growth hormone (GH) is indicated in children with
GH deficiency. The recombinant GH is given in a dose
of 0.23-0.3 mg/kg/week (1 mg = 3 IU) divided in 6-7
doses subcutaneously, preferably at night, till adult
height is reached. There are very few side effects reported
in children who have received GH for GH deficiency.
Contrary to earlier suggestions, there is no report of
increased susceptibility to tumors or leukemia in treated
children. Children gain on an average 10-12 cm in the
first year of therapy and 6-8 cm/year thereafter every
year. However, the high cost of therapy has limited its
use in the subcontinent.
GH has been used to increase height in a number of
other disorders with limited success. These include
Turner syndrome, end stage chronic renal failure, and a
group of children with IUGR with poor catch up growth.
It is also used in children with Russell-Silver syndrome.
It has been shown to be effective in some groups of
children with constitutional delay and idiopathic short
stature. The dose used is higher than that used in GH
deficiency. In Turner syndrome, a combination of GH
with low dose estrogen and/or oxandrolone has been
shown to produce excellent height gain. The chances for
development of side effects are higher in these children.
Hence, regular monitoring of therapy with recording of
height is essential to obtain good results. Recently
aromatase inhibitors such as anastrozole and letrozole
have been tried with some success in adolescent boys
with short stature. These aromatase inhibitors delay the
tempo of bone age acceleration by estrogen blockade.
TALL STATURE
Compared to short stature, referrals for tall stature are
rather uncommon. A list of common causes for tall
stature is given in Table 17.1.3.
Some children have constitutional tall stature with tall
parents. Tall stature is usually evident early in childhood.
They have a high growth velocity and often a slightly
advanced bone age. If the tall stature is a matter of
psychological concern, sex steroids appropriate for sex
may be given at the onset of puberty to achieve early
epiphyseal fusion.
918

TABLE 17.1.3: Etiology of tall stature in children
Constitutional tall stature

Exogenous obesity
Precocious puberty
Hyperthyroidism
Growth hormone excess Gigantism
Sotos syndrome
Marfan syndrome
Homocystinuria
BeckwithWiedemanns syndrome
Klinefelter syndrome
Fragile X-syndrome
Many children with exogenous obesity appear tall, but

the adult height is normal. Children with precocious
puberty appear to be taller than peers due to the growth
enhancing action of gonadal steroids. However, early
epiphyseal fusion makes them short as adults, unless
treated early.
Gigantism is due to excessive production of GH by an
acidophil adenoma of the pituitary gland. It is
characterized by tall stature with prognathism, increased
soft tissue of hands and feet, broad root of nose, increased
sweating, hypertension and glucose intolerance. The
diagnosis is confirmed by detection of raised IGFI levels
and lack of suppression of GH (levels <1 g/ml)
following administration of oral glucose, 1.75 gm/kg.
Treatment is by trans-sphenoidal pituitary surgery.
Recurrence can be managed by octreotide, a somatostatin
analogue.
Sotos syndrome (cerebral gigantism) is characterized
by increased birth weight and length, macrocephaly and
dolichocephaly, hypertelorism and mental retardation.
Marfan syndrome is characterized by tall stature,
arachnodactyly (long thin fingers) and long thin limbs
with an abnormally long lower segment resulting in arm
span more than height. In addition there may be
hypotonia, hyperextensible joints, scoliosis, flexion
contractures, dislocation of the lens, and cardiac
anomalies. Klinefelter syndrome is associated with tall
stature, abnormally long legs, gynecomastia, mental

retardation and behavioral abnormalities with a
karyotype of 47, XXY.
BIBLIOGRAPHY
1. Allen DB. Growth hormone therapy for short stature: Is
the benefit worth the burden? Pediatrics 2006;118:34348.
2. Bajpai A, Sharma J, Menon PSN: Practical Pediatric
Endocrinology. 1st edition. Jaypee Brothers Medical
Publishers (P) Ltd: New Delhi, 2003.
3. Consensus guidelines for the diagnosis and treatment
of growth hormone (GH) deficiency in childhood and
adolescence: summary statement of the GH Research
Society. J Clin Endocrinol Metab 2000;85:3990-93.
4. Desai MP, Menon PSN, Bhatia V. Pediatric Endocrine
Disorders, 2nd edition. Orient Longman Ltd, Hyderabad.
2008;60-179.
5. Drop SL, Greggio N, Cappa M, Bernasconi S;
International workshop on management of puberty for
optimum axiological results. Current concepts in tall
stature and overgrowth syndromes. J Pediatr Endocrinol
Metab 2001; 14 (Suppl 2):975-84.
6. Farber RS, Kerrigan JR. The multiple indications for
growth hormone treatment of pediatric patients.
Pediatric Annals 2006;35(12):926-32.
7. Khadilkar VV, Khadilkar AV, Choudhury P, et al. IAP
growth monitoring guidelines for children from birth to
18 years. Indian Pediatr 2007;44:187-97.
8. Menon PSN. Use of growth hormone (GH) in non-GH
deficient short stature. Indian J Pediatr 2008 75(Suppl):
S14-S19.
9. Ranke MB, Lindberg A, Chatelain P, et al. Prediction of
long-term response to recombinant human growth
hormone in Turner syndrome: development and
validation of mathematical models. KIGS International
Board. Kabi International Growth Study. J Clin
Endocrinol Metab 2000;85:4212-18.
10. Rosenthal S, Cohen P, Clayton P, et al. Treatment
perspectives in idiopathic short stature with a focus on
IGF-I deficiency. Pediatr Endocrinol Rev 2007;4(Suppl.
2):252-71.
11. Tanner JM: Normal growth and techniques of growth
assessment. Clin Endocrinol Metab 1986;15:411-51.
Endocrinology
919
17.2 Disorders of Pituitary

PSN Menon
PHYSIOLOGY
The anterior pituitary develops from the Rathkes pouch
and the posterior pituitary from the infundibulum, which
is a downgrowth from the floor of the diencephalon. The
principal hormones produced by the anterior pituitary
are:
Thyroid stimulating hormone (TSH),
Adrenocorticotropic hormone (ACTH),
Follicle stimulating hormone (FSH),
Luteinizing hormone (LH),
Growth hormone (GH), and
Prolactin (PRL).
These hormones act on target glands and a variety of
tissues in the body. The hypothalamus produces a
number of hormones which regulate pituitary function.
These include:
Growth hormone releasing hormone (GHRH)
regulates GH release.
Gonadotropin releasing hormone (GnRH)
regulates LH and FSH release.
Thyrotropin releasing hormone (TRH) regulates
TSH and PRL release.
Corticotropin releasing hormone (CRH) regulates
ACTH release.
Somatostatin (SS) or growth hormone release
inhibiting hormone (GHRIH) inhibits GH release.
Prolactin inhibiting factor (PIF) inhibits release of
PRL, TSH and GH.
Ghrelin regulates GH release.
Vasopressin (AVP) has a role in ACTH release.
GH has specific growth promoting actions on protein
synthesis, skeletal growth and intermediary metabolism.
A number of regulatory proteins or transcription factors
are important for the development and function of the
pituitary. They act at different stages of pituitary
development and trigger the expression of specific genes
involved in hormone release and action. These
transcription factors include HESX1, POU1F1 (PIT-1),
PROP-1, LHX3, LHX4, GLI2 and SOX3.
The growth hormone binding proteins (GHBP) act
as a reservoir for circulating GH. Their levels reflect the
GH receptor concentration, with the GHBP constituting
the extracellular domain of the GH receptor. A single

molecule of GH released from circulation binds to two
GH receptors to form a dimer complex. The actions of
GH are mediated through synthesis of insulinlike
growth factorI (IGFI). IGFI in turn circulates bound
to binding proteins called IGFBP; the major one being
IGFBP3. The GHIGF1 axis plays a key role in
regulating growth and the growth promoting effects of
IGFI can be both GHdependent and GHindependent.
GROWTH HORMONE DEFICIENCY (GHD)
Growth hormone deficiency is characterized by short
stature. The growth impairment starts within a few
months after birth, but a clinical diagnosis is usually not
obvious till the child is about 1 or 2 years old.
Etiology
The spectrum of GHD varies from complete to milder
grades of insufficiency. Incidence varies from 1 in 3500
to 4000 in USA and UK. The common causes of GHD are
given in Table 17.2.1. The most common form however
is idiopathic.
Clinical Features
The height is usually less than the 3rd percentile for the
age and the height gain is often as low as 1 cm/year.
These children have normal body proportions and are
somewhat overweight for their height with increased
subcutaneous fat, truncal obesity and normal body
proportions. Bone age is delayed to a variable extent. The
height age is less than the bone age and both are less
than chronological age.
The typical child with GHD is very short and plump
with immature facies and prominent forehead (Fig
17.2.1). They look much younger than their actual age.
Some of the features of congenital hypopituitarism
include midline facial abnormalities such as cleft palate
and lip, single central upper incisor tooth and prominent
philtrum. The eyes appear very prominent with a
depressed nasal bridge with a saddle shaped nose. In
addition there may be underdeveloped mandible and
920
TABLE 17.2.1: Causes of growth hormone deficiency
CongenitalDevelopmental defects of the hypothalamus

and/or pituitary
Anencephaly, holoprosencephaly
Septo-optic dysplasia, Hall-Pallister syndrome
Midline brain and facial abnormalities: Single central
incisor tooth, cleft lip/palate
Associated with abnormal pituitary morphology on MRI:
Hypoplasia of anterior lobe, interruption or hypoplasia of
stalk, ectopic posterior pituitary
Defects in genes necessary for pituitary development
and function
Isolated GHD: Autosomal recessive, autosomal
dominant, Xlinked (mutations of GH1, GHRHR,
SOX3, HESX1)
Combined pituitary hormone deficiencies: autosomal
recessive (mutations of PIT1 (POUF1), PROP 1,
LHX3, LHX4, HESX1); autosomal dominant (mutations
of PIT1 (POUF1), PROP 1); and Xlinked, Riegers
syndrome
Acquired
Tumors within the hypothalamicpituitary axis:
Craniopharyngioma, germinoma, teratoma
Cranial irradiation: Leukemia, meduloblastoma,
astrocytoma/glioma, ependymoma, rhabdomyosarcoma
Trauma to the hypothalamicpituitary region: Perinatal
(breech, forceps) or postnatal
Infiltration: Langerhans cell histiocytosis, thalassemia
major
CNS infections: Tuberculosis
Figure 17.2.1: Nine-year-old boy with growth hormone

deficiency. Note immature facies, hypoplastic scrotum and
micropenis
chin, crowding of teeth, nystagmus with impaired vision

and a high pitched voice. The hands and feet are small
with slowly growing nails and hair. The skin is thin, with
a tendency for premature wrinkling.
Most children with GHD have normal length at birth.
Only 25% of children with GHD have suggestive clinical
signs in early infancy and present by the age of 2 years.
Thus regular height monitoring may help in early
detection. Hypoglycemia and prolonged jaundice in
neonatal period are early pointers to the diagnosis of
GHD. Neonatal hypoglycemia and convulsions are often
associated with ACTH deficiency. Hypogonadism may
be evident in boys as small sized genitalia (Fig 17.2.2).
Pubertal growth spurt is less than normal. Mental
development and intelligence are normal.
Diagnosis
Children with a height below 3rd percentile and height
gain less than 4 cm per year over a period of observation
for at least 6 months, with a bone age below the
chronologic age needs evaluation for GHD. The diagnosis
of GHD depends on demonstration of absent or low levels of
GH in response to stimulation. Since GH levels are
fluctuating because of its pulsatile nature, random or
fasting blood GH level measurements are not helpful in
diagnosis.
Pharmacological stimuli are preferred to
physiological stimuli. Tests which are based on the
physiological stimuli include physical exercise and deep
Figure 17.2.2: Ten-year-old boy with GHDplease note

micropenis and hypoplastic scrotum
Endocrinology
sleep. Standard provocation tests use insulin, clonidine,
arginine, Ldopa, glucagon or GHRH. Of these insulin
(0.050.1 IU/kg IV) and clonidine (0.15 g/m2 orally) are
the most preferred stimuli. Blood samples are collected
before and at 15 to 30 minute intervals for 2 hours.
Diagnosis of GHD is suspected when the peak GH level
is < 10 ng/ml following stimulation. The tests are not
foolproof and there is often an overlap between normal
short children and children with GHD. Hence two
standard provocative tests are usually suggested before
recommending GH therapy. Insulin administration
carries the risk of hypoglycemia and seizures. Hence in
infancy glucagon test is preferred. Priming with sex
steroids is required in short children with delayed
puberty and a bone age of 10 years or more (Boys: Depot
testosterone 100 mg IM 35 days before the test; Girls:
Premarin 5 mg orally the night before and morning of
the test). Euthyroid state is essential before GH testing.
The spontaneous secretion of GH can be evaluated
by measuring GH levels every 15 to 20 minutes during a
12 or 24hour period. However this is not a practice in
India.
IGFI and IGFBP3 are increasingly used for initial
testing in the diagnosis of GHD. There are technical
limitations to IGFI assays. Their levels vary with age,
nutritional status and certain disease states. IGFI is low
in infancy and less dependable in young children (< 5
years of age) and there may be an overlap with GHD. It
is not dependable in GHD associated with brain tumors
and/or cranial irradiation. IGFBP3, not IGFI, is helpful
for diagnosis during infancy and can be used in suspected
neonatal GHD. The IGFBP3 assay is technically simple,
and plasma concentrations vary much less with age and
nutritional status. It is a good predictor of GHD in a child
with short stature.
GHD may be associated with deficiencies of other
anterior pituitary hormones. Hence a complete
evaluation of anterior pituitary function is undertaken
in each patient with GHD.
CT or MRI of brain is useful in the evaluation of GHD
to rule out organic causes and study pituitary
morphologyectopic posterior pituitary, anterior
pituitary hypoplasia, interruption or absence of pituitary
stalk, midline anomalies and tumors. Approximately
15% of children with GHD have an abnormality of
pituitary on imaging.
Molecular genetic testing provides an additional
useful diagnostic tool. Inherited forms of genetic
921
abnormality may be the probable underlying cause of

GHD in 1015% of all patients.
Increased serum concentrations of GH, both basal and
stimulated, together with low IGFI and low IGFBP3
levels, suggest growth hormone insensitivity. Estimation
of GH binding proteins (GHBP) is helpful in the diagnosis
of GH insensitivity.
Treatment
It is important to observe the child with regular growth
records for 6 months to one yeara child who gains more
than 4 cm/year is unlikely to have hypopituitarism. If
GH levels are low, the child may be given recombinant
GH in a dose of 0.230.3 mg/kg/week (1 mg = 3 IU)
subcutaneously, till adequate growth is achieved. Dosage
is titrated with the growth rate, pubertal stage, bone age
and serum IGFI levels. Depot GH preparations are
under investigation.
GH therapy in children with GHD induces rapid
catch up growth during the first 2 to 3 years of treatment,
increasing the height gain 2 to 4 fold above the
pretreatment rate. The child on an average gains a height
of 1012 cm in the first year of therapy and 6-8 cm/yr
thereafter every year. In subsequent years, the height gain
typically declines and follows normal patterns of growth.
Younger children and those receiving a higher dose show
a better response than older children with conventional
dose.
GH is administered daily by subcutaneous injection
in the evening 6 to 7 times a week, varying the site of
injection. Pen devices and prefilled syringes are available
which simplify daily administration. Many centers start
GH therapy at half the normal replacement dose and
increase the dose during the first month to avoid the
possible adverse effects of fluid retention. In addition to
growth, serum IGFI levels should act as a guide during
GH dose titration. If IGFI levels are low, an assessment
of injection technique and compliance might be necessary
before dose adjustment. If IGFI levels are above the
normal range and height gain is adequate, a reduction
in dose should be considered.
The cessation of GH therapy at the end of linear
growth is guided by the following criteria:
Height gain decreasing to 1 cm/year,
Attainment of an acceptable height close to target
height,
Bone age is greater than 16 years in boys and 14 years
in girls.
922
After final height has been achieved, GH therapy

should be discontinued and GH status reassessed to
identify those with persistent severe GHD (peak GH < 5
ng/ml). Discontinuation of GH therapy is recommended
for a period of 1 to 3 months or longer before retesting.
GH therapy is relatively safe. Contrary to earlier
suggestions, there is no report of increased susceptibility
to tumors or leukemia in treated children. Salt and water
retention occurs within the first few months of initiation.
Treatment with GH increases the risk for slipped capital
femoral epiphysis, pseudotumor cerebri and worsening
of scoliosis. Impaired glucose tolerance may develop in
a few, hence blood glucose and HbA1c estimation is
recommended periodically.
There is also need for regular monitoring of thyroid
function during therapy with GH, as some patients
develop reversible hypothyroidism. Pituitary thyroid
axis should be checked annually. The dose required to
maintain euthyroid status is lower than in children with
primary hypothyroidism. Supplementation of other
pituitary/hypothalamic hormones along with GH
depending upon concomitant pituitary deficiencies is
important. Care should be taken while replacing steroid
replacement in children with ACTH deficiency as
hydrocortisone dose should usually not exceed 10 mg/
m2/24 hour. Sex steroid replacement should be at the
normal age around 1112 years in girls and 1213 years
in boys. Concurrent treatment with GH and a GnRH
analogue or aromatase inhibitor (anastrozole or letrozole)
has been recommended in some children presuming that
interruption of puberty will delay epiphyseal fusion and
prolong growth to give a better final height.
GH for NonGHDeficient Short Stature
Growth hormone enhances growth of many non
GHdeficient short children and is recommended in the
following situations:
Turner syndrome A number of early studies
demonstrated that GH therapy with or without
anabolic steroids accelerated growth velocity and led
to an improved final height. The current practice is
to use approximately 0.35 mg/kg/week. In clinical
practice, it may be useful to add oxandrolone as a
synergistic agent if response to GH becomes
attenuated in late childhood.
Chronic renal insufficiency prior to undergoing renal
transplantation FDA has approved GH (0.3 mg/
kg/week) in children with chronic renal insufficiency
with poor height gain over 6 months, prior to

undergoing renal transplantation.
Smallforgestational age (SGA) SGA children aged
4 years or older with failure to catch-up, height below
2.5 SD, and height SDS more than 1 SD below
midparental height SDS are eligible for GH treatment
in US since 2001 and in Europe since 2003. The
recommended dose is 0.230.35 mg/kg/week.
PraderWilli syndrome The indications for GH
therapy in PraderWilli syndrome are for the
improvement of both growth and body composition.
The recommended dose is 0.160.23 mg/kg/week.
Idiopathic short stature (ISS) ISS is a heterogeneous
group of disorders with two common featuresshort
stature (height less than 2 SD or below the third
percentile for age and gender) and normal GH
response to stimulation tests. The tempo of growth
may be slow or normal. It is a diagnosis of exclusion.
Longterm GH therapy (0.240.37 mg/kg/week) can
lead to increased adult height in children with ISS,
but the degree and predictability is uncertain.
IGFI DEFICIENCY AND GROWTH HORMONE
INSENSITIVITY (GHI)
IGFI deficiency can result from genetic or nongenetic
effects and has been found to be an important underlying
cause of short stature in children. One of the first
examples of insensitivity to GH was reported by Laron
and colleagues in 1966 in three Israeli Jewish siblings
presenting with hypoglycemia, and a clinical phenotype
of GHD, but with marked elevation of immunoreactive
serum GH. Similar cases have been reported from India.
This is a hereditary disorder with primary resistance to
actions of GH due to a molecular defect in the growth
hormone receptor.
The primary genetic form of GHI is associated with
abnormalities of the GH receptor, required to mediate
actions of GH. It may also follow postGH receptor
defects or molecular defects in IGFI. Children with
primary GH insensitivity have the classic clinical
phenotype of severe isolated GH deficiency in its most
severe form. The craniofacial features may be more
prominent with characteristic midfacial hypoplasia,
depressed nasal bridge and protruding forehead. Height
age is more severely retarded in relation to bone age.
Basal serum GH concentration may be normal or
elevated, with excessive GH response to provocative
stimuli. Typically these children have low levels of
Endocrinology
IGFI, IGFBP3, and very low or absent growth hormone
binding protein, GHBP. Administration of GH does not
bring about a rise in IGFI levels, which forms the basis
of the IGFI generation test. The final diagnosis of GHI
is based on the demonstration of the specific molecular
defect in GH receptor gene, in the presence of clinical
phenotype and laboratory criteria.
Initial results of treatment with IGFI appear to be
promising, but there are a number of limitations.
923
following administration of oral glucose, 1.75 g/kg.

Secretion of ACTH, TSH, LH and FSH may be impaired.
Treatment
Excess secretion of GH in children, usually due to a

pituitary adenoma, results in somatic overgrowth or
gigantism. When hypersecretion of the hormone occurs
after the fusion of skeletal epiphyses, it causes
acromegaly which is seen in adults.
Treatment of adenoma includes surgery, irradiation and

medical therapy. The pituitary microadenoma is resected
by trans-sphenoidal route if there is evidence for raised
intracranial tension. Larger tumours can be removed by
transcranial route. Conventional or high voltage
radiotherapy may halt the progress of the disease but
may not cause clinical improvement. Pituitary radiation
can also be carried out by implanting radioactive
isotopes. A long acting somatostatin analogue, octreotide
has been found to be better than bromocriptine in
suppressing the levels of GH, IGFI and IGFBP3
concentrations and reducing the size of tumor mass.
Clinical Features
DIABETES INSIPIDUS
There is rapid linear growth and the child is taller than

his/her peers. Peripheral parts of the body, the hands,
feet, nose and mandible are large. The head circumference is increased. Facial features are coarse with
prominent jaw, broad nose, enlarged tongue, bushy
eyebrows, thick skin and subcutaneous tissue, with
dorsal kyphosis. Muscle weakness, bony and
cartilaginous overgrowth, cardiomyopathies and
pigmentation of skin may be present. Diffuse or nodular
goiter or hyperthyroidism may be present. Involvement
of other endocrine organs may lead to hypogonadism,
hypocortisolism or diabetes mellitus. Headaches, visual
field defects including bitemporal hemianopsia,
papilledema followed by optic atrophy and external
ophthalmoplegia are common. Behavioural problems are
common. A GH-secreting adenoma may occur in
association with McCuneAlbright syndrome or multiple
endocrine neoplasia (MEN 1).
Diabetes insipidus results from lack of antidiuretic

hormone (ADH) or arginine vasopressin (AVP). AVP is
secreted from the supraoptic and paraventricular nuclei
of the hypothalamus. It is transported through axons to
posterior pituitary where it is stored until release. It acts
on receptors (V1 and V2) especially in the collecting ducts
of kidney. Binding of AVP to the V2 receptor leads to a
cascade of actions through the Gprotein-adenyl cyclase
system and release of a second messenger known as
aquaporin 2, which allows transport of water. AVP
release is primarily controlled by alterations in plasma
osmolality.
ACROMEGALY AND GIGANTISM
Diagnosis
The diagnosis is based on clinical examination, periodic
growth assessment and investigations. Enlarged sella
turcica with erosion of margins is seen on X-rays. Tufting
of phalanges and increased heel-pad thickness may be
present. Skeletal maturation is normal. CT or MRI scan
should be done to determine the extent of the tumor.
The diagnosis is confirmed by detection of raised IGFI
levels and lack of suppression of GH (levels <1 ng/ml)
Etiology
The deficiency may be partial, complete or transient.
Central or neurogenic diabetes insipidus results from
various abnormalities of AVP synthesis and/or action
due to lesions of neurohypophysis, such as suprasellar
tumors (craniopharyngioma, optic glioma), histiocytosis,
reticuloendotheliosis, encephalitis, tuberculosis,
granulomas and trauma. Diabetes insipidus can occur
in the newborn following asphyxia, intracranial bleeding,
and meningitis. Diabetes insipidus with diabetes
mellitus, optic atrophy and deafness is known as
Wolfram syndrome.
Nephrogenic diabetes insipidus is due to the inability of
the kidney tubules to respond to AVPfailure to increase
renal water reabsorption in the presence of adequate
924
AVP. It is often due to abnormalities in kidney function

and structure affecting collecting duct or mutations that
affect the V2 receptors.
There is a psychogenic form of polydipsia with
associated polyuria due to compulsive water drinking.
In central and nephrogenic diabetes insipidus,
diffusion of water from the distal tubules and collecting
ducts is reduced due to lack of AVP. Since sodium and
water transport from the loop of Henle and distal tubule
remains unchanged, urine becomes hypotonic and
cannot be concentrated beyond 150 mOsm/kg.
Clinical Features
These children are thirsty and pass large quantities of
urine and often report with nocturnal enuresis. The
symptoms are often not recognized by the parents.
Infants with diabetes insipidus thus may present with
intermittent high fevers, irritability, loss of weight, poor
feeding, dehydration and collapse. Abnormal behavior
and hyperactivity are common. In children who have
acquired bladder control, enuresis may be the first
symptom. Signs and symptoms of causative lesions may
be present and include growth retardation, cachexia,
obesity, sleep disturbances, precocious puberty, visual
disturbances and emotional disorders.
Diagnosis
Polyuria and polydipsia should be confirmed by 24 hour
intake and output records. Urinary specific gravity varies
from 1.0011.005 and osmolality 50200 mOsm/kg.
Serum osmolality may vary depending on the degree of
dehydration. Other renal function studies are normal.
Often DI is suspected in the presence of life-threatening
hypernatremia. Serum AVP levels are helpful in
establishing the diagnosis with the child in a
hyperosmolar state with voiding hypoosmotic urine.
Often the distinction between central and
nephrogenic DI requires a water deprivation test or
DDAVP test. During water deprivation test for a
minimum of 36 hours, children with central and
nephrogenic diabetes insipidus fail to concentrate urine
and plasma more than > 300 mOsm/kg, whereas, there
is urinary concentration in children with compulsory
water drinking. The interpretation of water deprivation
test is given in Table 17.2.2. If there is concentration of
urine following DDAVP, (5 g intranasal), the cause is
primary AVP deficiency. Failure to concentrate urine and
TABLE 17.2.2: Interpretation of Water Deprivation Test

Initial evaluation
Serum sodium
Plasma osmolality
Urine osmolality
Weight (calculate 5% weight)
Test not required if urine osmolality > 750 mOsm/kg or
plasma osmolality > 300 mOsm/kg
Monitoring
Urine osmolality and plasma osmolality hourly
Urine output and weight hourly
Look for features of dehydration
Termination of test
Weight loss > 5% or
Urine osmolality > 750 mOsm/kg or
Plasma osmolality > 300 mOsm/kg
Vasopressin response test
Aqueous vasopressin (0.10.5 unit/kg, intramuscularly)
DDAVP (12 mg subcutaneously)
Avoid intranasal DDAVP
Classification
Increase in urine osmolality
< 50% of baseline Nephrogenic DI
> 50% of baseline Central DI
Conversion of urine osmolality to urine specific gravity:300
mOsm/kg 1.005; 750 mOsm/kg 1.010
absence of response to DDAVP indicates nephrogenic

diabetes insipidus.
Radiologic studies including MRI may reveal
evidence for intracranial tumor such as calcification,
enlargement of sella, erosion of clinoid process and
increased width of suture lines or evidence of
reticuloendotheliosis such as rarefaction. MRI also can
demonstrate the absence of the bright hyperintense spot
in hypothalamic-pituitary lesions.
Treatment
Central diabetes insipidus can be treated by
administration of desmopressin (DDAVP), an analogue
of AVP given as a nasal spray, solution or tablets. The
usual dose is 510 g daily either as a single dose or
divided into two doses. Children under two years require
lesser doses (0.150.50 g/kg). Oral administration of
chlorpropamide 20 mg/kg/24 hours in 2 divided doses
may reduce polyuria and polydipsia in partial deficiency.
Hydrochlorothiazide and indomethacin may offer some
relief in nephrogenic diabetes insipidus.
Endocrinology
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11. Rosenthal S, et al. Pediatr Endocrinol Rev 2007;4(Suppl.
2):252-271.
12. Scott R, Hedley-Whyte E. N Eng J Med. 2002;347(20):16041611.
17.3 Obesity
Anju Virmani
Obesity is becoming an increasing problem in children
and adolescents, with an estimated 30% or more
overweight in the West. In urban and semi-urban India
too, obesity in childhood is increasing rapidly, and
recently the prevalence of obesity crossed the prevalence
of malnutrition. Obesity is now recognized as a disease,
which decreases longevity, not just a cosmetic problem.
Apart from impaired mobility and interference with daily
living activities, it also has several health consequences
hyperinsulinemia, hypertension, diabetes, polycystic
ovarian syndrome (PCOS), dyslipidemia, intertriginous
infections, sleep apnea with all its consequences, renal
alterations, hyperuricemia, psychosocial problems and
eating disorders. Obese children may suffer from feelings
of inadequacy and being different, and being stereotyped
as clumsy, lazy, stupid, or worthless. Almost half of
overweight children are overweight adolescents, and
almost 80% overweight adolescents are obese adults.
They in turn, in addition to all these problems, have more
coronary heart disease, osteoarthritis, cholecystitis and
fatty liver disease, higher risk of certain malignancies,
and worsening of asthma and renal disease. These
consequences are likely to be more severe in the coming
decades, as the duration of obesity will be longer with
childhood onset compared to adult onset.
The problem is worse in South Asians, as we tend to

have more body fat for the same body mass index (BMI)
and more adverse body fat patterning including
abdominal adiposity. Individuals with low birth weight
and subsequent obesity are at a very high-risk for
impaired glucose tolerance. Many of these problems can
be reversed with weight loss, but established obesity is
one of the most frustrating disorders to manage, as
sustained weight loss is difficult to achieve, and lost
weight returns rapidly. Currently, the goals of
management are not attainment of ideal body weight
(IBW), which may be near-impossible, but achieving and
maintaining a 10-20% weight profile. Because weight
reduction is so difficult, prevention is crucial, and
pediatricians today must be vigilant in preventing
obesity, while reducing the health impact in those who
are already obese.
In clinical practice, obesity and overweight are often
used interchangeably, though overweight refers to a
situation where the person is upto 20% more than the
IBW, while obesity is when the weight is > 20% above
IBW. The term most commonly used to quantify obesity
is body mass index or BMI, calculated as weight in kg
(height in m2). Adult obesity is defined as BMI > 25kg/
m2, though it has been recommended that for south
926
Asians, the cut-off should be 23 kg/m2. Morbid obesity

is BMI > 40, and super-obesity a BMI > 60. In children,
Poskitt suggests using percentage of BMI, i.e. actual BMI/
ideal BMI for age. Alternatively, weight for height can
be calculated, and if it is upto 120% to ideal, considered
overweight, and >120% obese.
PATHOGENESIS
Several hormones (e.g. insulin and leptin) and nutrients
(glucose and fatty acids) link the brain, GI tract and
adipose tissue, influencing appetite, energy expenditure,
and growth. A number of orexicants (including Ghrelin,
cholecystokinin, cortisol, agouti-related protein,
neuropeptide-Y, GABA, melanin con H and
endocannabinoids) and anorexicants (leptin, -MSH,
pro-opiomelanocortin, insulin, serotonin, dopamine,
glucagon-like peptide 1 and glucose dependent
insulinotropic peptide) are involved in the complex
processes of energy intake and expenditure and
maintenance of body weight. Many of them act via the
melanocortin 4 receptor (MC4R) in the arcuate nucleus
of the hypothalamus. Loss of function mutations of the
melanocortin 4 receptor (MC4R) cause severe obesity by
disrupting hypothalamic appetite control centers, and
promoting binge eating. Leptin, produced by adipose
tissue, suppresses food intake and increases energy
expenditure, but early hopes of its use in therapy were
belied as obese individuals are in a relatively leptin
resistant state. Other compounds are being explored for
possible therapeutic use.
The adipose tissue itself has been found to be an active
endocrine organ. It metabolizes sex steroids (e.g. converts
androstenedione to testosterone, and estrone to
estradiol), which in turn may play a role in fat
distribution. Thus increased fat deposits are seen in
hypogonadal states like Turner and Klinefelter
syndromes. Adipose tissue also secretes inflammatory
cytokines like TNF-, interleukin-6, plasma activator
inhibitor type 1, adiponectin, visfatin, etc. which link
central/ visceral obesity with cardiovascular disease.
CAUSES
Obesity is, simplistically, caused by an imbalance of
energy intake and output, but the exact mechanisms are
unclear. Genetic influences are very strong, as shown by
several studies on adopted children and twins.
Environmental factors are equally important
contributing factors are differences in food choices, levels
of physical activity, attitudes to food, activity, body

image, etc. A consistently strong correlation has been seen
with TV viewing, which reduces activity, and increases
calorie intake. In general, obesity runs in families, as they
share both genes and environment, and parental obesity
is a strong risk factor, with 80% of children of both obese
parents, and 40% of one obese parent being overweight.
Maternal weight, weight gain during the prenatal period,
and diabetes are important predictors of overweight at
birth and in infancy. These facts must be kept in mind
by the pediatrician, who can start delivering appropriate
messages from an early date.
Pathologic causes account for less than 1% of all cases
(Table 17.3.1). Corticosteroid or other drug therapy is the
commonest. Others include hypothyroidism, Cushing
syndrome, growth hormone deficiency (GHD) and
hypothalamic disorders. In Cushing syndrome, obesity
has a truncal distribution, but in infants the distribution
can be generalized (Fig. 17.3.1). A number of single gene
mutations can result in marked obesity. These include
syndromes like Prader-Willi, Laurence-Moon-Biedl,
pseudohypoparathyroidism type 1A, Alstrom,
Carpenter, Cohen, and POMC deficiency. The degree of
obesity is variable, ranging from very marked and
difficult to control, to mild. In craniopharyngioma,
obesity is multifactorial, and tends to worsen after
surgery.
CLINICAL EVALUATION
The most important clinical feature which distinguishes
pathological or endogenous from exogenous obesity is
the height. Children with endogenous obesity tend to be
taller than expected for age and genetic background,
while those with pathological states are shorter than
expected. History should include past growth
measurements (if available), any central nervous system
illnesses, drugs (e.g. corticosteroids, anticonvulsants and
antipsychotics), details of activity patterns, diet intake
(including total fat intake in cooking, milk and snacks),
mental development and school performance. Parents
may describe that during sleep the child snores loudly,
and sometimes appears to stop breathing this should
be taken seriously.
Examination should include accurate measurements
of height, weight, BP, waist and hip circumference, and
pattern of fat distribution. Parents heights (for
calculating mid-parental/ target height) and weights
should be measured, rather than just asked for. The
Endocrinology
927
Figure 17.3.2: Acanthosis nigricans seen in

the neck in an obese boy
Figure 17.3.1: An infant with Cushing syndrome
TABLE 17.3.1: Causes of pathological obesity

Endocrine:
Hypothyroidism
Growth hormone deficiency
Cushing syndrome
Hypothalamic:
Laurence-Moon-Biedl syndrome
Prader-Willi syndrome
Craniopharyngioma
Drugs:
Corticosteroids
Sodium valproate
Miscellaneous:
Achondroplasia
Muscular dystrophy
Severe mental retardation
evaluation and mental assessment must be done. In boys,

stretched penile length (SPL) must be measured, since
the penis is usually buried in abdominal fat. Even though
the penis looks small in exogenous obesity, and may
bring the child to medical attention with concerns about
small genitalia and hypogonadism, the SPL is normal,
while true micropenis may be found in GHD and some
syndromes. Adolescent boys may also be brought with
concerns about enlarged breasts, which could be due to
gynecomastia, lipomastia, or both. Orthopedic
complications of a mechanical nature (genu valgum,
slipped capital femoral epiphyses, Legg-Calve-Perthes
disease) are more common, and healing after ankle
sprains is slower. The childs behavior and level of selfesteem should be assessed, as those who are
embarrassed, withdrawn or depressed are less likely to
exercise and may be more prone to binge eating. Past
attempts at dieting, and parents attitudes should also
be assessed dieting to control weight and high degrees
of parental control have been shown to promote fatness.
childs facies (dysmorphic features, Cushingoid,

hypothyroid, etc.) and skin (white or red striae;
acanthosis nigricans, hirsutism score) provide valuable
clues. Acanthosis is best seen in the neck and axillae, but
knuckles are also often pigmented (Fig. 17.3.2). Rashes
in skin folds and inner thighs should be looked for, as
these might interfere with exercise programs unless
treated. Genital examination, pubertal staging, fundus
Investigations are guided by the clinical presentation, but

may include thyroid hormones (T4 and TSH), blood
glucose, lipids and insulin, and if necessary serum
cortisol. Fasting insulin level >20 IU/mL denotes
hyperinsulinemia (normal <15 IU/mL). Changes of
PCOS may be seen in the adolescent girl (raised
testosterone and/or DHEAS, altered LH/ FSH ratio, and
polycystic changes in the ovaries). Sleep studies, if
928
available, may reveal sleep apnea, which may be

obstructive, central, or combined. Bone age tends to be
advanced in exogenous obesity, usually being close to
the advanced height age. Bone age is usually retarded in
pathologic causes, e.g. hypothyroidism, GHD, and
Cushing syndrome. Further workup is hardly ever
required.
In exogenous obesity, levels of serum cortisol and
urinary metabolites of cortisol may be somewhat raised,
but are easily suppressible; urinary free cortisol levels
are normal. GH stimulation tests show a lowered
response, but IGF-1 and IGF-BP3 levels are normal. Other
findings in obese adolescents include proteinuria, fatty
changes in the liver, raised serum T3, decreased sexhormone binding globulin (SHBG), and pubertal levels
of FSH in 7-9 years old girls (with no increase in LH). In
adults, serum PTH has been found to be raised and an
independent predictor of obesity; high dairy calcium
intake has been shown to accelerate weight loss.
PREVENTION
All children and adolescents should have their weights
and heights measured periodically and plotted on a growth
chart throughout the growing years. All those at risk (one
or both obese parents, obese sibling(s), maternal age over
35 years at birth, single child, single parent, on certain
medications), and specially those showing rapid weight
gain (crossing percentile lines), must be focused upon
early as a family. Similarly, children with obesity-related
comorbidities should have early intervention.
All families must be given ongoing education to
breastfeed, avoid force feeding, keep fat and
carbohydrate intake moderate, encourage all forms of
physical activity, limit TV viewing (and in the Indian
context, limit/avoid home tuitions), and express affection
and approval through ways other than food. This should
be specially done if the birth weight was low, or high.
Schools should be encouraged to ensure that canteens
and vendors do not sell sugary drinks and fried snacks,
but offer attractive healthy food choices like fruit and
low fat dairy drinks. Some exercise should be mandatory
during school time for all children. The community in
general should be encouraged to make sure there is
enough space for children to cycle and to play an
unhealthy trend in cities has been to forbid games in
parks, and discourage cycling. Pediatricians involved
with school health programs must pay attention to
children with rapid weight gain. Such children should
not be dismissed with the label of simple obesity. Older

children and adolescents can be advised in the school
setting and also with parents, about sensible diets and
active life styles. The tendency to follow popular and
unbalanced diets should be discouraged. Pediatricians
are quick to pay attention to and refer a child with failure
to thrive, but usually intervene or refer the obese child
very late. Studies have shown that treatments started
many years after obesity onset, are usually ineffective.
MANAGEMENT
Management of pathological obesity depends on the
underlying cause, e.g. replacement of the relevant
hormone in hypothyroidism, GHD, etc. While treating
endogenous obesity, what is critical is not only to lose
weight, but to maintain the loss. Hence, efforts should
be made with those patients who are motivated to make
long-term diet and activity changes as a family. In terms
of health benefits, a small but long-term change is more
important than drastic, short-lived changes. Similarly,
changes made only for the child, not by the rest of the
family are doomed to fail. Rapid weight loss (e.g. very
low calorie diets) should be planned under careful
supervision, only if it is life-saving (extreme obesity,
severe sleep apnea or cardiopulmonary manifestations,
as in the Pickwickian syndrome). Management consists
of a combination of dietary measures and increased
activity, supported by behavioral modification
techniques. Diet change alone, or exercise alone, is
unlikely to give sustained benefit. Drug therapy and
surgery are less frequently advised in childhood and
adolescence.
Diet Therapy
Diet changes are critical for weight loss attempts.
Standard diet therapy restricts calories to a variable
extent, while utilizing the same nutritional principles as
for healthy people fat intake less than 30% of total
calories, protein 15%, and rest 55% as carbohydrates in
the form of complex carbohydrates, with adequate fiber
and micronutrients and plenty of liquids. In a child with
moderate to severe obesity, calorie restriction should be
moderate, aiming for a weight loss of up to 0.5 kg/week,
while ensuring adequate protein intake of 0.8 to 1 gm/
kg/day. Before initiating diet therapy, nutritional
deficiencies, e.g. iron, calcium, vitamin D, etc. (which are
quite common) should be corrected.
Endocrinology
Intake of foods with little or no processing and low
glycemic index (GI) such as fruits, salads, whole wheat
products, whole legumes, low fat dairy products, etc.
should be encouraged. The entire family is advised to
reduce intake of high calorie foods with high fat and/or
simple sugars (fried foods and snacks, rich desserts, full
fat milk and its products, aerated drinks, and nutritive
sweeteners). Diet foods may have higher rather than
lower calorie content, and may be over-consumed, and
so are best avoided. Large meals with long gaps, and
missed meals should also be avoided a grazing
eating pattern is better than a gorging pattern. Small
changes are made initially to ensure compliance. Care
must be taken not to over-restrict fat intake low fat
diets with a compensatory increase in sugary and starchy,
high GI foods (e.g. polished rice, potatoes, ready to eat
cereals, bread and other maida products) result in sharp
rises in insulin levels. Such diets may actually promote
weight gain. At no time should diet restrictions be viewed
as punishments.
Very low calorie diets (400-800 calories per day) for 2
to 6 weeks result in rapid weight loss and marked
improvement in BP and levels of blood glucose, insulin,
leptin, and lipids. However, they can be dangerous unless
they are done under close monitoring and supplemented
with adequate minerals and vitamins. Long-term results
are poor, with weight loss returning within 1-5 years.
Stringent dieting can cause poor height gain, slowed
pubertal development, osteopenia, irritability, behavioral
problems, and a weight loss plateau because of a slower
metabolic rate.
Exercise
All forms of physical activity increase energy
expenditure, and are essential for healthy weight loss.
Increased purposeful exercise, and non-exercise activity
thermogenesis (NEAT) help with weight control. Aerobic
exercise increases energy expenditure directly, while
anaerobic exercise helps build muscle mass and thus
energy expenditure. Physical activity has other benefits
psychological well-being, lesser irritability, lesser acne
and hirsutism, more regular menstrual cycles, better lipid
profiles, lower BP, and lower insulin levels. It also reduces
appetite while increasing metabolic rate (while calorie
restriction alone causes decreased metabolic rate).
In order to ensure compliance, it is important to make
sure active games are viewed as fun (walking with
friends, swimming, dancing, and sports). Initially low
929
impact, moderate-intensity exercise (30 min 5 days/

week) should be advised, as this level of exercise has been
shown to improve health-related outcomes. Later, the
time and intensity of exercise should be increased to
about 300 minutes per week (60 min 5 days/week), as
higher levels of activity are needed for long-term weight
loss and maintenance.
Behavior Modification and Social Support
These are absolutely critical in achieving and sustaining
weight loss, as long-term changes in eating and activity
patterns are necessary. Techniques include monitoring,
goal setting, contracting, stimulus control, social
reinforcement, reward and punishment, aversion
therapy, managing high-risk situations, and relapse
prevention. Reasonable, clear goals must be set by the
family and health care provider working together.
Maintaining food, activity and screen-time (TV,
computer, and videogames) diaries is crucial. Giving
small rewards (especially zero calorie, e.g. a hug or a
stationery item) and other motivational techniques
ensure better and longer compliance. Occasional treats
should be given so that frustration does not build up.
Too much denial can push the child into stealing food
and other dysfunctional behavior patterns. For best
results, the entire family must be convinced of the need
for weight loss, and be keen to participate wholeheartedly.
It is very important to avoid yo-yo weight patterns,
because each cycle of weight loss and gain causes
metabolic and psychological changes which make
subsequent attempts at weight control more difficult.
Treatment of Comorbidities
Associated problems hypertension, type 2 diabetes,
dyslipidemia, PCOS, psychological, orthopedic and skin
problems, sleep apnea are often not paid adequate
attention by health care givers. All these need proper
care in their own right.
Medications
A large number of anorexic agents, including amphetamines, non-amphetamine appetite suppressants, and
antidepressants are available, but are not recommended
for use in children. Medication should be considered only
after significant efforts at diet, exercise and behavior
control have failed, and only as an add-on to these efforts.
930
Insulin sensitizers, primarily metformin, have been

shown to safely achieve weight loss, decrease body fat,
and decrease plasma leptin, insulin and lipids, in PCOS
and other hyperinsulinemic adolescents, with or without
diabetes. Drugs approved for adult obesity include
sibutramine, orlistat and rimonabant. Sibutramine,
approved by the US FDA in adolescents (>16 years of
age), is a selective serotonin and noradrenaline re-uptake
inhibitor, which primarily increases satiety and thus
decreases food intake. It has been shown to cause weight
loss of 5 to 15% from baseline, with improvement in
metabolic parameters. The dose is 5 mg/day, going up
to 15 mg/day. Side effects include mild hypertension,
anxiety, headaches, and depression. Orlistat, approved
by the FDA for use in children over 12 years of age, is a
potent reversible inhibitor of gastrointestinal lipases,
which given with meals can decrease fat absorption by
30%, and thus causes significant weight loss, and
improves lipid and glycemic profile. The dose is 120 mg
three times per day. It causes oil spotting, flatulence and
frequent stools, and may lead to deficiency of fat soluble
vitamins like A and D. Rimonabant was not approved
by the FDA; it was approved in Europe but this approval
has since been suspended. Its side effects include
depression.
Surgery
Surgical treatment for morbid obesity is relatively
contraindicated in patients less than 18 years of age.
However, extreme obesity with severe sleep apnea or
other complications, not responding to nonsurgical
treatment, may call for bariatric surgery, after suitable
psychological preparation. Side effects can be significant
pulmonary embolism, wound infection, micro- and
macronutrient malabsorption, diarrhea, anemia,
cholecystitis, and dumping syndrome. Some patients
may regain lost weight within 1-5 years.
BIBLIOGRAPHY
1. Bhargava SK, Sachdev HS, Fall CH, et al. Relation of serial
changes in childhood body-mass index to impaired
glucose tolerance in young adulthood. N Engl J Med
2004;350:865-75.
2. Bhatia V; IAP National Task Force for Childhood
Prevention of Adult Diseases. IAP National Task Force
for Childhood Prevention of Adult Diseases: insulin
resistance and Type 2 diabetes mellitus in childhood.
3. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic

syndrome in childhood: association with birth weight,
maternal obesity, and gestational diabetes mellitus.
Pediatrics 2005;115:e290-6.
4. Dennison BA, Erb TA, Jenkins PL. Television viewing
and television in bedroom associated with overweight
risk among low-income preschool children. Pediatrics
2002;109:1028-1035.
5. Dubey S, Kabra M, Bajpai A, Pandey RM, Hasan M,
Gautam RK, Menon PS. Serum leptin levels in obese
Indian children: relation to clinical and biochemical
parameters. Indian Pediatr 2007;44:257-62.
6. Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T,
ORahilly S. Clinical spectrum of obesity and mutations
in the melanocortin 4 receptor gene. N Engl J Med 2003;
348:1085-95.
7. Hood MY, Moore LL, Sundararajan-Ramamurti A,
Singer M, Cupples LA, Ellison RC. Parental eating
attitudes and the development of obesity in children. The
Framingham Childrens Study. Int J Obes 2000;24:131925.
8. Laxmaiah A, Nagalla B, Vijayaraghavan K, Nair M.
Factors affecting prevalence of overweight among 12- to
17-year-old urban adolescents in Hyderabad, India.
Obesity (Silver Spring) 2007;15:1384-90.
9. Marwaha RK, Tandon N, Singh Y, Aggarwal R, Grewal
K, Mani K. A study of growth parameters and prevalence
of overweight and obesity in school children from Delhi.
10. Periera MA, Jacobs DR Jr, Van Horn L, Slattery ML,
Kartashov AI, Ludwig DS. Dairy consumption, obesity,
and insulin resistance syndrome in young adults: the
CARDIA study. JAMA 2002;287:2081-89.
11. Quattrin T, Liu E, Shaw N, Shine B, Chiang E. Obese
children who are referred to the pediatric
endocrinologist: characteristics and outcome. Pediatrics
2005;115:348-51.
12. Raj M, Sundaram KR, Paul M, Deepa AS, Kumar RK.
Obesity in Indian children: time trends and relationship
with hypertension. Natl Med J India 2007;20:288-93.
13. Ravussin E. Physiology. A NEAT way to control weight?
Science 2005;307:530-31.
14. Sachdev HS, Fall CH, Osmond C, Lakshmy R, Dey
Biswas SK, et al. Anthropometric indicators of body
composition in young adults: relation to size at birth and
serial measurements of body mass index in childhood
in the New Delhi birth cohort. Am J Clin Nutr
2005;82:456-66.
15. Singh R, Bhansali A, Sialy R, Aggarwal A. Prevalence of
metabolic syndrome in adolescents from a north Indian
population. Diabet Med 2007;24:195-99.
16. Warren JM, Henry CJ, Simonite V. Low glycemic index
breakfasts and reduced food intake in preadolescent
children. Pediatrics 2003;112:e414.
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17.4 Disorders of Thyroid Gland

Meena P Desai
INTRODUCTION
Disorders of the thyroid gland are frequently
encountered in childhood and adolescence and are
amongst the most common endocrine problems seen in
these age groups. These disorders manifest with
qualitative or quantitative alterations in hormone
secretion, thyromegaly (goiter) or both. Insufficient
hormone secretion results in hypothyroidism and
excessive secretion causes hyperthyroidism or
thyrotoxicosis. Thyroid dysfunction causes disturbance
of metabolic functions in children as well as adults, but
the effects on growth and development and brain
functions are unique to the pediatric age group.
Undiagnosed and untreated or suboptimally treated
congenital hypothyroidism in infancy can lead to
permanent subnormal intellectual/neurological
function. This emphasizes the crucial role of thyroid
hormones on developing brain during fetal and early
postnatal life.
PHYSIOLOGY
The human thyroid gland originates embryologically
from an evagination of the pharyngeal epithelium with
cellular contributions from the lateral pharyngeal
pouches, followed by a process of descent to the neck
with occasional persistence of the remnants along the
tract as lingual thyroid, ectopic thyroid, thyroglossal
cyst or nodules. Less commonly, lingual thyroid may be
the sole functioning thyroid tissue which may not be
adequate to maintain a euthyroid status. Three
transcription factors, TTF-1, TTF-2 and PAX8, are
important for thyroid gland morphogenesis and
differentiation. A transcription factor, Pit-1 is important
for growth and differentiation of pituitary thyrotrophs.
The thyroid gland concentrates iodide from blood and
synthesizes and secretes thyroxine (T4) along with
smaller amount of 3,35-tri-iodothyronine (T3). The
synthesis and secretion of thyroid hormones occurs
through a series of enzyme dependant steps. The
thyroglobin so formed is stored in colloid, functioning
as a thyroid hormone precursor releasing thyroid
hormones in circulation as required and also permitting
storage of iodine. T4 and T3 circulate bound to transport

proteins the thyroxine binding globulin (TBG) and
thyroxine-binding prealbumin (TBPA) and albumin.
Seventy-five percent of circulating T3 in blood is derived
by monodeiodination of T4 in liver, kidney and other
peripheral tissues with the simultaneous formation of
reverse T3 (rT3), which is metabolically inactive. There
is a certain amount of tissue autonomy in the production
of T3 from T4. The concentrations of free T4 and free T3,
active at the cellular level approximate 0.03 and 0.30
percent respectively, of the total hormone concentration.
T3 is almost four times more potent than T4 and 85
percent of the bioactivity of T4 is attributed to T3.
The thyroid gland is under the regulatory control of
the pituitary thyrotropin or thyroid-stimulating hormone
(TSH) which in turn is regulated by the hypothalamic,
thyrotropin-releasing hormone (TRH). The fetal thyroid
gland and the hypothalamic-pituitary-thyroid axis
function largely independently of that of the mother.
Maternal TRH, not TSH, can cross the placenta. The
placenta is also relatively impervious to the passage of
maternal thyroid hormones under normal circumstances.
However, during first half of pregnancy, maternal
euthyroid status and optimal levels of maternal thyroid
hormones seem to be neuroprotective for the fetus.
Simultaneous presence of maternal and fetal
hypothyroidism is detrimental to neuro-intellectual
outcome as in endemic iodine deficiency or in presence
of genetic abnormalities of thyroid function.
There are physiological variations in the levels of TSH
and circulating thyroid hormones after birth, with an
acute surge in the TSH level within 30 minutes of birth
in response to relative hypothermia. This is followed by
rise in serum T3 and T4 levels by 24 hours, with a gradual
decline in their levels as well as of TSH by end of 1st
week. TSH surge in the premature infant is of a lesser
magnitude with a greater decline in T4 concentration in
the following 2 weeks. Hence, appropriate interpretation
of TSH, T3, T4 values obtained in neonatal period is
extremely important in arriving at the correct diagnosis
when newborns are screened for congenital hypothyroidism. Subsequently circulating levels of T3 and T4 are
higher during infancy and childhood. TSH level may
remain upto 10 IU/ml during infancy beyond which it
declines below 5 IU/ml.
932
As stated earlier thyroid hormone actions also vary

with age, with maximal effects on somatic and skeletal
growth and maturation, brain growth and development
in infancy and childhood. Metabolic effects are more
pronounced in adulthood. The thyroid hormones
increase oxygen consumption, stimulate protein
synthesis, affect carbohydrate, lipid and vitamin
metabolism and promote growth and differentiation.
Approximately 100 g of thyroxine (T4) is secreted by
the thyroid gland daily and about 90 mg of iodide
(15 mg/kg) is the recommended daily intake during
infancy and childhood with higher requirements in
preterms.
HYPOTHYROIDISM
Etiology and Epidemiology
Amongst disorders of thyroid gland in pediatric age
group congenital form of primary hypothyroidism due
to thyroid dysgenesis is most common. Hypothyroidism
may be acquired little later in childhood when it is most
commonly due to autoimmune disease of the thyroid
gland. Pituitary or hypothalamic disease can cause
secondary or tertiary forms of hypothyroidism which
may be congenital or acquired, is less common and is
usually associated with deficiency of other pituitary
hormones (Table 17.4.1). The term thyroid dysgenesis
denotes developmental abnormalities of the thyroid
gland ranging from agenesis, and hypoplasia to ectopic
or lingual thyroid gland. The worldwide prevalence of
congenital hypothyroidism (CH) approximates 1:3500 to
4000 newborns as revealed by neonatal screening
programs implemented in several parts of the world.
Though there are some racial differences, it is twice as
common in females. Most of these infants detected on
screening are asymptomatic in the first few weeks of life,
but the main objective of screening is to detect and treat
them very early so as to prevent or minimize the
neuropsychologic damage which can be irreversible if
the treatment is delayed beyond the first few weeks of
life. Hereditary biosynthetic defects leading to
dyshormonogenesis as well as autoimmune thyroid
disease are some of the other causes of hypothyroidism
in children and adolescents. A variety of biosynthetic
defects causing dyshormonogenesis leading to
hypothyroidism usually associated with varying degrees
of goitrous enlargement of thyroid gland have been
identified. Autoimmune thyroid disease is a common
TABLE 17.4.1: Causes of hypothyroidism in childhood and

adolescence
A. Primary Hypothyroidism
I. Thyroid dysgenesis
Aplasia, hypoplasia
Ectopic or lingual thyroid gland.
II. Inborn errors of thyroid hormone synthesis, secretion or
utilization
III. Endemic iodine deficiency
IV. Autoimmune thyroiditis
V. Iatrogenic
Antithyroid drugs and goitrogens
Irradiation
Post-thyroidectomy
B. Secondary/tertiary Hypothyroidism
(Pituitary/hypothalamic)
I. Congenital
Isolated or Panhypopituitarism
II. Acquired
Trauma
Infection
Neoplastic / postsurgical
Irradiation
cause of hypothyroidism beyond midchildhood and in

adolescents. Endemic iodine deficiency still remains an
important cause of endemic cretinism and hypothyroidism in some parts of the world and in northern
regions of India.
The symptoms and signs of congenital hypothyroidism
in the neonatal period are nonspecific and vague, leading
to difficulties in clinical diagnosis. Less than 10 percent
of newborns detected on screening as having biochemical
hypothyroidism, can be recognized clinically. In the
newborns and in early infancy, symptoms predominate
over signs. Growth retardation which is so characteristic
of this disorder in postnatal life is not seen at birth. These
infants may be large at birth and may be postmature.
Some of the early manifestations like prolonged
physiological jaundice, constipation, feeding difficulties,
inactivity, macroglossia, constipation, wide fontanels,
mottling, hypothermia, and hoarse cry should arouse
suspicion. Clinical signs become more obvious over the
following weeks. Coarse hypothyroid facies often
associated with puffiness of eyes, protruding tongue,
pallor, lethargy, fullness in supraclavicular regions,
altered skin and hair texture, hypotonia, distended
abdomen with umbilical hernia, low pitched irritable
Endocrinology
933
Figure 17.4.1: Five months old male child with congenital

hypothyroidism presented for constipation, feeding difficulty,
and failure to grow. Not the protruding tongue, little puffiness
of eyes, distended abdomen and small umbilical hernia
prolonged cry, are features which combine to give a

characteristic appearance to these infants (Fig. 17.4.1).
Failure to grow and delayed milestones become
increasingly obvious. Bradycardia, muffled heart sounds,
delayed relaxation while eliciting deep tendon reflexes
are helpful signs. Children with dyshormonogenesis may
present with goiter at birth or during infancy. The
incidence of other associated congenital abnormalities
with CH is around 8 percent.
Hypothyroidism in older children is usually caused
by autoimmune thyroiditis but occasionally children
with thyroid dysgenesis having hypoplastic or ectopic
thyroid tissue or dyshormonogenesis may present late.
They may present with usual symptoms and signs of
hypothyroidism with lethargy, failure to grow or short
stature of insidious onset. Presence of a small goiter
which is firm in consistency with a pebbly surface favours
the possibility of thyroiditis as opposed to
dyshormonogenesis where the goiters may be small or
large but the consistency tends to be soft to firm with
occasional presence of a bruit (Fig.17.4.2). Obesity,
goiters, scholastic problems, delayed sexual maturation
or uncommonly sexual precocity or muscular
hypertrophy, are the other modes of presentation.
Diagnosis
The diagnosis of primary hypothyroidism is confirmed
by the presence of low serum T4 and T3 concentrations
Figure 17.4.2: Eight years old girl with goitrous hypothyroidism

due to dyshormonogenesis. Note hypothyroid facies, puffiness
of eyes, and goiter. (Had two more siblings with similar clinical
picture)
and elevated serum TSH values. Estimation of free T4

and free T3 is also available now. TSH is an extremely
sensitive index of primary hypothyroidism. Radiographic studies demonstrate significant delay in skeletal
maturation and occasionally epiphyseal dysgenesis. The
skeletal age may also suggest the approximate age at
which the disorder was initiated. Imaging studies like
ultrasonography and radioisotope scans in particular,
help in delineating the anatomical and functional status
of the gland but are not mandatory. Thyroid antibody
studies are helpful in identifying autoimmune basis of
the disease in the older age group. In secondary and
tertiary forms of disease, the TSH concentration may be
low or undetectable with subnormal levels of T3 and T4
as well as free T4 and T3. Usually associated deficiency
of other pituitary hormones is also present.
Treatment
Once the diagnosis is established, the need for life long
therapy in congenital hypothyroidism should be
adequately stressed. The goal of therapy is to maintain
the circulating serum T4 level in the upper normal range
934
and normalize the elevated TSH. The preferred

preparation is sodium-levothyroxine because of its
uniform potency, reliable absorption and increased
bioavailability. In newborns detected on screening and
in early infancy, 10 g/kg has been recommended. In
the newborn period, full replacement therapy can be
initiated promptly. In longstanding thyroid deprivation
where the diagnosis is delayed for months or occasionally
for years, of the daily dose can be administered initially
and stepped up gradually to full replacement dose, in 3
to 6 weeks. The daily requirement is about 100 g/m2.
The required dose is administered as one single dose,
preferably at a convenient fixed time during the day and
on empty stomach to maximize absorption. Regular
therapy is extremely important. Individualization of
therapy by monitoring serum thyroid levels and TSH is
ideal and necessary. Therapeutic monitoring is
recommended with blood samples obtained at periodic
intervals for TSH, T3 and T4 estimations. Clinical
evaluation and growth monitoring during therapy are
important.
Prognosis
The final outcome in CH is closely related to the nature
and severity of the underlying thyroid abnormality, the
age at diagnosis and onset of treatment, the adequacy
and regularity of therapy with the required degree of
clinical and laboratory follow-up. Worldwide neonatal
screening programs for CH have had a significant impact
on reducing intellectual deficits in hypothyroid infants
diagnosed and treated early.
HYPERTHYROIDISM
Hyperthyroidism (thyrotoxicosis) is an uncommon
disorder of childhood and adolescence. It results from
excessive secretion of thyroid hormones and is usually
the result of diffuse toxic goiter (Graves disease) in
children. Other uncommon causes are thyrotoxicosis
factitia (ingestion of thyroid hormones), thyroid
neoplasia or very rarely due to TSH producing pituitary
tumors. In infants born of mothers with Graves disease,
hyperthyroidism may occur as a transitory phenomenon
during neonatal period due to transplacental passage of
thyroid stimulating immunoglobulin. Germ line
mutations of the TSH receptor known as gain of function
mutations can cause familial or sporadic hyperthyroidism, and may cause persistent hyperthyroidism
during infancy.
About 5 to 10 percent of all patients with hyperthyroidism are under 15 years of age with a peak
incidence in adolescent. The incidence is nearly five times
higher in girls. The clinical course is variable but less
severe than in adults. The onset of symptoms is often
insidious with the interval between the onset of the
disorder and diagnosis ranging between 3 to 12 months.
Emotional disturbances, behavioral changes
characterized by excitability, irritability and tendency to
emotional outbursts may herald the onset of the disease.
Motor hyperactivity and restlessness may be
misdiagnosed as chorea. Increased appetite with no
increase in weight or actual loss of weight, diarrhoea,
heat intolerance and excessive sweating and mild fever
are some of the other findings. Tremors of the hands
become evident with further progression. Exophthalmos
may be present but not severe. Lid lag on looking
downward, impairment of convergence, retraction of
upper eyelids with infrequent blinking may be
noticeable. The degree of thyroid enlargement is variable
but never marked and may escape detection. Goiter is
present in almost 90% of cases. Bruit may be heard. Palms
may be warm and moist. Muscular weakness is
uncommon. Patient may complain of feeling of weakness,
tiredness and palpitations. Tachycardia is appreciable
and a wide pulse pressure is often noted. Dyspnea,
cardiac decompensation and rarely atrial fibrillation may
occur. Thyroid crisis or storm and the apathetic,
cachectic type of hyperthyroidism are uncommon in
childhood.
Laboratory Data
Serum levels of T4, T3, free T4 and free T3 are elevated.
In some patients, T3 may be higher with T4 levels in the
upper normal range or minimally elevated. TSH is
suppressed below normal and thyroid antibodies are
present. Radioiodine uptake and assay for TSH receptor
antibodies are not essential for diagnosis. Advanced
skeletal maturation may be noted. Craniostenosis may
occur in infants.
Treatment
The therapy is directed toward reducing the production
of thyroid hormones and blunting their effects. Medical
therapy is the preferred modality of treatment in children
rather than subtotal thyroidectomy or radioiodine
Endocrinology
therapy. The thionamide drugs in use are propylthiouracil (PTU), methimazole, and carbimazole. The
therapy has to be continued for long to prevent relapses.
Toxic reactions like agranulocytosis, hepatic dysfunction
and lupus like syndrome do occur. Transient urticarial
rashes are most common. Propranolol helps in
controlling symptoms due to hyperactivity of the
sympathetic nervous system. Other modalities of therapy
such as radioiodine thyroid ablation or subtotal surgical
excision are indicated, if medical therapy fails after
adequate trial.
GOITER
Presence of goiter may be the initial complaint for which
children and adolescents may seek medical attention. In
these patients underlying cause of the thyromegaly needs
to be determined and the functional status of the thyroid
gland whether euthyroid, hypothyroid or hyperthyroid
needs to be ascertained. Common causes which lead to
goitrous enlargement in this age group are simple goiter
or physiological enlargement. Often this may be related
to iodine deficiency or other causes such as chronic
lymphocytic thyroiditis, dyshormonogenesis or rarely
malignancy. WHO has defined a goiter as a thyroid gland
where the size of the lateral lobes exceed the size of the
terminal phalanx of the subject examined. Prevalence of
small asymptomatic goiters in school children to the
extent of 6% have been noted though the incidence is
higher in regions of endemic iodine deficiency. Based
on the functional status of the thyroid gland and the
underlying cause of goiter further strategies for
935
management need to be planned. Nodular goiter or

single nodule need careful evaluation for the presence
of thyroid malignancy.
BIBLIOGRAPHY
1. Brown RS, Huang S. The thyroid and its disorders. (Eds.)
CGD Brooke P.E. Clayton, RS Brown, MO Savage.
Blackwell 5th ed. 2005; publishing 218-53.
2. Delang F. Iodine deficiency as a cause of brain damage.
Postgrad Med J 2001;77:217-20.
3. Delang F. Neonatal screening for congenital hypothyroidism results and perspectives. Horm Res
1997;48:51.
4. Desai MP. Disorders of the Thyroid Gland. In Pediatric
Endocrine Disorders ed. Meena Desai, PSN Menon, V
Bhatia. 2nd ed. Orient Longman Pvt. Ltd., 2008;282-310.
5. Fisher DA. Disorders of the thyroid in the newborn and
infants. In Pediatric Endocrinology ed. M.A. Sperling,
Philadelphia: WB Saunders 2002; 161-86.
6. Fisher DA. Thyroid disorders in childhood and
adolescence. In Pediatric Endocrinology ed. M.A.
Sperling, Philadelphia; WB Saunders 2002; 187-204.
7. Gruters A, Krude H, Beibermann H, et al. Alterations of
neonatal thyroid function. ACTA Paediatr. 1999;428:1722.
8. Halac I, Zimmermann D. Thyroid nodules and cancers
in children. Endocrinol Metab Clin N Am. 2005;34:
725-44.
9. Koch CA, Sarlis NJ. The spectrum of thyroid diseases in
childhood and its evolution during transition to
adulthood: Natural history, diagnosis, differential
diagnosis and management. J Endocrinol Invest. 2001;
24 : 659.
10. Kraeim Z, Newfield RS. Graves disease in children.
J Pediatr Endocrinol Metab. 2001;14:229.
17.5 Disorders of Bone and Mineral Homeostasis

INTRODUCTION
The role of the skeleton in maintaining mechanical
stability of the body and aiding locomotion is easily
appreciable. Its role as an important metabolic organ is
more subtle but equally important. The skeleton is the
largest reservoir of calcium and phosphorus. It is vital
for extracellular concentrations of calcium to be
maintained within a narrow range. This is brought about

via the actions of hormones such as parathyroid hormone
(PTH), 1,25-dihydroxy-cholecalciferol (1,25(OH)2D or
calcitriol) and calcitonin on bone, kidney and gut. In bone,
the osteoblast cells are responsible for bone formation,
the osteocytes are the mature bone cells and the
osteoclasts bring about bone resorption to restore serum
calcium as well as to enable bone remodelling.
936
MINERALS
Calcium
Ninety nine percent of total body calcium resides in bone.
The plasma levels range from 9 to 10.5 mg/dl in children.
Approximately half the plasma calcium is present bound
to plasma proteins and half in the free ionized form.
Intestinal absorption of calcium is vitamin D-dependent
when present in the gut in smaller quantities. Urinary
calcium excretion is of the order of 4 mg/kg/day. Dietary
sources of calcium are mainly milk products and fish;
smaller amounts are available from green vegetables, ragi
and til. The daily requirement of calcium ranges from
about 300 mg in infants to 600 to 800 mg in childhood
and 1000 mg in adolescence, pregnancy and lactation.
Phosphorus
About 85 percent of the total body content of phosphate
is in the bone, in the form of the calcium salt,
hydroxyapatite. Serum phosphorus is higher in infancy
(4.5 to 7.5 mg/dl) and falls gradually during childhood
to adult levels of 2.5 to 4.5 mg/dl. Serum phosphorus
concentration is largely maintained by variable renal
reabsorption. Normally about 85 percent of the filtered
load is reabsorbed 75 percent in the proximal tubules
and 10 percent in distal tubules. Both proximal and distal
reabsorption of phosphate is decreased by PTH and
calcium. Phosphorus deficiency results in effective and
complete reabsorption. Phosphorus is available in
commonly eaten staple foods such as cereals and lentils.
Its deficiency is encountered only in special circumstances such as prematurity or parenteral nutrition.
Magnesium
Magnesium is an important component of the adenylate
cyclase system. Its deficiency leads to hypocalcemia, both
by inhibiting PTH release and inducing resistance to its
action. Hypomagnesemia may be seen in the setting of
diarrhea, malnutrition, malabsorption, and parenteral
nutrition. Normal serum magnesium level is 1.8 to 3.0
mg/dl.
THE CALCIOTROPIC HORMONES
Parathyroid Hormone (PTH)
PTH is an 84-amino acid chain, but its biologic activity
resides in the first 34 residues. The major stimulus to the
secretion of PTH is a fall in the ionized fraction of plasma

calcium, detected by the calcium-sensing receptor on the
parathyroid gland. The biological actions of PTH at a
variety of target organs serve to increase plasma calcium.
PTH stimulates activity of 1-hydroxylase in the kidney,
enhancing production of calcitriol. The increased level
of calcitriol induces synthesis of a calcium-binding
protein in the intestinal mucosa with resultant absorption
of calcium. PTH also mobilizes calcium by directly
enhancing bone resorption. The effects of PTH on bone
and kidney are mediated through binding to specific
receptors on the membranes of target cells and through
activation of a transduction pathway involving a G
protein, coupled to the adenylate cyclase system.
Vitamin D
Vitamin D (cholecalciferol) is produced in the dermis,
by conversion from cholesterol, under the influence of
ultraviolet rays from sun exposure. Latitude, season,
cloud cover, pollution, skin pigment, clothing and
sunscreen affect dermal vitamin D. Cholecalciferol is
hydroxylated to form 25 hydroxyvitamin D (25-OHD)
in the liver. In the next step, 25-OHD is further
hydroxylated in the kidney to produce the active form
of the hormone 1,25(OH)2D (calcitriol). The production
of 1,25(OH)2D is directly related to body needs. Its
formation is enhanced by PTH, vitamin D and dietary
calcium depletion, hypocalcemia and hypophosphatemia. 25-OHD (calcidiol) is the major transport form
of vitamin D and its circulating concentration reflects an
individuals vitamin D nutritional status. Serum 25-OHD
below 20 ng/ml indicates vitamin D deficiency. Diet is a
poor source of vitamin D except in communities who
consume large quantities of fatty fish (such as the
Eskimos). Therefore in many temperate countries, where
sunshine is poorly available during winter, food is
fortified with vitamin D.
Calcitonin
Calcitonin is a 32-amino acid polypeptide secreted by
the parafollicular or C cells of the thyroid. It is the only
hormone in humans capable of actively lowering plasma
calcium. The hypocalcemic action results from inhibition
of bone resorption and increased bone mineral
deposition.
Endocrinology
HYPOCALCEMIA
Presentation
Hypocalcemia in the older child presents with tetanic
spasms of the fingers and wrist or toes and foot, perioral
numbness, tingling, or seizures. Mental changes include
irritability, impairment of memory, paranoia, depression,
and frank psychosis. Papilledema may be present.
Subclinical hypocalcemia may be elicited by the Chvostek
or Trousseau signs. Chronic hypocalcemia leads to
cataracts and basal ganglia calcification. However, in
neonates, hypocalcemia may present quite differently,
with jitteriness, apneic spells or laryngeal stridor, in
addition to seizures.
Etiology
The causes of hypocalcemia are highlighted in Table
17.5.1. They can be categorized into early (typical
neonatal) causes occurring in the first 4-5 days of life and
late causes occurring thereafter. A brief discussion of
some of the etiologies follows below.
Early neonatal hypocalcemia: The fetus is supplied with
calcium via active transport across the placenta.
Interruption of this enriched supply at birth,
compounded by a relatively poor PTH response to
hypocalcemia, makes the newborn baby vulnerable to
hypocalcemia. Various neonatal situations such as
prematurity, birth asphyxia, infant of a diabetic mother,
IUGR, polycythemia, alkali therapy, and sepsis, among
others, enhance the risk.
937
day of life are included in this category (Table 17.5.1).

Precipitation of hypocalcemia by the high phosphorus
content of cow milk (six times the concentration in breast
milk) is commonly encountered. An increasingly
diagnosed cause for late neonatal hypocalcemia is
maternal (and hence neonatal) vitamin D deficiency. This
may present as late as 1 or 2 months of age, and is often
characterized by resistance to the phosphaturic action of
PTH, exhibiting hyperphosphatemia instead of low
phosphorus as expected. Renal failure is another
condition associated with high serum phosphorus.
Various causes of hypoparathyroidism are responsible for hypocalcemia in childhood (Table 17.5.1). Manifestations of mucocutaneous candidiasis, Addison
disease, alopecia, lymphocytic thyroiditis, pernicious
anemia, hepatitis and primary gonadal insufficiency may
be associated with that of hypoparathyroidism as part
of the APECED (autoimmune polyendocrinopathy
candidiasis ectodermal dysplasia) syndrome. Dental
enamel hypoplasia may be seen as part of hypocalcemia
(Figure 17.5.1). Pseudohypoparathyroidism (PHP) describes a group of disorders characterized by biochemical
hypoparathyroidism (i.e. hypocalcemia and hyperphosphatemia), increased secretion of PTH, and target
tissue unresponsiveness to the biological actions of PTH
due to mutations in the alpha subunit of G proteins. There
is an association between PHP and somatic abnormalities. These include short stature, round face, short neck,
and shortening of the metacarpals and metatarsals.
Late neonatal hypocalcemia: Conditions which

generally present with hypocalcemia after the 4th or 5th
TABLE 17.5.1: Etiology of hypocalcemia

Early neonatal hypocalcemia
Prematurity
IUGR
Infant of diabetic mother
Birth asphyxia
Late neonatal and childhood hypocalcemia
Cow milk ingestion
Hypoparathyroidism
Familial hypercalciuric hypocalcemia
Secondary to maternal hyperparathyroidism.
Pseudohypoparathyroidism
Severe vitamin D deficiency
Hypomagnesemia
Critical illness
Figure 17.5.1: Enamel hypoplasia (highlighted with arrows) in

a child with hypoparathyroidism. The same could be seen in
children with calcipenic rickets of any etiology.
938
Characteristic radiographic findings include shortening

of the fourth, fifth or all metacarpals and metatarsal
bones. Resistance to other hormones with G protein
mediated actions may coexist.
Diagnosis
Besides confirmation by serum total and ionized calcium,
an ECG is useful as it may reveal a prolonged QT interval.
Serum magnesium should be performed in all cases of
hypocalcemia. CT head may show calcification of the
basal ganglia. Serum creatinine, albumin (every gm/dl
of serum albumin below normal decreases total calcium
by 0.8 mg/dl), blood gases, 25-OHD, PTH, and 24 hour
urinary calcium or calcium/creatinine ratio, complete the
armamentarium for investigation.
Treatment
Calcium gluconate (10 % solution) 0.2 ml/kg slow
intravenous injection (over 10 minutes at least), corrects
hypocalcemia initially. Maintenance doses are about
50 to 75 mg of elemental calcium/kg/day.
Hypoparathyroidism is treated with oral calcium and
calcitriol in a dose of 3070 ng/kg/day. Calcitriol has a
short half-life and hence should be given in two equal
divided doses. It has a rapid onset of effect (1-4 days)
and rapid reversal of hypercalcemia after discontinuation, in the event of over-dosage.
Hypovitaminosis D must be treated with calcium and
vitamin D. While there is no objective evidence at this
time for recommendation of doses of vitamin D for
nutritional rickets, about 10,000 to 60,000 units orally
weekly for a month (the lower end dose to be used in
infancy to avoid any risk of hypercalcemia), followed by
1 sachet (60,000 units) every 2 months approximately for
another 3 to 6 doses should suffice. During this time the
importance of sun exposure is reinforced.
Hypomagnesemia is treated with 0.2 ml/kg/dose of
a 50 % solution of magnesium sulphate. The oral
maintenance dose of elemental magnesium is 12 -20 mg/
kg/day, best provided as gluconate, lactate or chloride
to minimize the side effect of diarrhea.
HYPERCALCEMIA
Presentation
The symptoms of hypercalcemia may be nonspecific and
include anorexia, constipation, vomiting, failure to thrive,
polyuria, muscular weakness, dehydration.
Etiology
Table 17.5.2 highlights the causes of hypercalcemia.
Inactivating mutations of the calcium sensing receptor,
which cause mild asymptomatic hypercalcemia when
inherited heterozygously, result in severe neonatal
hypercalcemia when inherited homozygously. PTH is
low or inappropriately normal for the state of
hypercalcemia. This condition is a mirror image of the
hypocalcemic disease, which is due to activating
mutations of the same receptor. Primary hyperparathyroidism, due to an adenoma or hyperplasia of the
parathyroid glands, in India is still dominated by the
manifestations that are characteristic of advanced
disease, bones (fractures and brown tumours due to
osteitis fibrosa cystica, stones (renal), groans (bone pain),
and psychic overtones, though in developed countries it
is often diagnosed incidentally by routine serum
chemistry. William syndrome is characterized by
hypercalcemia, elfin facies and supravalvular aortic
stenosis. A deletion of part of the long arm of
chromosome 7 is seen in a majority of the patients.
Hypercalcemia subsides after 2 to 3 years of age. Till then,
low calcium diet and sunscreen are used to minimize
calcium absorption.
Diagnosis
Serum calcium, phosphorus, potassium, urinary calcium
or calcium/creatinine ratio, PTH, and 25-OHD are
relevant investigations. Plain radiology of the hand
shows subperiosteal resorption and endosteal and
intracortical tunneling. There may be tufting of the
terminal phalanges. The skull is characterized by salt and
pepper erosions. Hyperparathyroidism in growing
children causes appearances which radiologically
resemble rickets but which are quite different histologically. This is due to resorption of metaphyseal bone
which may give rise to crippling, skeletal deformities.
TABLE 17.5.2: Etiology of hypercalcemia
Transient neonatal hyperparathyroidism (secondary to

maternal hypoparathyroidism)
William syndrome
Granulomatous disease e.g. sarcoidosis
Vitamin D toxicity
Primary hyperparathyroidism
Multiple endocrine neoplasia
Familial hypocalciuric hypercalcemia and neonatal severe
hyperparathyroidism
Tertiary hyperparathyroidism
Non-endocrine malignancies. (PTHrP excess)
Endocrinology
Treatment
Hydration and forced diuresis with a loop diuretic are
the cornerstones of treatment of hypercalcemia.
Reduction of calcium absorption by corticosteroid
administration is useful in vitamin D intoxication,
William syndrome and sarcoidosis. Inhibition of bone
resorption can be brought about by calcitonin or
bisphosphonate (pamidronate) administration. Life
threatening hypercalcemia can be reversed by dialysis.
Surgery is the treatment for primary hyperparathyroidism.
RICKETS
939
TABLE 17.5.3: Causes of rickets

Calcipenic rickets
Phosphopenic rickets
Vitamin D/calcium deficiency
Prematurity (calcium plus

phosphorus deficiency)
Anticonvulsant induced
Fanconi syndrome (proximal

RTA)
Congenital hypophosphatemic
rickets X-linked/autosomal
dominant
Hypophosphatemic rickets with
hypercalciuria
Malabsorption
Distal renal tubular acidosis
Chronic renal failure
1 hydroxylase defect
Tumor induced (mesenchymal

tumor, epidermal nevus)
Calcitriol receptor defect
Nutritional Rickets
Rickets occurs due to deficiency of vitamin D or calcium
or both. Deficiency of phosphorus leading to rickets is
found only in special circumstances such as prematurity
or parenteral nutrition where adequate care has not been
given to supplementation of all minerals, as dietary
sources of phosphorus are common. In India, vitamin D
deficiency is particularly encountered in the neonate or
infant, due to poor maternal stores. Thereafter, it is
prominent during adolescence, especially in girls, who
cannot take advantage of sunshine due to modest
clothing and poor outdoor activity. In toddlers and midchildhood (and also in older age groups), dietary calcium
deficiency plays a predominant role. Nutritional rickets
is discussed in detail in the chapter on vitamins.
Non-nutritional Rickets
When vitamin D and calcium supplementation has been
given in adequate doses for at least 2 months without
onset of radiological healing or improvement in serum
alkaline phosphatase, non-nutritional or resistant rickets
should be suspected. Alternatively, in the presence of
clues to a non-nutritional cause, it may be investigated
for without waiting. Such clues include alopecia, features
of malabsorption, hypokalemia, nephrocalcinosis,
polyuria, or dense bones, among others (Figure 17.5.2).
Resistant rickets may be categorized into calcium
deficiency or phosphorus deficiency rickets for ease of
differential diagnosis and investigative pathway
(Table 17.5.3).
Figure 17.5.2: Skeletal radiograph of a child with calcitriol

receptor abnormality (vitamin D resistant rickets type 2),
showing alopecia, rachitic rosary and widened malleoli at the
ankles (highlighted by arrows) (reproduced with permission
from Pediatric Endocrine Disorders, Desai M, Menon PSN,
Bhatia V eds, 2nd edition, Orient Blackswan, Chennai)
Etiology and Presentation

Children with renal tubular acidosis (RTA) may present
with polyuria, failure to thrive, hypokalemia, and in the
case of distal RTA, with dental enamel hypoplasia,
nephrocalcinosis or nephrolithiasis. Anemia, abdominal
940
pain, diarrhea, Bitots spots or night blindness, or

hypoalbuminemia may alert the pediatrician to the
presence of malabsorption. Hypophosphatemic rickets
typically presents at the end of the first year of life.
Ricketic features predominantly affect the skull and
lower limbs, with relative sparing of upper limbs and
chest.
Diagnosis
Typical clinical differentiating features of calcium versus
phosphorus deficiency rickets are highlighted in Table
17.5.4. If a good clinical examination does not provide a
clue to etiology, then PTH should guide further work
up. Primary and secondary hyperparathyroidism result
in increased phosphorus leak from the proximal tubule.
Thus a child with any cause of calcipenic rickets, such as
malabsorption or distal renal tubular acidosis, due to
concomitant secondary hyperparathyroidism, may
appear to have hypophosphatemic rickets. Serum PTH
is useful investigation at this juncture, being only
marginally elevated in hypophosphatemic rickets, and
significantly raised in calcipenic rickets.
Cases with high PTH should be investigated for distal
RTA by serum potassium, blood and urine pH,
ammonium chloride loading test if necessary, and
ultrasound of kidneys for nephrocalcinosis. Malabsorption tests include ESR, anti-endomyseal antibodies, DTABLE 17.5.4: Features of calcipenic versus
phosphopenic rickets
Calcipenic
rickets
Phosphopenic
rickets
Hypotonia
Present
Absent
Bone pain
Present
Absent
Tetany/seizure
Present
Absent
Dental enamel
hypoplasia
Present
Absent
Dental caries
Absent
Present
Serum calcium
Low
Normal
Serum phosphorus
Low
Low
Alkaline phosphatase
Markedly raised
Moderately raised
Parathyroid hormone
Raised
Normal / minimally
raised
Plain radiology
Lucent bone,
osteitis fibrosa
cystica
Dense bone
xylose test and endoscopic duodenal biopsy. If these are

negative, serum 25OHD and 1,25(OH)2D can throw light
on 1-hydroxylase defect and calcitriol receptor defect
(VDRR 1 and 2). Low PTH type of resistant rickets should
be worked up for phosphate clearance (phosphate
clearance/creatinine clearance) and TmP/GFR
measurement. Proximal RTA is tested by bicarbonate
loading test and documenting amino aciduria, glycosuria
and uric aciduria in addition to phosphaturia. Plain
radiology reveals coarse trabecular pattern in RTA and
renal failure, and dense bone in hypophosphatemic
rickets.
Treatment
RTA is treated with alkali, the distal variety requiring 35 mmol/kg/day and proximal RTA a greater amount
such as 10-15 mmol/kg/day of bicarbonate. Citrate as
the source of alkali is useful in distal RTA, to diminish
renal calcium deposition. Potassium replenishment is
provided as necessary. Investigation and treatment of
the primary disease, if any, producing RTA, must be
performed. Anticonvulsant therapy should be
accompanied by 500 to 1000 units daily of vitamin D
supplementation. VDRR 1 is treated with calcitriol in
physiological or minimally higher doses, and VDRR 2
with very high doses of calcitriol or with intravenous
calcium. Hypophosphatemic rickets requires phosphorus
supplementation to produce healing of bone and
calcitriol to suppress the secondary hyperparathyroidism
which is invariably produced. Deformity often
normalizes with years of growth and remodeling, in all
etiologies of rickets. Therefore, one need not rush for
corrective osteotomy unless deformities come in the way
of locomotion.
Metabolic Bone Disease of Prematurity
The preterm baby is deprived of the large supply of
calcium normally accrued during the third trimester of
pregnancy via active transport across the placenta. Breast
milk is not adequate to supply similar amounts of calcium
and phosphorus. The resulting bone disease presents
with fractures upon minimal handling, and X-ray picture
showing lucent bones. It can be prevented by using
commercially available human milk fortifiers providing
the required 200 mg/kg/day of calcium and 100 mg/
kg/day of phosphorus.
Endocrinology
Conditions of Increased Bone Fragility
While the prototype disease of fragile bones in children
is osteogenesis imperfecta, the most common condition
in this category encountered by pediatricians is
glucocorticoid induced osteoporosis (GIO). Since
pediatricians care for children on pharmacological doses
of glucocorticoids for diverse conditions, they must be
familiar with the precautions to be taken for preventing
or minimizing GIO. These include adequate calcium,
protein and vitamin D nutrition, institution of gonadal
steroids in a timely manner in adolescents, in whom
pubertal delay has occurred due to the basic systemic
disease, avoiding immobilization and encouraging
regular appropriate weight bearing exercise. Needless
to say, the minimum effective dose of glucocorticoid
should be used, to minimize bone fragility as well as
diverse other side effects of systemic glucocorticoid
therapy.
A discussion on osteogenesis imperfecta, fibrous
dysplasia and osteopetrosis is beyond the scope of this
book. A few useful bibliographies are mentioned below.
BIBLIOGRAPHY
1. Chesney RW. Metabolic bone disease. In: Behrman RE,
Kliegman RM, Jenson HB (Eds). Nelson Textbook of
Pediatrics, WB Saunders Co 2004;17:2341-48.
941
2. Doyle DA and DiGeorge AM, Disorders of the

parathyroid glands. In: Behrman RE, Klaus G, Watson
A, Edefonti A, Fischbach M, Ronnholm K, Schaefer F, et
al. Prevention and treatment of renal osteodystrophy in
children on chronic renal failure: European guidelines.
Pediatr Nephrol 2006;21(2):151-9.
3. Kliegman RM, Jenson HB (Eds). Nelson Textbook of
Pediatrics, 17th ed, WB Saunders Co 2004; Pp 1890-97.
4. Mughal Z. Rickets in childhood. Semin Musculoskelet
Radiol 2002;6:183-190.
5. Rauch F, Schenau E. Skeletal development in premature
infants: a review of bone physiology beyond nutritional
aspects. Arch Dis Child Fetal Neonatal Ed 2002;86:F82F85.
6. Seibel MJ. Biochemical markers of bone remodeling.
Endocrinol Metab Clin N Am 2003;32:83-113.
7. Teotia M, Teotia SPS, Nath M. Metabolic studies incongenital vitamin D deficiency rickets. Indian J Pediatr
1995;62:55-61.
8. Thornton J, Ashcroft DM, Mughal MZ, Elliot R, ONeill
TW, Symmons D. Systematic review of effectiveness of
bisphosphonates in treatment of low bone mineral
density and fragility fractures in juvenile idiopathic
arthritis. Arch Dis Child 2006;91(9):753-61
9. Van Staa TP, Cooper C, Leufkens HGM, Bishop N.
Children and the risk of fractures caused by oral
corticosteroids. J Bone Miner Res 2003;18:913-918.
10. Yamamoto T. Clinical approach to clarifying the
mechanism of abnormal bone metabolism in McCune
Albright syndrome. J Bone Miner Metab 2006;24(1):7-10.
17.6 Disorders of Puberty

Prisca Colaco
Puberty marks the transition of a child into an adult. The
age of onset of puberty is variable but usually occurs at
about 10.5 years in girls and between 11 and 12 years in
boys. In girls, puberty usually begins with breast
development (thelarche) but occasionally with the
appearance of pubic hair (pubarche). Menarche usually
occurs about 2 years after breast development begins. In
boys, testicular enlargement (more than 3 ml) marks the
onset of puberty and is followed by the appearance of
pubic hair and development of the external genitalia. The
pubertal growth spurt is an early event in girls usually
at Tanner stage B2, while in boys the growth occurs late,
usually at the time when a testicular volume of 10 ml is
achieved. What triggers the onset of puberty is still
hypothetical. The first neuroendocrine event is an

increase in the frequency and amplitude of GnRH pulses.
Loss of tonic CNS inhibition and decreasing sensitivity
to the negative feedback of gonadal steroids occur at the
time of puberty. The age at onset of puberty is controlled
by both genetic and extrinsic factors, and therefore, may
sometimes occur earlier or later than normal.
PRECOCIOUS PUBERTY
Puberty is considered precocious if its onset occurs before
the lower limits of normal. This was considered to be 8
years in girls and 9 years in boys. However a large study
in the US showed that puberty is being achieved about a
year earlier in white girls and 2 years earlier in African
942
American girls. New guidelines recommended that

puberty be considered precocious only when breast
development or pubic hair appears before the age of 7
years in white girls and 6 years in black girls. However
rapid progression of puberty in children below the age
of 8 years or the occurrence of menarche before the age
of 9 years merits evaluation. For boys, the onset of
puberty before the age of 9 years is considered precocious.
Classification
Sexual precocity can be classified as:
i. Central or true precocious puberty which is due to
the premature activation of the hypothalmicpituitary-gonadal (HPG) axis and is therefore
isosexual.
ii. Peripheral or pseudoprecocity This results from the
production of sex steroids independent of the HPG
axis and may be isosexual or heterosexual.
iii. Incomplete forms or pubertal variants premature
thelarche, premature pubarche and premature
menarche.
Etiology
The common causes of precocious puberty are given in
Table 17.6.1.
Central Precocious Puberty
Central precocious puberty (CPP) is the most common
form of precocious puberty and is about five times more
common in girls than in boys. CPP in girls is most often
idiopathic (about 75%). But, the younger the child the
greater is the likelihood of underlying pathology. In
idiopathic CPP the appearance of sexual characteristics
is merely a normal event occurring early and puberty
progresses normally. In contrast to girls, in about twothirds of boys, CPP is secondary to CNS pathology.
Hypothalamic hamartomas are the most common
tumors causing precocious puberty. These are benign
tumors which contain measurable GnRH and act as
ectopic GnRH pulse generators. In India CNS infections,
particularly tubercular meningitis, are important causes
of neurogenic CPP (Fig. 17.6.1). Hypothyroidism,
untreated or inadequately treated, is sometimes
associated with precocious puberty. The cause is not clear
but it is thought to be due to the effect of markedly
elevated TSH levels on the FSH receptor (Fig. 17.6.2).
TABLE 17.6.1: Causes of Sexual Precocity

A. Central Isosexual Precocious Puberty
Idiopathic
Neurogenic:
1. Intracranial tumors Hypothalamic hamartoma,
glioma, pineal tumor
2. Post-infectious Meningitis, encephalitis
3. Congenital malformations Hydrocephalus,
porencephaly, microcephaly
4. Traumatic Perinatal, accidental
Other diseases:
1. Neurofibromatosis
2. Tuberous sclerosis
3. Russell-Silver syndrome
4. Hypothyroidism
5. Advanced somatic maturation due to androgen
exposure
6. Idiopathic epilepsy
B. Peripheral Isosexual Precocious Puberty
Girls:
1. Ovarian McCune Albright syndrome, follicular cysts,
tumors
2. Adrenal Feminizing adrenal adenoma
3. Exogenous estrogens
Boys:
1. Testes Leydig cell tumor, familial testotoxicosis
2. Adrenal Congenital adrenal hyperplasia, adenoma,
carcinoma, Cushing syndrome
3. hCG secreting tumors
4. Exogenous androgens
C. Contrasexual development
Virilization in girls CAH, virilizing ovarian and adrenal
neoplasms
Feminization in boys Adrenal neoplasms, extraglandular
conversion of circulating steroids to estrogens
D. Variations of Pubertal Development
Premature thelarche
Premature pubarche
Premature menarche
Peripheral Precocious Puberty

Peripheral precocious puberty is only about one-fifth as
common as CPP. Virilizing conditions in boys and
feminizing conditions is girls may be due to adrenal or
gonadal causes. Adrenal disorders, most commonly
congenital adrenal hyperplasia (CAH), are the most
common causes of peripheral precocity in boys. PPP is
therefore much more common in boys as compared to
girls. The prepubertal size of the testes suggests the
diagnosis. Ovarian disorders are much more likely in
girls with PPP. McCune Albright syndrome (MAS)
Endocrinology
943
consists of fibrous bony dysplasia, skin pigmen-tation

and precocious puberty, and predominantly affects girls.
Autonomous secreting follicular cysts of the ovary
without any evidence of MAS may also result in sexual
precocity. These cysts are often more than 2 cm in
diameter in contrast to the smaller cysts which may be
normally present in the prepubertal ovary or in true
precocious puberty. Pubertal signs often develop rapidly.
Subsequent atresia of the cysts results in withdrawal
bleeding.
Pubertal Variants
The incomplete forms of sexual precocity can be
differentiated from precocious puberty by the absence
of other signs of puberty and a normal growth rate.
Figure 17.6.1: A five-year-old girl with central precocious

puberty following tuberculous meningitis at 2 years of age. Note:
Breast development and 3rd nerve palsy on the left side
Premature thelarche: In premature thelarche breast

development persists for more than 6 months or occurs
anew. It usually occurs before 3 years of age and rarely
after 4 years. There is no other evidence of estrogen effects
such as increase in uterine size, changes in external
genitalia, growth acceleration or bone age advancement.
The cause is unknown. It could be caused by transient
estrogen secretion by follicular cysts of the ovary.
Exogenous estrogens in food or environmental exposure
could also lead to breast development.
Premature pubarche: It is due to increased adrenal
DHEAS secretion (adrenarche) which results in the
appearance of pubic hair. It is more commonly seen in
girls in the 3 to 8 years age group. Pubarche is not
progressive. Occasionally these children may develop
slight acne, axillary hair, and adult type body odor but
no other secondary sexual characteristics. Skeletal maturation and linear growth are at upper normal limits. Signs
of severe androgen excess should prompt a search for a
virilizing condition such as an adrenal tumor or CAH.
Premature menarche: This is a rare condition and local
lesions must be ruled out. It is due to transient ovarian
activity resulting in an isolated follicular cyst. It may
occasionally be the first sign of puberty.
Evaluation
A detailed history and clinical evaluation is helpful in
arriving at a diagnosis and directing investigations.
History
Figure 17.6.2: A seven-year old girl with hypothyroidism

and precocious puberty
Age at onset: Idiopathic CPP usually presents between

6 and 7 years of age. The earlier the onset of puberty
the greater the likelihood of there being an underlying
944
organic cause. Hypothalamic hamartomas and

familial testotoxicosis present very early in the first 3
to 4 years of life.
Pubertal progression: In idiopathic CPP the rate of
progression may sometimes be very slow with
menarche occurring upto 5 years after breast
development. Very rapid progression of puberty is
seen in androgen-producing tumors, ovarian cysts
and some CNS tumors such as hypothalamic
hamartomas.
Accelerated growth is a feature of both central and
peripheral precocious puberty but is not seen in
pubertal variants.
Irregular vaginal bleeding is more common in
functioning ovarian tumors and hypothalamic
hamartomas.
History of past CNS infection, headaches, visual
disturbances, personality changes, seizures and
developmental delay would suggest a neurologic
disorder.
Drug exposure should be enquired into.
Symptoms suggestive of hypothyroidism should be
looked for.
A family history of precocious puberty would suggest
constitutional precocious puberty or familial
testotoxicosis. A history of precocious puberty in boys
and genital ambiguity in girls of the same family
would suggest CAH.
Evaluate (a) androgen effects acne, hirsutism,
increased muscle mass and clitoromegaly and (b)
estrogen effects breast development and changes in
vaginal mucosa.
Pubertal staging according to Tanners staging.
Abdominal and rectal examination for uterine size,
ovarian masses and adrenal tumors.
Testicular palpation: A testicular volume of more than
3 ml indicates the onset of true precocious puberty.
Scrotal masses suggest testicular tumors or adrenal
rests.
Inspection of the skin is helpful in McCune Albright
syndrome, neurofibromatosis and tuberous sclerosis.
Neurologic examination should include fundus
examination and perimetry.
Examination for signs of hypothyroidism.
Investigations
Hormonal Evaluation
Sex steroids: In girls serum estradiol levels are not very
helpful in determining the stage of puberty. Levels
overlap between normal pre-puberty, early puberty,
precocious puberty and premature thelarche. Levels
> 20 pg/mL suggest that puberty has started.
Markedly elevated levels (>100 pg/mL) are seen in
estrogen secreting ovarian tumors and sometimes in
follicular cysts.
In boys, serum testosterone levels <30 ng/mL are
generally prepubertal, though in some laboratories
levels of 10-30 ng/mL by may indicate early puberty.
Testosterone levels may be very high related to the
stage of puberty in boys with primary gonadotropin
excess.
Serum gonadotropins and the response to GnRH
stimulation: Gonadotropin levels are elevated in CPP
and suppressed in PPP. Basal serum FSH and LH
were of limited value in early puberty. But with the
availability of sensitive third-generation assays the
random LH is a good screening test for central
precocious puberty. An LH level of <0.1 IU/L is
prepubertal and levels of 0.3 IU/L or more are
pubertal. Random FSH levels are not helpful in
discriminating between prepubertal and pubertal
children.
GnRH stimulation test is more helpful in distinguishing
central from peripheral precocity. In CPP, an LH
predominant response is seen with GnRH stimulation. An increase in FSH levels much more than LH
indicates that the child is prepubertal. In PPP,
gonadotropin levels do not rise in response to GnRH
stimulation.
Serum dehydroepiandrosterone sulfate (DHEAS) levels
are elevated in premature adrenarche. and can be
very high in virilizing adrenal problems.
Serum17-hydroxyprogesterone (17OHP) and the response
to ACTH or serum 11-deoxycortisol may be required to
rule out CAH.
hCG levels in the serum, if an hCG secreting tumor is
suspected.
Thyroid hormone studies in suspected hypothyroidism.
Radiology
Bone age: Skeletal maturation is advanced in all cases
of precocious puberty except if associated with
Endocrinology
hypothyroidism, but remains normal in the

incomplete forms. It is also helpful in predicting adult
height.
CT or MRI brain to determine the etiology of CPP.
Pelvic and abdominal sonography: To evaluate the size
and morphology of the uterus, ovaries and adrenals.
This is essential in PPP to find the cause. In CPP the
size of the uterus is increased and an endometrial
shadow seen. The ovaries will also be enlarged
bilaterally, and may show multiple small follicular
cysts.
Testicular sonography: if a tumor is suspected.
Skeletal survey: In suspected cases of MAS.
945
childs psychological development corresponds with the

chronologic age. No major psychopathology is associated
with precocious puberty. Future fertility is maintained.
DELAYED PUBERTY
Delayed puberty is defined as the absence of any sign of
puberty in a girl by the age of 13 years or by 14 years of
age in a boy. It also includes incomplete pubertal
development such as no menarche at 15 years or no
progression from an intermediate stage for 2 years.
Classification
Treatment
Delayed puberty can be classified as (i) temporary and

(ii) permanent (Table 17.6.2).
Surgery
Evaluation
Tumors of the ovary, testis and adrenals require surgical

removal. Ovarian cysts more than 3 cm in size should be
explored surgically. Smaller cysts require repeated
evaluation. Surgery of hypothalamic hamartomas is
hazardous and is not recommended, because they do not
grow or become malignant. Germ cell, pineal tumors and
hCG-producing suprasellar tumors can be treated by
radiotherapy.
History
Medical Treatment
Treatment of precocious puberty is indicated if:
There is evidence that adult height may be significantly compromised.
Menarche occurs before 6 years of age.
Pubertal development is psychologically distressing
to the child.
Pubertal development progresses rapidly over an
observation period of about 6 months.
Therapy aims at reversing the development of sexual
characteristics and decreasing the acceleration of growth
and bone age by using GnRH analogue therapy.
Antigonadotropic and antiandrogen drugs such as
medroxyprogesterone and cyproterone acetate cause a
regression of pubertal signs but have no effect on growth
acceleration and bone age progression. Other drugs
which may be used in PPP include ketoconazole,
spironolactone and testolactone.
Psychological Support
Psychological support for the child and parents is an
essential part of the general management scheme. The
Medical history should focus on a review of symptoms

which may indicate a chronic systemic disease,
TABLE 17.6.2: Etiology of delayed puberty
Temporary causes:
1. Constitutional delay in growth and puberty (CDGP)
sporadic or familial.
2. Nutritional disorders
3. Chronic systemic disease
4. Hormonal disturbances e.g. hypothyroidism, isolated
GH deficiency and excess glucocorticoids
Permanent causes:
A. Hypogonadotropic:
Congenital:
1. Isolated gonadotropin deficiency
2. LH deficiency
3. Associated with syndromes e.g. Kallmann, Prader-Willi,
Laurence-Moon- Biedl
4. Panhypopituitarism
Acquired: Tumors, surgery, trauma, hyperprolactinemia
B. Hypergonadotropic: (Primary gonadal failure)
Congenital:
1. Sex chromosome anomalies e.g. Turner syndrome, XO/
XY, Klinefelter
2. Anomalies of testosterone synthesis or action
3. Pure gonadal dysgenesis
4. Associated with other syndromes, e.g. Noonans,
Alstrom, Smith-Lemli-Opitz
Acquired:
1. Surgical or traumatic castration
2. Orchitis/oophoritis
3. Chemotherapy, radiotherapy
4. Idiopathic
946
prolonged drug therapy or drug abuse, poor

nutrition, head trauma and anosmia.
Family history of delayed puberty or hypogonadism
and a history of parental consanguinity should be
enquired into. In CDGP, a history of delayed puberty
is often obtained in either a parent or sibling.
Drawing a growth curve and calculation of the growth
velocity may help in distinguishing between CDGP
and growth hormone deficiency (GHD). In CDGP the
growth velocity is appropriate for the childs
bone age while in GHD it is subnormal. In
hypogonadotropic hypogonadism, height is usually
normal and the growth curve shows a deceleration
only at the time of puberty.
Rate of pubertal progression: In CDGP, the rate of
pubertal progression is normal. Slow progression
suggests a partial gonadotropin deficiency.
Investigations
Hormonal Evaluation
Serum gonadotropin levels, FSH and LH, distinguish
between hypogonadotropic and hypergonadotropic
hypogonadism.
Serum gonadotropin response to GnRH stimulation may
show a pubertal response in CDGP but is not usually
helpful in distinguishing it from isolated gonadotropin deficiency.
Serum testosterone/estradiol.
Serum DHEAS levels are usually normal for
chronologic age in hypogonadotropic hypogonadism
but are low for age and corresponds with the bone
age in CDGP, where the tempo of maturation is
delayed.
Serum thyroxine (T4), prolactin, IGF-1 and GH
stimulation tests if indicated.
Examination
System review: Search for the presence of chronic
disease, malnutrition, anosmia, midline defects,
endocrine disorders, and dysmorphic syndromes.
Neurological assessment should include fundus
examination and evaluation of visual fields.
Signs of puberty should be noted and staged according
to Tanners staging.
Height measurement: Children with temporary delay
are commonly short. In hypogonadotropic hypogonadism associated with GH deficiency the height
is markedly short, while in those with isolated
gonadotropin deficiency the height is normal, but the
pubertal growth spurt is absent. The height of those
with primary gonadal failure is usually normal unless
associated with syndromes.
Body proportions: Eunuchoid proportions are a feature
of the prepubertal child with Klinefelter syndrome
and of hypogonadotropic hypogonadism due to the
absence of the pubertal spurt. Weight related to height
is decreased in malnutrition and chronic disease and
increased in most hormonal disorders, e.g.
hypothyroidism, GHD and cortisol excess. Obesity
is also a feature of many syndromes associated with
hypogonadism.
Radiographic Investigations
Bone age: In CDGP, the bone age is delayed and
corresponds with the height age and stage of puberty.
Bone age is usually slightly delayed in isolated
gonadotropin deficiency. It helps distinguish the two,
as in CDGP evidence of sexual maturation should be
evident by a bone age of 13 years whereas this may
not be so in isolated gonadotropin deficiency. In
patients with multiple pituitary hormone deficiency
the bone age is markedly delayed.
Pelvic ultrasonography provides information about the
development of the uterus and ovaries.
CT/MRI if indicated.
Treatment
Treatment of the cause whenever possible will result in
subsequent pubertal development. Patients with
constitutional delay require reassurance that there is
nothing wrong and that puberty though delayed, will
progress normally. Short-term low-dose hormonal
treatment with testosterone or estrogens for 3 to 6 months
may occasionally be required if the patient is
psychologically stressed. Permanent hypogonadism
Endocrinology
requires long-term replacement therapy with monthly
testosterone injections in boys and cyclic estrogenprogesterone treatment in girls.
BIBLIOGRAPHY
1. Bajpai A, Sharma J, Kabra M, Gupta A, Menon PSN. Long
acting GnRH analogue triptorelin therapy in central
isosexual precocious puberty. Indian Pediatr 2002;39:63339.
2. Bourguignon JP, Bertrand J, Rappaport R et al. Delayed
puberty and hypogonadism. In: Pediatric Endocrinology
- Physiology, Pathophysiology and Clinical Aspects,
Second edition. Maryland, 1993;404-19.
3. De Luca F, Argente J, Cavallo L, Crowne E, DelemarreVan de Waal HA, De Sanctis C, et al. Management of
puberty in constitutional delay of growth and puberty.
J Pediatr Endocrinol Metab 2001;14 Suppl 2:953-57.
947
4. Grumbach MM, Styne DM. Puberty: Ontogeny,

Neuroendocrinology, Physiology, and Disorders. In:
Wilson JD, Foster DW, Kronenberg HM, Larsen PR,
(Eds). Williams Textbook of Endocrinology, 9th edition.
WB Saunders Company; Philadelphia 1998;1509-625.
5. Rosenfield RL. Puberty in the female and its disorders.
In: Sperling MA (Ed). Pediatric Endocrinology, Second
edition. Saunders; Philadelphia, 2002;455-518.
6. Sizonenko PC, Bertrand J, Rappaport R, et al. Precocious
Puberty. In Pediatric Endocrinology Physiology,
Pathophysiology and Clinical Aspects, 2nd edition.
Maryland, 1993;387-403.
7. Styne DM. The testes. In: Sperling MA (Ed) Pediatric
Endocrinology, Second edition. WB Saunders,
Philadelphia, 2002;565-628.
8. Tat L, Savage MO, Antoniazzi F, Buzi F, Di Maio S,
Oostdijk W, et al. Optimal therapy of pubertal disorders
in precocious/early puberty. J Pediatr Endocrinol Metab
2001;14 Suppl 2:985-95.
17.7 Disorders of Sexual Differentiation

P Raghupathy
Normal Sexual Differentiation
All mammalian embryos are traditionally believed to
have an inherent tendency to develop as female. The SRY
gene on the Y chromosome actively induces the
formation of the testis and the male phenotype. The
gonads, internal genitalia (genital ducts) and the external
genitalia, which are bipotential are all influenced by
several genes and other factors necessary for male sexual
differentiation. In the absence of such influences, female
phenotype results. In recent years, many genes
contributing to the process of sex determination and
normal sexual differentiation during fetal life have been
discovered. There are also several claims made that
female sexual differentiation may no longer be
considered as a passive process or as occurring by
default.
than the ovary. Fetal testicular differentiation begins in

the seventh week of gestation, whereas ovarian development begins not earlier than 17 weeks of gestation.
Testicular Differentiation
The SRY (sex-determining region on the Y-chromosome)
gene (with 204 amino acids) located on the short arm of
the Y chromosome (Yp 11.3) is the trigger for testicular
differentiation, by inducing development of Sertoli cells
and subsequently, seminiferous tubules and Leydig cell
formation in that order. SRY activates SOX9 (SRYhemeobOX-like gene), an autosomal gene (chromosome
17q24) and SF1 (steroidogenic factor 1) to induce
differentiation of the bipotential gonad into a testis. SRY
suppresses DAX1 which normally inhibits SOX9.
The Gonads
Ovarian Differentiation
The gonads in the embryo remain undifferentiated until

the sixth week of gestation. Subsequent evolution into
either a testis or ovary is directed by the genetic sex (XX
or XY) depending on whether the sperm fertilizing the
ovum carries a Y or X. The testis develops more rapidly
DAX1, SOX3 and Wnt4 are the three candidate genes

currently known to suppress testicular differentiation.
DAX1 and SOX3 inhibit SF1 and SOX9, preventing Sertoli
cell differentiation, favoring granulosa cell development.
Wnt4 arrests the Leydig cell precursors and induces
948
development of Mullerian ducts into fallopian tubes,

uterus, cervix and upper third of vagina. FOXL2 helps
in follicular development in the ovary and in suppression
of somatic testis formation in genetic females. Though
the effects of these genes have been argued to result in
ovarian differentiation, it should be remembered that
active testicular differentiation occurs much earlier when
compared to the ovarian.
Internal Genitalia
Testosterone initially under the control of human
chorionic gonadotropin is produced locally (paracrine)
by Leydig cells of the fetal testis on either side. It helps
in ipsilateral differentiation of the Wolffian ducts into
epididymis, vas deferens, seminal vesicles and
ejaculatory ducts. Anti-Mullerian hormone (AMH)
secreted by the Sertoli cells causes ipsilateral involution
of the Mullerian structures.
In female fetuses, Wolffian structures regress in the
absence of testosterone and Mullerian ducts persist in
the absence of AMH. However, Wnt4 gene appears to
play an important role in Mullerian duct differentiation
and fetal ovarian function.
External Genitalia
From the initial undifferentiated stage of the external
genitalia, masculinizing features develop under the
influence of dihydrotestosterone (DHT) formed
peripherally from testosterone by the action of
5-reductase. This process is dependent on an adequate
number of functioning androgen receptors in the pubic
skin. Formation of female external genitalia does not
require any active process and will persist with normal
ovaries, in androgen insensitivity or even in the absence
of gonads, sex chromosome abnormalities, streak gonads
or non-functioning testes.
Abnormalities of Sexual Differentiation
When SRY protein undergoes mutation in its HMG box
(high mobility group) protein, testicular failure or genital
ambiguity will result. SOX9 mutation in 46,XY males
leads to a female phenotype and streak ovarian-like
gonads. Chromosomal abnormalities may lead to
disorders of male gonadal differentiation or give rise to
true hermaphroditism.
Wolffian development and Mullerian regression on
each side are dependent on the ipsilateral production or
testosterone and AMH respectively. Hence, abnormalities of the internal genitalia will be encountered,
based on the presence of gonadal elements on that side.
A streak gonad which produces neither testosterone nor
AMH, will give rise to poorly formed Mullerian
structures such as a hypoplastic or hemiuterus on the
side of the defective gonad.
Variable degrees of virilization of the female external
genitalia leading to sexual ambiguity will result when
exposed to androgens, either from the mother (intake or
excessive production of androgens in her body), or from
the fetus (congenital adrenal hyperplasia, aromatase
deficiency, true hermaphroditism or mixed gonadal
dysgenesis). Partial virilization producing ambiguity of
the external genitalia or complete virilization with a
normal-looking male external genitalia (penis and a fully
formed by empty scrotum) may occur in a genetic female
with congenital adrenal hyperplasia (CAH) due to 21hydroxylase deficiency. A normal-looking female
external genitalia (with testes in the labioscrotal folds)
may be a case of androgen insensitivity syndrome. A
genetic male may have undervirilization and present
with underdeveloped and ambiguous genitalia as in 17
-hydroxylase deficiency or 3 -hydroxysteroid dehydrogenase deficiency. The appearance of the external
genitalia does not always give any diagnostic clinical
clues, for example, an infant with true hermaphroditism
and a virilized female with genital ambiguity may look
similar.
Ambiguous Genitalia (hermaphroditism)
Ambiguous genitalia may be defined as a developmental
discrepancy between the external genitalia and the
gonads. The genital abnormalities which need to be
investigated are listed in Table 17.7.1. In the past, these
disorders were usually classified into female pseudohermaphroditism (FPH), male pseudohermaphroditism
(MPH) or true hermaphroditism (TH). The new
terminology recommended for disorders of sex
development (DSD) are mentioned in Table 17.7.2. The
new classification of DSD is presented in Table 17.7.3.
46,XX DSD
In this condition, the genotype is XX and the gonads (not
palpable) are ovaries, but the external genitalia are
virilized partially or fully. This results from exposure of
female fetus to androgens during the period of sexual
differentiation in early gestation.
Endocrinology
TABLE 17.7.1. Genital abnormalities which
need to be investigated
Ambiguous genitalia
Severe hypospadias
Undescended testes
Micropenis
Bifid scrotum
Male with nonpalpable testes
Female with bilateral inguinal hernias
Isolated clitoromegaly
Isolated labial fusion
Genital anomalies in syndromes
TABLE 17.7.2: New terminology recommended for DSD
Old nomenclature
Proposed terminology
Intersex
DSD
Male pseudohermaphrodite
46,XY DSD
Undervirilisation of an XY male
Undermasculinisation of an XY male
Female pseudohermaphrodite
Overvirilisation of an XX female
Masculinisation of an XX female
46,XX DSD
True hermaphrodite
Ovotesticular DSD
XX male or XX sex reversal
46,XX testicular DSD
XY sex reversal
46,XY complete gonadal

dysgenesis
949
TABLE 17.7.3: Suggested classification of DSD

1. 46,XX DSD
A. Disorders of gonadal (ovarian) development
i. Ovotesticular DSD
ii. Testicular DSD (e.g., SRY +, dup SOX9)
iii. Gonadal dysgenesis
B. Androgen excess
i. Fetal (e.g., 21-hydroxylase deficiency, 11-hydroxylase
deficiency)
ii. Fetoplacental (aromatase deficiency, P450
oxidoreductase)
iii. Maternal (luteoma, exogenous etc.)
C. Other
(e.g., cloacal extrophy, vaginal atresia, other syndromes)
2. 46,XY DSD
A. Disorders of gonadal (testicular) development
i. Complete gonadal dysgenesis (Swyer syndrome)
ii. Partial gonadal dysgenesis
iii. Gonadal regression
iv. Ovotesticular DSD
B. Disorders in androgen synthesis or action
i. Androgen biosynthesis defect (e.g., 17-hydroxysteroid
dehydrogenase deficiency, 5-reductase deficiency,
StAR mutations
ii. Defect in androgen action (e.g., complete or partial
androgen insensitivity)
3. Sex chromosome DSD
A. 45,X (Turner syndrome and variants)
B. 47,XXY (Klinefelter syndrome and variants)
C. 45,X/46,XY mixed gonadal dysgenesis
D. 46,XX/46,XY (chimeric)
46,XY DSD
In these cases, the genotype is XY, gonads (palpable) are
testes but the external genitalia are incompletely virilized,
ambiguous or completely female.
Sex Chromosome DSD
With the karyotype of 46,XX/46,XY (chimeric), both
ovarian and testicular tissues are present either in the
same gonad (ovotestis) or opposite gonads (one gonad
may be palpable or both gonads not palpable). The
clinical features may resemble either 46,XX or 46,XY DSD.
Majority of these cases have 46,XX karyotype.
CLINICAL APPROACH TO THE DIAGNOSIS OF
INFANTS WITH AMBIGUOUS GENITALIA
Examination of the external genitalia is often unhelpful.
In the case of ambiguity, the possibilities will be:
1. 46,XX DSDa genetic female with evidence of virilization following exposure to fetal (very common) or
maternal androgens.
2. 46,XY DSDa genetic male with undervirilization

due to indequate production of androgens.
3. Sex chromosome DSD (i) an infant with both
ovarian and testicular tissues, (ii) Mixed gonadal
dysgenesisan infant with 45, X/46, XY karyotype,
or
4. The genital deformity may be a developmental error
as in severe hypospadiasis, persistent Mullerian duct
syndrome, etc.
Maternal history of drug intake during pregnancy
and details of mothers medical condition need to be
obtained. History of familial genital ambiguity and
consanguinity is often helpful. CAH has an autosomal
recessive inheritance. History of multiple fetal wastages
and early neonatal deaths due to severe salt-losing variety
is common in CAH. If physical examination reveals the
presence of a gonad, it is most often a testis and the infant
is a male. If there is no external gonad palpable, the
genetic sex cannot be identified without the help of a
950
karyotype. The phallus is measured for its length and

width of erectile tissue and examined for chordee.
Presence of separate openings of vagina and urethra
should be looked for as also pigmentation and rugosity
of labioscrotal folds.
It is often the responsibility of the pediatric
endocrinologist or primary care physician to inform the
parents of an infant born with uncertain sex and to
discuss with them openly about the nature of the defect
observed, details of all the investigations that will be
needed to establish the diagnosis, the sex of rearing best
suited for the infant, the available modalities and plan
of treatment, as well as to allay the anxiety and guilt of
the parents and other family members in repeated
sessions. To deal with this condition optimally, a full team
is ideal, viz. pediatric endocrinologist, family
pediatrician, pediatric surgeon or urologist, radiologist,
ultrasonologist, biochemist, cytogeneticist, pediatric
psychologist and most importantly, the childs parents.
It is always important to collect together all possible
evidence for arriving at a diagnosis and then have
discussions with the parents. Although urgency is still
necessary, most parents will be willing to wait for a few
days longer and prefer to have all the diagnostic results
before making their decision about their childs future.
Until the decision is made, it is better to refer to the infant
as baby and not as he or she.
Investigations
1.
2.
3.
4.
5.
6.
7.
8.
9.
Serum sodium, potassium

Serum 17-hydroxyprogesterone (17OHP)
Serum DHEAS
Plasma renin activity
Serum 11-deoxycortisol
Ultrasound pelvis for the presence of uterus, gonads
Ultrasound abdomen for renal malformations
Retrograde genitogram
Karyotype.
Management
The commonest cause of ambiguous genitalia is 21hydroxylase deficiency in genetic females. Nearly 75
percent present with salt loss typically during the second
week of life. Hyperpigmentation of the skin, especially
the nipples, umbilicus and external genitalia should alert

one to the diagnosis even before salt losing manifestations appear. This clinical sign is particularly useful in
males with CAH as they do not present with any
abnormality of the external genitalia but have a high risk
of shock due to salt loss. In the presence of a previous
family history, biochemical investigations may be
performed earlier to hasten the diagnosis. Virilized
females with CAH having uterus and ovaries are
assigned the female sex. Clitoral reduction and
genitoplasty are usually undertaken around 1 year of age
and care is taken to preserve the glans and the
neurovascular bundle. Recommendations for assignment
of sex in an individual with fully virilized male external
genitalia and presence of female internal sex structures
are still controversial. Reconstructive surgery for
hypospadias is needed in those with 5 reductase
deficiency at the time of puberty. Assignment of a female
sex to an individual with microphallus and fused
scrotum is being reconsidered and not always accepted
today by many in the medical profession. Testosterone
therapy is recommended for microphallus and fused
scrotum. In summary, there are no easy answers always
for the assignment of sex in disorders of sexual differentiation.
BIBLIOGRAPHY
1. Federmann DD. Three facets of Sexual differentiation.
New Eng J Med 2004;350:323-4.
2. Grumbach MM, Hughes IA, Conte FA. Disorders of sex
differentiation. In: Larsen PR, Kronenberg HM, Melmed
S, Polonsky KS (Eds). Williams Textbook of Endocrinology, Saunders: Philadelphia 2003;10:842-1002.
3. Hughes IA. Disorders of sexual differentiation. Hormone
Research 2007;67(Suppl 1):91-95.
4. Lee PA, Houk CP, Ahmed SF, Hughes IA. Consensus
statement on management of intersex disorders.
Pediatrics 2006;118:488-500.
5. MacGillivray MH, Mazur T. Management of infant born
with Ambiguous Genitalia. In: MacGillivray MH,
Radovick S (Eds). Pediatric Endocrinology. Humana
Press, Totowa 2003;429-49.
6. MacLaughin DT, Donahoe PK. Sex determination and
differentiation. New Eng J Med 2004;350:367-78.
7. Quigley CA. Genetic basis of sex determination and sex
differentiation. DeGroot LJ, Jamesson JL, (Eds). Endocrinology, 4th edn. WB Saunders: Philadephia 2001;
1926-46.
Endocrinology
951
17.8 Disorders of Adrenocortical Biosynthesis

P Raghupathy
The adrenal cortex produces several steroid hormones
such as cortisol, aldosterone and androgens. The ability
to convert cholesterol into steroidal hormones (steroid
biosynthesis) is present only in the adrenal cortex, gonads
of both sexes and the placenta. An enzymatic defect of
steroidogenesis may not affect the adrenal cortex and
gonads equally. Hence, disorders of sexual differentiation
may result from the biosynthetic pathway defects in the
adrenal cortex or the gonads or both.
Steroidogenesis
The adrenal cortex functions as two separate units
because of the enzymatic differences between the zona
glomerulosa and the inner two zoneszona fasciculata
and zona reticularis. The zona glomerulosa lacks
17 -hydoxylase activity and therefore, cannot synthesize
17 -hydroxypregnenolone and 17 -hydroxyprogesterone (17-OHP), the precursors of cortisol and
androgens. The synthesis of aldosterone by this zone is
totally regulated by the renin-angiotensin system and by
potassium.
The two inner zones produce cortisol, androgens and
small quantities of estrogens. These two zones are
directly controlled by adrenocorticotropic hormone
(ACTH). They lack 18-dehydrogenase and so cannot
synthesize aldosterone.
The various enzymes involved in the biosynthetic
pathway of cortisol are given in Figure 17.8.1.
Corticotropin-releasing factor (CRF) produced by the
hypothalamus regulates ACTH. ACTH in turn induces
synthesis and secretion of steroids within minutes. The
conversion of cholesterol to pregnenolone is the major
site of ACTH action on the adrenal cortex and is the ratelimiting step.
CONGENITAL ADRENAL HYPERPLASIA
In congenital adrenal hyperplasia (CAH), cortisol
synthesis from cholesterol is affected due to deficiency
of one of the several enzymes in the adrenal cortex (Fig.
17.8.1). ACTH elevation is secondary to plasma cortisol
deficiency via the negative feedback mechanism.
Overproduction of the hormonal precursors proximal to
the block and deficiency of the hormones distal to the

blocked enzymatic step are responsible for the clinical
features encountered. Each of the five enzymatic defects
is inherited by an autosomal recessive mode and
produces a characteristic clinical and biochemical picture.
The genes and enzymes involved in adrenal steroidogenesis are listed in the Table 17.8.1.
21-Hydroxylase Deficiency (21-OHD)
This is the most common enzyme deficiency seen in
nearly 90 percent of individuals with CAH. The exact
incidence of 21-OHD in India is unknown. In the West,
the incidence is reported to be 1 in 5,000 to 1 in 15,000.
17-OHP accumulates in the serum because it is not
converted to 11-deoxycortisol in the absence of 21hydroxylase. Similarly, progesterone accumulates
following lack of conversion to 11-deoxycorticosterone
(Fig. 17.8.1). The ultimate effect is cortisol deficiency and
ACTH elevation giving rise to adrenocortical
hyperplasia. As the formation of mineralocorticoids and
glucocorticoids from cholesterol is blocked, the
conversion of cholesterol flows largely into the androgen
pathway. The clinical varieties of this deficiency are:
a. Salt-wasting type in nearly 75 percent of 21-OHD. This
is the classic disorder presenting usually between 1
week and 1 month of age occurring with cortisol
deficiency along with salt wasting and hypovolemia
arising from aldosterone deficiency and the
natriuretic effect of accumulated precursors like
17-OHP. The effects of this enzyme deficiency begin
in the intrauterine period. Hence the accumulation
of excessive adrenal androgens causes virilization of
the external genitalia of a female infant seen at birth,
in both the salt-wasting and simple virilizing types.
b. Simple virilizing type without salt loss. Non-salt losers
with virilization account for about 25 percent of cases.
The absence of salt loss can be explained by a partial
defect in 21-OHD. Virilization is seen at birth in girls.
c. Non-classic (late onset) type. The presentation may also
be varied, such as adrenarche, early growth spurt, or
accelerated skeletal maturation. The manifestations
can also occur for the first time during adulthood as
hirsutism in women or reduced fertility in both sexes.
952
Figure 17.8.1: Scheme of adrenal steroidogenesis. Chemical names of enzymes are shown next to the arrows, enclosed numbers
indicate traditional names of the enzymes: 1. 20, 22-desmolase, 2. 3-hydroxysteroid dehydrogenase / isomerase, 3. 17hydroxylase, 4. 17, 20-lyase, 5. 21-hydroxylase, 6. 11-hydroxylase, 7. 18-hydroxylase, 8. 18-oxidase, 9. 17-hydroxysteroid
dehydrogenase, 10. aromatase.
StAR = steroidogenic acute regulatory protein; DOC = 11-deoxycorticosterone
There is no hypertension. Use of appropriate sized

cuffs for measurement of blood pressure is essential. If
siblings are affected, they tend to have the same clinical
type.
Salt Loss
Salt loss may present as hypovolemic shock, especially
as unexplained dehydration and may also occur beyond
neonatal period in cases of infection induced stress
situations.
Virilization
The diagnosis of 21-OHD is easily identified in girls
because of genital ambiguity. In boys, however, the
condition can go unnoticed until toddler years, when
increased height velocity, increase in the size of the

external genitalia, early appearance of pubic hair and
other signs of male secondary sexual characteristics are
observed. Hyperpigmentation involving external
genitalia, nipples and umbilicus with a tanned
appearance of skin may be a very important clue for
early diagnosis.
The degree of genital ambiguity does not correlate
with the form of 21-OHD. Virilization in the female may
present as mild clitoral hypertrophy, varying degrees of
ambiguity or complete masculinization with normal
looking male genitalia but with an empty scrotum. Thus,
absence of testes would be helpful in diagnosis.
Apart from the external virilizing and biochemical
features, there are no abnormalities in genetic sex,
Endocrinology
953
TABLE 17.8.1. Genes and enzymes involved in adrenal steroidogenesis

Gene
Chromosomal
location
Enzyme
Enzymatic activity
Cellular location
CYP11A1
15q23-q24
P450scc (CYP11A1)
Mitochondrion
HSD3B2
1p13.1
3bHSD (3bHSDII)
Cholesterol desmolase
(side chain cleavage)
3b-hydroxysteroid dehydrogenase
CYP17
10q24.3
P450c17 (CYP17)
17a-hydroxylase/17,20 lyase
CYP21A2
6p21.3
P450c21 (CYP21A2)
21-hydroxylase
CYP11B1
CYP11B2
8q2122
8q2122
P450c11 (CYP11B1)
P450c18 (CYP11B2)
11b-hydroxylase
Aldosterone synthase
(corticosterone 18-methylcorticoster one oxidase/ lyase)
gonadal differentiation, or development of the internal

genitalia. The female infant will have normal ovaries,
fallopian tubes, uterus and proximal vagina. Postnatally
in untreated cases there will be continued virilization
effects with clitoromegaly or penile enlargement,
accelerated growth, advanced skeletal maturation far in
excess of the height age and premature appearance of
secondary sexual characteristics.
Laboratory Features
Hyponatremia, hyperkalemia, increased urinary sodium
losses due to renal salt wasting, high plasma renin
activity (PRA), accompanied by low serum and urinary
aldosterone levels, acidosis and uremia are the
biochemical features in salt-wasting type. Hypoglycemia
may also be present. Elevated serum 17-OHP, markedly
lowered serum cortisol, elevated levels of serum DHEAS,
and testosterone are diagnostic. On short synacthen
(ACTH) stimulation test, serum 17-OHP and DHEAS rise
more than 23 folds but there is no significant elevation
of serum cortisol. Urinary estimation of steroid
metabolites is not preferred nowadays. The difficulty
experienced in the 24-hour urine collection from an infant
with ambiguous genitalia is considerable. The results are
quite often difficult to interpret.
Nonclassic 21-OHD may be totally asymptomatic and
presents only with biochemical abnormalities as in the
classic cases and may be picked up only during family
studies. Non-classic cases may have only milder elevation
of 17-OHP, especially when performed in the afternoon
Endoplasmic
reticulum
Endoplasmic
reticulum
Endoplasmic
reticulum
Mitochondrion
Mitochondrion
or late forenoon. Hence it is preferable to get the

hormonal profile always in the mornings.
Treatment
The essential principles of treatment are to replace the
deficient hormones and to suppress the overproduction
of precursor hormones. Hydrocortisone is required in a
dose of 10 to 20 mg/m2/day in two or three divided
doses. Salt wasters require, in addition, 9 -fluorohydrocortisone 0.1 to 0.3 mg (100300 g) per day. Sodium
chloride supplementation up to 1-3 g daily may be
needed in the infants and young child. The hormonal
profile reverts to the normal range with appropriate
treatment, which is monitored 3 to 6 monthly by
estimating 17-OHP and PRA values and appropriate
dosage adjustment is effected. The daily dose of
hydrocortisone may be doubled during acute stress
periods like infection.
In the newborn period at presentation, a large dose
of hydrocortisone and fluorohydrocortisone may be
required. Dosages are modified by monitoring serum
sodium and potassium daily and frequent serum 17-OHP
and PRA. Dose of hydrocortisone is gradually reduced
and changed over to 5 mg twice a day orally. In older
children, when higher dosage is given, a larger dose is
given at night, e.g. if the child needs 12.5 mg of
hydrocortisone per day, 5 mg is given in the morning
and 7.5 mg in the evening. This is done with a view to
suppress ACTH pulses during the night.
954
Appropriate Sex Assignment

Assigning the appropriate sex is of paramount
importance. The affected female with CAH has the
potential for a normal fertile female role. Surgical
correction of the genital abnormality is carried out in girls
around 1 year of age by doing reduction clitoroplasty.
Definitive vaginoplasty will also be required.
It is very important that the parents understand the
nature of the disease, chronicity of the treatment required
lifelong, the complication arising from poor compliance,
and how steroids play an essential role in stress situations
which can be life-threatening if in appropriately
managed. Early epiphyseal fusion in both sexes will
eventually cause short stature, if treatment is irregular
and incomplete with the disease being poorly controlled.
The parents are given adequate health education
regarding this condition. They are advised that daily dose
of hydrocortisone must be doubled or tripled for a few
days during stress situations.
Prenatal Treatment
In families with an affected infant, prenatal treatment is
useful in subsequent pregnancies. The aim of prenatal
treatment is to prevent external genital deformity in the
female fetus due to virilization. As soon as pregnancy is
confirmed, the mother is commenced on oral
dexamethasone 20 g/kg/day in 3 divided doses, even
prior to the fetal diagnosis being established. Karyotype
and DNA analysis are obtained by chorionic villus
sampling around 9-11 gestational weeks. If the fetus is a
male or an unaffected female, treatment is stopped.
Treatment is continued in the case of an affected female
infant. When conclusive evidence is obtained that the
fetus is affected, the parents may also be given the choice
of termination of pregnancy, irrespective of the sex of
the fetus.
Neonatal Screening
Screening of all newborns with filter paper 17-OHP is
carried out in many developed nations. It is not yet
determined whether this is mandatory.
11
-HYDROXYLASE DEFICIENCY
In this disorder which accounts for nearly 5 percent of
cases of CAH, cortisol and corticosterone are deficient
with overproduction of 11-deoxycortisol and 11-deoxy-
corticosterone. The precursor hormones are shunted into

the androgen pathway causing prenatal and postnatal
virilization. The accumulation of deoxycorticosterone
results in sodium and water retention, increased plasma
volume and hence causes hypertension. Serum level of
11-deoxycortisol elevation is diagnostic, PRA is
suppressed, serum aldosterone is lowered and
hypokalemia may be present. Glucocorticoid therapy is
effective in reversing all the abnormalities and inducing
remission.
17-HYDROXYLASE/ 17,20 LYASE DEFICIENCY
This is a rare disorder occurring with cortisol deficiency,
ACTH excess, overproduction of DOC causing
hypertension and hypokalemia. Affected males are
incompletely virilized (male pseudohermaphroditism)
owing to diminished androgen production and may be
phenotypically female or ambiguous. In addition, ACTH
excess driven by cortisol deficiency causes
mineralocorticoid excess and hypertension. PRA and
aldosterone are low. Glucocorticoid therapy suppresses
overproduction of the hormones.
3
-HYDROXYSTEROID/ 4,5 ISOMERASE
DEFICIENCY
Classic and nonclassic forms are seen in this disorder.
Salt wasting, deficiency of cortisol and aldosterone are
the usual manifestations of this condition. In the
nonclassic form, there is no aldosterone deficiency. Males
with this condition may show undervirilization with
ambiguity of external genitalia owing to underproduction of testosterone in utero. Pseudovaginal
hypospadias may be present in the males due to absence
of potent androgens. But the excessive collection of the
weak androgen, DHEAS, may cause clitoral enlargement
in the female. Most of them have aldosterone deficiency
with elevation of PRA. Hyperpigmentation is seen and
serum ACTH level is high. Treatment is with
glucocorticoids.
LIPOID ADRENAL HYPERPLASIA
In this rare StAR protein deficiency disorder, there is a
global deficiency of all adrenal hormones; glucocorticoids, mineralocorticoids and sex hormones, which
affects adrenal cortex and gonads. Gonadal steroids are
also absent. Clinical presentation is very early in life with
salt wasting crisis. Females have no abnormality of
Endocrinology
internal or external genitalia. Males are phenotypically
female but may have inguinal gonads. Sex hormone
replacement will be necessary in those with undervirilization or in those with delayed puberty with the
objective of achieving normal pubertal development,
normal sexual function, and fertility.
Conclusion
Knowledge regarding CAH is widening constantly. The
chromosomal locations and nature of the genes encoding
the various enzymes needed for adrenocortical
biosynthesis, the cellular locations, functions and
abnormalities of these enzymes, the pathophysiology of
adrenocortical disorders, the clinical features and
laboratory parameters have been documented further.
Prenatal diagnosis and treatment as well as newborn
955
screening are practised widely. However, we are yet to

find an ideal way of keeping the disease under good
control in an effort to mimic normal physiology.
BIBLIOGRAPHY
1. Grumbach MM, Hughes IA, Conte FA. Disorders of sex
differentiation. In: Larsen PR, Kronenberg HM, Melmed
S, Polonsky KS (Eds). Williams Textbook of Endocrinology, 10th edn. Saunders, Philadelphia 2003:;913-33.
2. Hughes IA. Congenital adrenal hyperplasia: a lifelong
disorder. Hormone Research 2007;68(suppl 5):84-89.
3. New MI, Ghizzoni L. Congenital Adrenal Hyperplasia.
In: Lifshitz F (Ed). Pediatric Endocrinology. 4th ed.
Marcel Dekker, New York 2003;175-92.
4. Wajnrah MP, New MI. Defects of Adrenal Steroidogenesis.
In: DeGroot LJ, Jamesson JL, (Eds). Endocrinology, 4th
ed. WB Saunders, Philadelphia 2001;1721-39.
5. White PC, Speiser PW. Congenital adrenal hyperplasia due to
21-hydroxylase deficiency. Endocrine Reviews 2000;21:245-91.
17.9 Disorders of Adrenal Glands

PSN Menon
The adrenal cortex comprises of three distinct anatomical
areasouter zona glomerulosa (responsible for
mineralocorticoid production), middle zona fasciculata
(responsible for glucocorticoid production) and inner
zona reticularis (responsible for androgen production).
The adrenocortical hormones are crucial for maintenance
of fluid and electrolyte balance (mineralocorticoids),
intermediary metabolism (glucocorticoids) and sexual
development (androgens).
Steroidogenesis involves conversion of cholesterol to
steroid hormones in a process mediated by a group of
P450 enzymes. The disorders resulting from various
enzyme deficiency states are discussed in Chapter 17.8.
The hypothalamicpituitaryadrenal (HPA) axis is
responsible for the maintenance of normal cortisol levels.
This involves close interaction of three hormones
corticotropin secreting hormone (CRH) produced by the
hypothalamus, ACTH produced by the anterior pituitary
and cortisol secreted by the adrenals. Aldosterone and
androgen secretions are independent of the HPA axis.
This explains the lack of salt wasting crisis in children
with hypothalamicpituitary disorders.
ADRENAL INSUFFICIENCY
Adrenal insufficiency is relatively rare in children. Signs
and symptoms are often nonspecificas a result the
diagnosis may not be suspected early. If unrecognized,
adrenal insufficiency may present with lifethreatening

cardiovascular collapse.
Classification
Adrenal insufficiency can be classified as primary or
secondary; congenital or acquired. In primary adrenal
insufficiency (commonly referred to as Addison disease)
production of glucocorticoid (cortisol) and, frequently,
mineralocorticoid hormones by adrenal cortex is
decreased. In secondary adrenocortical insufficiency,
there is lack of CRH secretion from the hypothalamus
and/or ACTH secretion from the pituitary resulting in
hypofunction of the adrenal cortex. In secondary adrenal
insufficiency, mineralocorticoid function is preserved.
Etiology
The common causes of adrenal cortical insufficiency are
given in Table 17.9.1. Primary adrenal deficiency is
relatively uncommon. Adrenal infiltration by tuberculosis is uncommon in children compared to adults. In
a large pediatrics series, CAH accounted for over 70% of
cases of primary; the most common was CAH due to
21hydroxylase deficiency. Compared to primary,
secondary form is much more common. The most
common cause of acute adrenal insufficiency in the West
is withdrawal or omission of glucocorticoids in patients
being treated with long term pharmacologic doses.
956

TABLE 17.9.1: Etiology of adrenal insufficiency
A. Primary
Congenital
1. Congenital adrenal hyperplasia (CAH)
21hydroxylase deficiency (CYP21)
3hydroxysteroid dehydrogenase deficiency
(HSD3B2)
11hydroxylase deficiency (CYP11B2)
Cholesterol desmolase deficiency (CYP11A)
Lipoid hyperplasia (STAR)
2. Congenital adrenal hypoplasia (SF1, DAX1)
3. Triple A or Allgrove syndrome (AAAS)
4. ACTH resistance (MC2R, MRAP)
5. Glucocorticoid resistance (GCCR)
6. Metabolic diseasesAdrenoleukodystrophy (ABCD1),
Zellweger syndrome (PEX), SmithLemliOpitz
syndrome(DCHR7), Wolman disease (LIPA)
7. Mitochondrial diseases KearneSayre syndrome
Acquired
1. Autoimmune adrenalitis
Isolated
Polyglandular syndromesTypes I (AIRE) and II
2. Hemorrhage and infarctionTrauma, Waterhouse
Friderichsen syndrome
3. DrugsAminoglutethimide, mitotane, ketoconazole,
metyrapone
4. Infections
Viral: HIV, cytomegalovirus
Fungal: Coccidiomycosis, histoplasmosis
Mycobacterial: Tuberculosis
Parasitic: Amebic
5. InfiltrationHemochromatosis, histiocytosis, neoplasm
B. Secondary
Hypothalamus
1. CongenitalSeptooptic dysplasia (HESX1), CRH
deficiency
2. Acquired
a. Steroid withdrawal after prolonged administration
b. Inflammatory disorders
c. Trauma
d. Radiation therapy
e. Surgery
f. Tumors
g. Infiltrative disease: Sarcoidosis, histiocytosis X
Pituitary
1. Congenital
a. Aplasia/hypoplasia
b. Multiple anterior pituitary hormone deficiencies
(PROP1)
c. Isolated ACTH deficiency
2. Acquired
a. Steroid withdrawal after prolonged administration
b. Trauma
c. Tumors: Craniopharyngioma
d. Radiation therapy
e. Lymphocytic hypophysitis
Clinical Features
Clinical features depend on the severity and the etiology
of the disease. Children with acute adrenal insufficiency
generally present with acute dehydration, hypotension,
hypoglycemia, or altered mental status. Acute adrenal
insufficiency may be triggered by infection or trauma,
but may also occur without an obvious concomitant
illness or stress. Hypoglycemia is most common in young
children.
Patients with chronic adrenal insufficiency usually
complain of fatigue, muscle weakness, nausea, vomiting,
appetite loss, weight loss and recurrent abdominal pain.
Blood pressure is often low. Often hyperpigmentation is
seen over genitalia, axillae, nipple, joints, umbilicus,
palmar creases, buccal mucosa, recent scars and other
exposed parts of skin due to elevation of pro
opiomelanocortin and melanocytestimulating hormone.
Salt craving is common in chronic primary adrenal
insufficiency. Hyperpigmentation and salt craving are
not observed in patients with secondary adrenal
insufficiency.
Unless there is a history of recent pharmacologic
glucocorticoid therapy, secondary adrenal insufficiency
is usually associated with signs of other pituitary
hormone deficiencies such as growth failure, delayed
puberty, secondary hypothyroidism, and/or diabetes
insipidus (polyuria and polydipsia).
Congenital Adrenal Hypoplasia
Two forms of this condition are known. In the autosomal
recessive form the adrenal glands are extremely small.
The second, cytomegalic type is inherited as an Xlinked
recessive disorder and is caused by mutations of the
DAX1 gene. It usually manifests in the neonatal period
with severe salt wasting, but the onset may be delayed
for several years. It may also be associated with
hypogonadotropic hypogonadism, Duchenne muscular
dystrophy and cerebral malformations.
Diagnosis
Hyponatremia and hyperkalemia are common in
primary adrenal insufficiency due to poor aldosterone
secretion. Hypoglycemia is common in both primary and
secondary adrenal insufficiency. It is advised to collect a
venous sample at the time of hypoglycemia in all
neonates for glucose, cortisol, GH, and insulin levels.
Primary adrenal insufficiency is confirmed by
documentation of an elevated plasma ACTH level (>100
Endocrinology
pg/mL) and a low serum cortisol level (generally < 10
g/dL). If doubtful, ACTHstimulation test (250 g or
15 g/kg for infants < 2 years, IV) is performed in
primary adrenal insufficiency, the peak cortisol level is
subnormal (< 18 g/dL 60 minutes after ACTH
administration). Mineralocorticoid deficiency is
confirmed by relatively low aldosterone levels with high
renin or PRA, with or without hyponatremia and/or
hyperkalemia.
Secondary adrenal insufficiency is associated with
low blood cortisol and low ACTH levels. Confirmation
of HPA axis insufficiency may be more difficult. The
insulininduced hypoglycemia (serum cortisol measured
60 minutes after 0.050.15 U/kg of IV regular insulin) is
not preferred because of the risk of hypoglycemic seizure.
There may not be any increment after short (1 g IV)
and long (250 g) ACTH stimulation (expected cortisol
response >18 g/dL after 3060 minutes). Other
alternatives include CRH test (1 g/kg IV over 2 minutes;
expected response: 2 fold increase in ACTH level at 15
minutes and 34 fold increase in cortisol levels at 1530
minutes) and glucagon test (0.1 mg/kg SC).
Further evaluation for multiple pituitary hormone
deficiencies, isolated ACTH deficiency, or primary
adrenal insufficiency will depend on the preliminary
tests. Xray abdomen may show adrenal calcification.
Ultrasound or CT scans are useful in diagnosis of adrenal
lesions. MRI of brain may show abnormalities of HP axis.
Antibody screen may be useful.
Management
Management of acute adrenal crisis should be immediate.
In the hypotensive patient, rapid restoration of
intravascular volume with IV infusion of 2025 ml/kg
of 0.9 percent saline in 510 percent dextrose is needed.
Additional dextrose should be administered as required
to treat hypoglycemia.
Glucocorticoid should be given simultaneously in
stress doses. Hydrocortisone is the treatment of choice
because of its mineralocorticoid activity. The recommended stress dose of hydrocortisone is 50 to 75 mg/m2 IV
initially, followed by 50 to 75 mg/m2/day IV divided in
4 doses. Once acute manifestations are controlled, cortisol
may be given orally 5 mg twice a day for infants or
1015 mg daily for older children. The dose should be
increased in stress situations.
A salt retaining agent such as fluorohydrocortisone
should be given in a dose of 0.050.1 mg daily to maintain
electrolyte balance. Liberal salt intake is advised.
957
HYPERFUNCTION OF THE ADRENAL CORTEX

Hyperfunction of the adrenal cortex may be associated
with excess production of glucocorticoids, mineralocorticoids, androgens or estrogens. Most children with
adrenocortical hyperfunction have increased secretion
of more than one hormone. These disorders are rare in
childhood. A high index of suspicion is essential for
diagnosis as most of them present with nonspecific
features.
GLUCOCORTICOID EXCESS STATESCUSHING
SYNDROME
Cushing syndrome is the most common disorder of
adrenocortical hyperfunction. It is a generic term used
to describe clinical findings caused by prolonged
glucocorticoid excess. Cushing syndrome has been
described at all age groups including neonatal period
and infancy and account for 510% of all reported cases.
Etiology
Hypercortisolism in Cushing syndrome may be due to
increased endogenous production or exogenous administration. Pharmacological glucocorticoid treatment is the
most common cause of childhood Cushing syndrome.
Increased adrenal glucocorticoid production might occur
in response to increased ACTH levels or represent
autonomous adrenal hyperfunction (Table 17.9.2).
Adrenal pathology is more likely in young children,
while pituitary causes are more common after puberty.
Excessive adrenal production of cortisol may be due to
an adrenal adenoma, carcinoma or nodular hyperplasia.
Adrenal tumours are more common in girls. Adrenal
TABLE 17.9.2: Etiology of Cushing syndrome in children
ACTHdependent
Hypothalamic Increased CRH production by tumor
Pituitary Increased ACTH production Microadenoma,
macroadenoma
Ectopic Neuroblastoma, carcinoids, Wilms tumour, islet
cell tumor
ACTHindependent
Adrenal tumors Carcinoma, adenoma
Pigmented nodular hyperplasia
McCuneAlbright syndrome
Multiple endocrine neoplasia
Exogenous
Glucocorticoid High dose or prolonged oral, parenteral,
topical, inhaled
ACTH
958
adenomas almost always secrete cortisol with minimal

secretion of mineralocorticoids or sex steroids, while
adrenal carcinomas tend to secrete excess cortisol,
mineralocorticoids and androgens.
Cushing syndrome may be secondary to an ACTH
secreting tumor of the pituitary, termed Cushing disease,
often a basophilic pituitary adenoma. It leads to bilateral
adrenal hyperplasia. The incidence of pituitary Cushing
disease in children is rare as compared with adults.
Cushing syndrome may be due to ectopic production
of ACTH from malignant tumors of bronchus, thymus
or pancreas. It is extremely rare in children.
McCuneAlbright syndrome due to a somatic mutation
of Gs protein, may present with ACTHindependent
Cushing syndrome due to constitutional activation of
ACTH receptor. It is associated with fibrous dysplasia,
caf-au-lait spots and other endocrinopathies including
precocious puberty and hyperthyroidism.
Clinical Features
Unlike adults, the clinical manifestations of Cushing
syndrome especially in the young child are frequently
due to an adrenal tumor. Children differ from adults in
their clinical features. The classical features such as
central obesity, striae, moon facies and buffalo hump are
rare in young children. Growth failure coupled with weight
gain is the most common feature in children. However,
it is an extremely rare cause of childhood obesity. The
fat distribution is often centripetal with accumulation on
the face, neck and abdomen. The extremities appear
wasted with muscle weakness (Figs 17.9.1 and 17.9.2).
Other common clinical features include hypertension,
delayed puberty, lethargy, bone pain, and obsessive
compulsive behavioural disorders. There may be
thinning of skin with purple striae (frequently seen on
the abdomen, buttocks, thighs and axillae) and easy
bruising. ACTHdependent Cushing syndrome is
characterised by hyperpigmentation due to increased
secretion of melanocyte stimulating hormone (MSH).
Impaired immune function is also known. Androgen
excess leads to hirsutism, acne, deepening of voice and
rarely clitoral hypertrophy.
Children with ectopic ACTH production usually lack
classical features of Cushing syndrome. This is due to
rapid progression and shorter duration of the disease.
These children usually present with hypertension and
hypokalemic alkalosis.
Figure 17.9.1: Eight-year-old girl with Cushing syndrome due

to pituitary microadenoma. Note central obesity and moon
facies
Figure 17.9.2: Eight-year-old girl with Cushing syndrome.

Note buffalo hump and hypertrichosis
Diagnosis
The first step in the evaluation of a child with suspected
Cushing syndrome is to exclude exogenous causes of
hypercortisolism. Associated signs of androgen excess
leading to virilisation with premature pubarche, acne,
clitoromegaly and penile enlargement, thus, suggest the
possibility of virilising adrenal carcinoma. The evaluation
of children with Cushing syndrome after exclusion of
an adrenal tumor is more complex because many of the
diagnostic tests are based on studies in adults, and then
extrapolated for children. An algorithmic approach to
diagnosis of Cushing syndrome is given in Fig. 17.9.3.
Endocrinology
959
Figure 17.9.3: Approach to a child with Cushing syndrome (Source: Bajpai A, Sharma J, Menon PSN. Practical Pediatric
Endocrinology, 1st edition. Jaypee Brothers Medical Publishers (P) Ltd., New Delhi, 2003)
960
Loss of diurnal rhythm is the earliest biochemical

marker of hypercortisolism. Usually cortisol is highest
at 9 AM and lowest at midnight. The normal plasma
cortisol levels range between 5-25 g/dL (140690 nmol/
L) in the early morning, which is reduced to less than
half by 11 pm. Morning cortisol levels are not elevated
in many patients with Cushing syndrome, whereas late
night cortisol is usually increased.
Estimation of urinary excretion of free cortisol (UFC) is
a good screening test for Cushing syndrome. Normal
levels vary between 25-75 g/m2/day and UFC levels
>75 g/m2/day are suggestive of Cushing syndrome.
Although UFC may be useful to confirm Cushings
syndrome, its sensitivity and specificity are not optimal
as an initial screening test.
Salivary cortisol is better alternative and being used
in advanced laboratories. Salivary cortisol level > 8.6
nmol/L is suggestive of Cushing syndrome.
Overnight dexamethasone suppression is a commonly
used screening test for adrenal pathology. Following
administration of 1 mg of dexamethasone at 12 midnight,
plasma cortisol is estimated in the morning sample.
Cortisol levels below 5 g/dl indicate non-adrenal cause
for obesity.
Low dose dexamethasone suppression test (LDDST) is
used for confirmation of Cushing syndrome. It is based
on the principle that dexamethasone will suppress
ACTH, and hence cortisol release in normal subjects,
whereas patients with corticotroph adenomas will not
suppress below a specified cutoff. This test involves the
measurement of serum cortisol or UFC before and after
oral dexamethasone (5 g/kg per dose, every 6 hours
for 2 days or 1.25 mg/m2/day divided into 4 doses given
over 2 days). Serum cortisol levels > 5g/dL is diagnostic
of Cushing syndrome. It should be remembered that
there is significant variability in the biological behavior
of corticotroph adenomas, as a result neither the
overnight nor LDDST test reliably rules out Cushing
syndrome using standard cutoffs for serum cortisol.
Urinary 17ketosteroids are increased if virilization
is present. Adrenal androgens such as DHEA and
DHEAS are normal.
ACTH levels are low in adrenal tumors and nodular
hyperplasia; normal or mildly elevated in Cushing
disease and markedly elevated in ectopic ACTH
syndrome. Currently available ACTH assays reliably
differentiate ACTHindependent (ACTH levels <5 pg/
mL) from ACTHdependent conditions (ACTH levels
>15 pg/mL). Children with ACTH levels between 515

pg/mL are best evaluated by the CRH stimulation test.
Increase in ACTH levels after intravenous CRH (1 g/
kg, maximum 100 g, sampling basal and after 30 and
60 minutes) is suggestive of ACTHdependent etiology
while no increase is expected in children with autonomous
adrenal production or ectopic ACTH production.
High dose dexamethasone test (HDDST 2 mg every
6 hours or 40 g/kg every 6 hours for 2 days) will reduce
plasma cortisol in normal children and bilateral adrenal
hyperplasia, but not in children with adrenal tumors or
ectopic ACTH syndrome.
Other lab features include polycythemia, eosinopenia
and lymphopenia. Intermittent hyperglycemia without
glucosuria is common. There may be hypokalemia and
metabolic alkalosis. Serum calcium is normal.
Phosphorus concentrations may be low.
Radiological evaluation shows retarded bone age
usually, but may be advanced in children with
virilization. Osteoporosis and pathological fractures may
be present. If adrenal tumor is present, there may be
calcification and displacement of kidney. The tumors can
be localized by adrenal imaging using ultrasound, CT or
MRI. Pituitary MRI imaging often picks up corticotroph
microadenomas in < 25% cases. The use of dynamic MRI
(with IV gadolinium) with spoiled gradient sequences
may increase the sensitivity. Radiological evaluation
should not be performed before definitive endocrine
characterization. This is extremely important as non
functional pituitary and adrenal lesions are common.
Thus, identification of an adrenal or pituitary lesion alone
in the absence of endocrine features is not sufficient to
establish the cause.
Inferior petrosal sinus sampling (IPSS) is the test
available for identifying the source of ACTH production
and may be performed in children with ACTH
dependent CS with normal neuroimaging. The
experience with children is limited.
Management
Resection of adrenal lesion is recommended in children
with adrenal adenoma and carcinoma. Prolonged cortisol
excess causes suppression of the normal contralateral
adrenal. This mandates close monitoring for adrenal
insufficiency in the perioperative period. Unilateral
adrenalectomy is advised for benign cortical adenoma
and subtotal adrenalectomy for bilateral. Total
adrenalectomy can result in Nelsons syndrome
Endocrinology
characterized by enlargement of sella and hypermelanosis. Transsphenoidal resection of pituitary
adenoma is recommended for children with Cushing
disease. The success rate varies from 6680%. Pituitary
irradiation has been tried in surgical failure.
Adrenal carcinoma is highly malignant and has a high
rate of recurrence. Chemotherapy with mitotane or
cisplatin is ineffective in children with recurrence of the
disease. Medical management of childhood CS with
inhibitors of steroidogenesis (ketoconazole, cyproheptadine and mitotane) has been tried but is largely
disappointing.
HYPERALDOSTERONISM
Primary hyperaldosteronism due to increased adrenal
aldosterone production is extremely rare in children.
These include aldosterone producing adrenal adenoma,
familial primary hyperaldosteronism and much rarely
adrenal carcinoma. Secondary hyperaldosteronism
results from factors that activate reninangiotensin
system. The most common clinical features of primary
hyperaldosteronism are due to hypertension and
hypokalemic alkalosis manifesting as fatigue, muscle
cramps and weakness, polyuria, nocturia and poor
growth. This condition needs to be differentiated from
Bartter syndrome, in which plasma renin activity is
elevated with normal blood pressure.
Hyperaldosteronism should be managed with salt
restriction and antialdosterone agent, spironolactone.
PHEOCHROMOCYTOMA
Pheochromocytoma is a catecholaminesecreting tumor
which arises from the chromaffin cells of adrenal
medulla. It may arise from abdominal sympathetic chain,
periadrenal area, urinary bladder, thoracic cavity or
cervical region. It is rare in children and accounts for only
2 percent of cases of secondary hypertension. It usually
coexists with other syndrome or tumors such as
neurofibromatosis (von Recklinghausen disease and von
HippelLindau disease). Pheochromocytoma also forms
a part of the multiple endocrine neoplasia type II.
Clinical Features
Clinical features are due to hypersecretion of
catecholamines. These include hypertension, sustained
more often than paroxysmal. There may be associated
961
headache, palpitation, pallor, sweating, nausea,

vomiting, visual disturbances, polyuria and polydipsia.
Convulsions due to hypertensive encephalopathy may
occur.
Diagnosis
Demonstration of increased urinary excretion of
catecholamines and their derivatives confirms the
diagnosis. The predominant plasma catecholamine is
noradrenaline and the total urinary catecholamines are
more than 300 g/24 hours. Urinary excretion of
vanillylmandelic acid (VMA), which is a major
metabolite of catecholamine, is increased. Plasma renin
levels are elevated. Ultrasound, CT scan or MRI scans,
arteriography, 123IMIBG (metaiodiobenzylguanidine)
scintigraphy and vena caval samplings are used for
localization of the tumor. Often the tumors are multiple.
Management
Surgical removal of the tumor is the choice of treatment.
Preoperative alphablockade is done by administration
of phenoxybenzamine or prazocin. Recently calcium
channel blocking agent, nifedipine, has been tried with
some success.
BIBLIOGRAPHY
1. Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and
classification of Cushing syndrome: A consensus
statement. J Clin Endocrinol Metab 2003;88:5593602.
2. Bajpai A, Sharma J, Menon PSN. Practical Pediatric
Endocrinology, 1st edition. Jaypee Brothers Medical
Publishers (P) Ltd: New Delhi, 2003.
3. Desai MP, Menon PSN, Bhatia V (Eds). Pediatric
Endocrine Disorders, 2nd edition. Orient Longman,
Hyderabad. 2008;326398.
4. Findling JW, Raff H. Screening and diagnosis of Cushing
syndrome. Endocrinol Clin Metab North Am 2005;
34:385402.
5. Lindsay JR, Nieman LK. Differential diagnosis and
imaging in Cushing syndrome. Endocrinol Clin Metab
North Am 2005;34:40323.
6. Miller WL. The adrenal cortex. In Clinical Pediatric
Endocrinology, (eds) C Brook, P Clayton, R Brown. 5th
edition. Oxford: Blackwell Scientific. 2005;293351.
7. Moshang T Jr. Cushings disease, 70 years later. And the
beat goes on. J Clin Endocrinol Metab 2003;88:313.
8. Perry R, Kecha O, Paquette J et al. Primary adrenal
insufficiency in children: twenty years experience at the
Sainte-Justine Hospital, Montreal. J Clin Endocrinol
Metab 2005;90:324350.
962
9. Root AW, Shulman DI. Clinical adrenal disorders. In:

Pescovitz OH, Eugster EA, eds. Pediatric Endocrinology,
Mechanisms, Manifestations, and Management.
Philadelphia, PA: Lippincott, Williams and Wilkins;
2004;568600.
10. Shulman DI, Palmert MR, Kemp SF, for the Lawson
Wilkins Drug and Therapeutics Committee. Adrenal
11.
Insufficiency: Still a Cause of Morbidity and Death in

Childhood. Pediatrics 2007;119:e484e494
Storr HL, Chan LF, Grossman AB, Savage MO. Paediatric
Cushings syndrome: epidemiology, investigation and
therapeutic advances. Trends Endocrinol Metab
2007;18:16774. Epub 2007 Apr 6.
17.10 Diabetes Mellitus

INTRODUCTION
Diabetes mellitus is a common disorder of fuel
metabolism. In children, it is found most frequently due
to an absolute deficiency of insulin secretion, due to
destruction of the beta cells of the pancreatic islets. The
disease is associated with a number of short and longterm complications, many of which are linked with the
degree of blood glucose control. In addition, diabetes in
childhood and adolescence affects growth and puberty,
and often psychological wellbeing. Diabetes is best
managed by a team of personnel including a diabetes
nurse/educator, dietician and psychologist in addition
to the doctor.
CLASSIFICATION AND DIAGNOSTIC CRITERIA
Diabetes mellitus is not a single entity. It is a group of
disorders of varying etiology and pathogenesis, resulting
in the same metabolic syndrome. The old classification
by the World Health Organization categorized patients
as insulin-dependent and non-insulin-dependent. This
was replaced in 1997 by a classification based on etiology
(Table 17.10.1). By this classification, the typical insulindependent, ketosis-prone patient is classified as type 1
diabetes. The non-insulin-requiring, non-ketosis-prone,
usually obese patient seen during adolescence is
classified as type 2 diabetes. Pediatricians in India may
occasionally encounter an additional type of diabetes that
is due to a calcific chronic pancreatitis, which may
clinically be insulin-dependent or non-insulindependent, which is now be classified under diseases of
the pancreas. Another type of diabetes presentation seen
in developing countries is that of a non-obese patient
requiring insulin for glucose control but not exhibiting
ketosis when off insulin. This was earlier termed protein

deficient pancreatic diabetes (PDPD) by the WHO. This
terminology has largely been discarded now, as no direct
role of protein deficiency in the etiology of permanent
diabetes has been found. This entity has not found a place
in the new classification because its etiology is not clear.
TABLE 17.10.1: Etiological classification of diabetes mellitus
1. Type 1 diabetes
A. Immune mediated
B. Idiopathic
2. Type 2 diabetes
3. Other specific types
A. Genetic defects of beta cell function
HNF-1 alpha, 4 alpha and glucokinase (formerly MODY
3, 1 and 2)
Mitochondrial DNA.
B. Genetic defects in insulin action
Type A insulin resistance, leprechaunism, RabsonMendenhall syndrome, lipoatrophic diabetes.
C. Diseases of exocrine pancreas
Fibrocalcific pancreatopathy, cystic fibrosis, hemochromatosis .
D. Endocrinopathies
Cushing syndrome, pheochromocytoma, hyperthyroidism,
gigantism/acromegaly.
E. Drug or chemical induced
Pentamidine, glucocorticoids, phenytoin, thiazides,
diazoxide.
F. Infections
Congenital rubella, cytomegalovirus
G. Uncommon forms of immune-mediated diabetes
Stiffman syndrome, anti-insulin receptor antibodies.
H. Other genetic syndromes associated with diabetes
Down, Klinefelter, Turner, Wolfram, Friedreichs ataxia,
Laurence-Moon-Biedl, Prader-Willi, myo-tonic dystrophy.
4. Gestational diabetes mellitus
Endocrinology
TABLE 17.10.2: Diagnostic criteria for diabetes mellitus
1. Symptoms of diabetes plus random plasma glucose > 200
mg/dL (on two separate occasions if symptoms not typical
or hyperglycemia not unequivocal), or
2. Fasting plasma glucose > 126 mg/dL on two occasions, or
3. Two-hour plasma glucose > 200 mg/dL during oral
glucose tolerance test on two occasions (glucose load 1.75
gm/kg).
The cut-off limits for the diagnosis of diabetes mellitus

have also been lowered in the last decade (Table 17.10.2).
Most children with diabetes present with classical
symptoms, and hence need only two random blood sugar
values to confirm the diagnosis.
Only type 1 diabetes will be further discussed.
TYPE 1 DIABETES MELLITUS
Epidemiology
The prevalence of diabetes among school children (up
to 18 years of age) in USA is approximately 1 in 500.
Prevalence in migrant Indian children in the UK (0.54
per 1000) was found to be less than that of the local
childhood population (0.99 per 1000). Reliable prevalence
and incidence data from India are not available. The
incidence of new cases varies with geographical location,
being highest in Finland and Sweden (40 per 100,000
children per year) and lowest in Japan (less than 1 per
100,000 children per year). Boys and girls are equally at
risk. The incidence in European countries is increasing
at the rate of 3% per year.
Etiology and Pathogenesis
Type 1 diabetes is a chronic autoimmune disease
involving only the beta cells, with gradual loss of insulin
secretion. Patients have a genetic predisposition to the
disease, though only a few subjects so predisposed
develop the disease. It is thought that an environmental
factor is necessary to trigger the onset of autoimmunity.
Autoimmune destruction is a slow process, and the
decline in insulin production occurs over a period of
months to years, overt diabetes becoming manifest when
beta cell reserve is below 20 percent of normal.
Genetics of Type 1 Diabetes
The inheritance of diabetes is polygenic. In comparison
to a 0.6 percent lifetime risk (for a white Caucasian) to
963
develop diabetes, a sibling of a proband may be said to

have a 3 to 6 percent risk of developing diabetes, and an
offspring a 2 to 6 percent risk (with a diabetic father
conferring greater risk than a diabetic mother). The major
susceptibility loci are the human leukocyte antigen (HLA)
Class II genes, and the insulin gene. Two other recently
discovered loci are the CTLA 4 (Cytotoxic T-Lymphocyte
Antigen 4) and PTPN22 gene (protein tyrosine
phosphatase N22). In almost all races, including Indians,
HLA-DR3 and DR4 antigens are associated with
increased risk of type 1 diabetes, whereas HLA-DR15/
DQ6 confers protection. Further analysis has shown that
HLA-DQ region alleles confer even greater risk for type
1 diabetes. If position 57 of the beta chain of the DQ region
is occupied by the amino acid, aspartic acid, protection
against type 1 diabetes is conferred. Conversely, a nonaspartic acid residue at this position is associated with a
100-fold increased relative risk in white Caucasians. More
importantly, it is being recognised that genetic
susceptibility is associated not with particular DR or DQ
molecules but with an entire haplotype. However,
studies in identical twins with type 1 diabetes have
shown that the identical twin of a proband has only a 50
percent risk of developing type 1 diabetes, suggesting a
role for postnatal (environmental) factors.
Environmental Factors
Viruses especially coxsackie and other enteroviruses, are
the most commonly implicated environmental factor.
Evidences include seasonal differences in the incidence
of diabetes and episodes of viral infection frequently
preceding the onset of diabetes. However, the only viral
infection directly predisposing to diabetes is congenital
rubella infection, in which 20 percent of affected children
develop diabetes. Other proposed environmental agents
include the role of early weaning to cows milk (through
albumin/casein), toxins (e.g. nitrosamines) and stress.
Environmental factors may induce autoimmunity by
molecular mimicry or by directly stimulating cytokine
production.
Pathogenesis of Autoimmune Destruction
Numerous evidences exist for an autoimmune etiology
of type 1 diabetes. Diabetes is frequently associated with
conditions of known autoimmune etiology like
Hashimoto thyroiditis, pernicious anemia and Addison
disease. It is also associated with the presence of many
964
autoantibodies. About 80 to 90 percent of newly

diagnosed type 1 diabetes patients (30 to 40% in India)
have islet cell antibodies (ICA). A similar number is also
positive for antibodies against glutamic acid
decarboxylase (GAD), an enzyme present in the islet and
other neuroendocrine tissue. Anti-insulin autoantibodies
are present in 30 to 40 percent of newly diagnosed
patients. Studies in siblings of type 1 diabetes probands
have shown that 60 to 80 percent of first degree relatives
positive for more than 2 autoantibodies go on to develop
diabetes within 5 years.
Lastly, abnormalities in T lymphocyte function
exist in type 1 diabetes patients and animal models.
Experiments with animal models of type 1 diabetes have
shown that manipulation of the immune response can
enhance or decrease the development of diabetes, and
type 1 diabetes can be transferred by T cells.
With these evidences, a clearer picture of the
pathogenesis is emerging. Some crucial antigen(s) of the
beta cell, presented by the antigen presenting cells of the
immune system, are presented to specific T
lymphocytes in conjunction with specific HLA-D locus
molecules. The activation of T lymphocytes sets off a
series of responses including cytokine production, which
amplify the immune response, ultimately resulting in
beta cell destruction.
These evidences of the autoimmune nature of type 1
diabetes, together with the possibility, albeit imperfect,
of predicting which siblings of a proband will go on to
develop diabetes, have led to the commencement of
many trials (using insulin, nicotinamide, etc.) for the
prevention of type 1 diabetes. A discussion of these is
beyond the scope of this book. It may be said that all
trials for the prevention of type 1 diabetes are at best
experimental at present.
and growth hormone) aggravates hyperglycemia and

ketogenesis.
While lipolysis is caused by insulin deficiency,
enhanced oxidation of the fatty acids so produced is
induced by glucagon. Glucagon induces the carnitine
palmitoyl transferase system of enzymes, which
translocates fatty acids into mitochondria for beta
oxidation, and thus causes ketogenesis.
When blood sugar exceeds the renal threshold of 180
mg/dL, glycosuria, diuresis, electrolyte loss, dehydration
and hyperosmolality result. Untreated dehydration and
acidosis cause cerebral obtundation as well as circulatory
failure.
Pathophysiology
Diagnosis
Insulin acts mainly on three tissues: liver, muscle and

adipose tissue. It induces glucose-uptake, glycogen
synthesis and lipogenesis in the liver, and stops
gluconeogenesis. In muscle, insulin brings about glucose
uptake and oxidation, and glycogen synthesis. In adipose
tissue, glucose-uptake and lipid synthesis occur. Thus,
in diabetes mellitus, hyperglycemia results due to
glycogenolysis, gluconeogenesis, lipolysis and absence
of glucose uptake. Concomitant rise in the counterregulatory hormones (glucagon, epinephrine, cortisol
In a patient who presents with the classical symptoms of

polyuria, thirst and weight loss, the diagnosis of diabetes
is straightforward, and requires only the demonstration
of hyperglycemia. In a child with an accidental finding
of glycosuria, one must differentiate diabetes mellitus
from renal glycosuria or Fanconi syndrome. Ketonuria
can occur in starvation, and, in adolescents, after an
alcohol binge on an empty stomach. Both these
conditions will not be accompanied by hyperglycemia
and ketonemia will be mild (not positive in dilute serum).
Clinical Features
Diabetes in childhood typically presents with polyuria,
polydipsia, polyphagia, weight loss and weakness.
Ketoacidosis is heralded by vomiting, dehydration,
abdominal pain, deep and rapid (Kussmaul) respiration
and the fruity odor of acetone in the breath. Ketoacidosis
may mimic an abdominal surgical emergency. Severe
acidosis is accompanied by decreasing consciousness and
hypotension. The presence of fever is an important clue
to infection.
Laboratory findings include glycosuria, hyperglycemia, ketonemia and ketonuria. Leukocytosis may
be present without infection. Hypertriglyceridemia is
typical. Diabetic ketoacidosis (DKA) is usually
characterized by normal serum sodium, normal or
initially raised serum potassium, significant ketonemia
(serum ketone positive on a qualitative test even on 1:1
dilution), blood pH below 7.3 and bicarbonate below 15
mEq/L. The metabolic acidosis of DKA exhibits an
increased anion gap (>10 mmol), due to unmeasurable
anions of ketoacids.
Endocrinology
The child presenting with acidosis must be
differentiated from other causes of metabolic acidosis
with increased anion gap, like uremia, lactic acidosis and
salicylate poisoning. Every child presenting in a coma
must have a blood sugar and urine ketone test to detect
diabetic ketoacidosis.
965
Though total body phosphorus is also depleted in

DKA, its administration has not been shown to alter the
course of the patient, on critical evaluation of available
studies. Recent recommendations do not advise
phosphorus administration.
Alkali Therapy
MANAGEMENT
Management of diabetes mellitus includes treatment of
DKA, post-acidosis therapy in hospital and management
of diabetes at home.
Treatment of Ketoacidosis
Initial laboratory evaluation should include blood sugar,
blood and/or urine ketone, serum sodium, potassium,
chloride, bicarbonate, calcium, phosphorus, arterial
blood gas analysis, electrocardiogram, blood culture and
urine microscopic examination. The bladder should be
catheterized in comatose patients.
In mild DKA (with blood glucose below 500 mg/dL,
small urine ketones, mild dehydration and no acidosis),
the child can be given oral rehydration with appropriate
(sugar-free) fluid and insulin therapy started as below
(see Post-acidosis Insulin Therapy).
Treatment of Severe DKA
Fluid and Electrolytes
The child in DKA is usually moderately to severely
dehydrated. Therefore, the quantity of deficit fluid to be
replaced is 75 to 85 ml per kg of current weight. A rate of
10-20 ml per kg within the first hour helps establish
circulatory stability if needed. The remainder of the
deficit fluid is given over the next 48 hours, along with
the maintenance for the period.
Sudden introduction of hypo-osmolal fluids has been
implicated in the etiology of cerebral edema, a dreaded
complication of DKA. The most commonly used
approach in children is to start therapy with normal
saline, but to switch to half normal saline after the first
hour or after circulatory stability is achieved. Potassium
(40 mEq/L) should be added to the infusion as soon as
urine formation is ascertained, after the first hour of
fluids, as body potassium is severely depleted in DKA.
It may be temporarily delayed it there is evidence of
hyperkalemia on the electrocardiogram.
Unnecessary alkali therapy in DKA is dangerous. It can

precipitate cerebral edema by increasing central nervous
system acidosis, precipitating hypokalemia, shifting the
oxygen dissociation curve to the left and causing
alkalosis. Sodium bicarbonate may be indicated for
symptomatic hyperkalemia or if the blood pH persists
at < 6.9 after the first hour of rehydration, with
cardiovascular instability. The dose to be infused is
calculated by the formula: (ml of sodium bicarbonate =
0.15 base deficit kg body weight). The amount
(usually 40 ml) is never given as a bolus, but added to a
0.5 N saline infusion over 2 hours. Alkali therapy should
be stopped when pH is > 7.0.
Insulin Therapy
The continuous low-dose insulin infusion is the method
of choice for treating children with DKA. Regular insulin,
0.1 units per kg, is given as a continuous normal saline
infusion at the rate of 0.1 units per kg per hour (recent
recommendations do not advise an insulin bolus for
children). The goal is to slowly decrease blood sugar by
50 to 100 mg/dL every hour. The infusion of insulin is
stopped only when acidosis has normalized, which
occurs only after normalization of hyperglycemia.
Therefore, when blood glucose decreases to 250 to 300
mg/dL, 5 percent dextrose is added to the intravenous
fluid infusion.
After correction of acidosis (which may take 24 hours
or longer in severe DKA), the child is ready to be started
on subcutaneous insulin therapy. An initial dose (0.2 to
0.4 units per kg) of regular insulin is given, half an hour
after which the insulin infusion is stopped and the child
allowed to eat. Such a regimen of insulin plus meal is
carried out every 6-8 hours until the child can be reliably
predicted to eat, after which twice daily doses of regular
(plain) plus intermediate-acting (NPH) insulin before
breakfast and dinner are started, with a lunch time dose
of plain insulin if needed.
966
Monitoring During DKA
Subcutaneous Insulin Therapy
Clinical parameters like vital signs, hydration, sensorium,

pupils, urine output, fluid infused, insulin infusion rate,
etc. must be monitored every hour and a flow sheet
should be carefully maintained. Capillary blood glucose
by fingerprick should be done at the bedside every hour
initially and later every 2 hours. Serum sodium,
potassium and bicarbonate should be measured every 4
hours initially and later 6 hourly. Urine ketones, serum
phosphorus and calcium may be done every 8-12 hours.
Urine ketones may seem to worsen or persist for long,
despite clinical improvement. This is because with insulin
therapy, betahydroxy-butyrate, an unmeasured ketone
present in larger quantities in DKA, is converted to
acetone and acetoacetate, the measured ketones. This
should not be interpreted as indicative of worsening.
Subcutaneous insulin therapy should be started when

acidosis subsides. A mixture of regular and intermediateacting (NPH) insulin is given twice a day, half an hour
before breakfast and dinner. This is the so-called splitmix regimen. The total daily dose (0.5 to 1.0 units per kg)
is roughly divided into two-thirds to be given before
breakfast and one-third before dinner. Two-thirds of each
dose should consist of NPH insulin, and one-third,
approximately, of regular insulin. These are just initial
guidelines. From the next day, doses should be titrated
according to blood sugar responses obtained the previous
day. The addition of a plain insulin dose at lunchtime is
useful for better control of blood sugars.
Bovine insulin, previously the least expensive insulin
available in India, is now no longer available. Insulins
available in India contain 40 units per ml or 100 units
per ml. Care must be taken to administer U40 insulin
only with a U40 syringe and likewise U 100 insulin must
be matched with a U 100 syringe. The two insulins,
regular and NPH, can be drawn into the same syringe,
first regular, followed by NPH, to be given as a single
subcutaneous injection. Disposable insulin syringes have
clearer markings and less dead space than glass ones.
Suitable sites for insulin injection are the back of upper
arm, front of thigh, abdomen and buttocks. The injection
site must be different each time, to avoid lipodystrophy.
Insulin is ideally stored in a refrigerator (never frozen).
Families who do not have the facility can store it in a
damp cloth in the coolest portion of the house. In addition
to insulin, analogs of insulin are now available, which
have unique features providing greater flexibility and
lower chances of hypoglycemia. Insulin lispro and aspart,
which have minor amino acid differences from insulin,
have a quicker onset and shorter duration of action than
regular insulin. This makes them suitable for use in
toddlers, who cannot be depended upon to eat at a
particular time, as the injection can be given after the
child has actually started eating. The analogs glargine
and detemir are poorly soluble at the pH of subcutaneous
tissue and hence are peakless. They provide a basal 24
hour insulin in blood, without the extent of hypoglycemia
found with NPH. Unfortunately, these analogs cost
significantly more than regular and NPH insulins.
Complications of DKA
Cerebral edema: Clinically symptomatic cerebral edema
occurs in 1 to 2 percent of children with DKA and has a
high mortality of 50 percent. It usually occurs during
insulin therapy, when the child actually appears to be
responding to treatment. The etiology is not clear, but
has been linked to too rapid correction of hyperosmolality, excessive use of alkali, high initial blood urea
and greater hypocapnia, and lack of rise of serum sodium
during treatment. Early signs include change in
sensorium (drowsiness or agitation), headache, vomiting,
comparative decrease in heart rate or increase in blood
pressure. Pupillary changes, papilledema and upgoing
plantars are late signs. Prompt therapy with mannitol
(without necessarily waiting for a CT scan to confirm
the diagnosis) is indicated.
Others: Acute gastric dilatation or erosive gastritis,
vascular thromboses and respiratory distress syndrome.
POST-ACIDOSIS THERAPY
After stabilization of the acidotic state, the following
issues must be addressed: (i) management of
precipitating factor for DKA, like infection or emotional
stress, (ii) subcutaneous insulin therapy, (iii) nutrition,
(iv) education of the family for home management of
diabetes, and (v) psychological and social support for
the patient and the family.
Endocrinology
Nutrition
The ideal diet for a child with diabetes is nothing but a
healthy meal plan for any member of the family, with
the additional requirement of avoidance of simple sugars.
The total daily calories should be calculated from age,
weight, pubertal status and recommended dietary
allowance calculations, tempered with the knowledge
of the childs dietary pattern before the illness. A rough
guideline is 1000 calories at 1 year age, and additional
100 calories per year of age after that, up to puberty.
Approximately 55 to 65 percent of calories should derive
from carbohydrates, 15 percent from protein and 20 to
30 percent from fat. Foods rich in fiber (whole pulses,
whole grain cereal, vegetable, and fruit) should be
encouraged as they have a low glycemic index. Foods
rich in fat, especially saturated fat, are to be avoided. The
days meal plan should be divided into 3 meals
(breakfast, lunch and dinner) and 2 to 3 snacks
(midmorning, evening and bedtime). However, these
schedules can be tailored according to the individual
needs of the child and family, with insulin doses adjusted
accordingly. It must be borne in mind that the patient is
a child, for whose emotional wellbeing we must accept
some flexibility in the dos and donts of dietary
management. Hence, items with simple sugar or excess
fat must be allowed on special occasions like birthdays
or festivals.
Monitoring
The importance of excellent blood glucose control in
minimizing, preventing or delaying long-term
complications of diabetes is now well-established. To this
end, it is essential for blood sugars to be monitored
frequently so as to take steps to prevent or treat high
blood sugars.
Home Monitoring
With the advent of glucose oxidase strips, blood glucose
can be measured at home using strips with a reflectance
meter. Urine glucose (positive only when blood glucose
rises above 180 to 200 mg/dL) is less informative than
blood glucose testing. Unfortunately, blood glucose
testing is expensive. A combination of blood and urine
glucose testing schedules can be used.
Ideally, capillary blood glucose should be tested daily
fasting, pre-lunch, pre-dinner and at bedtime. Post-meal
sugars may be tested on one or two days a week, and a 1
967
or 2 a.m. test to rule out nocturnal hypoglycemia, once

in 2 weeks. Blood glucose should also be tested to confirm
symptoms of hypoglycemia, whenever possible. A high
blood sugar before a meal may be dealt with by taking a
small additional dose of regular insulin. When blood
sugar is persistently high (> 300 mg/dL) and on days of
fever/other sickness, urine must be tested for ketones.
This rigorous schedule of testing requires a motivated
patient and supportive family interested in excellent
blood glucose control. The pediatrician must be careful
to individualize these instructions. Table 17.10.3
describes the blood glucose goals for intensive therapy
as well as conventional therapy.
Those who test urine sugar must do so on a second
void specimen. Urine sugar testing by test strips does
not work out costlier than using Benedicts reagent, and
due to far greater convenience, is likely to encourage
compliance.
Laboratory Monitoring
Home glucose monitoring does not give an integrated
picture of blood glucose control over the long-term. This
deficiency is made up by performing glycosylated
hemoglobin (HbA1c) measurement once in 3 months. It
represents the fraction of hemoglobin to which glucose
has got attached, over the lifespan of a red blood cell.
The normal value in people without diabetes is 4 to 6
percent. A value of up to 7 percent in a patient indicates
excellent blood glucose control; a value between 7 and 8
percent is regarded as good, and greater than 8 percent
indicates scope for much improvement.
Education of the Patient and Family
Blood sugar patterns in diabetes are not necessarily stable
from day to day. Variations are brought about by changes
in exercise and meal pattern, emotional status, etc. Thus,
successful therapy of diabetes is not possible without the
patient and/or family assuming responsibility for day to
TABLE 17.10.3: Goals of conventional and intensive therapy
Conventional therapy
HbA1c 7.58.5 percent
Pre-meal blood glucose 120160 mg/dL
Absence of polyuria and ketonuria
Intensive therapy
HbA1c 6.07.0 percent
Pre-meal blood glucose 80120 mg/dL
Post-meal blood glucose < 180 mg/dL
968
day care. This requires that the family be educated in

diabetes management techniques. Diabetes management,
as well as teaching, is best carried by a team consisting of
the doctor, diabetes nurse/educator, dietician,
psychologist and social worker. In addition to insulin
therapy, nutrition, monitoring, and hypoglycemia,
patients must be taught the importance of exercise as well
as management during days of unrelated sickness.
Perhaps the single most important message for patients,
in relation to sick days, is that insulin must not be stopped.
On the other hand, insulin requirement may actually rise
during illness.
Complications of Diabetes
Hypoglycemic Reaction
Mismatch between insulin dose on the one hand, and
meal and exercise on the other, results in hypoglycemia
quite frequently in the life of a child with diabetes.
Defined as a blood sugar of < 60 mg/dL, it is heralded
by adrenergic symptoms like sweating, pallor, trembling
and tachycardia. Patients are taught to recognize these
symptoms and institute treatment (see below). If
unrecognized, blood glucose levels may drop further,
leading to neuroglycopenic symptoms like drowsiness,
confusion, coma or seizures. Most often, though, the
release of counter-regulatory hormones at a level of 55
to 60 mg/dL leads not only to the warning (adrenergic)
signs, but also to a rebound rise in blood glucose.
Treatment of Hypoglycemia
It is always advisable to first confirm the symptoms of
hypoglycemia with a blood sugar test. For immediate
rise in blood sugar, simple sugar (5 to 10 gm) in the form
of sugar, glucose, fruit juice or a carbonated drink must
be taken. In addition, a small snack of protein plus
carbohydrate must be eaten. The unconscious child with
hypoglycemia can be treated at home with 0.5 mg (1.0
mg in the adolescent) of glucagon given subcutaneously.
If glucagon is not available, the child should receive
intravenous glucose in the nearest emergency center.
After an episode of severe hypoglycemia is treated,
the family must assess the reasons for its happening.
Preventable factors like missed meals or exercise
uncompensated with food, must be recognized.
Necessary reductions in insulin dosage must be

instituted, if hypoglycemia shows a recurring pattern.
Long-term Complications
Microvascular (affecting the eye, kidneys and nerves) and
macrovascular (causing cerebrovascular and coronary
heart disease) complications are responsible for longterm morbidity and mortality in diabetes mellitus.
Growth retardation and pubertal delay are additional
issues in childhood and adolescent diabetes. Pathogenetic
mechanisms implicated include glycosylation of proteins,
abnormalities in the polyol pathway, growth factors,
platelet function defects, hyperinsulinemia, and free
radical induced damage. While the pathogenesis of each
is not yet perfectly clear, large follow-up studies like the
diabetes control and complications trial (DCCT) have
clearly established a strong correlation between poor
blood glucose control and frequency of complications.
Thus, the onus is on all those who care for children with
diabetes, to encourage the best possible metabolic control.
Intensive insulin therapy aimed at maintaining near
normal blood sugars is however, associated with a 3 times
greater risk of severe hypoglycemia (coma/convulsions)
than conventional insulin therapy. Therefore, it is not
advisable in young children (particularly below 7 years
of age), or for those who do not have constant access to
emergency care.
Complications of diabetes usually do not set in before
a duration of diabetes of at least 3 to 5 years. Background
retinopathy occurs in almost 90 percent after 15 years
duration, but vision threatening (proliferative) retinopathy occurs in only 25 percent patients after 25 years.
Similarly, end-stage renal disease occurs in 15 to 20
percent of patients after a similar duration. These figures
have almost halved in the last 3 decades, the fall in
complication rate being attributable to improved blood
glucose control due to availability of home blood glucose
testing strips. It has been hitherto believed that
complications do not occur in the prepubertal diabetic
child, irrespective of duration of diabetes. However,
recent prospective studies indicate that this may not be
entirely true, and that prepubertal children must be
screened for complications after a duration of diabetes
of 3 to 5 years.
Endocrinology
BIBLIOGRAPHY
1. Alemzadeh R, Wyatt DT: Diabetes mellitus. In Behram
RE, Kliegman RM, Jenson HB, et al (Eds): Nelson
Textbook of Pediatrics (17th ed). Philadelphia 2004;
1947-72.
2. American Diabetes Association: Clinical practice
recommendations Updated yearly and available free of
cost at www.diabetes.org
3. Atkinson MA, Maclaren NK. The pathogenesis of insulindependent diabetes mellitus. N Engl J Med 1994;
331:1428-36.
4. Daneman D. Type 1 diabetes. Lancet 2006;367:847-58.
5. Diabetes Control and Complications Trial. The effect of
long-term intensified insulin treatment on the
development of microvascular complications of diabetes
mellitus. N Engl J Med 1993;329:304-9.
969
6. Dunger DB, Sperling MA, Acerini CL, et al: ESPE/LWPES

consensus statement on diabetic ketoacidosis in children
and adolescents. Arch Dis Child 2004;89:188-94.
7. Glaser NS, Barnett P, McCaslin I, Nelson D et al: Risk
factors for cerebral edema in children with diabetic
ketoacidosis. The Pediatric Emergency Medicine
Collaborative Research Committee of the AAP. N Eng J
Med 2001;344:264-69.
8. Rachneil M, Perlman K, Daneman D. Insulin analogues
in children and teens with type 1 diabetes: advantages
and caveats. Pediatr Clin North Am 2005;52:1651-75
9. Report of the American Diabetes Association expert
committee on the diagnosis and classification of diabetes
mellitus. Diabetes Care 1997;20:1183-97.
10. Rosenbloom AL, Schatz DA, Krischer JP et al: Prevention
and treatment of diabetes in children. J Clin Endocrinol
Metab 2000;85:494-522.
18.1 Basic Genetics for Genetic Counseling: ML Kulkarni ..................................................................................................................... 972

18.2 Common Genetic Disorders: ML Kulkarni ......................................................................................................................................... 989
18.3 New Genetics and Advances in Genetics: ML Kulkarni ................................................................................................................ 1013
18.4 Inborn Errors of Metabolism: ML Kulkarni ....................................................................................................................................... 1029
972
18.1 Basic Genetics for Genetic Counseling

ML Kulkarni
INTRODUCTION
Genetic diseases are ubiquitous, affecting all human
beings wherever they live. They place considerable health
and economic burden not only on affected people and
their families but also on the community. As more
environmental diseases are successfully controlled, those
that are wholly or partly genetically determined are
becoming more important.
Despite a general fall in perinatal mortality rate, the
incidence of lethal malformations in newborn infants
remains constant. Between 2 to 5 percent of all liveborn
infants have genetic disorders or congenital malformations. Many common diseases in adult life also have a
considerable genetic predisposition, including coronary
heart disease, diabetes, and cancer.
The prevalence of various genetic diseases is given in
Table 18.1.1.
TABLE 18.1.1: Types and prevalence of genetic disorders
Types of genetic diseases
Estimated
prevalence per
1000 pop.
Single gene
Autosomal dominant
Autosomal recessive
X-linked recessive
Chromosomal abnormalities
Common disorders with appreciable
genetic component
Congenital malformation
20
Total
38-51
2-10
2
1-2
6-7
7-10
In general, human diseases may be seen as being on a

spectrum from those diseases which are exclusively genetic
to those which are exclusively environmental. Conditions
like Duchenne muscular dystrophy and Down syndrome
are purely genetic in origin, whereas scurvy and
tuberculosis are purely environmental. Between the
extremes, are many common diseases like diabetes
mellitus, ischemic heart disease and congenital malformations in which both genetic and environmental factors
are involved and these conditions are referred to as
multifactorial.
With emphasis on small family size, people are more

concerned about total wellbeing of children and in a
situation like this, even rarer genetic disorders should
cause concern to medical people. Further in south India
where inbreeding has been practiced for more than 3500
years, the load of genetic disorders due to autosomal
recessive genes is high and needs greater emphasis on
prevention and early treatment of these disorders. The
younger medical graduates should walk into the 21st
century armed with basic and practical knowledge of
common genetic disorders.
GENETIC COUNSELING
Definition
Genetic counseling has been defined as an educational
process that seeks to assist affected and/or at risk
individuals to understand the nature of the genetic
disorder, its transmission and the options available to
them in management and family planning. The counselor
offers investigations, options and support whereas the
consultant (the person who seeks the advice) makes his
own decision which is known as non-directive counseling.
Indications for Genetic Counseling
Conventional
(i) A diagnosed genetic disease, (ii) Detection of carrier
state in family members for Mendelian disorders, (iii)
Investigation and diagnosis of possible genetic disease,
(iv) Diagnosis of mental handicap or dysmorphic child,
(v) Diagnosis of malformation in neonates or stillbirths,
(vi) Genetic investigation of recurrent pregnancy loss, (vii)
Genetic management of high risk pregnancies, (viii) Interpretation of abnormal prenatal tests, (ix) Environmental
exposure to drugs, infections, radiation, (x)
Consanguineous marriages, (xi) Advanced maternal age.
In Modern Era
(i) Involvement of the members of the family for genetic
linkage or gene tracking studies, (ii) Counseling those
patients on genetic register for long-term contact and
support with modern information available for those
diseases, e.g. Duchenne muscular dystrophy.
Genetics
TABLE 18.1.2 Classification of genetic disorders
Classification of genetic disorders
A. Genetic disorders due to traditional modes of inheritance.
i. Mendelian disorders: (Single gene)
Autosomal dominant (AD)
Autosomal recessive (AR)
X-linked recessive (XLR)
X-linked dominant (XLD)
ii. Chromosomal disorders:
Numerical abnormalities
Structural abnormalities
iii. Multifactorial disorders
iv. Somatic cell mutations
B. Genetic disorders due to nontraditional modes of inheritance.
i. Mosaicism
ii. Genomic imprinting
iii. Uniparental disomy (UPD)
iv. Inheritance of unstable mutations
v. Cytoplasmic/mitochondrial inheritance
A brief review of basic principles of genetics is reviewed

in the following paragraphs that are relevant for genetic
counseling. Table 18.1.2 gives the types of genetic disorders
and their classification.
973
Mendelian (Single Gene) Disorders

Disorders caused by a defect in a single gene follow the
patterns of inheritance described by Mendel. Individual
disorders of this type are often rare but are important
because they are numerous (3000-4000 single gene traits
have been listed). Risks within an affected family are
usually high and are calculated by knowing the mode of
inheritance and details of the family pedigree. Table 18.1.3
summarizes the concept of single gene disorders.
Autosomal Dominant Disorders
The disorders have the following features:
a. Normally, there is a pair of genes (alleles) for each
function that are located at same loci on homologous
chromosomes. A single mutant gene is dominant if it
causes an evident abnormality, i.e. in the heterozygous state, the disease manifests itself.
b. The abnormal gene is passed from one generation to
another in a vertical fashion, i.e. parents and patients
are similarly affected (Fig. 18.1.1A).
TABLE 18.1.3: Normal and major mutant gene inheritance (Mendelian inheritance)
(adapted from Smiths Recognizable Pattern of Human Malformation)
Normal
Except for the XY, there is a pair of genes for each function, located at the same loci on sister chromosomes.
One pair of normal genes is represented as dots on a homologous pair of chromosomes
Dominant
A single mutant changed gene is dominant if it causes an evident abnormality. The chance of inheritance of the
mutant gene () is the same as the chance of inheriting a particular chromosome of the pair: 50 percent
Heterozygous
recessive
A single mutant gene is recessive () if it causes no evident abnormality, the function being well covered by
the normal partner gene (allele). Such an individual may be referred to as a heterozygous carrier
Homozygous
recessive
When both genes are recessive mutant (), the abnormal effect is expressed. The parents are generally
carriers, and their risk of having another affected offspring is the chance of receiving the mutant from one
parent (50%) times the chance from the other parent (50%), or 25 percent for each offspring
An X-linked recessive will be expressed in the male because he has no normal partner gene. His daughters,
receiving the X, will all be carriers, and his sons, receiving the Y, will all be normal
X-linked recessive
An X-linked recessive will not show overt expression in the female because at least part of her active Xs will
contain the normal gene. The risk for affected sons and carrier daughters will each be 50 percent
974

syndrome 30 percent; in Apert syndrome 96 percent;
in Neurofibromatosis 40 percent.
h. Examples of autosomal dominant disorders: achondroplasia, Huntingtons chorea, Marfan syndrome,
acute intermittent porphyria, myotonic dystrophy,
adult polycystic kidney disease, Noonan syndrome,
neurofibromatosis, tuberous sclerosis, epidermolysis
bullosa (some forms), osteogenesis imperfecta (some
forms), fascioscapulohumeral dystrophy, polyposis
coli, familial hypercholesterolemia.
i. Homozygosity i.e. the offspring getting double dose of
the defective gene from both parents is rare but when it
occurs, the disease is very severe, e.g. in homozygous
achondroplasia the infant dies in the neonatal period
(Fig. 18.1.ID).
Autosomal Recessive Disorders
Figure 18.1.1A to D: AD disorders: (A) Vertical transmission,

(B) 50% risk at each pregnancy, (C) Lack of penetrance in *,
(D) Homozygosity
c. If one of the parents is affected the risk of recurrence is

50 percent in each subsequent pregnancy (Fig. 18.1.IB).
d. Both sexes may be affected.
e. The degree of expressivity may vary in the same family,
e.g. in a full blown picture, the individual with Marfan
syndrome may have defects of the skeletal system,
cardiovascular system and of the eye, but in a family
of Marfan syndrome, the manifestations may vary in
different individuals.
f. The unaffected members of the family will not transmit
the disease. Except in a rare situation there can be lack
of penetrance, wherein the person carries the gene but
disease is not manifested in him, but has transmitted
to his offspring (Fig. 18.1.1C).
g. Spontaneous new mutations should be suspected if a
dominantly inherited condition is seen in a patient
whose parents are normal. Proportion of patients
affected by new mutations varies in autosomal
dominant disorders, e.g. in achondroplasia, 80 percent
of cases are due to fresh mutations; in Marfan

a. Autosomal recessive disorders occur in a person
whose both healthy parents carry the same recessive
gene.
b. The pattern of transmission is called horizontal
because the siblings are affected and the parents are
phenotypically normal. However, they are genotypically abnormal, i.e. heterozygous carriers
(Fig. 18.1.2A).
c. If both parents are carriers, the risk of having an
affected child is 25 percent for each pregnancy and
risk for producing a carrier child is 50 percent for each
pregnancy (Fig. 18.1.2B).
d. Males and females are equally affected.
e. Parental consanguinity is often found in autosomal
recessive traits (Fig. 18.1.2C).
f. All children of an affected individual will be carriers if
the partner is normal.
g. Heterozygous carriers though phenotypically normal
may have some biochemical abnormalities, e.g.
hemoglobinopathies, Tay-Sachs disease, etc.
h. Examples of autosomal recessive disorders: Congenital
adrenal hyperplasia, cystic fibrosis, galactosemia,
Friedreichs ataxia, epidermolysis bullosa (some
forms), diastropic dwarfism, hemochro-matosis,
homocystinuria, Hurler syndrome, Laurence Moon
Biedl syndrome, oculocutaneous albinism, phenylketonuria, sickle cell disease, Tay-Sachs disease,
thalassemia.
Genetics
975
Figures 18.1.3 A and B: XLR disorders: (A) Oblique transmission, and (B) Boys-50% risk affected, girls-50% risk carrier
Figures 18.1.2 A to C: AR disorders: (A) Horizontal transmission, (B) 25% risk, and (C) Consanguinity in AR (affected
marrying a carrier
X-Linked Recessive Disorders

These disorders have the following features:
a. In X-linked recessive conditions only males are affected
as there is no corresponding allele (Fig. 18.1.3A). All
his daughters will be carriers as they receive abnormal
X from father.
b. An X-linked recessive trait will not manifest in females
as the other X contains normal partner gene. Fifty
percent sons will be affected and 50 percent daughters
will be carriers when the mother is a carrier (Fig.
18.1.3B).
c. Normal sons cannot transmit the disease.
d. The pattern of inheritance here is called oblique as
only males on the maternal side are affected, i.e.
maternal uncles, patients mothers maternal uncles
and mothers sisters sons (Fig. 18.1.3A).
e. Females may be affected if an affected male marries a
carrier female or in Turner syndrome where there is
only one X (45, X).
f. Fresh mutations are known.
g. Carriers may have biochemical abnormalities, e.g.

increased CPK levels in Duchenne muscular dystrophy.
h. Examples of XLR conditions: Hemophilia A, B;
Duchenne muscular dystrophy, Becker muscular
dystrophy, anhidrotic ectodermal dysplasia, color
blindness, Fabrys disease, glucose-6-phosphate
dehydrogenase deficiency, Hunter syndrome, LeschNyhan syndrome, Menkes syndrome, ocular albinism.
X-linked dominant Disorders
These disorders have the following features:
a. These disorders manifest even in XX females as it is a
dominant gene (Fig. 18.1.4).
b. The gene is transmitted in families in the same way as
X-linked recessive genes, giving rise to an excess of
affected females.
c. In some disorders the condition is lethal in hemizygous
males. In this case there will be fewer males than
expected in the family, all of whom will be healthy,
and an excess of females, half of whom will be affected.
d. There is no male to male transmission in this pattern
of inheritance.
Examples of XLD disorders: Incontinentia pigmenti,
orofaciodigital syndrome, hypophosphatemic familial
vitamin D resistant rickets.
976
Figure 18.1.4: XLD disorders
Figure 18.1.6: X and Y chromosomes with banding

patterns and idiogram
Figure 18.1.5: Y-linked disorders
Y-linked disorders are rare and cause minor phenotypic

features. Only males are affected who get their abnormal
genes from their father (Fig. 18.1.5). Examples: Porcupine
skin, hairy pinna, webbed toes and frontal baldness. Like
surname, the trait is transmitted only to sons. Here the
disorder is transmitted father to son like surname.
Chromosomal Disorders
The correct chromosome complement in humans was
established in 1956, and the first chromosomal disorders
(Down, Turner, and Klinefelter syndromes) were defined
in 1959. Since then refinements in techniques of performing
and examining samples have lead to the description of a
number of disorders that are due to chromosomal
abnormalities.
Chromosomes (chromos = coloured; soma = body), are
thread like structures within the nucleus of the cell that
have special affinity for certain stains.
The chromosomes are package materials for DNA that
carry hereditary information. There are 46 chromosomes
in the nucleus of each somatic cell (diploid number),
whereas mature germ cell, i.e. ovum and sperm contain 23
chromosomes (haploid number).
The 46 chromosomes in somatic cell, are organized
into 23 pairs. The paired chromosomes responsible for
sex-determination are known as sex chromosomal pair;

these are XX in females and XY in males (Fig. 18.1.6). The
22 pairs of chromosomes other than sex chromosomes are
known as autosomes. One chromosome in each pair
comes from mother and the other from the father.
Each chromosome has a short arm designated as p
and a long arm q, both arms are joined by a constriction
known as a centromere C (Fig. 18.1.7). The types of
chromosomes are metacentric (centromere is in the
middle), submetacentric (centromere towards the short
arm) and acrocentric (with secondary constriction and
satellites).
Each chromosome can be identified by light microscopy with staining technique that give banding features
specific for each chromosome (Fig. 18.1.6). High resolution
banding techniques help detection of minor structural
abnormalities.
Mitosis, occurs in dividing somatic cells from
fertilization onward, and it is the process whereby the
genetically identical daughter cells are generated from a
cell (Fig. 18.1.8). During meiosis (Fig. 18.1.9), which is the
nuclear division giving rise to gametes, recombination
occurs between homologous parental chromosomes. The
exchange of chromosomal material leads to the separation
of genes originally located on the same chromosome, and
gives rise to genetic variation within families.
The great majority of chromosomal disorders have an
extremely low risk of recurrence in a family. Chromosomal
Genetics
977
Figure 18.1.7: Structure and types of chromosomes
Figure 18.1.8: Human mitosis
Figure 18.1.9: Human meiosis
aneuploidies have a relation with maternal age.

Recurrence risks for various chromosomal disorders are
calculated based on empiric risk figures available. These
risk figures are calculated from the actual study of the
population.
Multifactorial Disorders
i. Nearly 60 percent of birth defects are due to this kind
of inheritance. Here, the abnormality is as a
consequence of minor differences at many gene loci,

no one of which may be held totally responsible for
the abnormality. These disorders are influenced
strongly by environmental factors, e.g. congenital
dislocation of the hip is more common in breech
deliveries.
ii. Recurrence risks are much less compared to single
gene disorders. The risk of same type of defect in
offspring of unaffected parent is around 2 to 5 percent
and this is 20 to 40 times the risk for general
population.
978
iii. Rarer the disorders, lower the recurrence risk,

iv. More severe the degree of structural defect, greater is
the recurrence risk from the same.
v. The risk increases with the number of affected
members.
vi. When there is a marked sex difference in incidence,
the risks are greater when the affected individual is
of the rarely affected sex. Ex: In congenital hypertrophic pyloric stenosis, when a female child is
affected, recurrences are very high in the family.
vii. Risk is less for distant relatives.
viii. Examples of multifactorial disorders are schizophrenia, asthma, cleft lip and palate, coronary heart
disease, hypertension, neural tube defects and
dislocation of hip.
Somatic Cell Mutations
Some cancers can be inherited as simple Mendelian traits,
with clear patterns of transmission, this is the exception
rather than the rule. Even though most cancers involve
quite substantial changes in the genetic material, such
mutations are somatic and there is no risk to further
generations.
GENETIC DISORDERS DUE TO NONTRADITIONAL
MODES OF INHERITANCE
Some genetic traits are not determined by an equal genetic
contribution from both parents, and disorders that were
previously thought to be inherited on a Mendelian fashion
are now being assigned alternate genetic mechanisms.
These nontraditional modes of inheritance include: (a)
mosaicism, (b) genomic imprinting, (c) uniparental disomy,
(d) inheritance of unstable mutations, (e) cytoplasmic
inheritance (mitochondrial inheritance).
Mosaicism
Somatic mosaicism is the term used to describe the finding
of two different cell lines in one individual that are derived
from a single zygote (i.e. coming from a single egg and
sperm). It occurs as a postzygotic event (after fertilization).
The mosaicism may be for (i) chromosomal abnormalities
or (ii) single gene mutations.
Chromosomal Mosaicism
It has been recognized in cultured lymphocytes of patients
with chromosomal aneuploidy syndromes.
Example: (i) Down syndrome: 1 to 2 percent of cases are

mosaic for trisomy 21. (ii) Turner syndrome: 30 to 40 percent
of cases are mosaics with two cell lines 45X/46 XX and/
or 45 X/46 XY, (iii) triploid phenotype: lethal, (iv) diploid/
triploid phenotype: IUGR, dysmorphism and mental
retardation, (v) Pallister-Killian syndrome: due to
mosaicism for isochromosome 12p, characterized by
mental retardation, coarse facies, pigmentary skin
anomalies and cardiovascular anomalies, (vi) hypomelanosis of Ito characterized by pigmentary abnormalities of the skin (hypopigmented whorls), ocular,
dental, musculoskeletal and central nervous system
abnormalities.
Single Gene Mosaicism
Somatic mosaicism for single gene mutations.
Example: McCune-Albright syndrome (MAS) is a sporadic
disorder characterized by polyostotic fibrous dysplasia,
cafe-au-lait pigmentation, sexual precocity, and
hyperfunction of multiple endocrine glands. Recent
research has shown that MAS is due to mutations in the
stimulatory G protein of adenyl cyclase.
Germline Mosaicism
Germline mosaicism refers to the presence of mosaicism
in the germ cells found in the gonads. The mosaicism may
be for chromosomal abnormality or a singlegene mutation.
Germ line mosaicism has been found in Duchenne
muscular dystrophy, chronic granulomatous disease and
osteogenesis imperfecta.
Genomic Imprinting (Fig. 18.1.10)
During the last decade, several new mechanisms of genetic
inheritances have been recognized and one such is genomic
imprinting. For many years it was thought that the
expression of the gene is the same whether it came from
father or mother. Genomic imprinting means that the
expression of the gene depends on the parent of origin.
The genes are modified during gametogenesis and as a
result either inactivated or activated. The modification
mechanism is not yet understood but methylation of genes
may be an important mechanism.
Two best known examples for genomic imprinting are
Prader-Willi syndrome and Angelman syndrome. PraderWilli syndrome is characterized by neonatal hypotonia
with subsequent hyperphagia and obesity. Angelmans
Genetics
979
Figure 18.1.10: Paternal and maternal imprinting
syndrome (Happy Puppet Syndrome) is characterized by

mental retardation, characteristic movements (ataxia or
puppet like gait) and sociable character often with bursts
of laughter. Both disorders are due to deletion in the
chromosome 15q 11-13 region. If the deletion is inherited
from the father, Prader-Willi syndrome will result and if
the deletion is inherited from the mother it results in
Angelmans syndrome.
There are several other examples for imprinted gene
like Beckwith-Wiedemann syndrome and transient
neonatal diabetes mellitus.
Uniparental Disomy
An individual inherits a pair of homologous chromosomes, one from the father and the other from the mother.
Recent DNA technology has revealed that an individual
may inherit both homologous chromosomes from only one
of his parents and this situation is called as uniparental
disomy. This is possible because of an error in either stages
of meiosis.
This type of inheritance has been shown to be the cause
of a father with hemophilia having an affected son and of
a child with cystic fibrosis being born to a couple in which
only the mother was a carrier. It is to be noted that sons of
a hemophilic father are normally not affected and a child
will be born with cystic fibrosis only when both the parents
are carriers for the abnormal gene. Uniparental disomy is
also responsible for a rare overgrowth syndrome known
as Beckwith-Wiedemann syndrome.
Unstable Mutation (Triplet Nucleotide Repeats)
One of the examples of unstable mutation or triplet
nucleotide repeats is Fragile X syndrome. Fragile X
mutation consists of an increase in the size of region in
fragile X mental retardation gene (FMR-1). This region
contains a long CGG trinucleotide repeat sequence. In the
DNA of normal person there are between 10 to 15 copies
of this triplet repeat and these are inherited in a stable
fashion. A small increase between 50 to 200 makes this
repeat sequence unstable a condition called as premutation.
A man carrying pre-mutation is known as normal
transmitting male. All his daughters will inherit the
premutation and will be of normal intelligence. But when
the daughters have their sons there is a significant risk
that the premutation will undergo a further increase in
size during meiosis. If this reaches a critical size of greater
than 200 CGG triplets it becomes a full mutation. Full
mutation is unstable during female meiosis and in somatic
mitotic division, the expansion suppresses transcription
of FMR-1 gene and possibly adjacent genes also. In males
980
with large expansion and to a lesser extent in females this

results in clinical features of fragile X syndrome.
Similar mutations have been reported in myotonic
dystrophy, Huntingtons chorea, and Kennedys disease
(spinal and bulbar muscular atrophy). Variability in age
of onset and clinical severity is common to all.
Mitochondrial Inheritance (Figs 18.1.11 and 18.1.12)
Mitochondria are intracellular organelles which are
ubiquitous in eukaryotes and are essential for survival.
Their primary function is to support aerobic respiration
and to provide ATP for intracellular metabolic pathways.
Mitochondria contain their own DNA (mtDNA), which is
thought to be a remnant from the time that they were free
living organisms before forming a symbiotic relationship
with eukaryotes. Human mtDNA is a circular double
stranded molecule (Fig. 18.1.11) and codes for 22 tRNAs 2
rRNAs and 13 proteins. The human mtDNA is still entirely
dependent on the nuclear DNA for the provision of
enzymes for replication, transcription and translation.
Disease characteristics Mitochondrial diseases are a
clinically heterogeneous group of disorders that arise as a
result of dysfunction of the mitochondrial respiratory
chain. They can be caused by mutations of nuclear or
mitochondrial DNA (mtDNA). Some mitochondrial
disorders only affect a single organ (such as the eye in
Leber hereditary optic neuropathy [LHON]), but many
involve multiple organ systems and often present with
Figure 18.1.11: A mitochondrion with its

circular DNA is illustrated
prominent neurologic and myopathic features. Mitochondrial disorders may present at any age. In general
terms, nuclear DNA mutations present in childhood and
mtDNA mutations (primary or secondary to a nuclear DNA
abnormality) present in late childhood or adult life. Many
affected individuals display a cluster of clinical features
that fall into a discrete clinical syndrome. Table 18.1.4
enumerates the clinical features which should make the
clinician keep mitochondrial disorders in his differential
diagnosis.
Diagnosis/testing In some individuals, the clinical picture
is characteristic of a specific mitochondrial disorder (e.g.,
LHON, NARP, or maternally inherited LS), and the
diagnosis can be confirmed by molecular genetic testing
of DNA extracted from a blood sample. In many
individuals, such is not the case, and a more structured
approach is needed, including family history, blood and/
or CSF lactate concentration, neuroimaging, cardiac
evaluation, and muscle biopsy for histologic or histochemical evidence of mitochondrial disease, and
molecular genetic testing for a mtDNA mutation. Table
18.1.5 shows some of the common mitochondrial disorders
with their salient clinical features.
Management
The management of mitochondrial disease is largely
supportive. Management issues may include early
diagnosis and treatment of diabetes mellitus, cardiac
pacing, ptosis correction, and intraocular lens replacement
for cataracts. A shot gun therapy with multiple vitamins
and cofactors has also been recommended. These
supplements serve two possible roles: enzyme function
enhancement and serving as antioxidants which may
slow the progression of the disease. Table 18.1.6 shows
some of the supplements that may be useful in supporting
a mitochondrial disorder. The use of supplements remains
controversial, as no benefit has been proven under
controlled conditions.
Genetics of mitochondrial disorders: Mitochondrial
disorders may be caused by defects of nuclear DNA or
mtDNA. Nuclear gene defects may be inherited in an
autosomal recessive manner or an autosomal dominant
manner. Mitochondrial DNA defects are transmitted by
maternal inheritance (Fig. 18.1.12). Mitochondrial DNA
deletions generally occur de novo and thus cause disease
in one family member only, with no significant risk to
other family members. Mitochondrial DNA point
Genetics
981
TABLE 18.1.4: When to suspect mitochondrial disorders?

Organ system
Possible problems
Brain
Developmental delays, mental retardation, dementia, seizures, neuropsychiatric disturbances, atypical

cerebral palsy, migraines, strokes
Nerves
Weakness (which may be intermittend), neuropathic pain, absent reflexes, gastrointestinal problem
(GE reflux, constipation, pseudo-obstruction), fainting, absent or excessive sweating resulting in
temperature regulation problems
Muscles
Weakness, hypotonia, cramping, muscle pain
Kidneys
Proximal renal tubular wasting resulting in loss of protein, magnesium, phosphorous, calcium and
other electrolytes
Heart
Cardiac conduction defects (heart blocks), cardiomyopathy
Liver
Hypoglycemia (low blood sugar), liver failure
Eyes
Visual loss and blindness
Ears
Hearing loss and deafness
Pancreas and Other Glands
Diabetes and exocrine pancreatic failure (inability to make digestive enzymes), parathyroid failure
(low calcium)
Systemic
Failure to gain weight, short stature, fatigue, respiratory problems including intermittent air hunger,
vomiting
TABLE 18.1.5: Mitochondrial disorders and their salient features

Disorder
Primary features
Additional features
Chronic progressive external

ophthalmoplegia (CPEO)
External ophthalmoplegia
Bilateral ptosis
Mild proximal myopathy
Kearns-Sayre syndrome (KSS)
PEO onset before age 20 years

Pigmentary retinopathy
One of the following: CSF protein greater than
1 g/L, cerebellar ataxia, heart block
Bilateral deafness
Myopathy
Dysphagia
Diabetes mellitus
Hypoparathyroidism
Dementia
Pearson syndrome
Sideroblastic anemia of childhood

Pancytopenia
Exocrine pancreatic failure
Renal tubular defect
Infantile myopathy and lactic acidosis

(fatal and non-fatal forms)
Hypotonia in the first year of life

Feeding and respiratory difficulties
Fetal form may be associated

with a cardiomyopathy and/or
the Toni-Fanconi-Debre syndrome
Leigh syndrome (LS)
Subacute relapsing encephalopathy

Cerebellar and brain-stem signs
Infantile onset
Basal gangila lucencies

Maternal history of neurologic disease
or Leigh syndrome
Neurogenic weakness with ataxia

and retinitis pigmentosa (NARP)
Late-childhood or adult-onset
peripheral neuropathy
Ataxia
Basal ganglia lucencies

Abnormal electroretinogram
Sensorimotor neuropathy
Stroke-like episodes before age 40 years

Seizures and/or demetia
Ragged-red fibers and/or lactic acidosis
Diabetes mellitus
Cardiomyopathy (initially
hypertrophic; later dilated)
Bilateral deafness
Cerebellar ataxia
Mitochondrial
encephalomyopathy with lactic
acidosis and stroke-like episodes
(MELAS)
Contd.
982
Contd...
Disorder
Primary features
Additional features
Myoclonic epilepsy with raggedred fibers (MERRF)
Myoclonus
Seizures
Cerebellar ataxia
Myopathy
Dementia
Optic atrophy
Bilateral deafness
Peripheral neuropathy
Spasticity
Multiple lipomata
Leber hereditary optic

neuropathy (LHON)
Subacute painless bilateral visual failure

Males:females ~ 4:1
Median age of onset 24 years
mutations and duplications may be transmitted down the

maternal line. The father of a proband is not at risk of
having the disease causing mtDNA mutation, but the
mother of a proband (usually) has the mitochondrial
mutation and may or may not have symptoms. A male
Dystonia
Cardiac pre-excitation syndromes
does not transmit the mtDNA mutation to his offspring. A

female harboring a heteroplasmic mtDNA point mutation
may transmit a variable amount of mutant mtDNA to her
offspring, resulting in considerable clinical variability
among sibs within the same family. Since each cell contains
several mitochondria, the diseased cell may contain a
mixture of normal and mutated mitochondria; a state
called heteroplasmy.
Genetic Counseling
In essence genetic counseling consists of an effective
communication process that addresses an individuals
concerns relating to the development and/or transmission
of a hereditary disease.
There are five steps in genetic counseling (Table 18.1.7).
Figure 18.1.12: Mitochondrial disorders

TABLE 18.1.6: Shotgun therapy for mitochondrial disorders
Supplement
CoQ10
Dose Range
4.3 mg/kg/day or 60-120 mg per day or

a dose to reach a
target blood level
levo-carnitine (Carnitor) variable, 25-100 mg/kg/day, some argue
against carnitine
unless carnitine deficient
Thiamine (Bl)
50-100 mg a day
Riboflavin (B2)
50-100+ mg a day
Nicotinamide (B3)
50-100 mg a day
Vitamin E
200-400 IU; 3 times a day
Vitamin C
100-500 mg SR; 3 times a day
Lipoic Acid (a-lipoate)
12.5 mg/kg/day in 3 divided doses
Selinium
25-50 micrograms a day
b-carotene
10,000 IU; every other day to daily
Diagnosis
An accurate diagnosis is the first essential requirement
for genetic counseling. This may not always be
straightforward as genetic disease is often variable in its
expression and different members of a family with the
same disorder may present to different specialties with
disease manifestations of the condition. Conversely,
disorders which are clinically similar, may follow different
inheritance patterns in different families.
The first and most important step in diagnosis of genetic
disorders is construction of a family tree. The pattern of
inheritance can be shown from the pedigree, for example,
vertical transmission in autosomal dominant disorders,
horizontal transmission in autosomal recessive disorders
and oblique transmission in X-linked recessive disorders.
Standard pedigree symbols in pedigree charting are given
in (Fig. 18.1.13).
Genetics
TABLE 18.1.7: The steps in genetic counseling
1. Diagnosis-based on history, physical examination and
investigations
2. Risk assessment
3. Communication
4. Discussion of option
5. Long term contact and support
983
relatives and older members of the family should be

interviewed and special investigations like radiology,
cytology, DNA studies and histology may have to be done.
A team approach, with the help from other specialists like
orthopedicians, radiologists and ophthalmologists for
arriving at a proper diagnosis can be conducted. Newer
tests should be applied when available for reconfirmation
of previous diagnosis.
Risk Estimation
The mathematical risk calculated from data on a pedigree
may often be modified by additional information from
specific tests to detect carriers. Risk can be expressed as
either a percentage or a fraction. Approximate risks in
some multifactorial disorders are represented in
(Table 18.1.8).
Detection of carriers: A carrier is an individual who
possesses in heterozygous state the gene determining an
inherited disorder, and who is essentially healthy at the
time of the study. Identifying carriers of genetic disorders
in families or populations at risk plays an important part
in preventing genetic disease.
Obligate carriers: Families in which there is a genetic
disorder, some members must be carriers because of the
way in which the condition is inherited, these are called
as obligate carriers. A pedigree will indicate a person to
be an obligate carrier, the following are some of the
examples in different modes of inheritance: (i) Autosomal
dominant: Person with affected parent and child, (ii)
Autosomal recessive: Parents and child (children) of
affected person, (iii) X-linked recessive: Woman with two
affected sons or one affected son and another affected male
maternal relative and all daughters of an affected man.
Table 18.1.9 gives examples of various Mendelian
disorders amenable to carrier detection.
The carrier state can be determined by clinical signs,
analysis of genes, analysis of gene products and secondary biochemical abnormalities such as raised serum
creatine kinase activity in Duchenne and Beckers
muscular dystrophies. The various techniques used for
carrier detection are depicted in Table 18.1.10.
Figure 18.1.13: Pedigree symbols
All affected individuals must be examined, asymptomatic individuals should also be examined to exclude
mild or early disease. Home visits should be made, distant
Communication
Counseling should be done as early as possible. A good
rapport should be established between the patient and
the counselor. Both parents should be present for the
discussion. The genetic basis for the problem should be
984

TABLE 18.1.8: Empirical recurrence risk in common multifactorial disorders
Disorder
Incidence
per 100
Dislocation of hip
Club foot
Scoliosis
Spinabifida
Cleft palate
Cleft lip and palate
Asthma
Diabetes mellitus
Schizophrenia
0.07
0.10
0.22
0.30
0.04
0.10
3-4
0.20
1-2
Sex ratio
M:F
Normal parents
having 2nd
affected child
(Risk in %)
1:6
2:1
1:6
2:3
2:3
3:2
1:1
1:1
1:1
4
3
7
5
2
4
10
8
10
Affected parents
having an affected
child (Risk in %)
Affected parents
having 2nd affected
child (Risk in %)
4
3
5
3
7
4
26
8
16
10
10
15
10
10
-
TABLE 18.1.9: Mendelian disorders amenable to carrier detection

Autosomal dominant
1. Familial hypercholesterolemia
2. Adult polycystic kidney disease
3. Neurofibromatosis
4. Tuberous sclerosis
5. Myotonic dystrophy
6. Malignant hyperpyrexia
7. Huntingtons chorea
Autosomal recessive
Population based screening
1. Thalassemia
2. Tay-Sachs disease
3. Sickle cell disease
Family based screening
1. -1-Antitrypsin deficiency
2. Congenital adrenal hyperplasia
3. Cystic fibrosis
4. Galactosemia
5. Mucopolysaccharidosis
6. Phenylketonuria
described using simple language and visual aids. Patients

or relatives should be encouraged to clear their doubts
about the condition.
Discussion of options: Options like prenatal
diagnosis, abortion, not having children or adoption
should be discussed.
Long-term Contact and Support
A combined approach is necessary for continuing support
to the patient and his family. Involvement of the genetic
counselor, family practitioner, specialist genetic nurse,
social worker and enlistment of other medical specialties
for diagnosis, treatment, etc. should be ensured. Support
groups provide psychological support for families by
bringing them into contact with others with a similar
problem. All families with an affected member, and carriers
of specific genetic disorder, should be put in touch with
relevant support groups where those exist. Such groups
identify the concerns of families and allow the community
to participate in developing service. Long-term follow-up
should also be ensured via genetic registers.
X-linked recessive
1. Ocular albinism
2. Hemophilia A
3. Hemophilia B
4. Duchenne muscular dystrophy
5. Mucopolysaccharidosis
II (Hunters syndrome)
Genetic Counseling in an Era of Prenatal Diagnosis

Prenatal diagnosis of genetic disorder has been possible
because of great advances in techniques of obtaining fetal
tissues, as well as development in cytogenetics,
biochemical techniques and recombinant DNA
technology. The technical advances especially in
molecular genetics and availabilities of various prenatal
diagnostic techniques have added a new dimension in
the process of genetic counseling.
Prenatal diagnosis: Determination of the status (genetic
or otherwise) of the fetus by a variety of techniques
(chromosomal, biochemical, DNA, etc.), using a variety of
procedures.
Chorionic villus sampling (CVS): A technique for
obtaining fetal cells for prenatal diagnosis by biopsy of
the placenta, now usually done transabdominally after
10 weeks of pregnancy. Transcervically it can be done at
8-11 weeks of gestation.
Genetics
TABLE 18.1.10: Approaches of carrier detection
Approaches
1. DNA analysis
Specific gene probe:
deletion detectable in
some cases.
Unique change in a
restriction fragment
length polymorphism
2. Biochemical, primary
defect known
Enzyme deficiency
disease
Nonenzymatic protein
defect
3. Biochemcial, primary
defect
Unknown
Inaccessible
4. Physiological
Electroretinography
electromyography
5. Cytogenetic studies
6. Microscopy
Blood
Biopsy
Ocular slit-lamp
7. Radiology
8. Clinical
Examples
Thalassemias, Duchenne and
Becker muscular dystrophy,
hemophilia A and B, a1antitrypsin deficiency,
Sickle cell disease
Hexosaminidase A(Tay-Sachs)
Factor VIII assays
(hemophilia A)
Serum creatine kinase

(Duchenne muscular dystrophy)
Phenylalanine Ioad
(phenylketonuria)
X-linked retinitis pigmentosa
Muscular dystrophies
(myotonic and Duchenne)
Chromosome translocation
Minor deletion syndromes
Fragile X syndrome
Sickle cell disease,
Thalassemias
Duchenne dystrophy
X-linked ichthyosis, myotonic
dystrophy
Tuberous sclerosis (cerebral
calcification)
Skin (Fabrys disease)
Eye (choroideremia)
Muscle (Duchenne dystrophy)
Amniocentesis: It is the withdrawal of amniotic fluid from

the amniotic sac surrounding the fetus. If amniocentesis
is done at 15 to 16 weeks of gestation, the process is called
conventional amniocentesis, and if done between 11 to
15 weeks then called early amniocentesis; the latter
procedure is still experimental. Early amniocentesis is
considered to be useful for cytogenetic studies.
Cordocentesis: Withdrawing blood from the umbilical
vein under ultrasound guidance, cordocentesis helps in
prenatal diagnosis of genetic disorders and understanding of fetal physiology, development and metabolism.
985
Fetoscopy: A fine caliber endoscope is inserted into the

uterus. The direct visualization of the fetus is possible
and fetal blood sampling can be done.
Embryoscopy: This is an experimental technique used in
the first trimester of pregnancy. A rigid endoscope inserted
through the cervix into the space between the amnion and
chorion is used to visualize the embryo and for diagnosis
of structural malformations.
FISH Molecular cytogenetics has given rise to the powerful
new technology or fluorescent in situ hybridization (FISH).
A fluorescently labeled DNA probe is hybridized to a
standard chromosome preparation on a microscopic slide.
This method is useful in detecting chromosomal
abnormalities, both numerical and microdeletion
syndromes.
The various techniques used in prenatal diagnosis,
their timing, method and complications are summarized
in Table 18.1.11.
MANAGEMENT OF GENETIC DISORDERS
A brief discussion of principles of management of genetic
disorders is given in the following paragraphs, which is
of relevance to genetic counseling. The successful
treatment of genetic disorders requires accurate diagnosis,
knowledge of biochemical basis of the disorder and early
intervention.
Major Principles
(i) Restriction of potentially toxic environmental agents,
(ii) Replacement of missing gene product, deranged organ
or even gene itself, (iii) Removal of either toxic substances
of organs, (iv) Metabolic manipulation, (v) Surgical
management.
Restriction
Examples for restriction are: (a) Phenylketonuria
phenylalanine should be restricted in the diet, (b)
Galactosemia galactose should be eliminated from the
diet early in life. If prenatal diagnosis is made, the mother
should not drink milk in pregnancy, (c) G-6-PD deficiency
primaquine, sulpha drugs and fava beans should be
restricted, (d) Acute intermittent porphyria phenobarbitone, sulpha drugs, estrogen, etc. should be restricted,
(e) Alpha-1 antitrypsin deficiency restriction of cigarette
smoking prolongs or prevents the development of
pulmonary emphysema, (f) Familial hypercholesterolemia cholesterol and saturated fats should be restricted.
986

TABLE 18.1.11: Prenatal diagnosis
Fetal tissues
Amniotic
fluid
a.
b.
Amniocytes
a.
b.
Chorionic
villi
a.
b.
Fetal blood
a.
b.
Fetal liver
a.
b.
Fetal skin
a.
b.
Fetal muscle
a.
b.
Maternal serum
Fetal cells
in maternal
circulation
Preimplantation
embryo biopsy
Techniques
Timing
(weeks)
Studies done
on tissues
Risk
Conventional
amniocentesis
Early
amniocnetesis
15-16
AFP/AChe
hCG
Abortion, needle
puncture injuries,
placental abruption
chorioamnionitis,
preterm labor.
Conventional
amniocentesis
Early
amniocentesis
Transvaginal
Transabdominal
Fetoscopic
aspiration
Cordocentesis
Fetoscopic
biopsy
Percutaneous
biopsy
Fetoscopic
biopsy
Percutaneous
biopsy
Fetoscopic
biopsy
Percutaneous
biopsy
Maternal blood
Flow cytometry,
PCR/monoclonal
antibodies
IVF biopsy of
blastocysts
AFP Alpha fetoprotein

PCR Polymerase chain reaction
AChe Acetylcholinesterase
PROM Premature rupture of membranes
hCG human chorionic gonadotrophin
OTC Ornithine trans carbamylase
11-14
15-16
Cell culture for

karyotypes,
enzyme assay
DNA studies, FISH
Biochemical,
Chromosomal
DNA
Coagulation factor
Immunoglobulin
antibodies
estimation; DNA
and enzyme study,
karyotype, FISH
Enzyme assay as in
OTC deficiency
2% fetal loss, limb

defects, mosaicism and
maternal bleeding.
1 % fetal loss,
Rhesus
sensitization, fetal
infection, PROM
18-20
Histopathology
18-20
Histopathology
12-14
1st
trimester
AFP/UE3/hCG
FISH, fetal sexing
DNA tests
Nil
Nil
4-8 cells
stage
DNA, PCR,
enzyme assay
11-14
9-11
12-24
18-20
16-20
18-20
IVF In vitro fertilization

UE3 Unconjugated estriol
Replacement
Examples for the replacement mode of treatment are:
a. Hemophilia A and B: The treatment aims at replacement
of factor VIII and factor IX by transfusion respectively.
b. Diabetes mellitus: Insulin is the agent replaced.
c. Alpha-1 antitrypsin deficiency: Can be successfully
treated by replacement with recombinant alpha-1 antitrypsin.
d. Congenital adrenal hyperplasia: The agents replaced
are cortisone and aldosterone.
e. Cystinosis Kidney transplantation.

f. Adenosine deaminase deficiency: Bone marrow transplantation or somatic cell gene therapy.
g. Familial hypercholesterolemia: Liver transplantation.
Removal
The examples are: (a) Wilsons disease: It is an autosomal
recessive disorder characterized by accumulation of
copper in various organs like the liver, brain and kidneys.
The copper can be effectively chelated by oral
Genetics
administration of penicillamine; (b) Hemochromatosis:
The excess iron stores are removed by repeated
phlebotomy; (c) Familial Polyposis coli: Colectomy is
advised to prevent carcinoma of colon, which develops
during the fourth decade of life.
Metabolic Manipulation
Metabolic manipulation can correct certain types of
disorders which are: (a) Neural tube defects: Periconceptional folic acid therapy has shown to prevent neural tube
defects (b) Homocystinuria: Classic homocystinuria is due
to deficiency of cystathionine synthetase. Among these,
40 percent of patients respond to high doses of vitamin B6.
(c) Crigler-Najjar syndrome type II: These patients benefit
by oral phenobarbitone administration which induces
hepatic glucuronyl transferase activity; (d) Methylmalonic
acidemia: Administration of vitamin B12; (e) Multiple
carboxylase deficiency: Administration of biotin (cofactor); (f) Familial hypercholesterolemia: Lovastatin to
block endogenous synthesis of cholesterol; (g) Ornithine
transcarbamylase deficiency: Sodium benzoate and
phenylacetate to conjugate glycine and glutamate.
Surgical Management
Surgical management can be considered in certain cases
like: (a) Congenital adrenal hyperplasia: Clitoroplasty and
vaginal reconstruction surgery; (b) Marfan syndrome:
Surgery for aortic dilatation; (c) Hydrocephalus: Shunt
surgery; (d) Obstructive uropathy: Intrauterine shunt or
correction; (e) Diaphragmatic hernia: Repair.
GENE THERAPY
Gene therapy was conceptualized in early 1970s and has
been subjected to many clinical trials since then. In spite
of the technical difficulties, recent advances in gene
transfer is likely to increase its clinical usefulness.
Definition
Gene therapy is a novel approach to treat, cure, or
ultimately prevent a disease by changing the expression
of a persons genes. This involves the efficient introduction
of functional genes into the appropriate cells of the patient
in order to produce sufficient amounts of protein encoded
by the transferred gene (transgene) so as to precisely and
permanently correct the disorder.
987
Approaches to Gene Therapy

Two general strategies are used to deliver genes to specific
tissues and correct genetic defects.
1. Ex vivo approach: The target cells are removed from the
body and a new gene is introduced in vitro by one of
the gene delivery methods.
2. In vivo approach (Direct gene transfer): The
therapeutic gene is introduced directly into the affected
tissue without removing cells from the body. This
requires specially designed vehicles for cells specific
gene targeting.
Types of Gene Therapy
Somatic Cell Therapy
This involves insertion of a therapeutic gene into somatic
cells such as fibroblasts, myoblasts, epithelial cells,
endothelial cells, nervous, glial cells, etc. which can correct
the genetic defect in the individual, but transgene cannot
be passed on to the siblings of the individual.
Germline Therapy
This involves the introduction of a foreign gene into germ
cells like sperm, ovum or fertilized egg, resulting in their
expression in both somatic as well as germ cells of the
offspring. This is not advocated in humans.
Methods of Gene Delivery
A therapeutic gene can be delivered into target cells by a
variety of methods, which include physical, chemical and
biological methods, which can be used either individually
or in combination, these methods are given in Table
18.1.12.
Hurdles in Gene Therapy
Gene therapy is very young and experimental. Many
factors have prevented researchers from developing
successful gene therapy techniques.
Identification of an ideal gene delivery tool or vector.
An ideal vector should have the following merits.
- Efficiently transfer genes to appropriate cells.
- Accommodate foreign genes of sufficient size.
- Achieve sufficient expression in the recipient cell.
- Non-immunogenic, non-toxic, non-infective and
safe.
988

TABLE 18.1.12: Methods of gene delivery
Physical
Parenteral injection
Microinjection
Aerosol
Gene gun
Chemical
Calcium phosphate
DEAE-dextran
Liposomes
Biological
Viral vectors
- Retro virus
- Adeno virus
- Herpes simplex virus
Neo-organ implants
Tissue transplantation
Human artificial chromosome
Others
Receptor-mediated delivery
Virally directed enzyme prodrug therapy
Understanding the precise function of a gene in terms

of its action and interaction with other genes and
environmental factors.
Some diseases involve more than one gene.
High cost and ethical issues.
Clinical Trials
Even though gene therapy was initially conceptualized
for treatment of single gene disorders, presently most of
the clinical trials are directed towards cancer therapy.
Induction of immune response against tumor cells,
replacement of tumor suppressor genes, introduction of
toxic genes, which can induce selective killing of tumor
cells, introduction of tumor cell specific lytic viruses, etc.
are the approaches that are being tried in cancer
treatment.
In X-linked severe combined immunodeficiency (SCID)
due to deficiency of interleukin-2 receptor gamma chain
defect resulting in deficiency of antigen specific immunity,

introduction of genetically reconstituted stem cells and
bone marrow cells have demonstrated clinical efficacy. In
SCID due to adenosine deaminase deficiency similar
treatment was found to be beneficial. Following are the
other candidate monogenic disorders under trial for gene
therapy.
Cystic fibrosis
-1 antitrypsin deficiency
Hemophilia A and B
Gauchers disease
-hemoglobinopathies
Familial hypercholesterolemia
Phenylketonuria
Prenatal Treatment
Certain genetic disorders when diagnosed prenatally can
be treated effectively; for example, in the case of
methylmalonic acidemia, if B12 is given to the mother, the
deficiency can be reverted.
Other modalities of prenatal treatment, still in an
experimental stage are:
1.
2.
3.
4.
5.
Stem cell transplantation

Somatic cell therapy
Germ cell therapy
Organ transplantation
Preimplantation embryo treatment.
BIBLIOGRAPHY
1. Emery AEH (Ed): Principles and Practice in Medical
Genetics. (3rd edn): London: Churchill Livingstone 1999.
2. Gelehrter TD (Ed): Principles of Medical Genetics. (2nd
edn): Baltimore: Williams and Wilkins 1998.
3. Harper PS (Ed): Practical genetic counseling. (3rd edn):
London: Butterworth Heineman 1998.
4. Zeviani.M, Donato SD: Mitochondrial disorders. Brain
2004;127, 2153-72.
Genetics
989
18.2 Common Genetic Disorders

ML Kulkarni
CHROMOSOMAL DISORDERS
About 15 to 20 percent of all first trimester conceptions are
estimated to be lost spontaneously, and half of these have
chromosomal abnormality. The incidence of chromosomal
abnormalities increases in offspring born to mothers after
the age of 35 years, after the birth of one baby with
chromosomal anomalies or when either of the parents is
carrying a balanced translocation of the chromosome. The
different types of chromosomal abnormalities have been
described in Table 18.2.1
Numerical Abnormalities
A cell with the exact multiple of the haploid number, e.g.
46, 69, 92 is referred to as euploid. Euploid cells with
more than the normal diploid number of 46 chromosomes
is called polyploid. Cells deviating from one of the
euploid numbers are called aneuploid. The most
common type of aneuploidy is trisomy. Lack of

chromosome is called monosomy.
Trisomy: The presence of one chromosome additional to
the normal homologous pair, e.g. Trisomy 21 (Down
syndrome).
Monosomy: A chromosomal number one less than the
diploid number, i.e. (45 X ), example Turner syndrome,
where there is only one X in a female instead of two.
Monosomy for autosomes is not compatible with life.
Mosaicism: An individual with two or more cell lines
derived from a single zygote. The clinical examples
include 1 percent of all Down syndrome cases and some
cases of Turner syndrome.
Polyploidy: Pure polyploidy is lethal in humans, but
individuals with mosaicism have been known to survive.
TABLE 18.2.1: Types of chromosomal disorders

S. No Types of disorder
1.
Numerical
Polyploidy
2.
Aneuploidy
1.
Structural
Deletion
2.
3.
Inversion
Duplication
4.
5.
6.
Ring chromosome
Fragile site
Translocation
Examples
Outcome
Triploidy
(69 chromosomes)
Trisomy of chrom 21
Trisomy of chrom 18
Trisomy of chrom 13
45X chrom monosomy
47XXY
Lethal
Terminal deletion 5p
Interstitial deletion 11 P
Inversion 9q
Isochromosome X
(fusion of long arms
with loss of short arms)
Ring chromosome 18
Fragile X
Reciprocal
Cri-du-chat Syndrome
Found in Wilms tumor
Normal variant
Infertility in Females
Robertsonian
Down syndrome
Edward syndrome
Patau syndrome
Turner syndrome
Klinefelter Syndrome
Mental retardation syndrome

Mental retardation syndrome
Balanced translocations, cause no
abnormality.
Unbalanced, cause spontaneous abortions
or syndromes of multiple physical and mental
handicaps
990
Structural Abnormalities
Deletion (Fig. 18.2.1)
Translocation (Fig. 18.2.1)
Loss of portion of a chromosome, either terminal or

interstitial: A deletion at the terminal portion of short
arm of the 5th chromosome produces cri-du-chat
syndrome. A deletion in the middle portion of short arm
of the 11th chromosome (interstitial deletion), is seen in
Wilms tumor.
The transfer of all or a segment of a chromosome from one

chromosome to another nonhomologous chromosome,
usually through a reciprocal event during meiosis.
It can be :
i. Balanced in which a full complement of genetic
material is present. In the next generation there is a
risk of offspring inheriting an unbalanced form.
ii. Unbalanced Full complement of genetic material is
not present due to deletion or duplication. Balanced
translocation cases have no abnormalities.
Unbalanced translocations result in spontaneous
abortions or syndromes of multiple physical and
mental defects, e.g. 4 percent of Down syndrome cases
are due to translocation between chromosome 21 and
chromosomes 13,14, or 15. During the translocation
of 2 acrocentric chromosomes in this type, the small
fragment formed by fusion of 2 short arms is usually
lost, which is known as Robertsonian translocation.
(Fig. 18.2.2)
Fragile Site (Fig. 18.2.3)

Constriction at sites other than centromere is known as
fragile site and show a tendency to break. A fragile
site on the long arm of the chromosome is associated
with one of the most common types of X-linked mental
retardation, known as Fragile X syndrome.
Duplication
It is the presence of two copies of a segment of chromosome.
It arises by unequal crossing over during meiosis.
Contiguous Gene Syndrome (CGS) (Fig. 18.2.4)
CGS arises by involvement of genes that are adjacent to
each other on a chromosome. Contiguous gene syndromes
Figure 18.2.1: Different types of chromosomal aberrations. For simplicity

hypothetical loci A-D are marked on the chromosome
Genetics
991
Figure 18.2.2: Robertsonian translocation of the two acrocentric chromosomes 14 and 21, the small fragement formed by
fusion of the two short arms is usually lost
Figure 18.2.4: Contiguous gene syndrome Wilms tumor,

Aniridia, Genitourinary malformations and Retardation
techniques have to be used. Examples for CGS are Wilms

tumor (Deletion 11p 15), Prader Willi/Angelman
syndrome, Rubinstein-Taybi syndrome, Miller Dieker
syndrome, DiGeorge syndrome, etc.
Mutation in Triplet Repeat Exapansion
These result in neurological disorders. Examples include:
Fragile X syndrome, Huntington chorea, spinocerebellar
ataxia, spinal and bulbar muscular atrophy, and myotonic
dystrophy. Features of some less common chromosomal
disorders have been described in Table 18.2.2.
Figure 18.2.3: Fragile site
involve micro deletion or micro duplication. Most of these

occur as sporadic events but sometimes may simulate
Mendelian inheritance. The clinical presentation can be
extremely variable as deletion and duplication vary in
size. Some deletions are so small that they cannot be
detected by cytogenetic techniques but molecular
DOWN SYNDROME
Down syndrome is one of the best recognized and the
most common serious chromosomal disorder which is
usually caused by an extra copy of chromosome 21
(Trisomy 21), (Fig. 18.2.5) characterized clinically, by
growth retardation, varying degree of mental retardation
and a spectrum of somatic abnormalities including head
and facial features.
992

TABLE 18.2.2: Features of some less common chromosomal disorders
Condition
Incidence
Clinical features
Trisomy 18 (Edward syndrome)
1 in 8000 births
Mental retardation, hypertonia, failure to thrive, low birth weight, prominent

occiput, micrognathia, low set malformed ears, congenital heart disease
mainly VSD and PDA, short sternum, diaphragmatic hernia, renal anomalies,
overlapping of fingers, rocker bottom feet, death in infancy.
Trisomy 13 (patau syndrome)
1 in 20,000 Births
Mental retardation, microcephaly, cleft lip paiate, midline scalp defects,

microphathalmia, colobomata, low set malformed ears, congenital heart
disease, polycystic kidneys, cryptorchidism, polydactyly, simian crease,
early death.
Multiple X female
47 XXX,
48 XXXX
49 XXXXX
1 in 1200 female births
Triple X female are apparently normal except for tall stature, higher the
number of X chromosome, more severe is the mental retardation. Menstrual
abnormalities may be present.
XYY
Syndrome
1.5 per 1000 newborn

male infant
Although more prevalent among inmates of high security institutions,the

syndrome is less strongly associated with aggressive behavior than
previously thought. Mild mental retardation, behavioral problems and tall
stature are usual features.
during the formation of egg or sperm (meiotic

nondysjunction). In more than 75 percent of cases, the
extra 21 is of maternal origin and in the remaining paternal.
The incidence of trisomic Down syndrome in live births
increases with advancing maternal age and the recurrence
risk is approximately 1 percent. The recurrence in
translocation type of Down syndrome does not depend
on maternal age, but is related to sex of the parent carrying
the translocation and the involved chromosome in
translocation and the risk is usually higher. Patients with
mosaic Down syndrome tend to have less marked physical
stigmata and higher intelligence.
Clinical Features
Figure 18.2.5: Down syndromeKaryotype showing

Trisomy 21 in a female
Etiology
Down syndrome has an incidence of approximately 1:700
live births. Ninety five percent of individuals with Down
syndrome have three copies of chromosome 21 (Trisomy
21); in 4 percent the extra chromosome is not free but is
translocated to another chromosome, usually to number
14 and occasionally to 22 or 21 and in 1 percent there is
mosaicism, wherein, both normal and trisomy 21 cell lines
are present in the body (Mosaic). In trisomic Down
syndrome, the extra 21 results from faulty cell division
A large number of clinical characteristics have been

described in Down syndrome (Table 18.2.3), many of them
have diagnostic value. Except for the mongoloid facies,
no single feature is always present or pathognomonic.
Mental retardation is constant but nonspecific finding that
becomes apparent in later part of infancy.
Brachycephaly with flat occiput, small head, flat
rounded face, upward slant of the eyes (mongoloid slant),
small nose with depressed nasal bridge, inner epicanthic
folds, protruding tongue and small misshapen ears form
the characteristic mongoloid facies (Fig. 18.2.6). oblique
palpebral fissure, epicanthic folds, spotting of iris
(Brushfields spots) and cataract, form the most
characteristic and diagnostically valuable ocular signs in
Down syndrome. The neck is short and broad and skin
and subcutaneous tissue may be loose and abundant
especially during infancy. Asymptomatic atlantoaxial
Genetics
TABLE 18.2.3: Clinical Features of Down Syndrome
Mongoloid facies
Brachycephaly with flat occiput
Small head, Flat round face
Depressed nasal bridge
Inner epicanthal folds
Protruding tongue
Small ears
Ocular system
Brushfield spots
Congenital cataract
Nystagmus, Strabismus
Hypotelorism (decreased interpupillary distance)
Blepharitis
Keratoconus
Refractory errors
Cataract after 25 years of age
Ears
Small low set ears
Deafness (sensorineural/conductive)
Hands and feet
Simian crease
Short broad hands, Clinodactly
Hypoplasia of middle phalanx of 5th finger
Gap between 1st and 2nd toes (sandle gap)
Distal position of palmar axial triradius
Ulnar loops in all digits
Mental retardation
Hypotonia
Autistic behavior
Reactive depression in adolescents
Alzheimers disease after 25 years of age
Congenital heart disease in 40% cases
AV canal defects Ostium primum, atrioventricularis communis
are most common.
VSD, PDA, TOF, Secundum ASD, Simple pulmonary stenosis,
Isolated aberrant subclavian artery.
Gastrointestinal system
Atresia of gut- duodenal, oesophageal and anal.
Genitalia
Small penis
Cryptorchidism
Bulbous vulva
Immune system
Frequent infection, Trace element deficiency
Autoimmune disease, Celiac disease
Endocrine system
Congenital hypothyroidism
Girls- fertile
Boys- always sterile.
Musculoskeletal system
Hypotonia
Contd.
993
Contd.
Joint laxity
Short stature
Dislocation of patella and hip
Small pelvis
Atlantoaxial dislocation
12th rib anomaly- either absent or rudimentary.
Hematological system
Higher incidence of Acute leukemia
Congenital thrombocytopenia
Neonatal jaundice
Dental problems
Delayed dentition
Small and malformed teeth
Aplasia of enamel
Congenital absence of various permanent teeth
Malocclusions and Periodontal diseases
Ten critical signs of Down syndrome in Newborn
(Halls criteria)
Oblique palpebral fissures
Dysplastic ears
Excessive skin on back of neck
Flattened features
Single palmar crease on either hand
Dysplastic middle phalynx on the 5th digit of either hand
Hyper flexibility
Muscular hypotonia
Dysplastic pelvis
Absence of Moros reflex
dislocation occurs in 12 to 20 percent of individuals with

Down syndrome.
Short stature is a characteristic finding in Down
syndrome, varying in degree at different ages. The
shortness of extremities is typical of Down syndrome. The
Figure 18.2.6: Down syndrometypical facial feature
994
hands are short, the fingers are short and the fifth finger is
short and incurved (clinodactly). The feet are short, broad
and thick. The space between first and second toes is
frequently widened(sandle gap) and a plantar crease
extends proximally from this space.
Approximately 40 percent of children with Down
syndrome have congenital heart disease which are
responsible for early mortality in these children. The most
often observed cardiac lesion is an atrioventricular canal
(as a part of endocardial cushion defect), followed by
ventricular septal defect, tetralogy of Fallot, patent ductus
arteriosus, and atrial septal defect. Patients with Down
syndrome have an increased incidence of duodenal
atresia, annular pancreas and imperforate anus.
Hematological malignancies are more often associated
with Down syndrome than in general population. A
transient myeloproliferative disorder in the newborn or
infant, a well recognized increased incidence of acute
leukemia during the first decade of life and recently
described rare variant of acute megakaryoblastic leukemia
are frequent hematological abnormalities seen in Down
syndrome.
Respiratory diseases mainly pneumonia, represent one
of the major causes of mortality in Down syndrome. In
addition to muscular hypotonia, associated congenital
heart disease and pulmonary hypertension, the defects in
immunological system play an important contributory role
for respiratory diseases. A derangement of B-cell function,
a profound impairment of T-cell mediated immunity and
an alteration of the phagocytic function of polymorphs,
account for the well-known high incidence of infections
in Down syndrome. Hypothyrodism, increased frequency
of thyroid auto antibodies both in children with Down
syndrome and their mothers are frequent associations,
whereas, hyperthyroidism is an occasional association.
Both males and females with Down syndrome, display
fairly normal sexual development. Skin infection and
psychiatric disorder are the problems in adolescents. The
girls may menstruate and can be fertile but males are
always infertile and have low serum testosterone levels.
The adult patients with Down syndrome have additional
problems of cataract, hypothyroidism, mitral valve
prolapse, hearing loss and Alzheimers disease.
Scalp hair in Down syndrome is fine, soft and often
sparse. The prevalence of alopecia areata is high (6%) and
it tends to be extensive and persistant possibly due to
autoimmune mechanism.
Loose folds of skin are found on the nape of the neck in

early infancy. Cutis marmorata, acrocyanosis of extremities
are common in early infancy. With advancing years, the
skin tends to become more dry and hyperkeratotic specially
in areas of abrasion like wrists, elbows, ankles and knees.
Angular stomatitis, chronic blepharitis and a purulent
nasal discharge presumably related in part to abnormalities of the skin of the margins of the mouth, eyelids
and nose are frequently seen in Down syndrome patients.
Chelosis, fissuring of tongue (scrotal tongue) become
more obvious with advancing age. The syringomas,
represent benign tumors of eccrine structures and children
with Down syndrome have an incidence of 10 to 37
percent.
Young children with Down syndrome, usually develop
skin infection in the perigenital area, buttocks and thighs.
These infectious lesions usually start out as follicular
pustules, which subsequently, may develop into abscesses
if not treated promptly. Approximately 50 to 60 percent of
adolescents with Down syndrome have skin infection.
The dentition is usually delayed and irregular. The
teeth are consistently small and malformed and aplasia
of enamel is common. Congenital absence of various
permanent teeth and malocclusions are common, whereas
caries is less common. A relatively high incidence of
periodontal disease has been reported in patients with
Down syndrome.
Many dermatoglyphic changes like simian crease,
distal position of palmar axial triradius and ulnar loops
in all digits are characteristic.
Diagnosis
Diagnosis depends mainly on the characteristic clinical
features. Cytogenetic studies have important etiological
implications and help in genetic counseling.
Prenatal diagnosis of Down syndrome is offered to
women with high risk, i.e. advanced maternal age,
previous history of a child with Down syndrome and
translocation carriers or partners of translocation
carriers.
Prenatal Diagnosis
Confirmation of Down syndrome in an unborn fetus
requires cytogenetic studies done on chorionic villi,
amniocytes or fetal blood cells. However, screening can
Genetics
TABLE 18.2.4: Prenatal diagnosis Down syndrome (Figures
in parenthesis indicate appropriate time for the test.)
MATERNAL SERUM MARKERS
Alpha fetoprotein (AFP)
Unconjugated estriol (UE3)
Human chorionic gonadotropins
(hCG)
Pregnancy associated placental
protein A (PAPP-A)
AMNIOCENTESIS
Early (11-14 weeks)
Conventional
(14-16 weeks)
- decreased (14-16 weeks)

- decreased (14-16 weeks)
- increased (14- 16 weeks)
- increased (10- 13 weeks)
- Karyotype on cultured
amniocytes
- FISH on uncultured cells
used as a biochemical marker, when the test is called

quadruple test, and the detection rate is around 80 percent.
Biochemical markers like pregnancy associated
placental protein A (PAPP A) and hCG are being used
recently for assessing risk of Down syndrome in the first
trimester, called combined test. Further it has been observed
that in Down syndrome during 8 to 12 weeks of gestation,
the nuchal fold thickness is increased (>4mm). the
increased nuchal fold thickness along with increased hCG
and presence of PAPP A in first trimester when taken
together is called as first trimester integrated test. The
combination of quadruple test and first trimester
CORDOCENTESIS (18-20 weeks)

Fetal lymphocytes; culture for karyotype; FISH on non dividing
fetal cells
CHORIONIC VILLUS SAMPLING (9-11 weeks)
Direct preparation or short term culture for karyotype
ULTRASOUND (11-20 weeks)
Nuchal fold >4mm (8-12 weeks)
Double bubble in abdomen (duodenal atresia)
Choroid plexus papilloma
Decreased interorbital distance
Pyelectasia
Short femur
Clinodactly
Macroglossia
Absent nasal bone (8-12 weeks)
Echogenic bowel
Echogenic spot in the heart
FETAL ECHOCARDIOGRAPHY
Atrioventricular canal defects
FISH
Fetal cells in maternal circulation
be done for Down syndrome during pregnancy taking

into account factors like maternal age and the levels of
some biochemical markers in maternal blood. Methods of
prenatal diagnosis in Down syndrome are summarized
in Table 18.2.4.
Screening Tests
It is observed that pregnancy associated with Down
syndrome has low AFP (-feto protein), low UE3
(unconjugated estriol) and high hCG (human chorionic
gonadotrophin) during second trimester. If all the
3 markers are included, the so called triple test detects
60 percent of all Down syndrome pregnancies. Recently
elevated levels of inhibin during second trimester is also
995
SCREENINGFIRST TRIMESTER
Markers
Predictive value
False positive
Maternal serum markers

PAPP-A
Free -hCG
65%
Fetal markers
Nuchal thickness of
> 4mm on
ultrasound.
5%
57-73%
5%
SCREENING SECOND TRIMESTER

Maternal serum
markers
AFP
hCG
E3
Inhibin A
Cut-off value (MoM) Predictive

value
0.5
2.5
0.5
1.9
False
positive
Triple
69%
5%
Quadruple
76%
5%
INTEGRATED FIRST AND SECOND

TRIMESTER SCREENING
1st Trimester
PAPP-A
Free hCG
Nuchal translucency
2nd Trimester
MSAFP
E3
hCG
Inhibin
85%
94%
69%
76%
(percentage indicates accuracy of predicition)
996
integrated test is called integrated test of second trimester,

which has a detection rate of 94 percent. Serum integrated
test is a variant of the integrated test using serum
biochemical markers only (PAPP-A in first trimester and
quadruple test in second trimester). This test is being
evaluated.
For screening Down syndrome associated pregnancies,
there has been a recent interest in ultrasound markers
during second trimester of pregnancy that include choroid
plexus papilloma, atrioventricular canal defect, short
femur, duodenal atresia, pyelectasia, hyper echoic bowel,
etc. For ultrasonographic evaluation exact gestational age
assessment is required.
Confirmatory Test
Chorionic Villus Sampling
This procedure is done between 8 to 11 weeks of gestation
under ultrasound guidance either by transcervical or by
transabdominal aspiration of chorionic villi.
Chromosomal analysis can be directly done on the
specimen obtained, as these cells are dividing and the
results will be obtained within 24 hours. The sample can
be used for FISH technique to detect Down syndrome.
Sometimes chromosome analysis is done after a short term
culture for 2 to 3 days. The advantage of chorionic villi
biopsy is early results and early termination of pregnancy
if Down syndrome is confirmed. The procedure associated
risk of pregnancy loss is around 2 to 3 percent.
Fetal Umbilical Blood Sampling
This is done at 18 to 20 weeks of gestation and the fetal
blood cells obtained are subjected to chromosomal culture.
The results will be available within a week. By FISH
technique results can be obtained within few hours.
Fetal Cells in Maternal Circulation
It is recently observed that fetal cells are present in the
maternal circulation in the first trimester. These cells can
be separated by special techniques like flow cytometry
and used for chromosomal analysis using FISH and PCR.
Fetal DNA in Maternal Plasma
Recently it has been possible to get fetal DNA in maternal
plasma in the first trimester, that is used for molecular
diagnosis of Down syndrome.
Amniocentesis
The conventional amniocentesis done at 14 to 16 weeks of
gestation involves the aspiration of 10 to 20 ml of amniotic
fluid through the abdominal wall under ultrasound
guidance using no. 20 G needle. The sample is centrifuged
to yield a pellet of cells and supernatant fluid. In Down
syndrome, AFP levels will be low in amniotic fluid. The
cell pellet is cultured for about 2 to 3 weeks to obtain
sufficient cells for chromosomal study. Uncultured cells
can be used for FISH. The procedure of amniocentesis is
associated with 0.5 to 1 percent risk of miscarriage. Recent
trials of early amniocentesis at 12 to 14 weeks have yielded
comparable result.
Counseling
A parent of a child with Down syndrome should be
counseled with tact, compassion and truthfulness. The
parents should be told about the associated problems and
the importance of early stimulation should be highlighted.
The risk of recurrence should be clearly told to the parents.
The risk of Down syndrome increases with maternal age,
the risk at 20 years of age is 1:1528, at 30 years it is 1:909,
35 years it is 1:384 and 45 years it is 1:28.
The risk of Down syndrome in relation to maternal
age found at amniocentesis is 3.9 per 100 at 35 years of
age and 44.2 per 100 at 45 years of age. The risk of
translocation Down syndrome in subsequent live births
is given in Table 18.2.5.
TABLE 18.2.5: Translocation Down syndrome: Risk in
subsequent live births
Types of
translocation
Parent carrying balanced

Translocation
Risk to
offspring (%)
14/21
Mother
Father
Neither parent
10
2.5
<1
100
21/21
Health Supervision
In the Table 18.2.6 enumerates the health supervision
guidelines put forth by the American Academy of
Pediatrics.
TURNER SYNDROME
Turner syndrome was first described in 1938 by Dr Henry
Turner and subsequently became the first disorder
recognized to have a chromosomal basis.
Early childhood, 1 to 5 years
S/0
S/0
S/0
S/0
S/0
S/0
S/0
0
0
S/0
0
0
S/0
S/0
0
0
0
S/0
S/0
S/0
S/0
S/0
0
0
S/0
S/0
S/0
S/0
S/0
0
0
0
S/0
S/0
0**
S/0
0
0
0
S/0
S/0
Neonatal 2 months 4 months 6 months 9 months 12 months 15 months 18 months 24 months 3 years
Infancy, 1 Month to 1 year
* Assure compliance with the American Academy of Pediatrics Recommendations for Preventive Pediatric Health Care
- to be performed; S - subjective, by history; and 0 - objective, by a standard testing method
Or at time diagnosis
Discuss referral to specialist
Give once in this age group
According to state law
# As needed
Diagnosis
Karyotype review
Phenotype review
Recurrence risk
Anticipatory guidance
Early intervention services
Reproductive options
Family support
Support groups
Long-term planning
Sexuality
Medical evaluation
Growth
Thyroid screening
Hearing screening
Vision screening
Cervical spine roentgenogram
Echocardiogram
CBC
Psychosocial
Development and behavioral S/0S/0
School perfomance
Socialization
Prenatal
S/0
0
0
0
S/0
S/0
4 years
TABLE 18.2.6: Health supervision for children with down syndromecommittee on genetics
S/0
0
S
0
S
0
0
S/0
S/0
0
0
S/0
S/0 #
Late Childhood, Adolescence,

5 to 13 years 13 to 21 years
Annual
Annual
Genetics
997
998
Etiology
TABLE 18.2.8: Clinical features of Turner syndrome
The incidence is approximately 1 in 2500 female live births

and parental age has no effect on the incidence. Although
60 percent of patients with Turner syndrome have a 45X
karyotype, a variety of chromosomal abnormalities are
seen with the syndrome (Table 18.2.7).
TABLE 18.2.7: Chromosome abnormalities in Tuner syndrome
1.
2.
3.
4.
5.
6.
45X
Mosaic XX/X
Isochromosome Xq or Xp
46 X del(X)
46 X ring (X)
With Y chromosome
60 percent
15 percent
10 percent
5 percent
5 percent
5 percent
It usually arises from mitotic rather than meiotic error

and is not associated with an increase of recurrence in
further pregnancies. The X-chromosome is maternal in
origin in 76 percent and paternal in 24 percent. The
presence of XY cell line in mosaic Turner syndrome may
be associated with virilization at birth and again at puberty
and 20 percent risk of gonadoblastoma.
Clinical Features (Table 18.2.8)
The clinical features depend on chromosome constitution
of the individuals. The patients with 45X Turner syndrome
(classical Turner syndrome) show many characteristic
somatic abnormalities. However, short stature and streak
ovaries are constant findings irrespective of chromosomal
constitutions.
At birth : The newborn may present with lymphedema
especially in the dorsum of the hands and feet and there
may be redundant skin over the back of the neck. Hydrops
and cystic hygroma are seen in utero and may occasionally
be present in the neonate.
Childhood (Fig. 18.2.7): In childhood, Turner syndrome
may present with short stature, short webbed neck with
low posterior hairline, shield shaped chest and widely
spaced nipples, cubitus valgus, pigmentary naevi, cardiac
anomalies like coarctation of the aorta, around 60 percent
will have renal tract abnormalities (horse shoe kidneys
and duplex ureters), mental development is normal.
Typical features
Short stature
Webbed neck
Lymphedema in infancy
Low posterior hair line
Cubitus valgus
Gonadal dysgenesis
Craniofacial anomalies
Triangular face
Antimongoloid eye slant
Ptosis
High arched palate
Multiple naevi
Convex nails
Broad chest, widely placed nipples
Scoliosis
Deafness
Horse-shoe kidneys
Glucose intolerance
Skeletal dysgenesis
Cardiovascular system 1/3 cases
Bicuspid aortic valve (50%)
Coarctation of aorta (20-50%)
Mitral valve prolapse
Dissecting aortic aneurysm
Idiopathic hypertension
Others
Variable psychomotor development
Defects in spatial perception
Perceptual motor organization and fine motor skills
At birth
Lymphedema especially in the dorsum of hand
Redundant skin over the back of neck
Hydrops and cystic hygroma are seen in utero
Puberty
Primary amenorrhea
Failure of secondary sexual development
Streak gonads
Almost invariably sterile females
Puberty
At puberty, Turner syndrome may present for the first time
with primary amenorrhea and failure of secondary sexual
development. Streak gonads are found with ultrasound
Figure 18.2.7: Turner syndromeShort stature and cubitus valgus
Genetics
and at laparotomy. The patients are almost invariably
sterile, but menstruation and secondary sexual development
may be induced by estrogen replacement. Girls with Turner
syndrome have a normal life span. Hypertension and
osteoporosis may be complications in adult life.
Diagnosis
In the past Turner syndrome was diagnosed solely by
buccal smear analysis, this technique is not always reliable,
therefore chromosome analysis with full banding should
be done.
Treatment
Health supervision for Turner syndrome is given in Table
18.2.9. Cyclic estrogen and progesterone therapy in
phenotypic female at postpubertal age will improve
physical development, induce regular menstrual cycles
thus have great psychological benefit. Several attempts
are made to accelerate the growth rate and increase the
adult height of girls with Turner syndrome by use of
999
growth hormone, anabolic steroids and estrogens.

Oxandrolone (an anabolic steroid) in very low doses of
1.25 mg daily is helpful.
KLINEFELTER SYNDROME
This syndrome was first described by Klinefelter,
Reifenstein, and Albright in 1942 with characteristic
feature that become evident at adolescence (Table 18.2.10).
Etiology
Approximately 1 in 1000 newborn males has a 47 XXY
Karyotype and an additional1.2 per 10,000 show 46 XY/
47 XXY mosaicism. The extra X is maternal in origin in 67
percent and paternal in 33 percent. Advanced maternal
age results in increased meiotic nondisjunction resulting
in Klinefelter syndrome. The classical Klinefelter syndrome
has 47 XXY chromosomal constitution. In the so called
Variant Klinefelter syndrome there are multiple Xchromosomes or mosaicism. The greater the number of
chromosomes from XXY to XXXXY, the more severe the
mental retardation and other clinical features.
TABLE 18.2.9: Health supervision for Turner syndrome

System
Timing
Clinical issue
Intervention
Auditory
At diagnosis and every 1-5 yrs

thereafter
Sensorineural deafness
Hearing evaluation, audiology;

hearing aids
Childhood
Recurrent otitis media
Pressure equalizing tubes
Bones
10 yrs to adulthood
Osteopenia; osteoporosis
Vitamin D supplementation
Bisphosphonate therapy
Cardiovascular
At diagnosis
Congenital heart defects
Cardiovascular evaluation
Dental
7yrs and older
Malocclusion
Orthodontic evaluation
Genetic
At all ages
Presence of Y chromosomal material Laproscopic gonadectomy to

prevent gonadoblastoma
Immune
At diagnosis
Thyroditis (hypo or hyperthyroid)
Thyroid function test
Hepatic
Every 1-2 yrs after 6 yrs of age
Liver enzymes persistently elevated
USG to evaluate for hepatic

steatosis; hepatology consult
Lymphatic
Younger than 2 yrs
Lymphedema
Support stockings; decongestive

physiotherapy
Metabolic
All ages
Diabetes; obesity
Annual fasting plasma glucose

screening, target body mass index
Skeletal
9 mths to adulthood
Short stature
hGH+/- oxandrolone
Ophthalmic
At diagnosis
Strabismus;hyperopia
Ophthalmic evaluation
Renal
At diagnosis
Congenital malformation
Renal USG
Reproductive
Prepubertal Adulthood
PubertyInfertility
Adulthood
Estrogen deficiency
Estrogen therapy Assisted

reproduction or infertility consult
Female sex hormone replacement
1000
TABLE 18.2.10 : Klinefelter syndrome (47 XXY-characteristics)
Infertility (azoospermia or oligospermia)

Small, firm testis
Small phallus, cryptorchidism, hypospadiasis
Hypergonadotropic hypogonadism
Gynecomastia
Tall (+10 cm on the average), slender body with long legs
Osteoporosis
Breast cancer
High FSH, LH and low testosterone
Motor delay or dysfunction
Speech and language difficulties
Attention deficits
Learning disabilities
Dyslexia
Psychosocial or behavioural problems
Clinical Features (Fig. 18.2.8)

Patients with classical description with mental retardation, hypogonadism and gynecomastia form only a
small minority of large spectrum. Most of the patients are
tall with eunuchoid proportions and long legs. They are
on an average 10 cm taller than XY males and have altered
body proportions with low upper-to-lower-segment ratio.
The concentration of testosterone tends to be low. The

concentrations of serum estriol are normal or increased
and gonadotropin concentrations are elevated. Gynecomastia occurs in 40 to 50 percent of the patients at puberty,
as a result of increased ratio of serum estriol to testosterone.
Breast cancer occurs in approximately 4 percent of the
patients, an incidence 20 times higher than in normal
males.
Small testes, phallus, cryptorchidism and hypostasis
occur in some patients. azoospermia and infertility are
common.
Most patients have psychiatric and behavioral
disorders. Affected children may be immature, excessively
shy, anxious and aggressive and may engage in antisocial
acts.
Increased incidence of pulmonary disease, varicose
veins, diabetes in Klinefelter syndrome is known.
Extragonadal germcell tumors especially of the mediastinum and cerebral germinomas also occur with higher
frequency.
Diagnosis
The diagnosis should be suspected in prepubertal
children who have long legs, smaller than normal testes,
small phallus, learning disorders, delay in language
development. Mental retardation or psychosocial behavior
problems. Diagnosis of the syndrome in patients after
puberty is not difficult, by the findings of the typical
phenotype of tall stature; incomplete virillization, small
firm testes, and elevated serum gonadotropin concentrations. The diagnosis can be confirmed by the finding of
the 47, XXY karyotype. Testicular biopsy after puberty
reveals hyalinization of seminiferous tubules, adenomatous clumping of Leydig cells and azoospermia.
Treatment
Figure 18.2.8: Klinefelters syndromeGynecomastia

and long limbs
It has been suggested that treatment with testosterone

should be stated by 11 to 12 years of age to initiate puberty
and prevent physical and psychological complications of
hypogonadism. At the same time this would prevent
excessive adult height. Psychologically disturbing or
persisting gynecomastia should be corrected by reduction
mammoplasty. Early intervention for learning and
behavioral disorders may be beneficial.
Testosterone therapy: it has been suggested that
treatment with testosterone should be started by 11
12 years of age to initiate puberty and prevent physical
and psychosocial complications of hypogonadism.
Genetics
Treatment could be started with 50mg of testosterone

enanthate IM monthly and when the bone age is 11 or
12, increasing to 100mg IM; when bone age is
14 increases the dose to 200-250mg every three to four
weeks, when full virilization is desired or when
growth is ending.
Speech therapy: to develop skills in understanding
and production of complex language. Early intervention for learning and behavioral disorders may be
beneficial.
Physical therapy: in boys who are hypotonic or having
delayed motor skills.
Occupational therapy: if boys with 47 XXY have fine
motor dyspraxia, occupational therapy is indicated.
Educational services: males with 47 XXY should
receive a comprehensive psycho educational evaluation to assess their areas of strengths and
weaknesses.
FRAGILE X SYNDROME
Fragile X syndrome has the unique distinction of being
both the most common inherited cause of learning
difficulties and the first disorder in which a dynamic
mutation was identified. Martin and Bell described the
condition in 1940s before the chromosome era, and it has
been also called Martin-Bell syndrome, which has an
incidence rate of 1 in 5000 males and accounts for 4-8% of
all males with learning difficulties.
Etiology
The term fragile X syndrome derives from the presence of
a fragile site expressed as a isochromatid gap in the
metaphase chromosome at map position Xq 27.3 on the
distal portion of the long arm of X-chromosome in a
proportion of cells of affected individual.
The gene was designated FMR-1 for fragile X mental
retardation. The DNA segments show a peculiar stretch
of trinucleotide repeats in the FMR 1 gene that increase
the size of the specific DNA fragment of the X-chromosome
in Xq 27.3; a trinucleotide sequence (cytosine, guanine,
guanine = CGG) repeated a number of times. In normal
individual the repeat copies range from as low as 6 to as
high as 45 (Fig. 18.2.9).
In the members of families affected with the fragile X
syndrome, there are two types of mutations:
(i) Premutation; (ii) Full mutation.
1001
Figure 18.2.9: Fragile site on X-chromosome has CGG repeats

more than 230 and normal X has 6 to 52 CGG repeats
Premutation
Members with trinucleotide repeat copies ranging between
50 to 230 have no phenotypic effect and no intellectual
impairment, and the mutations are termed premutations.
These are fragile X carriers and may produce children or
grandchildren affected with the syndrome. Premutations
may become full mutations after oogenesis, although
premutations may also remain as premutations in some
offsprings. The daughters of transmitting males (normal
males with a premutation) always inherit approximately
the same number of CGG repeats as found in the fathers.
There may be some variations in the number of repeats,
but the number remains in the premutation range, less
than 230.
In daughters of transmitting males, amplification of
the premutation to a full mutation occurs much more
frequently, resulting in a risk of 74 percent in grandsons
produced by the daughters of normal transmitting males.
Full Mutation
In members affected with the fragile X syndrome, the
trinucleotide repeat is expanded, so that many hundreds
of copies are present, more than 230 copies, and this
mutation is called full mutation. Only approximately
53 percent of females with the full mutation are mentally
impaired. In general the expression of phenotypic
manifestation is less severe in females, in keeping with
the X-linked dominant inheritance. This is probably
related to females having a functional allele on their
nonfragile X-chromosome.
The FMFR-1 gene is expressed in many tissues, the
brain showing the highest levels of expression, in addition
1002
to the heart, lymphocytes, testis, uterus, and placenta, but

it is not expressed in liver, lung, kidney, muscle or pancreas.
Clinical Features (Fig. 18.2.10)
In the fragile X syndrome, 20 percent of the males (normal
transmitting males) and about 50 to 65 percent of
heterozygote females have no obvious features. Eighty
percent of the males and 35 percent of the female carriers
of the fragile X gene are developmentally delayed. The IQ
of the males is between 30 and 55 and sometimes extends
into the mildly retarded, borderline normal range.
Diagnosis
The possibility of fragile X syndrome should be suspected
in males and females with mental retardation and the
phenotypic changes and the diagnosis confirmed by DNA
testing. DNA testing has replaced cytogenetic fragile X
testing as the diagnostic method. For cytogenetic
demonstration of fragile site on longarm of X chromosome (Figs 18.2.11 and 18.2.12), the cells have to be cultured
in folic acid deficient media. Cytogenesis demonstration
of fragile site even with this technique is only 50 percent
and large number of cells have to be examined for
demonstration of fragile site which is time consuming.
DNA testing can distinguish, in a single test, between
the normal genotype, the premutation, and the full
mutation. Candidates for testing for fragile X syndrome
include familial mental retardation specially when two
males are affected, prepubertal children with overgrowth,
developmental delay, autism, hyperactivity, hand
Figure 18.2.10: Plain karyotype picture showing fragile site

on long arm of X chromosome.
The characteristic features of fragile X syndrome

are outlined in the Table 18.2.11.
TABLE 18.2.11: Fragile X-characteristics

1. Growth
2. Craniofacial
3. Neurologic
4. Behavioral
5. Others
6. Genitalia
7. Inheritance
Overgrowth postnatally
Large ears, Prominent forehead, Long
face-Prominent jaw, Macrocephaly
palate, High-arched palate
Mental retardation
Temper tantrum, Hyperactivity, Autism,
Extreme shyness
Joint looseness, Pes planus, Soft skin,
Mitral value prolapse.
Macroorchidism (males) after puberty
X linked with premutations and full
mutations.
Figure 18.2.11 Electron microscopic view of

the fragile site on Xq.
Genetics
1003
4. Pelvis and abdomen-inguinal hernia, diastasis recti,

small iliac winds.
5. Hands and feet-short metacarpals or metatarsals,
partial syndactyly, pes planus, simian crease.
SINGLE GENE DISORDERS
MARFAN SYNDROME
Marfan syndrome is an autosomal dominant (sporadic in
15-30 percent) disorder with complete penetrance but
variable expressivity and with an incidence of 1 in 10,000
people.
Clinical Manifestations (Fig. 18.2.13)
The diagnosis of Marfan syndrome is made on the overall
pattern of malformations (typically skeletal, cardiovascular
and ocular; Table 18.2.12).
Figure 18.2.12: Cat cry syndrome
clapping, temperamental outbursts, extreme shyness, even

in the absence of other physical features or family history.
Treatment
No treatment is known, except for supportive measures
for the psychological and behavioral disorders. No
treatment is usually needed for the overgrowth.
5p- (CRI-DU-CHAT SYNDROME)
Cri-du-chat syndrome is one of the most common
chromosomal deletion syndromes, with an estimated
incidence of 1 in 50,000 births. About 70 percent of the
affected newborns are females, but the survival rate
appears to be better for males than females.
The syndrome derives its name from the striking cat
like cry that is heard in infancy. This cry is related to the
hyperplastic larynx and tends to lessen with increasing
age and growth of the larynx.
The clinical features in cri-du-chat syndrome are :
1. General low birth weight, mental retardation, catlike cry.
2. Craniofacies (Fig. 18.2.12) microcephaly, round face,
hypertelorism, epicanthus, antimongoloid palpebral
fissure, microphthalmia, low set malformed ears,
preauricular tags.
3. Thorax - congenital heart disease (occasional).
Figure 18.2.13: Marfan syndromearachnodactyly
For the proband, diagnosis requires the presence of

major criteria in at least two organ systems and
involvement of a third organ system. For a family member,
diagnosis requires the presence of one major criterion in
the family history and one major criterion in an organ
system and involvement of a second organ system.
Diagnosis
1. If the family and genetic history are not contributory,
then there should be a major criteria in at least 2
different organ systems and involvement of a third
organ system.
2. Diagnosis in the presence of an affected 1st degree
relative requires involvement of two systems with
preferably one major.
1004

TABLE 18.2.12 : Features of Marfan syndrome
SKELETAL SYSTEM
Two components of the major
criterion or one component of
the major criterion+two of the
minor criteria must be present.
OCULAR SYSTEM
The major criterion or at least
two of the minor criterion must
be present.
PULMONARY SYSTEM
One of the minor criteria must
be present
SKIN AND INTEGUMENT
The major criterion or one of
the minor criteria must be
present.
FAMILY HISTORY
One of the major criteria must
be present.
Major criteria
Minor criteria
Pectus carinatum, Pectus excavatum requiring

surgery, Reduced upper-to-lower segment
ratio or arm span-to-height ratio >1.05,
Positive wrist and thumb sign
Scoliosis of >20 or Spondylolithesis
Reduced extension of the elbows
Medial displacement of the medial malleolus
causing pes planus.
Pectus excavatum of moderate severity,

Joint hyper mobility
Highly arched palate with dental crowding,
Facial appearance (dolichocephaly, malar
hypoplasia, enophthalmos, retrognathia, and
down slanting palpebral fissures.)
Ectopia lentis
Abnormally flat cornea

Increased axial length of globe
Hypoplastic iris or Hypoplastic ciliary muscle
causing decreased miosis.
None
Spontaneous pneumothorax
Apical blebs (on CXR)
Lumbosacral dural ectasia (by CT Scan or MRI)
Stretch marks
Recurrent or incisional hernia.
Having a parent, child, or sibling with either:

Presence of a mutation in FBN1 known to cause
Marfans syndrome or Presence of a haplotype
around FBN1, inherited by descent, known to
be associated with Marfans syndrome in the
family.
Etiology
The basic defect in Marfan syndrome has now been traced
to a defective fibrillin in gene mapped to chromosome
15 (15q 21.1). Fibrillin is a recently discovered connective
tissue protein found in micro fibrils, a constituent of elastic
tissue and abundant in tissues affected in Marfan
syndrome, including the aorta, suspensory ligament of
the lens, and periosteum.
Treatment
Therapy for Marfan syndrome focuses on prevention of
complications and genetic counseling. The pediatrician
in consultation with the pediatric sub specialists should
coordinate and formulate rational approach to expectant
monitoring of potential complications. Use of blockers
reduce and postpone cardiac complications like aortic root
dissection and arrhythmias specially during pregnancies.
Children with Marfan syndrome should avoid competitive sports.

Tuberous Sclerosis Complex (TSC) (Fig. 18.2.14)
(Syn: Epiloia or Bournevilles Disease)
Tuberous sclerosis (TSC) is a type of neurocutaneous
syndrome, inherited as an autosomal dominant disorder
and involves multiple organs (brain, skin, kidney, eyes
and heart). The prevalence of TSC is 1:1000. The lesions in
this syndrome are caused by hamartomas and hamartias.
The major manifestation of this disorder includes skin
lesion (95%), mental retardation (50%), autism, seizures
(85%) (myoclonus in children), kidney diseases (60%) and
rarely cerebral giant cell astrocytoma. Mental retardation,
epilepsy and adenoma sebaceum were earlier considered
as triad of tuberous sclerosis.
Genetics
Figure 18.2.14: Tuberous sclerosisNote

adenoma sebaceum
The unique skin lesions and cranial MRI characteristics are most helpful for confirming diagnosis. For
definite diagnosis of TSC patient should have 2 of 11 major
features. Genetic blood tests for the two genes TSC1 and
TSC2 which cause the disease are also available but in 30
percent of patients the test results are negative.
Major Criteria
1. Facial angiofibromas or forehead plaque. Facial
angiofibromas originally misnamed as adenoma
sebaceum distributed usually over malar area are the
classical lesions of TSC and occur in 50 percent of
cases. They make their appearance around 4 years of
age. Forehead plaques are darker than surrounding
skin and appear very early in infancy.
2. Nontraumatic ungal fibroma. They are flesh colored
angiofibromas.
3. There are many hypomelanotic macules. These are
present in nearly 90 percent of cases that occur over
face, trunk and extremities. The size varies from 0.5
to 2 cm and is pale and has ash leaf shape. They are
usually present at birth and are better appreciated
with ultraviolet woods light in fair skinned people.
4. Shagreen patch. These are usually present over lower
back often appearing after two years and are
characterized by flesh colored or slightly darker of
redder elevated lesions with surface of an orange peel.
1005
5. Multiple retinal nodular hamartomas.

6. Cortical tubers (dysplasia plus migrating tracts count
as one features). These are seen both in cerebrum and
cerebellum. These are some times the source of seizure
activity and can be detected by MRI.
7. Subependymal nodules. They are present in more
than 80 percent of TSC patients and are commonly
calcified. MRI is superior to CT scan in detecting
cortical tubers, subependymal nodules and migration
tracts.
8. Subependymal giant cell astrocytoma.
9. Cardiac rhabdomyoma (single or multiple). These are
usually asymptomatic but may cause obstruction to
flow through the heart, CCF, arrhythmias including
WPW syndrome and sudden death. They are seen in
infancy.
10. Lymphangiomyomatosis usually in lungs.
11. Renal angiomyolipoma (when both lymphangiomyomatiosis and renal angiomyolipomas are present,
they count as one feature). Renal involvement is seen
in 60 percent of TSC patients and includes renal cysts,
angiomyolipomas and rarely renal cell carcinoma.
Renal diseases leading cause of death in TSC.
Minor Diagnostic Features Include
1. Multiple dental pits.
2. Hamartomatous rectal polyp (histologic confirmation
is needed)
3. Bone cyst (radiographic diagnosis is sufficient)
4. Cerebral white matter radial migratory lines.
5. Gingival fibroma.
6. Non-renal hamartoma.
7. Retinal chromic patch.
8. Confetti skin lesions.
9. Multiple renal cyst.
Probable TSC include one major plus one minor feature
and possible TSC include one major or two or more minor
features.
The patients with TSC should be thoroughly evaluated
by careful history including family history, skin
examination, ophthalmic examination for a retinal
hamartoma, renal ultrasound for renal lesions and
echocardiography to detect rhabdomyoma below 2 years
(after that period they regress with age), neurodevelopment testing for cortical tubers, subependymal giant cell
astrocytoma and hydrocephalus due to obstruction of
foramen of Monro due to tubers.
1006
Management of TS comprises treatment of seizures,

educational programs for mental retardation and autism
and pharmacological treatment of seizures. Facial
angiogfibromas may require laser therapy. Surgical
treatment is indicated for giant cell astrocytoma and renal
angiomyolipoma.
Contrary to earlier understanding, the disorder is
caused by 2 distinct genes, TSC-1 and TSC-2. TSC-1 gene
is localized to chromosome 9 and produces a protein
hamartin. TSC-2 is localized to chromosome 16 and
produces a protein tuberin. Both hamartin from TSC-1 and
tuberin from TSC-2 are thought to function at least in part
as tumor suppressor gene by which they regulate cell
growth and development. The disease is inherited as
autosomal dominant trait and most cases occur as
sporadic mutations. Variability in expression is seen
between cases and even within family like in many other
autosomal dominant disorders. Clinical differences
between TSC-1 and TSC-2 are now being recognized but
they are typically differences of degree and not of character.
3.
4.
5.
6.
Neurofibromatosis
Neurofibromatosis is one of the commonest neurocutaneous syndromes inherited as an autosomal
dominant disorder with variable expression. It is
historically associated with the name von Recklinghausen,
a German Pathologist who coined the term neurofibroma
in 1882. There are two main types of neurofibromatosis
known as NF-1 and NF-2. NF-1 has an incidence of
approximately 1 in 3000 and NF-2 has an incidence of 1
in 35,000.
The diagnostic suspicion of NF-1 is usually raised by
the presence of multiple cafe-au-lait spots, the hallmark of
NF-1. They are named as such because of its color, similar
to coffee with milk. Occasionally, facial malformation
caused by bone dysplasia and impaired vision from optic
nerve glioma brings the child to medical attention.
The diagnosis of NF-1 requires two or more of the
following diagnostic features.
1. Six or more cafe-au-lait spots 1.5 cm or larger in
postpubertal individuals and 0.5 cm or larger in
prepubertal children. These are macular lesions with
irregular border seen over trunk, face and body.
2. Two or more neurofibromas of any type or more
plexiform neurofibromas. Neurofibromas arise from
peripheral nerve sheath. They are rare in young
children but increase in number with advancing age.
7.
They have no malignant potential. Plexiform

neurofibromas have ill defined borders and are diffuse
and highly vascular and do not follow tissue plane.
Skin over the lesions is pigmented and hairy. A small
percentage (1-4 percent) of plexiform neurofibromas
may turn malignant.
Freckling in the axillary or inguinal region. They
develop in early childhood and by 5 years 84 percent
have them.
Optic nerve glioma (optic pathway tumor). Decreased
visual acuity, optic pallor or atrophy, visual field
defects, proptosis, restricted eye movements,
hypothalamic dysfunction and headache are the
clinical manifestations of these slow growing low
grade astrocytomas of optic nerve.
Two or more Lisch nodules (iris hamartomas). These
are benign iris hamartomas visible usually by slit lamp
examination. They are uncommon in young children
but by 10 years, 70 percent of children and 95 percent
of adults will have them.
A distinctive osseous lesion, such as dysplasia of the
sphenoid bone and dysplasia or thinning of long bone
cortex (pseudoarthroses).
A first degree relative with NF-1 according to the
preceding criteria.
Absence of cafe-au-lait spots, axillary freckling,

cutaneous neurofibromas and Lisch nodules by 5 years,
for all practical purposes excludes the diagnosis of NF-1.
Genetic tests are available but have a high false negative
rate.
Epilepsy, macrocephaly, short stature, scoliosis,
glaucoma, stroke, mental retardation and cognitive
problems are other complications in NF-1. Neuro imaging
studies are not important in the diagnosis of NF-1 but are
used for monitoring complications.
There is only one gene that causes NF-1. Most NF-1
mutation causes premature truncation of the neurofibromin protein. The NF-1 gene product, neurofibromin is
thought to function as a tumor suppressor.
The management of NF-1 mainly consists in evaluation for complications like focal neurological dysfunction, abnormal puberty, optic pathway trauma,
scoliosis, cognitive/learning problems, hypertension and
surveillance of plexiform neurofibromas for malignant
transformation and their appropriate treatment.
In NF-2 both cafe au lait spots and neurofibromata
can occur but these are less common than in NF-1. The
most characteristic feature of NF-2 is the development in
Genetics
early adult life of tumors involving 8th cranial nerves.
These used to be called acoustic neuromas and are now
known as vestibular schwannomas.
ACHONDROPLASIA
Achondroplasia occurs in about 1 in 25,000 births and is
inherited as an autosomal dominant trait. About 50 percent
of cases represent new mutations.
This disorder is due to a specific point mutation in
Fibroblast Growth Factor Receptor 3 (FGFR3) gene. The
mutations in the same gene produce two other short limb
dwarfs, viz. Thanatophoric Dwarf (a lethal severe short
limb dwarf with gross craniofacial abnormalities) and
Hypochondroplasia (a very mild benign short limb dwarf
with no craniofacial abnormalities).
Clinical Manifestations (Fig. 18.2.15)
The clinical manifestations include rhizomelic shortening
of the limbs, short stature, frontal bossing, depressed nasal
bridge, large head size, short and broad trident shaped
hands, spinal abnormalities like lumbar lordosis,
hypotonia, delayed motor development, mental development is usually normal.
Complications include hydrocephalus, recurrent otitis
media, and chronic serous otitis media, leading to a high
incidence of conductive hearing loss in adulthood, lumbar
cord and nerve root compression syndromes.
1007
Roentgenographic Manifestations
Short pelvis with broad iliac wings; horizontal acetabular
roofs; diminished vertebral interpedicular distance from
LI to L5; spinal canal is narrowed; anterior tonguing and
wedging of lower thoracic or upper lumbar vertebrae;
posterior scalloping of the lumbar vertebrae; the base of
the skull is shortened; foramen magnum is small and
irregular; the metaphyses have some flaring and may
appear V-shaped (circumflex sign); the short tubular bones
of the hands and feet are shorter and wider than normal;
the chest has a decreased anterioposterior diameter, with
anterior cupping of the ribs.
Health Supervision
The following table enumerates the guidelines for
supervision of children with achondroplasia, as stated
by the American Academy of Pediatrics (Table 18.2.13).
Treatment
i. Prompt recognition and appropriate treatment of
complications,
ii. Treatment of the psychological effects of severe short
stature and unusual appearance,
iii. Genetic counseling.
Rett Syndrome
Rett syndrome is characterized by a period of normal
development in the first few months after birth followed
by loss of developmental milestones, failure of head
growth, autistic behavior, seizures and dementia. This
syndrome affects female children only. It was first
described by Austrian Doctor, Andreas Rett in 1966. The
diagnosis is essentially clinical and the course of the illness
passes through four predictable stages.
Stage 1 (Birth to 18 months)
Acquired microcephaly
Disinterest in surroundings
Hypotonia
Stage 2 (1-2 year)
Figure 18.2.15: Achondroplasia
Loss of expressive language

Regression of gross motor milestones
Characteristic hand movements (Hand washing
movements)
Neonatal 2 mo
4 mo
6 mo
Infancy, 1 Month to 1 year

9 mo
S/O
S
S/O
S/O
XR
S
S/O
S
S/O
S/O
XR
S
24 mo
S/O
18 mo
X
X
X
X
15 mo
X
X
X
X
X
12 mo
Early childhood, 1 to 5 y
S/O
3y
XR
S
R
O
4y
S
S/O
O
XR
S
R
O
S
S/O
O
X
X
X
X
X
X
13 to 21 y
Annual
5 to 13 y
Annual
X
X
X
X
Adolescence
Late Childhood,
These guidelines ensure compliance with AAP recommendations for preventive health care. FGFR3 indicates fibroblast growth factor recepitro type 3;X to be performed;
S subjects; b history; O objective, by a standard testing method; R diseases referral to a specialist; continue to monitor.
Diagnosis
Radiography
Whenever the diagnosis is suspected
Review phenotype
Review proportions
Molecular testing [FGFR3] See text
When diagnosis is not certain
Genetic counseling
Early intervention
X
Recurrent risks
X
Reproductive options
Family support
X
Support groups
X
Long-term planning
Medical evaluation
Growth/weight/OPC
X
X
X
X
X
Orthopedic consult
Neurology consult
Hearing
Social readiness
Orthodontics
Speech
Medical evaluation
Radiology, only to make
diagnosis or II
complication
CT/MRT brain/cervical
X
Spine
X As indicated
Social adjustment
Psychosocial
S
Behavior and development
S/O
S/O
S/O
S/O
School
Sexuality
Prenatal
TABLE 18.2.13: Achondroplasia guidelines for health supervision
1008
Genetics
Seizures (50%)
Irritability
Insomnia
Stage 3 (2-10 year)
Stereotypic hand movements (wringing, patting,
clapping, tapping and mouthing)
Ataxia
Tremulousness
Breath holding spells
Stage 4 (> 10 years)
Scoliosis
Muscle wasting
Death in late adolescence from infection or cardiac
arrhythmia
Atypical presentations include onset from birth, late
onset, preservation of speech and hand skills and rare
occurrence in males.
The inheritance is X-linked dominant with lethality in
hemizygous males. The mutation is on MECP2 gene on
the long arm of X-chromosome. This mutation results in
shortage of MECP2 protein, which is required to recruit
other genes during early brain development. This results
in brain remaining developmentally immature in sensory,
motor, emotional and autonomic functions. Most
mutations are sporadic in nature. There are more than
100 mutations known in MECP2 gene. MECP2 mutation
can be detected by DNA test in more than 80 percent of
cases with clinical symptoms.
L-dopa has been tried for rigidity during motor
regression stage. Naltrexone, an opiate antagonist may
benefit irregular breathing, seizures and screaming spells.
Bromocriptine has shown some help in improving
communication and reducing agitation and hand
movements. L-carnitine tried in some patients showed
benefit in language skills. Dextromethorphan is being
studied because of its role in neurotransmitter mechanism.
POLYGENIC DISORDERS
Congenital Malformations
An anatomical defect that is present at birth is called as
congenital malformation.
1009
A malformation is a morphologic defect of an organ,

part of an organ, or larger region of the body resulting
from an intrinsically abnormal developmental process;
Intrinsic means the developmental potential of the organ.
From fertilization the organ never had a chance to develop
normal form or structure.
When the congenital malformation has a major impact
on health, function, survival and cosmetic aspects it is
called as congenital malformation major (e.g. Neural tube
defects, congenital heart disease, cleft lip and palate) and
when it has no impact on health function, survival and
cosmetic aspects it is called congenital malformation
minor (e.g. epicanthic fold, single palmar crease,
clinodactyly). When multiple anomalies which are
pathogenetically related, occur in a single baby it is said
to be a malformation syndrome (e.g. Down syndrome,
Nail-patella syndrome, Marfan syndrome).
A disruption is a morphologic defect of an organ, part
of an organ, or a larger region of the body resulting from
the extrinsic breakdown or an interference with an
originally normal developmental process (e.g. Amniotic
band syndrome). In contrast to a malformation, the
developmental potential of the involved organ was
originally normal. Secondly, an extrinsic factor such as
an infection, teratogen, or trauma interfered with the
development which thereafter proceeded abnormally. By
definition, a disruption cannot be inherited. However,
inherited factors can predispose to and influence the
development of a disruption, e.g. Amniotic band syndrome.
A deformation is an abnormal form, shape, or position
of a part of the body caused by mechanical forces. The use
of the term deformation is restricted to aberrations of form
considered a normal response of the affected tissue to
unusual mechanical forces. These forces may be extrinsic
to the fetus (e.g. as a result of intrauterine constraint) or
intrinsic (such as fetal hypomobility caused by a nervous
system defect). An example of a prenatal deformation is
an equinovarus foot, which may result from extrinsic
compression of the fetus caused by oligohydramnios.
A dysplasia is an abnormal organization of cells into
tissue(s) and its morphologic result(s). In other words, a
dysplasia is the process and the consequence of
dyshistogenesis. Osteogenesis imperfecta and Marfan
syndrome are dysplasias because the abnormalities in
each condition can be reduced to a defect in connective
tissue. In contrast to malformations, disruptions and
deformities, dysplastic lesions are frequently not confined
to single organs.
1010
Multiple anomalies in a given patient may be causally

or pathogenetically related, or occur together on a
statistical basis or by chance alone.
A polytopic field defect is a pattern of anomalies
derived from the disturbance of a single development field.
Dysmorphogenetically polytopic field defects represent
disturbances of long-distance inductive relationship as
between limb buds and meso and metanephros, gonads
and genitalia, circulation and cardiac morphogenesis, etc.
A sequence is a pattern of multiple anomalies derived
from a single known or presumed prior anomaly or
mechanical factor. A malformation, a disruption, or a
mechanical factor may give rise to a cascade of secondary
problems in subsequent morphogenesis. Thus, a myelomeningocele may lead to lower limb paralysis, muscle
wasting, club-feet, incontinence, urinary tract infection
and renal damage, constipation and dilatation of the
bowel, etc. The pattern is called the myelomeningocele
sequence. Other examples are Potter sequence, due to
oligohydramnios and Pierre Robin sequence due to
maldevelopment of mandible.
An association is a nonrandom occurrence in two or
more individuals of multiple anomalies not known to be a
polytopic field defect, sequence, or syndrome. It refers
solely to statistically, not pathogenetically or causally
related anomalies, e.g. VATER association (Vertebral
anomaly, anal atresia, tracheoesophageal fistula (TEF),
radial/renal dysplasia).
TABLE 18.2.14: Summary of human teratogens

Agents
I Drugs
1. Thalidomide
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Incidence
Approximately 3 percent of newborn babies have
congenital malformations. The figure doubles at 5 years if
these children are followed up.
13.
II.
1.
2.
Etiology
Etiological agents could be broadly divided into
4 categories-specific teratogenic agents (8-10%), monogenic (15-25%), chromosomal (15-28%) and unknown
(including multifactorial) (40-65%). A teratogen is an
agent, when applied during prenatal life, produces a
permanent postnatal damage, change in morphology, or
functions. Such agents can be chemicals, drugs, virus or
physical or deficiency states. Majority of the malformations
are due to complex involvement of genetic and environmental factors. The summary of human teratogens is given
in Table 18.2.14.
Most common major defects
3.
4.
5.
6.
III.
1.
2.
Limb reduction defects

Girdle hypoplasia
Ear Anomalies
Alcohol
Growth retardation
Reduced palpebral fissures
Microcephaly, mental retardation
Diethystilbesterol
Vaginal Adenosis
Cervical erosion and ridges
Adenocarcinoma of the vagina (rare)
Warfarin
Hypoplasia of nasal cartilage
Various CNS defects
Stippled epiphyses
Hydantoin
Growth retardation
(Dilantin)
Dysmorphic craniofacial features
Microcephaly, mental retardation
Trimethadione
Developmental delay
V-shaped eyebrows, low ears
Cleft lip or palate
Aminopterin and
Abortion
methotrexate
Hydrocephalus
(Folic acid
Growth retardation, mental
deficiency)
retardation
Antituberculous
Hearing loss
drugs (streptomycin)
Tetracycline
Stained teeth
Hypoplasias of enamel
Valproic acid
Neural tube defects
Retinoic acid
Abortion
(Vitamin A)
Craniofacial dysmorphism
Lithium
Neural tube defects
Ebstein heart anomaly
Other cardiac defects
Antithyroid drugs Hypothyroidism
Goiter
Infections
Rubella
Deafness, cataracts, heart defects
Cytomegalovirus
Growth retardation, mental
retardation,
Hearing loss
Toxoplasmosis
Hydrocephalus, blindness,
mental retardation
Varicella
Skin scarring, muscle atrophy,
Mental retardation
Venezuelan
Brain destruction, cataracts, death,
equine encephalitis
Syphilis
Abnormal teeth and bones
Mental retardation
Chemicals
Mehylmercury
Cerebral atrophy, Spasticity,
Seizures, Mental retardation,
PCP
Growth retardation
Skin discoloration
Contd.
Genetics
Contd.
1011
DYSMORPHIC CHILD
IV. Physical, nutritional and other factors

1. Smoking
Abortion, Intrauterine growth
retardation
2. Ionizing radiation
(Dependent on stage of pregnancy)
(exposures above Abortion
the diagnostic
Major organ malformations
range)
(18-36 d)
Microcephaly and mental
retardation (8-15 weeks)
3. Diabetes
Congenital heart defects
Caudal dysgenesis
4. Iodine deficiency
Goiter, mental retardation,
growth retardation
5. Maternal
Abortion, microcephaly,
phenylketonuria
Mental retardation
The common life-threatening congenital anomalies are

listed in Table 18.2.15.
Some simple procedures can be done to diagnose the
common congenital anomalies in the neonatal period:
Not able to pass nasal catheter: suspect choanal atresia
Not able to pass gastric catheter: suspect esophageal
atresia
If not able to pass anal catheter, suspect anal atresia
Positive Ortolonis test should clinch the diagnosis of
congenital dislocation of hip
In case of absence of femoral arterial pulsation, suspect
coarctation of aorta.
In case of presence of single umbilical artery, one
should suspect GIT anomalies.
Presence of a tuft of hair in the lumbosacral region
indicates spina bifida occulta.
Auscultate the heart for murmurs which suggests
congenital heart disease.
Approximately 1 percent of newborn infants have multiple

anomalies or syndromes. Only 40 percent of these have
recognized syndromes and the remaining need to be
further delineated. A syndrome literally means running
together (a Greek word) and clinically indicates a
constellation of malformations thought to be pathogenitically related.
Different systems of nomenclature are employed (Table
18.2.13), a single syndrome may be known by several
terms, thus causing confusion. For example, in past,
Williams syndrome has also been known as WilliamBeuren syndrome, idiopathic hypercalcemia, supravalvular aortic stenosis syndrome, and elfin facies
syndrome. In general, a syndrome may be denoted by (1)
an eponym, (2) one or more striking features, (3) an
acronym, (4) a numeral, (5) a geographic term, or (6) some
combination of the above. Examples are given in Table
18.2.16.
A proper approach begins with a careful history
including personal, family and pregnancy history. A
summary of important points in history is presented in
Table 18.2.17.
The physical recognition of genetic syndromes is done
either by (i) gestalt recognition, or by (ii) identifying suitable
handles.
Gestalt Recognition
Individual malformation can be easily organized into a
meaningful problem without consciously analyzing the
individual abnormalities. Recognition is immediate. For
instance, the diagnosis of Down syndrome is often
possible from the examination of craniofacial features
alone.
TABLE 18.2.15: Common life-threatening congenital anomalies

1. Choanal atresia
2. Tracheo-esophageal fistula
3.
4.
5.
6.
7.
8.
9.
Diaphragmatic hernia
Duodenal atresia
Ileal atresia
Omphalocele
Neural tube defects
Respiratory distress in labor room, inability to pass nasal tube. Suspect CHARGE syndrome
(coloboma, heart defect, atresia choane, retarded growth, genital abnormality, ear anomaly)
Polyhydramnios, aspiration pneumonia, excessive salivation, inability to pass NG tube, suspect
VATER syndrome
Scaphoid abdomen, bowels in chest, respiratory distress, cyanosis, apparent dextrocardia
Micrognathia, cleft palate, airway obstruction
Polyhydramnios
Bile stained vomiting, suspect Downs syndrome
Abdominal ditension
Polyhydramnios, intestinal obstruction
Polyhydramnios
1012

TABLE 18.2.16: Syndrome nomenclature
Basis of nomenclature
Examples
Etiology
Pathogenesis
Striking feature
Anatomic location
Eponym
Acronym
Patients name
Geographic location
Numerical nomenclature
Compound designations
Mythical nomenclature
Animal nomenclature
-L-iduronidase deficiency, 47, XXY syndrome, abused child syndrome

Dumping syndrome
Scalded skin syndrome, whistling face syndrome
Nail-patella syndrome, trichorhinophalangeal syndrome
Good pasture syndrome, Peutz Jeghers syndrome, Klippel-Trenaunay-Weber syndrome
Leopard syndrome, CREST syndrome
Cowden syndrome, BBB syndrome
Typus Amstelodamensis
MPS IV, type II achondrogenesis
Hurler syndrome (-L-iduro-nidase deficiency), Taybi oto-palato-digital syndrome
Gargoyle syndrome, elfin facies syndrome
Cat-cry syndrome, bird-headed dwarf syndrome
TABLE 18.2.17: Important points in history taking

Questions
Personal/family history
1. Elderly mother
2. Elderly father
3. Maternal disease (e.g. diabetes)
4. Poor social history
5. Racial origin of parents
6. Parental consanguinity
7. Other affected family members or multiple
malformations
Pregnancy history
8. Maternal drug or alcohol ingestion
9. Exposure to radiation (especially therapeutic)
10. Early rupture of membranes membranes
11. Oligohydramnios
12. Polyhydramnios
13. Poor fetal movements
14. Breech presentation
Relevance
? chromosomal aneuploidy
? New autosomal dominant mutation
Known associated fetal abnormalities (e.g. sacral agenesis with maternal
diabetes)
Possible alcohol/drug ingestion
Known genes of high frequency in certain racial groups (e.g. Ellis-van Creveld
syndrome in the Amish)
Autosomal recessive disorders
Single gene or chromosomal disorder. Possible maternal uterine abnormalities
Teratogenic effects
Possible mutagenic or teratogenic effects
Possible fetal compression leading to deformation
Renal agenesis or outflow obstruction
Esophageal atresia, neuro-muscular disorders
Fetal compression, neuro-muscular disorders
Neuromuscular disorders
Identification of Suitable Handles

When immediate recognition is not possible, it is necessary
to identify one or more features (handles) which might
lead to syndrome diagnosis. Useful handles for the
diagnosis are given in Table 18.2.18.
Features like mental retardation, simian crease,
clinodactyly are nonspecific and act as poor handles for
syndrome delineation.
If one handle does not lead to a diagnosis then other
combinations should be tried. Once a suitable handle is
identified, reference should be made to standard monograms on syndromology (e.g. Smiths recognizable
patterns of human malformation edited by KL Jones, 1988,
WB Saunders, Philadelphia) or computer databases (i)
possum (pictures of standard syndromes and unusual
malformations). The Murdoch Institute, Royal Children

Hospital, Flemington Road, Parkville Victoria 3053,
Australia, (ii) London medical database, Institute of child
health, Great Ormond street hospital, London.
BIBLIOGRAPHY
1. American Academy of Pediatrics. Committee on Genetics.
American Academy of Pediatrics: Health supervision for
children with Down syndrome. Pediatrics. 2001
Feb;107(2):442-9.
2. Bhasin S, Ma K, Sinha I, Limbo M, Taylor WE, Salehian B.
Genetic basis of male infertility. Endocrine Metab Clin
North Am 1998;27:345-48.
3. Chiurazzi P, Neri G, Oostra BA.Understanding the
biological underpinning of Fragile X syndrome. Curr
Opin Pediatr 2003;15:559-66.
Genetics
TABLE 18.2.18: Useful handles in diagnosis of a syndrome
Head
Mouth
Nails
Abnormal hair
Scalp defects
Craniosynostosis
Encephalocele
Microcephaly
Cleft lip/palate
Absent or abnormal
teeth
Dystrophic
Eyes
Limbs
Genitalia
Coloboma
Small/absent eyes
Cataract
Partial or total absence Micropenis

Joint webbing
Short limbed dwarf
Ears
Digits
Skin
Deafness
Malformed pinna
Syndactyly
Polydactyly
White pathches
Pigmented
patches
Preauricular tags
Arachnodactyly
Brachydactyly
1013
4. Conclusion of the 6th World Congress on Down

syndrome. In Rondal JA, (Ed): Down syndrome a review
of current knowledge. (1st edn). Philadelphia. WB
Saunders 1998.
5. Hersh JH; American Academy of Pediatrics Committee
on Genetics. Health supervision for children with
neurofibromatosis. Pediatrics. 2008 Mar;121(3):633-42.
6. HO NC, Tran JR, Bektas A. Marfans syndrome.Lancet.
2005 Dec 3;366(9501):1978-81.
7. Kandt RS. Tuberous sclerosis complex and NF typel: The
two most common neurocutaneous syndrome. Neur Clin
N Am 2003;20:983-1004.
8. Sybert VP. Turner syndrome. N Eng J Med 2004;351:
1227-38.
9. Trotter TL, Hall JG; American Academy of Pediatrics
Committee on Genetics. Health supervision for children
with achondroplasia. Pediatrics. 2005 Sep;116(3):771-83.
10. Visootsak J, Graham JM Jr. Klinefelter syndrome and
other sex chromosomal aneuploidies. Orphanet J Rare
Dis 2006 Oct 24;1:42.
18.3 New Genetics and Advances in Genetics

ML Kulkarni
INTRODUCTION
Basics of DNA
The contribution of genetics to the understanding of

pediatric disease has increased dramatically over recent
years. The identification of disease genes and the
understanding of disease process at the molecular level,
have implications for screening, diagnosis and therapeutic
manipulation. Inevitably, complex ethical issues have
arisen from such a rapid rate of scientific progress and
society may not be prepared for the consequences of such
advances.
The term New genetics was coined by Dr Coming DE
in the year 1980 shortly after, Dr Southern discovered the
method of detecting different sizes of fragments of DNA
produced by a technique known after his name Southern
blot.
Three important aspects of the subject are discussed
here: (i) Basics of DNA structure and function, (ii) Tools of
molecular genetics, (iii) Clinical application of molecular
genetics for the study of inherited diseases.
All genetic material (DNA) contained in a single germ cell

(sperm and ovum) is known as human genome, that
contains all the information of life. Therefore, each body
cell or somatic cell contains 2 sets of human genome. The
human genome contains about 3 billion base pairs which
is roughly the number of people on earth.
The noncoding stretch of DNA constitutes 95 percent
of the total DNA stretch of human genome and is often
referred to as junk, redundant or selfish DNA. (Fig.
18.3.1). The exact function of this large stretch of DNA is
still not known. The coding region of human genome is
called gene. The size of human genes varies considerably.
The Structure of DNA (Fig. 18.3.2)
DNA exists as a double stranded helix. The analogy of
rope ladder can be given for the structure of DNA. Each
side of the ladder is made up of chains of sugar(s) and
phosphates (P). The step of the ladder is made up of
1014
Figure 18.3.1: ABCDE = Genes (form only 5% of human genome, remaining is junk DNA, X = Pseudo-genes (structurally
similar to gene but does not code for protein
Figure 18.3.2: DNA structure
Genetics
2 nitrogenous bases from 2 poles projecting inward and
the two bases are joined by hydrogen bond. The
nitrogenous bases consists of the purines (adenine A,
guanine-G), pyrimidines (cytosine-C, thymine-T). A
always pairs with T and G with C (complementary
pairing). The rope ladder is twisted around its vertical
axis (helix formation).
Each pair of complementary nitrogenous base is
termed a base pair (bp), e.g. AT, GC, TA, CG. The length
of DNA is expressed as base pairs. One thousand base
pairs make one kilobase (kb). A nucleotide is defined as a
unit consisting of phosphate, sugar and nitrogenous pair
(Fig. 18.3.2). The order of base on one single strand is
known as DNA sequence. The DNA is packaged in
chromosomes (Fig. 18.3.3).
1015
Gene Structure
Genes are segments of DNA stretches and are transcribed
into RNA and later translated into proteins. The genes are
composed of exons (the coding region) and introns
(noncoding regions) in between exons (Fig. 18.3.4). At both
ends of the gene are some sequences which are important
in gene regulation. At the 5' end (in untranslated part), are
promoter regions like TATA BOX, CCAT BOX, enhancer,
sequences which are important in transcription, tissue
specific transcription, controlling quantity of RNA and
determining the start site for transcription and add Cap
to the 5' end of the RNA.
At the 3' end, the sequence AATTAA provides a signal
for polyadenylation of RNA (poly A tail). Poly A tail is
1016
Figure 18.3.4: Structure of a gene
essential for the RNA to exit from the nucleus to cytoplasm

for translation.
How Genes Act?
One strand of structural gene DNA forms a template for
the synthesis of a form of RNA known as messenger RNA
(mRNA). This process is called transcription. In the nucleus,
introns are excised and exons are joined together and the
AATAAA sequences signal the addition of a series of As
(poly A tail) producing the processed mRNA that leaves
the nucleus to cytoplasm for translation (protein
synthesis). A triplet of bases called codon, codes for
synthesis of a particular amino acid. mRNA becomes the
template in the ribosome for translation. The initiation site
AUG is recognized and translation begins (Fig. 18.3.5). A
tRNA contains a codon (anticodon) complementary to
mRNA codon for the specific amino acid that the tRNA
carries. When tRNA finds a complementary codon on the
mRNA, the particular amino acid is added to the growing
peptide chain. The ribosome then moves to the next codon
in a 5" to 3" direction adding amino acids until a stop
codon is reached. Then, protein is released from the
ribosome and is used by the cell.
Mutations (Fig. 18.3.6)
Mutations are structural changes in a DNA sequence.
Types
Large Scale Mutations
They occur in chromosomes
Figure 18.3.5: Gene action
Genetics
For example: Gain/loss of chromosomal regions.
Translocations (switching of parts between two
chromosomes).
1017
Mutations in non coding regions like promoter region

and introns in genes result in abnormal production, i.e. in
excess or in less. Mutations in intron/exon boundary may
lead to differently spliced mRNAs.
Small Scale Mutations

They include nucleotide base changes: For example:
Substitution,deletions and insertions.
There are different types of single base mutations that
can occur in coding regions of a DNA sequence.
Missense mutation: Mutation results in coding of a new
amino acid in place of the original (substitution) resulting
in an abnormal protein product.
Silent mutation: Mutation results in an abnormal codon
but the amino acid coded is the same as that of the original
codon.
Nonsense mutation: Mutation results in introduction of
a stop codon causing premature termination of protein
synthesis resulting in a truncated protein.
Frame shift mutations: Mutation causing single base
insertion or deletions resulting in a shift of the translational
reading frame which leads to production of a completely
different sequence of amino acids.
Causes of Mutations
Mutations may be generated spontaneously by rare errors
that occur during DNA replications. More frequently
mutations are produced by exposure to the so called
mutagens like high energy radiation (e.g. X-rays, UV rays)
and certain chemicals that can damage the DNA.
DNA Repair
There is a complex system of DNA repair enzymes called
proof reading polymerases that repair errors occurring
during DNA replication which prevents against deadly
accumulation of changes in the DNA sequence.
Somatic and Germ Line Mutations
Somatic mutations occur in all cells of the body except the
germ cells. They are transmitted to all daughter cells, but
are not carried on to the next generations. Some somatic
Figure 18.3.6: Example of different single base mutations
1018
mutations may cause suppression of the tumor suppressor

genes resulting in cancer.
Germ line mutations occur in the germ cells of the body
and these mutations can be inherited from the parents
and can be transmitted to the offspring. Some germ line
mutations occur in frequency of more than 1 percent in
the population. These are called polymorphisms and they
are responsible for the normal genetic variation. Most
polymorphisms have no relevance in health or disease
but some can have medical importance. Polymorphisms
may help in the process of evolution by making necessary
arrangements for the survival. Non-polymorphism
mutations are the causes for the genetic disorders. Some
mutations manifest only in pairs; one of the pair inherited
from each parent, the so called recessive traits. Others
manifest even in single; inherited from either of the parents,
the so called dominant traits.
even from mouth washings. The cells are dissolved in

detergent solutions and treated with Protein and RNA
degrading enzymes to purify the DNA. Alcohol is then
added to precipitate the genomic DNA as a fibrous thread.
The DNA fibre is then suspended in a mildly alkaline
buffer for storage. Purified DNA can be stored for long
periods in liquid nitrogen or at -80C.
II. Restriction Enzymes: (Fig. 18.3.7)
Certain bacterial enzymes known as restriction
endonucleases have the capacity to cut the double
stranded DNA at specific sequences. They are named after
the bacteria from which they have been obtained. The size
of the fragments produced is constant in an individual
subject but varies among subjects because of differences
in noncoding DNA sequences. This is the basis of many
DNA predictive tests.
RECOMBINANT DNA TECHNOLOGY

The process of manipulating genetic material, in which
DNA is artificially cut, joined and synthesized is termed
as Recombinant DNA technology or genetic engineering.
This technology has made it possible to analyze and
change the functions of genes and hence finding its many
applications in medicine (Table 18.3.1)
TABLE 18.3.1: Uses of recombinant DNA technology
I. Gene structure/Mapping/Function
II. Clinical Genetics
Preimplantation genetic diagnosis
Prenatal diag.
Presymptomatic diag.
Carrier detection
III. Diagnosis and pathogenesis of disease
Genetic
Infective
Malignant
IV. Biosynthesis
Recombinant products
Vaccines
V. Treatment of genetic diseases
VI. Gene therapy
Tools of Genetic Engineering

I. DNA Isolation
The first step in Recombinant DNA technology is to isolate
DNA in its pure form.DNA can be isolated from peripheral
leukocytes, skin fibroblasts, solid tissues, tumour cells or
III. Probes (Fig.18.3.8)

A probe is a piece of single stranded DNA that is tagged
either with a radioactive isotope P32 or by fluorophores
(Fluoroscein or rhodamine).The single stranded DNA
detects the presence of its complementary sequence. These
Genetics
1019
VII. DNA Ampilification

Cloning
Figure 18.3.8: Probes
probes are used to detect the gene of interest or a region of

DNA which is nearer to the gene of interest or to more
distant DNA sequences. There are four types of probes
Gene specific probe, Complementary DNA probe (C-DNA
probe), Oligonucleotide probe and Randomly generated
probe.
IV. Vectors
This refers to a carrier DNA molecule which contains the
DNA segment of interest. When a vector containg the target
DNA is introduced into the host cell, it replicates with the
DNA of the host cell resulting in production of multiple
copies of the target DNA. Commonly used vectors are
Plasmids and Bacteriophages
V. Plasmids
They are circular, double stranded DNA molecules that
occur naturally in bacteria and replicate extrachromosomally in bacteria or yeast. They usually carry
antibiotic resistance genes and can easily pass from one
bacterium to another; they are also distributed to daughter
cells during cell division. During cloning the DNA of
interest is incorporated into the plasmid DNA with the
help of restriction endonucleases and then introduced into
the bacteria, which multiply giving high yield of the DNA
of interest. Knowledge of the specific antibiotic to which
resistance is carried by the plasmid will help in allowing
the multiplication of only selected bacterium when grown
with that antibiotic.
VI. Bacteriophages
These are viruses that infect bacteria. A DNA fragment
can be introduced into a virus which then infects a
bacterium and multiplies. During replication, the inserted
DNA fragment also multiplies and gets incorporated into
the daughter cells.
DNA cloning is the selective amplification of a specific

DNA segment or sequence, so that it can be produced in
relatively large amounts, permitting the analysis or
manipulation of its structure and investigation of its
functions.
The DNA of interest is incorporated into a plasmid by
cutting both of them with the same restriction
endonucleases, the cut ends are then joined together
generating a recombinant molecule. The recombinant
plasmid is then introduced into a bacterial cell. The
bacterial cell is then cultured in broth or agar plates. As
the bacteria multiply the plasmid and inserted DNA
fragment will also replicate and a large amount of the
target DNA will be available.
Polymerase Chain Reaction (PCR): (Fig. 18.3.9)
PCR is a powerful technology that is used to amplify the
DNA segment of interest. To put it in lay mans language
it is molecular photocopying. The process runs as a
series of physicochemical cycles in a special device called
PCR chamber.
The steps involved include
1. The target DNA is denatured by heat, which makes
double stranded DNA to separate into 2 single strands.
These 2 ends can grow in 2 direction, 3 and 5 end of
DNA segments.
2. The primers are added to the chamber which contains
the DNA strands. These primers hybridize (bind) to
the complementary fragments of the now single
stranded target DNA.
3. Then bases (deoxynucleotide) and tag polymerase are
added while temperature increases. The bases are used
as building blocks for synthesis of DNA strands and
the polymerase begins to assemble them.
4. The primer extends in 3 direction as well as in 5
direction to produce new DNA.
5. Such cycles are repeated several times automatically
and in few hours the target DNA segment or sequence
can be amplified to one million fold.
6. The produced DNA (i.e. PCR product) can be analysed
using labelled probes, sequencing or by direct vision
with UV light after adding ethedium bromide to the
electrophoretic gel.
1020
Figure 18.3.9: Steps of PCR
Applications of PCR
1. Genetic disorder caused by single base pair changes,
small deletion or insertions. This helps in diagnosis,
carrier detection and for prenatal diagnosis. (E.g.
Thalassemia with base pair changes, DMD with DNA
deletions.)
2. Diagnosis of infectious diseases (E.g. HIV infection)
3. Diagnosis and follow up of cancers.
4. Study of bone marrow engraftment.
5. DNA fingerprinting for paternity cases and forensic
purposes.
6. HLA typing for Bone marrow transplant and Kidney
transplantation
7. Study of Gene linkage and gene mapping .
8. Study of Single Nucleotide Polymorphism (SNP) for
noting the susceptibility of a person to a disease or a
particular response of a drug to this disease
(PharmacoGenetics).
9. Study of evolution.
Limitations of PCR
1. At least part of the sequence of the target DNA must be
known for meaningful interpretation.
2. It can amplify few hundred base pairs sized segments.

Larger segments cannot be amplified, for which
cloning may be used.
3. There can be errors due to the inclusion of wrong bases,
since polymerase has no capacity to read the proof.
Multiplex PCR
In chromosomal disorders, deletion of a part of a gene can
be easily detected by the absence of the band due to nonamplification of the part of the gene corresponding to the
deleted region. This principle is used in Multiplex PCR
and groups of 6 or 9 exons are amplified simultaneously
in a tube. The products are separated by gel electrophoresis.
Each band in the gel represents an exon. In the presence of
a deletion in an exon, the corresponding band will be
absent.
However when the need to identify carrier females in
X-Linked disorders arises then a different technique called,
Quantitative PCR is used. In which the band corresponding to the deleted exons will have a decreased density
in carrier females when compared to those of non-deleted
exons of normal individuals.
Genetics
TECHNIQUES FOR DNA ANALYSIS
Southern Blot Hybridization (Fig. 18.3.10)
In this technique, first the DNA is cut into fragments by
the use of bacterial restriction enzymes. These millions of
pieces of DNA fragments are subjected to electrophoresis
in an agarose gel. The smaller fragments move faster than
the larger ones producing a track of DNA fragments. The
agarose gel with DNA tracks is fragile and needs to be
transferred for a permanent record, this is done by placing
a nitrocellulose paper on top of the agarose gel, over which
1021
dry paper towels are put. The fluid in the electrophoretic

tank then rises through the gel transferring the DNA on
the nitrocellulose paper, retaining the alignment of the
fragments (Blotting). The DNA bound to the nitrocellulose
membrane is a stable record. The record is then washed in
a solution containing radiolabelled DNA probe with
phosphorous 32. The probe, if it finds its complementary
fragments of DNA, unites with it (Hybridization). This
hybridized fragment then can be identified as a visible
band on an X-ray film, placed on the membrane and this
technique is known as autoradiography.
Figure 18.3.10: Southern blot
1022
Applications
1. To find the presence of a particular gene or a part of
the DNA fragment in the sample DNA
2. To know whether the size of the DNA fragment carrying
the gene is normal, increased or decreased.
3. To identify presence of large deletions, duplications
or large gene rearrangements.
AUTOMATED SEQUENCING
Sequencing means knowing the orderly arrangement of
bases (A,T,G,C) along the DNA ladder. This technique
uses primers or nucleotides labeled with fluorescent dyes,
which can be detected by a computerized laser detection
system, allowing rapid, accurate and automated sequencing. Since different fluorescent dyes are used in each of
the four base- specific reactions, all the four reactions can
be loaded in single lane. The output is in the form of
intensity profiles for each of the differently coloured
flurochromes. This technique is used in human genome
sequencing, detection of mutations in single gene disorders
and in mutationally heterogeneous disorder.
FLUOROSCENCE IN SITU HYBRIDIZATION (FISH)
(FIG.18.3.11)
The DNA being compactly arranged in chromosomes the
smallest visible deletion or duplication by routine
cytogenetics consist of 4 megabases i.e. 4x106 basepairs.
Thus, routine cytogenetics cannot resolve genetic
abnormalities smaller than this. This limitation of
cytogenetics has been overcome by a technical
advancement called Fluorescence in situ hybridization
(FISH).
The DNA of the subject is first denatured i.e. made into
2 separate single strands by heating. The fluorescent probe
of interest is added to the denatured DNA sample, which
then hybridizes (unites) with the complementary segment
if present and then reforms into a double helix (Reanneals).
The recombinant DNA is then seen through a fluorescent
microscope, which detects the presence or absence of the
fluorescent signal from the probe.
The following classes of DNA probes are used in FISH
technique for specific applications.
Total genome probes Chromosomes hybridized
with these probes show an evenly distributed signal along
their length.
Figure 18.3.11: Diagrammatic representation of FISH

technique
Chromosome specific painting probes In this the

probe consists of an entire chromosome e.g. Chromosome
1 probe will paint the whole chromosome 1 from one end
to other and also parts of chromosome 1, if it is attached to
some other chromosome. These probes cannot identify
intrachromosomal rearrangements like inversion and
areas containing repetitive elements like centromeres and
telomeres are not painted.
Chromosome specific Centromeric probes These
are mainly used in the determination of chromosome copy
number in interphase nuclei. These are used in aneuploidy
detection in uncultured amniotic fluid cells, for preimplantation diagnosis from a single cell from a blastocyst
and for analysis of nondisjunctional abnormalities in
sperm.
Genetics
Locus specific DNA probes These are probes from
small regions of a particular chromosome. These probes
can be used for diagnosis of microdeletion syndromes like
Prader Willi syndrome, Williams syndrome, retinoblastoma etc., where deletion may not be visible cytogenetically. They can also be used to delineate exact break
points of a chromosomal rearrangement and to identify
known chromosomal rearrangements in cancer.
1023
Spectral Karyotyping (SKY) (Fig. 18.3.12)

SKY is a multicolour genome wide FISH. It used probes
for all chromosomes simultaneously. Each chromosome
is labeled with a different coloured probe and hence
emitting a different fluorescence spectrum. This technique
combines the resolution and power of FISH with the
advantages of conventional cytogenetics methods to scan
simultaneously all human chromosomes in a single image.
Applications
1. Preimplantation chromosomal analysis. In this since
only one or two cells are available, the techniques
comes in handy.
2. Post natal and prenatal diagnosis for conditions
associated with aneuploidy (Downs Syndrome) and
translocations (Philadelphia chromosome).
3. Chromosomal microdeletion syndromes. Williams
syndrome ( Chr 7q), Prader-Willi and Angelman
syndrome (Chr. 15q), Digeorge syndrome (Chr. 22q)
4. Age related disorders. In which telomeric probes are
used to assess the length of the telomerese which is
decreased. (E.g. Cancer, Reproductive losses)
5. Oncology. (E.g. Philadelphia chromosome) In which
it is used for drug tailoring, staging and for prognostication.
6. Chromosomal structure study. In which multiple
probes for one chromosome are used which is called
chromosome painting.
7. Specific probe preparation. Probes are prepared for
specific areas of the chromosome. (E.g. Chromosome
specific probes for Downs syndrome and Locus specific
probes for Williams syndrome )
MODIFICATIONS OF FISH
Comparative Genomic Hybridization (CGH)
This method is found to be a very important tool in cancer
research and mapping of various genes involved in
tumourogenesis. CGH uses Fluroescein labeled tumour
DNA (Green) and Texas red labeled normal genomic DNA
(Red) in mixed forms, which is hybridized to normal
metaphases. The relative amount of tumour and normal
DNA that anneals to a particular region of chromosomes
depends on the number of copies of DNA complementary
to that region in the test sample. The abnormalities, thus
detected in tumour genome are used for identifying cancer
related genes.
Figure 18.3.12: Image of a normal karyotype obtained by SKY
Fiber FISH
This is used in contiguous gene syndromes (E.g. Williams
Syndrome). Probes hybridized to same chromosome can
only be differentiated if they are more than 2 to 3 bases
apart, so in order to identify multiple probes in a small
area ( as in contiguous gene syndromes) we need to stretch
the chromatin fiber. This is done by doing the process
during interphase when chromatin fibers are less
condensed and by further stretching the chromatin with
the help of melting agarose.
DNA Microarray Technique (Fig. 18.3.13)
This technique is used to study the expression of many
genes at a time and that too, on a single slide known as a
DNA CHIP.DNA CHIP is a glass slide in which several
miniature wells are arranged in an order i.e. microarray.
In these wells are placed oligonucleotide probes.
1024
Figure 18.3.13: Showing the use of microarray in the evaluation of a tumour Courtesy: National Human
Genome Research Institute
The messenger RNA(mRNA) is extracted from the

sample to be tested. The mRNA indicates that the DNA
has set into function, as we know the DNA forms the
mRNA and the mRNA form the proteins. This mRNA is
converted to cDNA(Coding DNA, i.e. has exons but not
introns ) which is then labeled with a fluorescent dye. The
mRNA from a normal cell is also extracted and from this
CDNA is prepared and tagged with a different fluorescent
dye. Both labeled cDNA are then mixed with the
oligonucleotide probes that are placed in the wells
(Microarray). Laser beams are then used to excite the
fluorochromes. The exciting pattern will depend on the
relative amount of normal and abnormal CDNA. Analysis
of the color pattern of the microarray after hybridization
is done by capturing the digital image and then with the
help of a computer analyzing the images. This is a gene
expression study (FUNCTIONAL GENOMICS).
This technique is important in drug designing,
pharmacogenetics, cancer research, analyzing several
mutations in a single go and in several others. This
technique is so powerful that hundreds of mutations can

be analyzed in a single test.
Linkage Analysis
If the disease causing mutation cannot be identified in a
patient or is difficult to test, DNA markers situated in or
near the gene can be used to trace the mutated gene in the
family. This method, known as linkage analysis, can be
used for prenatal diagnosis and carrier detection. The use
of linked markers is based on the fact that closely related
genes or DNA segments are transmitted together to the
next generation. This method is also useful for the
detection of carriers of X-Linked disorders such as DMD
and hemophilia.
Restriction Fragment Length Polymorphism (RFLP)
To understand this concept an example is taken. In Figure
18.3.14, G is the disease gene on X chromosome, which
has not been isolated, and therefore no gene probe is
available.
Genetics
Figure 18.3.14: Gene tracking
By studying a large number of family members by

linkage studies, a gene probe P has been identified which
hybridizes to X-chromosome very close to the disease gene
locus G. They are so close that they segregate together
(Inherited together) during meiosis; in other words they
show close genetic linkage. Closer the marker probe to the
disease gene, more accurate is the prediction of the genetic
pattern.
The markers (probes) that show less than 5 percent
recombination with a disease gene are useful in detecting
carrier status and in prenatal diagnosis. As 1 percent
recombination occurs between loci that are separated by
around 1 million base pairs, these probes may be up to 5
million bases away from the gene of interest.
A polymorphic restriction enzyme cutting site B is
identified very close to the disease gene G. (Polymorphic
means it may be present or absent in a particular
individual. This is because of variation in noncoding
region of DNA that effects restriction endonuclease cutting
sites, resulting in DNA fragments of different sizes). If it is
present, the probe P will hybridize to a 2 Kb fragment
and if absent, the probe will hybridize to a 5 Kb fragment.
The portions or segments produced using probe
enzyme combination which identifies a polymorphic
cleavage site are known as restriction fragment length
polymorphisms (RFLP). RFLPs are used in carrier
detection and prenatal diagnosis of conditions such as
DMD and BMD. Before prediction is possible , a family
must have DNA analysis performed to see if there is a
variation in the size of the fragments detected by an
appropriate probes that gives an informative pattern in
the family. After identifying the fragment associated with
the disease, the gene can be identified in carrier or in the
pregnancy being tested.
DNA BASED DIAGNOSIS OF GENETIC DISORDERS
Beta-Thallasemia
It is a heterogeneous hematological disorder due to many
mutations in the Beta-globin gene. Most gene defects are
1025
due to point mutations, deletions or insertions. Despite

marked heterogeneity at the molecular level, a set of
mutations are commonly prevalent in a given population.
In the Indian population the five commonest mutations
IVS1 -5{G!C}, 619bp deletion, IVS1-1{G!T}, Codon 8/9,
and Codon 41/42{-CTTT} account for 91.8% of all
mutations. Though an infant with marked microcytic
anemia with splenomegaly and raised fetal hemoglobin
level is diagnostic of Beta-Thallasemia, the following are
the techniques used for disease confirmation, prenatal
diagnosis and carrier detection.
Multiplex PCR [Described above]
Dot blot method Beta Globin genomic DNA adjacent to
the different mutations is amplified by PCR. The products
are immobilized onto 2 separate membranes and
hybridized with labeled Allele Specific Oligonucleotide
(ASO) probes complementary to the wild (Normal) and
mutant sequences. A person homozygous for the mutation
will show hybridization with the mutant probe, normal
individuals DNA hybridizes with the wild type probe
and heterozygote(Carrier) have hybridization with both
probes.
Reverse dot blot method It is the reverse of above
procedure, with membrane bound normal and mutant ASO
probes serving as hybridization targets for PCR amplified
DNA.
Amplification refractory mutation system (ARMS) - The
DNA to be tested is amplified by PCR technique using 2
sets of primers in 2 separate tubes. One primer is common
to both, while the other primer, in one tube has a sequence
specific for a mutation(Mutant type) and that in the other
tube has a normal sequence(Wild type) at the site of the
mutation. Genomic DNA will be amplified only in the
presence of complementary pairing of the primer and
genomic DNA. Electrophoresis will demonstrate a band
in the reaction of a homozygote for the wild type allele
and primer; a homozygous mutant for the mutant allele
and mutant primer; a heterozygote for both the alleles and
primers.
DUCHENNE AND BECKER MUSCULAR
DYSTROPHIES (DMD AND BMD)
These are X-Linked neuromuscular diseases resulting
from mutations of the Dystrophin gene which codes for a
muscular cytoskeleton protein, Dystrophin. 65% of the
mutations are deletions occurring predominantly in
1026
2 hotspots around the first 20 exons and around exons

45-55. Mutations that result in the failure of production of
a stable protein will result in DMD (severe phenotype),
mutations that result in production of a stable and partially
functional protein results in BMD (Milder phenotype).
Clinical presentation cannot give any clue to the type or
site of mutation; hence it is necessary to identify the
mutation of the proband prior to offering carrier detection
and prenatal diagnosis. The following are the techniques
used for confirmation, prenatal diagnosis and carrier
detection.
multiplex pcr Explained earlier. Cannot identify
duplication, insertions and point mutations which are
sometimes responsible for the condition.
linkage analysis Explained earlier. This technique
is limited by the fact that some individuals with muscular
dystrophy may have new mutations and cannot be
determined definitely. Hence there are possibilities of false
negative or false positive results which should be kept in
mind during prenatal diagnosis.
Spinal Muscular Atrophy
The spinal muscular atrophies represent a heterogeneous
group of diseases with predominantly AR inheritance and
characterized by degeneration of the motor neurons in the
anterior horn cells of the spinal cord and brainstem. There
are 4 types, of which 3 are of childhood onset, with SMA
Type I having the worst prognosis. Majority of them are
associated with homozygous deletion in the survival motor
neuron (SMN1) gene on chromosome 5q13 (Exon 7).
There is no non-cytogenetic diagnostic test for SMA
other than the supportive evidence of neurogenic changes
on EMG. Detection of the deletion in the SMN1 gene
confirms the diagnosis of SMA. This is done by PCR
followed by Restriction enzyme digestion, which confirms
the presence or absence of the Exon 7.
Carrier detection is done by Quantitative PCR based
assay. Prenatal diagnosis is straightforward once the
mutation in the SMN1 gene is identified in the carrier.
Preimplantation diagnosis in families at risk has also been
reported.
Fragile X Syndrome
Fragile X syndrome is an X-Linked condition which is
most common cause for inherited mental retardation. It is
due to the presence of a fragile site at the Xq27.3 locus in
which there is an abnormally large number of trinucleotide
(CGG) repeats. This can be detected by PCR technique.

Clinical features of the condition are subtle, and
characteristics such as facial dysmorphism and macroorchidism appear as the child grows. Hence, it is
necessary to conduct DNA tests for the diagnosis of this
condition in all males and females with idiopathic mental
retardation.
ADVANCES IN GENETICS
Human Genome Project
Genome refers to all the genetic material contained in a
cell, i.e. the DNA. The order of arrangement of the base
pairs (AT,GC) along the DNA molecule is called as its
sequence.
In 1990, the National Institutes of Health (NIH) and
the Department of Energy joined with international
partners in a quest to sequence all 3 billion base pairs in
the human genome. This concerted, public effort was the
Human Genome Project (HGP). In April 2003, researchers
successfully completed the HGP, under budget and more
than two years ahead of schedule.
Objectives
To know the arrangements of all the 3 billion base
pairs in the human genome.
To identify the roughly 30,000 genes in the human
genome and know their exact location on the different
chromosomes.
To develop new DNA technology, especially for
automated DNA sequencing.
To make all the data generated by the HGP, freely and
rapidly available on the internet, serving to accelerate
the pace of medical discovery around the globe
(Bioinformatics).
To study some model organisms like fruitfly,
earthworm, E.coli etc. for comparison.
To study and support the ethical, legal and social
implications that might arise from this science.
Outcomes
The human genome sequence was found to be almost
the same (99.9%) in all human beings, with only 0.1%
variations being responsible for the phenotype and
diseases susceptibility.
Single Nucleotide Polymorphisms (SNP), which have
been discovered in the genome are frequently occurring
Genetics
variation in individuals and are being studied for their

association with disease susceptibility to common
disorders and drug idiosyncrasy.
Human genome is very much similar to many other
organisms, for example the genome of the fruitfly
shares 40% of its genes with the humans, and the
chimpanzees DNA sequence is 96% similar to
humans; making man humble.
More than 1800 disease genes have been identified.
More than 1000 genetic tests have been devised for
diagnosis.
At least 350 biotechnology based products resulting
from the HGP are currently in clinical trials.
The study of mitochondrial DNA has revealed that
the origin of the human race is from central Africa, in
other words mankind took origin from an African
woman.
The study of the human genome has shed light on the
migration of the human race around the globe.
Functional Genomics
Genomics is the study of the entire genome of an organism.
Functional genomics is the study of the functions of the
genes in normal development and physiology and their
dysfunction in disease states. The main tool of functional
genomics is the DNA microarray technique which has
been explained earlier. Proteomics, an important
component of functional genomics is the identification of
proteins and elucidation of their involvement in the
biological pathways, as well as their interaction in
development, differentiation, health and disease.
Phenomics is a field of study concerned with the
characterization of phenotypes, which are characteristics
of organisms that arise via the interaction of the genome
with the environment. Metabolomics is the systematic
study of the unique chemical fingerprints that specific
cellular processes leave behind - specifically, the study
of their small-molecule metabolite profiles. The metabolome represents the collection of all metabolites in a
biological organism, which are the end products of its
gene expression
RNA Interference
RNA interference (RNAi) is a mechanism that inhibits or
silences gene expression at the stage of translation or by
hindering the transcription of specific genes. RNAi targets
include RNA from viruses and transposons (significant
1027
for some forms of innate immune response), and also plays

a role in regulating development and genome maintenance.
In 2006, Andrew Fire and Craig C. Mello shared the Nobel
Prize in Physiology or Medicine for their work on RNA
interference in the nematode worm C. elegans, which they
published in 1998. It is unusual for the Nobel committee
to award a prize in medicine so soon after the relevant
discovery. But then, hardly ever has such a discovery given
rise so quickly to such a broad range of promising medical
applications such as in diseases (amyotrophic lateral
sclerosis, spinocerebellar ataxia, hepatitis viral infections
etc.) in drug designing, in cancer genetics and in
biotechnology. It is also the principal behind the knockout
mice in which the consequences of the silencing of the
function of a particular gene is studied, to understand the
genes function.
Bioinformatics and Databases
Bioinformatics is the field of science in which biology,
computer science, and information technology merge to
form a single discipline. The ultimate goal of the field is to
enable the discovery of new biological insights as well as
to create a global perspective from which unifying
principles in biology can be discerned. The actual process
of analyzing and interpreting data is referred to as
computational biology.
A biological database is a large, organized body of
persistent data, usually associated with computerized
software designed to update, query, and retrieve components of the data stored within the system. A simple
database might be a single file containing many records,
each of which includes the same set of information. For
example, a record associated with a nucleotide sequence
database typically contains information such as contact
name, the input sequence with a description of the type of
molecule, the scientific name of the source organism from
which it was isolated, and often, literature citations
associated with the sequence.
NIH genetic sequence database GENBANK
www.ncbi.nlm.nih.gov/sites/entrez?db=nucleotide
European Molecular Biology Laboratory Nucleotide
sequence database EMBL www.ebi.ac.uk/embl
GDB human genome database - The Official WorldWide Database for the Annotation of the Human
Genome. www.gdb.org
Online mendelian Inheritance in man OMIM
Catalogue of inherited diseases in humans.
www.ncbi.nlm.nih.gov/omim
1028
Cancer Genetics
The aetiology of cancer is multifactorial, with genetic,
environmental, medical, and lifestyle factors interacting
to produce a given malignancy. Knowledge of cancer
genetics is rapidly improving our understanding of cancer
biology, helping to identify at-risk individuals, furthering
the ability to characterize malignancies, establishing
treatment tailored to the molecular fingerprint of the
disease, and leading to the development of new therapeutic
modalities. As a consequence, this expanding knowledge
base has implications for all aspects of cancer management, including prevention, screening, and treatment.
Following are some of the examples of the inherited
family cancer syndromes.
Breast cancer BRCA 1 (17q21), BRCA 2 (13q21)
Familial adenomatous polyposis APC (5q21)
Juvenile polyposis SMAD4/DPC4 (18q21.1),
BMPR1A(10q22)
Peutz-Jeghers STK11 (19p13.3)
Familial retinoblastoma RB1(13q14)
Multiple endocrine neoplasia(MEN) Type 1 MEN1
(11q13)
MEN Type 2 RET (10q11.2)
Patient Support Groups and Non Profit Organization
A patient support group is a gathering of people with the
same illness or condition who meet either physically or
online to share information, experiences, problems and
solutions. Run by members for members, the groups help
foster a sense of self-esteem and courage to help face the
social, financial, emotional difficulties that may lie ahead.
A strong body of literature shows that belonging to such a
group can optimise the outcome of the patient.
Support groups in India for common genetic conditions:
Downs Syndrome - www.downsyndrome.in
Thalassemia - www.thalassemicsindia.org
Haemophilia - www.hfindia.org
Enzyme Replacement Therapy
Though replacement of deficient substrates such as insulin
and factor VIII have been in use for a long time, certain
lysosomal storage disorders which are genetically
transmitted are currently amendable for treatment. This is
done by replacing the deficient enzyme; though the disease
itself is not cured, the morbidity and mortality are brought
down drastically.
1. Gauchers disease (Cerezyme)

2. Fabry disease
(Fabrazyme)
3. Mucopolysaccharidosis I
(laronidase)
4. Mucopolysaccharidosis VI
(Naglazyme)
5. Mucopolysaccharidosis II
(Elaprase)
6. Pompe Disease
(Alglucosidase alfa)
7. Niemann-Pick B Disease
Approved 1991
Imiglucerase
Approved 2001
Agalsidase
Approved 2003
Aldurazyme
Approved 2005
Galsulfase
Approved 2006
Idursulfase
Approved 2006
Myozyme
Phase 1 Trial
Stem Cell Therapy

Stem cells are unspecialized cells that are defined by their
capacity for self renewal and their ability to differentiate
into specialized cells along many lineages. Somatic stem
cells can differentiate into the cell types found in the
tissues from which they are derived. They are usually
described by reference to the organ of origin (E.g.
Hematopoietic stem cell)
Bone marrow transplantation is one form of somatic stem
cell therapy, and is being successfully used in genetic
conditions such as hemoglobinopthies, Adenosine
Deaminase deficiency, Severe combined Immunodeficiency, lysosomal storage disorders, fanconi anemia
etc.
Embryonic stem cell therapy is a newer form of stem cell
therapy in which the inner cell mass of the growing
embryo is isolated and disrupted to form embryonic cell
line. Under special culture conditions, the cells of the
embryonic lines can be coaxed to form certain kind of cell
type (e.g. Heart myocytes). In theory these different cells
could be used to replace deficient or injured cells or tissues.
This is being tried in conditions like myocardial infarction
and spinal cord damage.
Umbilical cord blood banking is a controversial area of
stem cell therapy. Umbilical cord blood, which contains a
rich source of hematopoietic stem and progenitor cells,
has been used successfully as an alternative allogeneic
donor source to treat a variety of pediatric genetic,
hematologic, immunologic, and oncologic disorders.
Because there is diminished risk of graft-versus-host
disease after transplantation of cord stem cells using
matched related donors, the use of less-than-completely
matched HLA cord blood stem cells may incur less risk of
graft-versus-host disease than mismatched cells from
Genetics
either a related or unrelated walking donor, although
this remains to be proven. As yet the American academy
of pediatrics states, Because there are no scientific data
at the present time to support autologous cord blood
banking and given the difficulty of making an accurate
estimate of the need for autologous transplantation and
the ready availability of allogeneic transplantation, private
storage of cord blood as biological insurance should be
discouraged.
BIBLIOGRAPHY
1.
2.
American Academy of Pediatrics Section on Hematology/

Oncology; American Academy of Pediatrics Section on
Allergy/Immunology, Lubin BH, Shearer W:Cord blood
banking for potential future transplantation. Pediatrics.
2007 Jan; 119(1):165-70.
Bernards R: Exploring the uses of RNAigene knockdown
and the Nobel Prize. N Engl J Med. 2006 Dec 7;
355(23):2391-3.
1029
3. Hessner MJ, Liang M, Kwitek AE: The application of

microarray analysis to pediatric diseases. Pediatr Clin
North Am. 2006 Aug; 53(4):579-90.
4. Morrison C: Fluorescent in situ hybridization and array
comparative genomic hybridization: complementary
techniques for genomic evaluation. Arch Pathol Lab Med.
2006 Jul;130(7):967-74.
5. National Institute of Health: Fact sheet Available at: http:/
/www.nih.gov/about/researchresultsforthepublic/
HumanGenomeProject.pdf.
6. National Library of Medicine. MEDLINE Fact Sheet
Available at www.ncbi.nlm.nih.gov/About/primer/
bioinformatics.html.
7. Rohrbach M, Clarke JT: Treatment of lysosomal storage
disorders: progress with enzyme replacement therapy.
Drugs. 2007;67(18):2697-716.
8. Turnpenny P, Ellard S. Emerys elements of medical
genetics. 13th ed. China. Churchill livingstone elsevier;
2007.
18.4 Inborn Errors of Metabolism

ML Kulkarni
INTRODUCTION
Inborn errors of metabolism result from mutations in DNA
that code for a specific protein, which may act as an
enzyme, receptor, transport vehicle, membrane pump or
structural element. In these disorders, biochemically one
observes accumulation of compounds proximal to the
enzymatic block and deficiency of product distal to it. Some
genetic changes may be clinically inconsequential
whereas others produce disease states which range from
very mild to lethal. Most disorders present in neonatal
period with nonspecific manifestations that include
lethargy, vomiting, jaundice, convulsions, coma, hurried
respiration, unusual body odor, hypoglycemia, acidosis
and hyperammonemia, elevated blood/urine levels of a
particular metabolite, for example an amino acid or
ammonia. In older children metabolic disorder should be
suspected in the following situations:
1. Unexplained mental retardation, developmental delay,
motor deficits or convulsions.
2. Unusual odor particularly during an acute illness.
3. Intermittent episodes of unexplained vomiting,
acidosis, mental deterioration or coma.
4. Hepatomegaly.
5. Dislocation of lens, cataract or corneal opacity.
6. Renal stones.
The common inborn errors of metabolism are discussed
here.
Phenylketonuria
Phenylketonuria (PKU) is the most common inborn error
of amino acid metabolism, characterized by diminished
activity of the enzyme phenylalanine hydroxylase and
thus an elevation of plasma phenylalanine. The symptoms
of hyperphenylalaninemia are usually absent in the
newborn, but ultimately result in light colored hair, blueeyed child with light complexion, eczema and mental
retardation. Seizures and behavioral problems frequently
result. The urine and sweat of these children have a
mousy odor, which is caused by phenylacetic acid in
the urine and sweat. There are four clinically and
biochemically distinct forms of hyperphenylalaninemia,
out of which classic phenylketonuria is the most common.
All defects of persistent hyperphenylalaninemia and PKU
are inherited as autosomal recessive traits. They have a
collective prevalence of 1:10,000 to 1:20,000 live births.
1030
Classic Phenylketonuria (PKU)

This form is caused by the complete or near-complete
deficiency of phenylalanine hydroxylase. The affected
infant is normal at birth. The clinical manifestations of
classic PKU are rarely seen in those countries in which
neonatal screening programs for detection of PKU are in
effect. The bacterial inhibition assay method of Guthrie is
widely used in the newborn period to screen for PKU.
This test requires a few drops of capillary blood, which
are placed on a filter paper and mailed to the laboratory
for assay. Blood for screening should be obtained after 72
hours of life and preferably after feeding proteins, in order
to reduce the possibility of false-negative results. The
criteria for diagnosis of classic PKU are: (i) a plasma
phenylalanine level above 20 mg/dl, (ii) a normal plasma
tyrosine level, (iii) increased urinary levels of metabolites
of phenylalanine (phenylpyruvic and hydroxyphenylacetic acids), (iv) a normal concentration of the cofactor
tetrahydrobiopterin.
The goal of therapy is to reduce phenylalanine and its
metabolites in body fluids in order to prevent or minimize
brain damage. This can be achieved by instituting a diet
low in phenylalanine; formulas low in this essential amino
acid are now available; it should be started soon after
birth as soon as the diagnosis is established. Dietary
management is almost always complicated by emotional
problems especially in the adolescent period; therefore,
parents and children need continuous skillful and
empathetic support and guidance.
Pregnancy in Mothers with PKU
Pregnant women with PKU who are not on a low
phenylalanine diet have a higher risk of spontaneous
abortion than the general population. Infants born to such
mothers have mental retardation, microcephaly and/or a
congenital heart disease. These complications are related
to high levels of blood phenylalanine. Prospective mothers,
who have PKU, should be started on a low phenylalanine
diet before conception, and every effort should be made to
keep blood phenylalanine levels below 10 mg/dl,
throughout pregnancy.
Hyperphenylalaninemia due to Deficiency of
Cofactor Tetrahydrobiopterin (BH4)
In about 2 percent of infants with hyperphenylalaninemia,
the defect resides in one of the enzymes necessary for
production or recycling of BH4 which is a cofactor for
tyrosine and tryptophan hydroxylases, which are

essential for biosynthesis of the neurotransmitters
dopamine and serotonin.
The clinical manifestations of this disorder are similar
and usually indistinguishable from those of classic PKU,
but neurologic manifestations such as loss of head control,
hypertonia, drooling, swallowing difficulties and
myoclonic seizures develop after 3 months of age, despite
adequate dietary therapy. Diagnosis of BH4 deficiency and
the responsible enzyme defect may be established by
performing one of the following tests: (1) Measurement of
neopterin and biopterin in body fluids (neopterin
biopterin ratio is low) (2) BH4 loading test (3) Enzyme
assay.
The treatment includes: (i) low phenylalanine diet; (ii)
administration of neurotransmitter precusors; L-dopa and
5-hydroxytryptophan seems to be most effective and may
prevent neurologic damage if started early in life; (iii) oral
administration of the BH4 cofactor in small daily doses
normalizes serum levels of phenylalanine. This should
be given in high doses of 20 to 40 mg/kg/day to cross the
blood brain barrier and stop the progression of neurological damage.
Benign Hyperphenylalaninemia
These infants have been detected by screening tests in the
neonatal period; they are asymptomatic and may develop
normally without special dietary treatment. These patients
have a deficiency of the phenylalanine hydroxylase enzyme
but with some residual enzyme activity. These children
should be systematically monitored with repeated
determinations of plasma phenylalanine and developmental evaluation.
Transient Hyperphenylalaninemia
Moderately elevated levels of phenylalanine occur in
transient tyrosinemia of the newborn infant. When the
infants ability to oxidize tyrosine matures, the elevated
levels of tyrosine and phenylalanine return to normal.
ALKAPTONURIA
It is the first inborn error of metabolism identified and
was reported by Sir A Garrod in the year 1908.
It is a rare autosomal recessive disorder caused by a
deficiency of the enzyme homogentisic acid oxidase. This
enzyme deficiency results in defective tyrosine metabolism
and the accumulation of homogentisic acid in tissues and
Genetics
urine. The elevated levels of homogentisic acid in the urine
with oxidation results in a dark brown-black color, and
the initial diagnosis may result from observation of
discolored urine. Visible pigmentary deposition may occur
in the face, nose, ears and eyes and is referred to as
ochronosis.
To aid in the diagnosis, one should consider the clinical
triad of: (1) black urine with increased levels of homogentisic acid, (2) ochronosis, and (3) degenerative arthritis.
Most of these patients have arthritis involving the
intervertebral disks, knees, shoulders, and hips, which
can be visualized radiographically. The urine gives a
positive Benedicts test and a purple black color with ferric
chloride test. The condition is generally benign and there
is no specific treatment available for this disorder.
ALBINISM
Albinism describes a group of genetically inherited
conditions caused by defective melanin production. The
biosynthesis of melanin by melanocytes requires the
oxidative enzyme tyrosinase. In albinism, the tyro-sinase
system appears to be defective. The disorder may be
generalized, affecting the skin, eyes and hair (oculocutaneous albinism), or localized, affecting primarily the
eyes (ocular albinism). Oculocutaneous albinism may be
tyrosinase-negative or tyrosinase positive depending on
the ability of a hair-bulb plucked from the patient and
incubated in tyrosine solution to synthesize melanin. This
test may not prove accurate until a child is 3 to 5 years of
age; thus, ascertaining the type of albinism when the
patient is younger than age 3 may be difficult.
Witkep recognized 10 different types of oculocutaneous
albinism (OCA) and 4 types of ocular albinism. Of these,
tyrosinase positive OCA is the most common form of
albinism with normal tyrosinase activity.
Albinism (all types) has a worldwide prevalence of 1
in 20,000. Oculocutaneous albinism is inherited as an
autosomal recessive trait except for a rare type that is
dominantly inherited; ocular albinism is inherited as an
X-linked or autosomal recessive trait; and partial albinism
(piebaldism) is inherited as an autosomal dominant trait.
Clinical manifestations common to almost all forms of
albinism include depigmentation of skin, iris, and retina.
Nystagmus, strabismus, photophobia, decreased visual
acuity, and presence of red reflex are common eye findings.
Blindness and skin cancer are the two major late sequelae
of albinism, in its severe form. It is important to make the
diagnosis of albinism as early as possible and to offer
1031
genetic counseling to the patient and parents. The family

should be informed that there is no cure but individuals
with this disorder can live a fairly normal life with
appropriate support. An ophthalmologist should provide
lenses to relieve glare intolerance and various low vision
aids, in conjunction with the patients best visual
correction, to allow sufficient vision for daily activities. A
dermatologist can provide instructions on skin protection
and regular examinations for cutaneous disorders and
malignancies. Support groups are essential to provide
social and psychological support to these patients.
HOMOCYSTINURIA
Homocystinuria is an autosomal recessive disorder and
is the second most common inborn error of metabolism.
Homocystinuria is due to deficiency in cystathionine Psynthetase resulting in an increased concentration of
homocystine and its dietary precursor, methionine, in
blood and other body fluids. The patient with untreated
homocystinuria is asymptomatic in infancy, but subsequently, develops mental retardation, skeletal disorders,
and thromboembolism in addition to numerous ocular
complications. Ectopia lentis is the most notable eye finding.
Other ocular features of this disorder include microcystic
peripheral retinal degeneration, secondary pupillary
block, glaucoma, retinal detachment, myopia, cataract,
strabismus, optic atrophy, spherophakia, iris atrophy,
uveitis and keratitis.
The skeletal abnormalities include scoliosis, arachnodactyly, and pectus excavatum.
Patients with homocystinuria are also susceptible to
thromboembolic episodes involving both arteries and
veins. Consequently, these patients are subjected to
premature deaths from myocardial infarctions, pulmonary
emboli, and cerebrovascular accidents. Surgeons must be
aware that affected patients experience a greater incidence
of postoperative thromboembolism with general anesthesia and surgical procedures and therefore, are best
performed under local anesthesia, if possible.
Elevations of both methionine and homocystine in
body fluids are the diagnostic laboratory findings. Freshly
voided urine should be tested, since homocystine is
unstable and may disappear as the urine is stored. The
diagnosis may be confirmed by assay of the enzyme in
liver biopsy specimens, cultured fibroblasts, or phytohemaglutinin stimulated lymphocytes. Prenatal diagnosis
is feasible by an enzyme assay of cultured amniotic cells
or chorionic villi.
1032
Homocystinuria is one of the few metabolic disorders

which are treatable. Pyridoxine (vitamin B6) combined
with dietary restriction of methionine benefits nearly 40
percent of these patients (Table 18.4.1).
TABLE 18.4.1: Diet for Homocystinuria patients
List A - Forbidden foods
(a) Meat, chicken, fish, eggs.
(b) Milk, cheese, curd, ice-cream, chocolates, horlicks,
oval-tine.
(c) Wheat flour, bajra, maize, barley, jowar, oat meal, bread,
cakes, biscuits and pasteries.
(d) Rice and pulses.
(e) Nuts and dried fruits.
(f) Maggi and other soup cubes.
(g) Peas.
(h) Methi, arvileaves.
List B - Foods to be consumed in moderate amounts
(a) Beans, beet root, cauliflower, bathua, cabbage, carrot,
onion, potatoes, radish, sweet potatoes, lowki, brinjal,
cucumber, bhindi, pumpkin, tomatoes.
(b) Banana, grapes, guava, mango, papaya, apple.
List C - Unrestricted foods
(a) Arrowroot, cornflour, sago, custard powder.
(b) Sugars, honey, jam, marmalade, jellies.
(c) Butter, cooking fat and oil.
(d) Tea, coffee, squash.
(e) Salt, pepper, vinegar, spices, curry powder.
(f) Lowki, tori, tinda.
MAPLE SYRUP URINE DISEASE (MSUD)

Decarboxylation of leucine, isoleucine and valine
(branched chain amino acids) is carried out by a complex
enzyme system (branched chain ketoacid dehydrogenase)
using thiamine pyrophosphate as a coenzyme. Deficiency
of this enzyme system causes MSUD, named after the sweet
odor of maple syrup, found in body fluids, especially urine.
Several forms of this condition have been reported.
The classic form presents in the neonatal period with
lethargy, poor feeding, hypertonicity, convulsions,
resistant hypoglycemia, metabolic acidosis and coma.
Death occurs in few weeks to few months in untreated
cases. Diagnosis is established by noting the peculiar odor
of urine, by noting elevated levels of branched chain amino
acids in urine and plasma.
Management in acute stage consists of provision of
high calories intravenously and doing peritoneal dialysis,
to remove excess amounts of branched chain amino acids
from circulation. The diet should be low in these amino
acids and synthetic formulas are; available. The long-term
outcome is guarded. Some forms of MSUD respond to

thiamine.
HARTNUP DISEASE
This rare autosomal recessive disorder is characterized
by a transport failure of tryptophan in the gut and in the
renal tubules with subsequent breaking down of this
amino acid by the intestinal flora, reabsorption of indols
and indicans, thus formed and their elimination into
urine. Plasma levels of all amino acids and even of
tryptophan are normal as absorption of small peptides
containing the latter, takes place in the usual manner.
The major degradative pathway of tryptophan leads
normally to formation of nicotinic acid, which is the main
component of NAD and NADP. Thus, the deficiency of
this amino acid or precisely of coenzyme I and II will give
a picture resembling pellagra, characterized by photosensitive dermatitis, tremor, headache, ataxia, diplopia,
psychiatric disturbances. The symptoms are usually
intermittent and precipitated by stress, infection, poor
nutrition and sulphonamide therapy.
Classical clinical picture and excretion of large
amounts of indoles and indicans in urine establish the
diagnosis. Avoidance of undue exposure to sun and daily
intake of 50 to 300 mg of nicotinamide helps these patients.
TYROSINEMIA
Tyrosine is used for protein synthesis and is a precursor
of dopamine, norepinephrine, epinephrine, melanin, and
thyroxine. At least two distinct clinical entities are
associated with increase in plasma concentrations of
tyrosine, but only in tyrosinemia II are signs and symptoms
attributed to high levels of tyrosine in body fluids. A
transient form of tyrosinemia is seen in newborn infants.
Tyrosinemia Type-I (Tyrosinosis,
Hereditary Tyrosinemia)
Tyrosinemia type-I is an autosomal recessive trait. This
condition is caused by a deficiency of an enzyme
fumarylacetoacetate hydrolase, which results in a
moderate elevation of serum tyrosine which in turn causes
severe involvement of the liver, kidney and central nervous
system. There are two main forms of the disease: the
neonatal or acute form and the chronic or latent form.
Infants having the acute form, become symptomatic
within the first 6 months of life. The common findings are
failure to thrive, developmental delay, irritability, vomiting,
diarrhea, fever, hepatomegaly, jaundice, hypoglycemia,
Genetics
bleeding tendencies, cabbage like odor and death from
hepatic failure usually occurs before the second year of life.
In the chronic form, clinical manifestations may not
appear until after the first year of age. It is characterized
by failure to thrive, developmental delay, progressive
cirrhosis, renal tubular dysfunction (Fanconis syndrome),
and vitamin D resistant rickets. Episodes of acute
polyneuropathy are seen in 40 percent of patients, which
is characterized by severe pains in the legs/abdomen,
hypertonia, vomiting, paralytic ileus and occasionally self
mutilation. Death usually occurs from liver failure or
hepatoma by 10 years of age.
The diagnosis is established by measurement of
fumarylacetoacetate hydrolase activity in liver biopsy
specimen or cultured fibroblasts. The degree of residual
enzyme activity dictates the severity of the disease.
A diet low in tyrosine, phenylalanine and methionine
may result in some clinical improvements in some patients.
Liver transplantation can be tried in those patients who
do not respond to diet therapy. Prenatal diagnosis has been
achieved by measurement of succinylacetone in amniotic
fluid and by the enzyme assay in chorionic villus biopsy.
TyrosinemiaType-ll (Oculocutaneous Tyrosinemia)
It is a rare autosomal recessive disorder which results in
mental retardation, palmar and plantar punctate
hyperkeratosis, and herpetiform corneal ulcers. Corneal
ulcers which occur during the first few months of life are
due to tyrosine deposition. Skin lesions may develop later
in life. Mental retardation may be associated with self
mutilation. The condition is due to the deficiency of the
cytosolic fraction of hepatic tyrosine aminotransferase
(tyrosine transaminase). In contrast to type-I, liver and
kidney functions, as well as serum concentrations of other
amino acids, are normal.
Treatment with a diet low in tyrosine and phenylalanine not only corrects the chemical abnormalities but also
results in healing of skin and eye lesions. Mental
retardation can be prevented by early dietary restriction
of tyrosine.
motor activity. Tyrosinemia usually resolves

spontaneously during the 1st month of life. The condition
is presumably due to delayed maturation of phydroxyphenyl pyruvic acid oxidase. The condition can
be corrected by reducing the amount of protein in the diet
and administration of vitamin C.
GLYCOGEN STORAGE DISORDERS
The glycogen storage disorders (GSD) are a heterogeneous
group of inborn errors of carbohydrate metabolism which
lead to abnormal accumulation of normal or altered
glycogen in various organs. These are about 12 major types
with subtypes in some of them (Table 18.4.2). Most GSDs
are inherited as autosomal recessive traits except for GSD
type IXB, which is inherited as X-linked recessive disorder.
TABLE 18.4.2: Classification of GSD
Types Enzyme
deficiencies
Major
organs
involved
Comments
Exceptional feature is
depletion of glycogen
in organ involved
Severe hypoglycemia
Assay enzyme of fresh
tissue
Glycogen
synthetase
Liver,
muscle
a. Glucose-6phosphatase
Liver
b. Glucose-6phosphatase
translocase
Acid
glucosidase
Liver
Debrancher
enzyme
Brancher
enzyme
Muscle
phosphorylase
Liver phosphorylase
Phosphofrutokinase
Not defined
Liver
muscle
Liver
III
IV
V
VI
VII
VIII
IX
Transient Tyrosinemia of the Newborn

In 0.5-10 percent of newborn infants, plasma tyrosine levels
may be as high as 60 mg/dl in the first 2 weeks of life.
Most affected infants are premature and receiving high
protein diets. Most infants are asymptomatic but some of
them present with lethargy, poor feeding and decreased
1033
X
XI
a. Liver phosphorylase
kinase
b. Liver phosphorylase
kinase
Cyclic 35 AMP
dependent kinase
Not defined
All
Muscle
Liver
Muscle
Brain
Liver
Liver
Liver,
muscle
Liver,
kidney
Lysosomal storage
disease
Late onset variety
confined to muscle
Mild type I, late onset
type involves muscle
Cirrhosis, liver
failure, uniformly fatal
Muscle weakness and
cramping in adult life
Mild type-I
Clinically similar to type V
Neurodegenerative
disorder
Mild type-I, recessive
Mild type-II, X-linked
recessive
Predominant renal
tubular disease,
resistant rickets
1034
GSD Type-0
This disorder is due to deficiency of glycogen synthetase
enzyme which catalyzes the synthesis of glycogen from
UDP glucose. Consequently in its absence, the glycogen is
depleted in the liver. Patients with this disorder will have
severe hypoglycemic convulsions in infancy. Hepatomegaly is absent in this disorder.
GSD Type-I (von Gierke Disease)
This is due to deficiency of glucose-6-phosphatase enzyme
in the liver which normally liberates glucose from glucose6-phosphate. Children with this disorder have enlarged
liver and kidneys, doll face, stunted growth, normal
mental development, tendency to develop hypoglycemia,
lactic acidosis, hyperlipidemia, acidemia, gout and
bleeding. In type Ib, the symptoms are as and those of
GSD type la; in addition, frequent neutropenia is present.
If untreated, the hypoglycemia and lactic acidosis lead to
death in infancy, but survivors tend to improve spontaneously after adolescence, though some ultimately develop
gout, uric acid nephropathy and hepatic adenomas.
GSD Type-II (Pompe Disease)
It is due to deficiency in lysosomal acid alphaglucosidase.
It is the only GSD due to lysosomal disorder. Excess
glycogen is stored in vacuoles derived from lysosomes in
nearly all types of cells. The infantile form presents with
severe hypotonia, mental retardation and cardiomegaly.
Death usually results in infancy due to congestive heart
failure. The adult form presents with mild wasting and
weakness of muscles in adult life (Table 18.4.3). The
disease runs a prolonged but benign course. The
diagnostic tests include estimation of acid glucosidase in
WBCs and demonstration of glycogen filled lysosomes in
muscles by electron microscopy.
TABLE 18.4.3: Signs and symptoms of pompe disease

Signs and symptoms of Pompe disease in infants
Rapidly progressive and profound muscle weakness(~96% of
infants)
Floppy baby appearance
Calf muscles feel firm on palpation
Axial hypotonia
Head lag
Laxity of facial muscles
Infant slips through when grasped under the arms
Areflexia (in late stages of disease)
Cardiomegaly and cardiomyopathy and/or cardiac failure (~95%
of infants)
Moderate hepatomegaly (~82% of infants)
Macroglossia (~62% of infants)
Feeding difficulties (difficulty sucking and swallowing) and poor
weight gain
Frequency respiratory infections
Respiratory distress or insufficiency with increased work of
breathing
Delayed motor milestones
Markedly elevated CK
Rapidly progressive disease course
Signs and symptoms of late-onset Pompe disease in children

(age 1 year and older)
Progressive muscular weakness (all patients)
Predominantly proximal
Delayed motor milestones
Lower limbs affected more than upper
Calf muscle hypertrophy
Involvement of paraspinal muscles (older children)
Gower sign
Hypotonia
Decreased deep tendon reflexes
Swallowing difficulty
Respiratory problems
Frequent respiratory infections
Respiratory insufficiency or failure
Exertional dyspnea
Obstructive sleep apnea
Orthopnea
Exercise intolerance
Elevated CK
Moderate hepatomegaly (~29%)
Cardiomegaly and cardiomyopathy (less severe than in infantileonset ~ 4%)
Macroglossia (infrequent)
Morning headache.
Somnolence
Wadding gait
Lower back pain
Decreased deep tendon reflexes
Lordosis, kyphosis, and/or scoliosis
Normal intelligence
Genetics
1035
GSD Type-lll
Prenatal Diagnosis
This is a rare disorder due to deficiency of debrancher

enzyme resulting in accumulation of glycogen of abnormal
structure that may result in cirrhosis in later life. The
patients present with many features of those with type-I
but in milder form.
Prenatal diagnosis is possible in GSD II, GSD IV by enzyme

estimation from cultured fibroblasts obtained from
amniocentesis at 14 weeks gestation. In GSD II (Pompes
disease) uncultured amniotic cells may show glycogen
laden lysosomes under electronmicroscopy.
In GSD type I, the enzyme deficiency is confined to the
liver; hence prenatal diagnosis is not possible. In GSD
types III, IX and X there is no need for prenatal diagnosis
as most of these patients live near normal lives.
GSD Type-IV
This is another rare GSD due to brancher enzyme
deficiency resulting in accumulation of abnormal glycogen
in the liver. This results in hepatosplenomegaly, severe
cirrhosis and death in early childhood due to liver failure.
GSDType-V (McArdle syndrome) and GSD Type VII
Enzyme deficiencies are confined to skeletal muscle and
both conditions present in a similar way. Symptoms may
start in childhood with progressive muscle weakness with
cramping pain on exertion. Very often patients are
asymptomatic till early adult life when they develop
muscle weakness and cramps after exercise. The diagnosis
of these disorders is done by characteristic histological
appearance of the muscle and confirmed by specific enzyme
assays.
GSD Types Vl and IX
These are mild disorders with massive hepatomegaly
which is often found on routine examination. Symptomatic hypoglycemia is rare.
Treatment
The most important disorder amenable to treatment is
GSD type-I. Maintaining euglycemia results in reversal of
most biochemical abnormalities seen in these patients.
Frequent day time feeds and night time glucose infusions
help these patients. The catch up growth takes place and
liver regresses remarkably. Those patients who develop
hyperuricemia may require allopurinol to prevent uric acid
nephropathy.
GSD types II, IV and VIII are fatal despite therapy.
There is no specific treatment.
GSD types V and VII that present later in life with
muscular cramps and weakness probably do not require
therapy. High protein diet may be of benefit.
Treatment is not needed in GSD types III, VI, IX and X
which run a benign course.
GALACTOSEMIAS
These are groups of disorders inherited as autosomal
recessive traits due to deficiency of enzymes involved in
the various steps of conversion of galactose to glucose.
There are three forms of this disorder.
Classic Galactosemia
Results from deficiency of galactose-1 phosphate uridyl
transferase. The absence of this enzyme results in
accumulation of galactose-1-phosphate. This accumulation causes injury to the kidney, liver and brain. The
clinical manifestations in the newborn include jaundice,
hepatomegaly, vomiting, hypoglycemia, convulsions,
lethargy, irritability, feeding difficulties, poor weight gain,
aminoaciduria, cataract, hepatic cirrhosis, ascites,
splenomegaly and mental retardation. Gram-negative
sepsis, especially with E. coli is common. Administration
of galactose results in increased galactose-1 -phosphate
which inhibits phosphoglucomutase resulting in
impairment of conversion of glycogen to glucose and thus
produces hypoglycemia. Galactose-1-phosphate is
responsible for liver and brain damage, whereas galactitol
a product of alternative pathway produces cataract.
The diagnosis is made by demonstrating a reducing
substance in several urine samples collected while the
patient is receiving milk. The reducing substance found
in the urine can be identified as galactose by chromatography or by enzymatic test specific for galactose. Final
confirmation of diagnosis is made by estimating transferase enzymes in erythrocytes.
The treatment consists of total elimination of galactose from the diet (milk and milk products) right from birth
to avoid liver injury, mental retardation, cataract and
recurrent hypoglycemia. Recent studies show that milk
eliminated from the diet of a pregnant women carrying a
fetus with galactosemia, prevents minor cognitive function
1036
disorders and ovarian failure noticed even in children

managed on strict diet postnatally.
Galactokinase Deficiency
This disorder results from absence of galactokinase that
catalyzes the initial phosphorylation of galactose and is
clinically characterized by galactosemia, galactosuria and
cataract without mental retardation or aminoaciduria.
Definitive diagnosis is made by demonstrating deficiency
of galactokinase activity in erythrocytes. Postnatal
institution of a galactose free diet prevents cataract
formation. The prognosis is good as apart from cataract
the children are otherwise normal.
Deficiency of Uridyl Diphosphogalactose-4 Epimerase
Deficiency
This disorder may be benign or like classical galactosemia depending on the type of disorder. Treatment is
with galactose free diet. This disorder has to be considered
in a symptomatic patient who has normal transferase
activity.
MUCOPOLYSACCHARIDOSIS (MPS)
The mucopolysaccharidoses are a group of inherited
disorders caused by incomplete degradation and storage
of acid mucopolysaccharides (glycosaminoglycans).
Accumulation of mucopolysaccharides in various organs
results in the clinical manifestations. Dermatan sulfate,
heparan sulfate, and keratan sulfate are the major

mucopolysaccharides involved in the pathogenesis of the
mucopolysaccharidoses. Specific degradative lysosomal
enzyme deficiencies have been identified for all the
mucopolysaccharidoses (Table 18.4.4).
Mucopolysaccharides are major components of the
intercellular substance of connective tissue; hence bony
changes are characteristic of the MPS. The skeletal
deformities seen on roentgenograms are referred to as
dysostosis multiplex, which includes large dolicocephalic
head, thickened calvarium, hyperostosis of the cranium,
boot or J-shaped sella turcica; thickened medial third of
clavicle, ovoid shaped vertebral bodies in the lower
thoracic and upper lumbar regions with beak like
projections on their lower anterior margins, resulting in
gibbus deformity, spatulated ribs, flaring of iliac bones
with shallow acetabulae, progressive coxa valga deformity,
tapering of the terminal phalanges and widening at the
proximal ends and tapering at the distal ends of the
metacarpals, irregular widening and cortical thinning in
the long bones and the articular surfaces of the radius
and ulna face one another forming a V.
The central nervous system, cardiovascular system,
liver, spleen, tendons, joints and skin may be involved.
The MPS follow an autosomal recessive mode of
inheritance, with the exception of Hunter syndrome, which
is inherited as an X-linked recessive trait. The general signs
and symptoms of MPS are included in Table 18.4.5.
TABLE 18.4.4: Biochemical classification of the mucopolysaccharide disorders

Number*
Eponym
Enzyme deficiency
Glycosaminoglycan stored
MPS I (severe)
MPS I (attenuated)
MPS I (attenuated)
MPS II (severe)
MPS II (attenuated)
MPS IIA
MPS IIIB
MPSIIIC
Hurler syndrome
Scheie syndrome
Hurler-Scheie syndrome
Hunter (severe) syndrome
Hunter (mild) syndrome
Sanfilippo A syndrome
Sanfilippo B syndrome
Sanfilippo C syndrome
-L-iduronidase
-L-iduronidase
-L-iduronidase
Iduronate sulfatase
Iduronate sulfatase
Heparan N-sulfatase
-N-acetyl-glucosaminidase
Acetyl CoA:-glucosaminidase
acetlytransferase
N-acetyglucosamine 6-sulfatase
Galactose-6-sulfatase
-galactosidase
N-acetylgalactosamine 4-sulfatase
(arylsulfatase B)
-glucuronidase
Dermatan sulfate, heparan sulfate

Heparan sulfate
Heparan sulfate
Heparan sulfate
MPSIIID
MPS IVA
MPS IVB
MPS VI
Samfilippo d syndrome
Morquio syndrome, type A
Morquio syndrome, type B
Maroteaux-Lamy syndrome
MPS VII
Sly syndrome
MPS IX
Hyaluronidase
*Note that MPS type designations V and VII are no longer used.
Heparan sulfate
Keratan sulfate, chondroitin 6-sulfate
Keratan sulfate
Dermatan sulfate
chondroitin 4-,6-sulfates
Hyaluronan
Genetics
TABLE 18.4.5: Possible presenting features of a MPS
disorder in infants and children*
Physical appearance
Macrocephaly
Progressively coarsening of facial features such as prominent
forehead, broad nose with flat nasal bridges, macroglossia,
and thickened lips
Protruding abdomen due to hepatosplenomegaly
Inguinal or umbilical hernias
Hirsutism
Neurologic/behavioral/developmental
Loss of development skills such as speech and learning
Mild mental deterioration
Behavioral problems
Hyperactivity
Hydrocephalus (communicating type)
Ophthalmologic
Corneal clouding
Photophobia
1037
Infants with Hurler syndrome appear normal at birth, the
features start appearing during the first year of life. The
features include large dolicocephalic head with frontal
bossing, depressed nasal bridge, flat and broad nose, facial
features become progressively coarser, clouding of the
cornea, developmental regression, mental retardation,
hepatosplenomegaly, exaggerated kyphosis and umbilical
and inguinal hernias. The downhill course continues
rapidly after the 2nd or 3rd year of life, they usually die by
their early teens. The diagnosis is suggested by clinical
and roentgenographic findings of dysostosis multiplex
and urinary exertion of dermatan and heparan sulfates.
Definitive diagnosis requires detection of -L-iduronidase
deficiency in white blood cells, serum, or cultured skin
fibrob lasts.
Ears, nose, and throat

Recurrent otitis media
Chronic rhinitis
Enlarged tonsils and adenoids
Hearing loss
Abnormal teeth (spacing and shape)
Pulmonary
Frequent pneumonias
Reactive airway disease
Noisy breathing
Snoring caused by upper airway obstruction
Cardiac
Murmur caused by valvular disease
Cardiomyopathy
Musculoskeletal
Decreased joint range of motion
Bone deformities (dysostosis multipex)
Decreased hand fine motor skills
Lumber kyphosis
Unusual gait or stance
*Note that these are collective findings; individual patients will have
varied presentations, and absence of a particular finding or findings
does not necessarily rule out a MPS disorder.
Hurler Syndrome (MPS IH) (Fig. 18.4.1)

This is the most severe of the MPS. The basic defect is a
deficiency of -L-iduronidase, which leads to accumulation of dermatan and heparan sulfates in tissues and
their urinary excretion. Almost every tissue in the body is
affected.
Figure 18.4.1: Hurler syndromeCoarse facial features

and corneal clouding
Scheie Syndrome (MPS IS)

This is the mildest of the MPS. It is a distinct clinical and
genetic entity; the enzyme deficiency, a-L-iduronidase, is
the same as in Hurler syndrome but is specific for dermatan
sulfate, which accumulates in tissues and is excreted in
excessive amounts in the urine.
Patients with this disease have normal intelligence,
mild facial coarsening, joint stiffness, carpal tunnel
syndrome, corneal clouding and aortic regurgitation. The
clinical features do not appear until after 5 years of age
1038
and the disease is compatible with close to normal life

expectancy.
The roentgenographic findings include mild dysostosis multiplex without vertebral involvement. Diagnosis
is confirmed by a deficiency of -L-iduronidase in white
blood cells or in cultured skin fibroblasts.
The basic defect is -L-iduronidase deficiency specific for

dermatan sulfate, which is excreted in urine and stored in
the liver, spleen and other tissues.
The clinical features usually develop in the first 2 years
of life. The patients develop mild coarseness of facial
features, corneal clouding, short stature, hepatosplenomegaly, joint contractures, hernias and cardiac valvular
lesions. Mental development is normal. The roentgenograms reveal severe dysostosis multiplex without gibbus.
The diagnosis is based upon the findings of dermatan
sulfate in the urine and a-L-iduronidase deficiency.
heparan sulfate. The coarse facial appearance and skeletal

involvement are milder than those seen in the Hurler and
Hunter syndromes. There are four enzymatic variants, all
leading to the same phenotype and mucopolysacchariduria. Heparan sulfate is stored in tissues, and its
accumulation is responsible for the neuronal damage and
atrophy underlying the profound mental retardation
associated with the disease.
The affected children have delayed developmental
milestones and are usually hyperactive. By the end of the
first decade, there is rapid neurologic deterioration and
they become bedridden. Most children die in their middle
teens. Mental retardation, joint stiffening, hepatosplenomegaly, hernias and dysostosis multiplex are common
but dwarfism and corneal clouding are rare.
Diagnosis should be considered in the presence of
heparan sulfaturia and the clinical features. The different
enzymatic variants can be confirmed by specific enzyme
assays provided by special laboratories.
Hunter Syndrome (MPS II)
Morquio Syndrome (MPS IV)
It is the only X-linked disorder among the MPS. It is milder

than Hurler syndrome. The enzyme deficient in tissues is
iduronate sulfatase. The severe form of the disease is
designated type A, and the mild disease, type B. Pebbly
skin lesions over shoulder area and back are pathognomonic.
This disorder is characterized by keratan sulfaturia and

skeletal dysplasia. The syndrome is associated with severe
somatic manifestations and lack of mental involvement.
Skeletal abnormalities include flat vertebrae (platyspondyly), short neck, genu valgum, flat feet, large and
unstable knee joints, large elbow joints, and large wrists
with ulnar deviation. The platyspondyly leads to short
stature and short trunk. The underdeveloped odontoid
process may cause atlantoaxial subluxation and translocation, with spinal cord compression. The other clinical
features are corneal clouding, midface hypoplasia, mild
hepatosplenomegaly, cardiac manifestations secondary
to respiratory failure caused by kyphoscoliosis, teeth
enamel defect, and hearing loss. These patients usually
die in the third or fourth decade.
Hurler-Scheie Syndrome (MPS IH/S)
Type A (Classic Form)

Coarse facial features, short stature, hepatosplenomegaly,
hernias, severe mental retardation and hearing loss are
common clinical manifestations.
Type B
Mental retardation is usually lacking or very minimal.
The physical features are similar to, but milder than, those
in type A, and patients have a longer life expectancy.
Diagnosis of Hunter syndrome is confirmed by enzyme
studies showing iduronate sulfatase deficiency in serum,
WBCs or cultured fibroblasts.
Sanfilippo Syndrome (MPS III)
This syndrome is a distinct entity and is based on clinical
findings and excessive urinary excretion of exclusively
Maroteaux-Lamy Syndrome
This syndrome resembles Hurler disease clinically but
does not involve mental retardation. The elevated urine
mucopolysaccharide is almost exclusively dermatan
sulfate, and N-acetylglucosamine-4-sulfate sulfatase
(arylsulfatase B) is the deficient enzyme. Deficiency of
arylsulfatase B in WBCs or cultured fibroblasts confirms
the diagnosis of Maroteaux-Lamy syndrome.
Genetics
SKELETAL DYSPLASIAS
Skeletal dysplasias are heterogenous group of bone
disorders characterized by intrinsic disturbances in bone
growth and structure that produce wide spectrum of
clinical and radiological manifestations and often have a
genetic basis.
These disorders affect metaphysis, epiphysis and
diaphysis in a generalized fashion that often result in
disproportionate dwarfism. Some skeletal dysplasias are
lethal, and need to be diagnosed antenatally, to help the
couple to avoid the psychological trauma at birth. But
most skeletal dysplasias produce orthopedic and body
image problems.
A good history is of paramount importance in the
evaluation of a patient with skeletal dysplasia. Following
are some of the important points:
1. Pregnancy history Increased/decreased uterine size;
polyhydramnios may be features in some lethal
varieties of skeletal dysplasia. Decreased fetal movements are observed, especially in lethal forms and those
associated with contractures, dislocations or fractures.
2. Drug history Warfarin produces dysplasia which is
similar to genetic chondrodysplasia punctata.
3. History of stillbirths and history of malformations in
other siblings and relatives may indicate the pattern
of inheritance,
4. Parental consanguinity may suggest autosomal
recessive inheritance,
5. In X-Iinked recessive disorders, only male members
on the maternal side are affected,
6. Age of onset may be of some help in identifying the
disorder.
7. Many lethal skeletal dysplasias like thanatophoric
dwarf, achondrogenesis, and perinatal osteogenesis
imperfecta can be diagnosed antenatally by ultrasound.
Few other dysplasias manifest only after 2 years of age.
Examination
The most important aspect in the examination is
measurement. Measure the height (length) to decide about
shortness and compare with normal standards and
normal relatives. Measure the upper segment and lower
segment. At birth, the ratio is 1.7:1, at 3 years it is 1.3:1,
and at 8-10 years, it becomes 1:1 and subsequently the
adult ratio is 0.9:1. In achondroplasia, the ratio is increased
and in Marfan syndrome it is decreased.
1039
Measure the arm span by taking the distance between

the tips of the middle fingers when both the hands are
stretched perpendicular to the trunk. Arm span is
increased in conditions like Marfan syndrome.
A small group of conditions are characterized by
asymmetric short stature. Those with asymmetric short
stature are further subdivided according to the body
segment, primarily involved in the shortening process.
Those with short extremities are called short limb dwarfs,
those with short bodies are short trunk dwarfs, while those
in whom the shortening is equally distributed between
the extremities and the body are referred to as
proportionate dwarfs (Table 18.4.6).
The upper and lower extremities each have three
anatomic segments: proximal, middle and distal.
Shortening of the extremities that is maximal in the
proximal segment is rhizomelic, maximal in the middle
segment is mesomelic and maximal in the distal segment
is acromelic. Examples are given in Table 18.4.6.
Associated malformations may be of paramount
importance in arriving at a specific diagnosis (Table
18.4.7).
The secondary effects due to the skeletal dysplasia are
also important in the categorization. Some of the secondary
effects (deformations) have been listed in Table 18.4.7.
Table 18.4.7 Parameters for the differential diagnosis
of skeletal dysplasias
Radiological Evaluation
The evaluation of skeletal dysplasia is incomplete without
proper radiological assessment of the case. The minimum
number of X-rays to be taken includes:
1.
2.
3.
4.
5.
6.
7.
8.
Lateral and AP X-rays skull

AP and lateral spine
Chest (including shoulders)
Pelvis /hips
AP of the one knee
AP of one forearm
AP of one hand/wrist
Feet-AP (including ankle).
Radiological evaluation is important in two aspects:

1. To decide about the areas primarily involved in the
disorders,
2. Radiology further delineates depending upon the
mineralization.
1040

TABLE 18.4.6: Types of short stature based on symmetry of body segment and limb segment.
Examples of various limb segment dwarfs are given
A. Asymmetric short stature (There is no symmetry between two halves of body)

Chondrodysplasia punctata
Osteogenesis imperfecta
Endochondromatosis
Multiples exostosis
B. Symmetrical short stature (Both halves of body are symmetrical)
1. Short limbed dwarf
a. Rhizomelic
b. Mesomelic
c. Acromelic
(proximal segment
(middle segment
(distal segment shortening
shortening like upper
shortening like
like hands, fingers,
arm and thigh)
forearm and leg)
feet and toes)
Dyschondroosteosis
Thanatotropic
Asphyxiating
Chondrodysplasia punctata
Camptomelic dwarf
Thoracic dystrophy
Achondroplasia
Short rib
Ellis-van Creveld
Metatropic dwarf
polydactyly II
syndrome
Hypochondroplasia
Various types of
Pyknodysostosis
Metaphyseal dysostosis
mesomelic
Pseudoachondroplasia
Camptomelic dwarf
d. Nonspecific
type II
Short rib polydactyly I
and II
Hypophosphatasia congenita
Diastrophic type
type III
Multiple epiphyseal dysplasia
2. Short trunk dwarfism

a. Associated with
b. Associated with
c. Associated with
mild micromelia
moderate micromelia
severe micromelia
Achondrogenesis type IV
Achondrogenesis III
Achondrogenesis type
Spondyloepiphyseal
Kneist syndrome
I-and-II metatropic dwarfism
dysplasia
Spondylometaphyseal dysplasia
Mucopolysaccharidosis
Mucolipidosis
Spondyloepiphyseal dysplasia tarda
3. Proportionate dwarfism (Upper segment to lower segment ratio is age appropriate)
Hypophosphatasia tarda
Cleidocranial dysplasia
Infantile osteopetrosis
Trichorhinophalangeal syndrome
TABLE 18.4.7: Parameters for the differential diagnosis of skeletal dysplasias

Extreme micromelia
Achondrogenesis
Thanatophoric d.
Fibrochondrogenesis
Short rib polydactyly
Diastrophic d.
Dysegmental d.
Roberts syndrome
Rhizomelia
Thanatophoric d.
Diastrophic d.
Congenital short femur
Chondrodysplasia punc.
Mesomelia
Mesomelic d.
COVESDEM assoc.
Acromesomelia
Ellis-van crevald synd.
Metaphyseal flaring
(Dumb-bell shaped bones)
Metatropic d.
Fibrochondrogenesis
Short rib polydactyly s.III
Long narrow thorax
Asphxiating thoracic d.
Chondroectodermal d.
Metatropic d.
Fibrochondrogenesis
Campomelic d.
Jarcholevin s.
Achondrogenesis
Hypophosphatasia
Hypoplastic thorax
Shortribpolydactyly
Thanatophoric d.
Achondroplasia homozygous
Congenital heart disease.
Chondroectodermal d. (Atrial septal
defect, common atria)
Shortrib polydactyly I (TGA, VSD, Double
outlet right and left ventricle).
Shortrib polydactyly II(TGA)
Large head
Achondroplasia
Thanatophoric dwarf
Cloverleaf skull
Thanatophoric d.
Campomelic S.
Contd...
Genetics
1041
Contd...
Normal long bone
Larsen s.
Craniosynostosis
Arthrogryposis multiplex
Jarcho Levin s.
Cleidocranial d.
Curved long bones
Campomelic d.
Dysegmental d.
Otopalatodigital s.
Hypophosphatasia
Thanatophoric d.
Roberts s.
Bone fractures
Achondrogenesis
Hypophosphatasia
Hypoplastic or absent fibula
Fibrochondrogenesis
Mesomelic D.
Otopalatodigital s.
Craniosynostosis
Jarcho-Levin s.
Arthrogryposismultiplex
Hypertelorism
Mesomelic dysplasia
Larsen s.
Roberts s.
Otopalatodigital s.
Depressed nasal bridge

Thanatophoric d.
Achondrogenesis
Achondroplasia
Campomelic d.
Larsen s.
Chondrodsyplais cong.
Postaxial polydactyly
Shortrib polydactyly s.
Preaxial polydactyly
Shortrib polydactyly
Hitchhikers thumbs
Diastrophoric d.
Cleft palate
Roberts s.
Larsen s.
Otopalatodigital s.
Diatrophic d.
Campomelic s.
Spondyloepiphyseal d.
Micrognathia
Campomelic d.
Diastophoric d.
Otopalatodigital s.
Achondrogenesis
Mesomelic d.
Pena shokir s.
Weissenbacher-zweymuller S.
Short upper lip

Hypoplastic Scapulae
Campomelic S.
Club foot
Diastrophic d.
Kriest d.
Metatropic d.
Mesomelic d.
Chondrodysplasia cong.
Roberts s.
Pena-shokeir phenotype
Larsen s.Arthrogryposis multiplex
Vertebral disorganization
Jarcho levin s.
Mesomelic d.
Dyssegmental d.
VACTERL assoc.
COVESDEM assoc.
Spine demineralization
Achondrogenesis
Hypertelorism
Mesomelic d.
Larsen s.
Robinow S.
Otopalatodigital S.
d.Dysplasia, s. Syndrome COVESDEM - costovertebral segmentation defect with mesomelia).
The Sclerosing Bone Dysplasias

The sclerosing bone dysplasias are a group of disorders
characterized by increased bone density and abnormalities of skeletal modeling. Examples are osteopetrosis,
pyknodysostosis, diaphyseal dysplasia, metaphyseal
dysplasia.
BIBLIOGRAPHY
1. Biswas S, Llyod IC. Oculocutaneous albinism.Arch Dis
Child. 1999; 80:565-69.
2. Cederbaum S. Phenyl ketonuria: An update.Curr Opin
Pediatr 2002; 14:702-06.
3. Chakrapani A, Cleary MA, Wraith JE. Detection of inborn
errors of meta-bolism in the newborn. Arch Dis Child
Fetal Neonatal ed. 2001;84:205-10.
4. Holdeman NR. Metabolic disease. In Blanstein BH (Ed):

Ocular Manifestation of Systemic Disease. Churchill
Livingstone: New York, 1994;102-05.
5. Holme E, Lindstedt S. Diagnosis and management of
Tyrosinemia type 1. Curr Opin Pediatr 1995;7:726-32.
6. International nomenclature and classification of the
osteochondrodysplasias (1997). International Working
Group on Constitutional Diseases of Bone. Am J Med
Genet. 1998;79(5):376-82.
7. Kaur M, Kabra M, Das GP, Suri M, Verma IC. Clinical
and biochemical studies in homocystinuria. Indian
Pediatr 1995;32: 1067-75.
8. Kishnani PS, Howell RR. Pompe disease in infants and
children. J Pediatr. 2004 May;144(5 Suppl):S35-43.
9. Muenzer J. The mucopolysaccharidoses: a heterogeneous
group of disorders with variable pediatric presentations.
J Pediatr. 2004 May;144(5 Suppl):S27-34.
19.1 Developmental Disabilities in Children: MS Mahadeviah ................................................................................................................ 1044

19.2 Cerebral Palsy: Pratibha D Singhi ....................................................................................................................................................... 1045
19.3 Attention Deficit Hyperactivity Disorders: Nandini Mundkur ........................................................................................................... 1049
19.4 Learning Disability: MS Mahadeviah .................................................................................................................................................. 1051
19.5 Childhood Autism: MS Mahadeviah ................................................................................................................................................... 1053
19.6 Early Detection and Early Intervention Therapy for Developmental Delay: MKC Nair, Babu George ......................................... 1055
19.7 Mental Retardation: Sunanda K Reddy ............................................................................................................................................... 1072
1044
19.1 Developmental Disabilities in Children

MS Mahadeviah
INTRODUCTION
Developmental disabilities are a group of disorders
resulting from injury to the developing brain (prenatal,
perinatal or postnatal). A suitable definition has been
given by the Federal Government of the United States,
of America (Federal Developmental Disability Act USA
Title V of the Rehabilitation Act 1978) as follows:
Developmental disability can be described as a
severe chronic disability that is attributed to a mental or
physical impairment or a combination of physical and
mental impairment, is manifest before the person attains
the age of 22 years; is likely to continue indefinitely;
results in substantial functional limitation in three or
more areas of major life activity specified as self care,
language, learning, motility, self-direction, capacity for
independent living and economic self sufficiency and
that reflects the person's need for life-long and
individually planned services.
Included in this broad definition of developmental
disabilities are:
1. Mental retardation (for details refer to sub-chapter
19.7)
2. Cerebral palsy
3. Communication disorders
4. Learning disability
5. Attention deficit hyperactive disorder
6. Childhood autism.
These disabilities can occur in isolation or in combination (multiple handicaps).
Together developmental disabilities account for 15
percent of the population of children (a conservative
estimate). Any medical graduate in India who enters into

general practice will have 40 percent of his practice
devoted to children. In modern day practice of medicine
with improved obstetrical and neonatal care, substantial
number of infants born are premature, or suffer from
severe perinatal adversities (hypoxic ischemic encephalopathies, meningitis, seizures) and will survive. At least
a third of this population will suffer from developmental
disabilities.
It becomes very necessary that an undergraduate
medical student should have a working knowledge to
identify these children as early as possible, so that
necessary guidance can be provided to the parents and
the child may attain his optimum potential.
Incidence of developmental disabilities are given in
Table 19.1.1.
TABLE 19.1.1: Incidence of developmental disabilities in
children per thousand (1000)
Mental retardation
25-30
Cerebral palsy
02-03
Attention deficit hyperactive disorder
75-100
Learning disability
75
Communication disorders including hearing loss
02-03
Childhood autism
02-03
The above mentioned disorders will be discussed in

more detailed form on an individual basis.
The details of mental retardation are covered in the
Chapter on Diseases of Central Nervous System (subChapter 19.7).
Childhood Disabilities
1045
19.2 Cerebral Palsy

Pratibha D Singhi
INTRODUCTION
Pathology
Cerebral palsy (CP) is a common cause of childhood

disability. It is defined as a group of nonprogressive
but often changing motor impairment syndromes
secondary to lesions or anomalies of brain arising in early
stages of its development.
It is a static encephalopathy and excludes all progressive neurological disorders. Other neurological deficits
are frequently associated and they add to the disability
caused by the motor deficit.
As CP is an umbrella term used for a wide variety of

conditions, the pathology accordingly varies widely. Some
correlations however exists with the type of CP. PVL is
characteristically seen in preterms with spastic diplegia.
Cerebral injury in the region of the middle cerebral artery
is frequent in hemiplegic CP indicating antenatal hypoperfusion. Children with spastic quadriplegia, secondary
to severe hypoxic ischemic events, often have multicystic
encephalomalacia, and cortical/subcortical atrophy.
Bilirubin staining of basal ganglia is seen in dyskinetic CP
secondary to kernicterus. Cerebellar lesions are found in
hypotonic and ataxic CP. Developmental malformations
may be found in any type of CP.
Epidemiology
The prevalence of CP varies from 1.5 to 2.5 per 1000 live
births. Exact incidence and prevalence figures from our
country are not available.
Etiology
CP is a condition with multiple etiologies which may be
antenatal, natal or postnatal. Adverse intrauterine factors
like developmental malformations of brain and intrauterine infections account for some cases. Significant
perinatal damage has been reported in 8 to 10 percent of
cases. Genetic factors contribute in about 2 percent cases.
Although birth asphyxia was earlier considered as an
important cause of CP, it is now suggested that asphyxia
may be a consequence rather than cause of the processes
that lead to cerebral palsy. However, severe prolonged
birth asphyxia increases the risk of CP considerably and
accounts for about 10 percent cases of CP.
Preterm birth is a major etiological factor. The
underlying pathological lesions in these babies are
periventricular leukomalacia (PVL) and periventricular
hemorrhagic venous infarcts (PHVI). Ultrasonographic
detection of hypoechoic periventricular areas has been
found to be a strong predictor of later development of
motor dysfunction in these preterm babies.
In majority of the cases of CP, the cause is unknown.
Some important causes of acquired CP include CNS
infections viz. meningoencephalitis, hyperbilirubinemia,
cerebrovascular accident and head trauma.
Clinical Features
CP can be subdivided into several types based on
predominant motor pattern. Classification based on
physiological characteristics (qualitative) and extent of
involvement or topography of motor deficits (quantitative) is given in Table 19.2.1.
TABLE 19.2.1: Classification of cerebral palsy
Physiological
Topographic
Spastic
Dyskinetic
Choreoathetoid
Dystonic
Ataxic
Hypotonic
Mixed
Tetraplegia/Quadriplegia
Diplegic
Triplegia*
Hemiplegia
Monoplegia*
*Very rare and may represent evolving forms
Spastic CP
It is the most common form and accounts for 70 to 75
percent of cases. It is characterized by upper motor
neuron signs, viz. clasp knife hypertonia, exaggerated
deep tendon reflexes and extensor plantar responses.
Spastic Quadriplegia
These patients are severely disabled. All four limbs are
affected with upper limbs being equally or more affected
1046
than lower limbs. Majority of the patients have microcephaly, severe mental retardation, pseudobulbar palsies,
growth failure, visual and hearing deficits and often
epilepsy. Hypertonicity leading to arching of the back
and scissoring of legs is frequently seen. Hip subluxation
or dislocation may occur because of severe spasticity.
Walking is markedly delayed and generally the child has
toe walking because of tendo-Achilles tightening. Arms
are internally rotated, elbows extended or lightly flexed
and hands fisted. Later flexion contractures develop at
ankles, knees and elbows.
Spastic Diplegia
Here, the lower limbs are involved more than upper
limbs. Intellectual involvement is minimal. Growth of
lower limbs may suffer, whereas upper torso grows
normally. It is characteristically seen in preterm babies
with (PVL).
overflow movements, and facial grimacing are prominent. These are exaggerated with intention and emotion.
Standing and walking are delayed. Intelligence is often
preserved, but because of severe physical and
communicative disabilities, children may appear to have
mental retardation.
Ataxic CP
This is an uncommon form of CP. These infants are
hypotonic and inactive. Walking is delayed. The gait is
ataxic, and wide-based. Cerebellar signs are present,
nystagmus is, however, rare. Ataxia may also be associated with spasticity (ataxic diplegia).
Hypotonic CP
Hypotonic CP is extremely rare. In most cases, it may
represent an evolving form of dyskinetic or spastic CP.
Other causes of hypotonia should be excluded.
Spastic Hemiplegia
Other Associated Problems in CP
This refers to involvement of one side of the body. The

arm is usually more severely affected than the leg. For
reasons not clear, right sided involvement is more
frequent than left. Milder cases are often missed by the
parents and even by the doctors. The following clinical
signs can help in making an early diagnosis:
i. Poverty of movements and fisting of hand on
affected side.
ii. Definite hand preference in children less than 12
months of age.
The child may start sitting and crawling at the normal
age but walking is delayed generally by 2 to 3 months.
In severe established cases, the arm is held adducted,
flexed and internally rotated at the shoulder, with the
elbow flexed, forearm pronated, wrist flexed and thumb
adducted. The leg is held adducted, semiflexed at knee
and plantar flexed at the ankle. In long-standing cases,
asymmetries of limb growth may occur.
Children with CP have various associated nonmotor

disabilities (Table 19.2.2). These are seen maximum in
spastic quadriplegia. Management of these associated
problems is important in the rehabilitation of these
children.
Diagnosis and Differential Diagnosis
The diagnosis of CP is essentially clinical. A detailed
prenatal, natal and postnatal history and a careful
physical and neurodevelopmental examination is
needed. In severe and long-standing cases, the diagnosis
TABLE 19.2.2: Problems associated with CP
Problem
1. Mental
retardation
2. Seizures
Frequency Remarks
(%)
50 to 75
25 to 33
Dyskinetic CP
This includes the dystonic and choreoathetoid forms. The
child has severe motor disability, with persistent neonatal
reflexes. Asymmetric tonic neck response (ATNR) is
prominent and postural reflexes appear late. Infants are
usually hypotonic with marked head lag, drooling of
saliva and feeding difficulties. Athetosis generally
manifests after one year of age. Flaying of fingers,
3. Hearing and
15 to 20
speech problems
4. Ocular
50 to 70
5. Behavior
30 to 50
problems
Most often in spastic

quadriplegia and ataxic CP
Most often in spastic
hemiplegia and spastic
quadriplegia; least in
dyskinetic CP
Most common in dyskinetic
CP and spastic quadriplegia
Refractory errors, strabismus
Stubborn,
aggressiveness, lack of
attention and hyperkinetic
behavior
TABLE 19.2.3: Signs useful in early diagnosis of CP
Decreased spontaneous motility

Stereotyped abnormal movements
Constant fisting after 2 months of age
Reduced head circumference or fall in its growth
Delayed social smile
Excessive extensor tone, dystonia
Primitive reflexes persisting beyond 6 months
Persistent asymmetric tonic neck response (ATNR)
Delayed appearance of postural reflexes and developmental
milestones
Persistent asymmetry in posture, movement and reflexes
Associated signs like roving eyes, no visual following,
nystagmus, persistent squint, and lack of auditory response
of CP is not difficult. Early diagnosis during evolving

stages and diagnosis of mild cases requires experience.
Some observations and signs that we have found useful
for prediction and early identification of CP are listed in
(Table 19.2.3). Repeated examinations over a period of
time may be required to ascertain the non-progressive
nature of the disorder and to exclude slowly the
progressive neurodegenerative disorders. Neuromuscular, spinal disorders, and other causes need to be
excluded in children with dyskinetic, hypotonic and
ataxic forms of CP. The clinical pattern of CP evolves
over a period of time. A hypotonic child may be found
to have spasticity or dystonia on follow-up.
Investigations
In preterm infants, ultrasound is useful for picking up
PVL and PVHI. The extent of these lesions correlates with
the prognosis. In straight forward established cases of
CP, investigations are not generally needed for making
a diagnosis. When the etiological factors are not clear,
neuroimaging or other genetic or metabolic tests may be
required to identify the underlying etiopathological
mechanisms and to rule out any progressive neurological disease which may in the beginning appear as static
encephalopathy.
Management
Proper management of a child with CP requires a
detailed assessment to find out the functional capacity
of the child and the nature and extent of the motor as
well as associated deficits. This is best done by a multidisciplinary team comprising of a neurodevelopmental
pediatrician as a team leader, physiotherapist, occupa-
1047
tional therapist, clinical psychologist, ENT specialist,

ophthalmologist, orthopedic surgeon, teacher and social
worker, preferably all under one roof. The main aim is
to maximize the functional capacity of the child and make
him or her as independent as possible through a planned
intervention program. Involvement of the family is
essential for the success of any management plan. The
different aspects of therapy include:
Physiotherapy
This is used to promote normal movement patterns,
inhibiting the abnormal ones, and prevent contractures
and deformities. Several methods have been used, but
there is no evidence to support the superiority of one
over the other. Neurodevelopmental therapy using
Bobath technique is most popular. An individualized
approach suitable to the child's needs should be used.
Occupational Therapy
An occupational therapist trains the child for daily
activities like feeding, bathing, dressing, toilet training,
etc. The activity is broken into its components and these
are taught one by one in the required sequence. Training
for sensory-perceptual-motor coordination is also
provided.
Speech Therapy
Children with problems in speech and hearing require
the services of an audiologist and a speech therapist.
For developing countries where rehabilitation services are not easily available, a home-based management
program in which parents are taught the correct method
of handling and lifting the child and carrying out specific
exercises, is emphasized. Multisensory stimulation is
provided through peg board, blocks, toys, etc. to enhance
co-ordination and sensory-perceptual integration. These
techniques are incorporated into the pattern of daily life
of the family.
In addition to therapies, some children with CP also
require adaptive and mobility devices like standing
frames, walkers, tricycles and wheelchairs. Simple lowcost aids can be made available indigenously, according
to the child's needs. Occasionally splints, casts and
callipers may be required to maintain normal postures
and to prevent deformity.
Some children may require surgical correction of their
deformities. Neurosurgical procedure of selective dorsal
rhizotomy (in which dorsal rootlets from L2 to S2 levels
1048
are selectively cut), is useful in some children with

predominant lower limb spasticity.
Management of Associated Problems
Various members of the team are involved in the management of associated problems. The clinical psychologist
helps with management of behavior problems using
behavior modification techniques, psychotherapy, family
counseling, etc. The audiologist and ENT specialist takes
care of hearing and speech problems by providing
hearing aids. The ophthalmologist provides remedies for
visual problemscorrective glasses, squint surgery, etc.
High technology devices like electronic feeding devices,
computerized speech systems and cochlear implants are
available for children with CP in Western countries. In
our country, very few can have access to such facilities.
Drugs
Drugs have a limited role in the overall management of
children with CP. Antispasticity agents like baclofen,
diazepam, tizanidine and dantrolene sodium are needed
in some children. Botulinum-A toxin (BAT) has also been
found to be a useful antispasticity agent.
Anticonvulsant drugs are required for control of
seizures which are of various types, and frequently
difficult to control. Selection of an appropriate anticonvulsant drug is important.
Other drugs include L-dopa and trihexyphenidyl for
severe extrapyramidal symptoms, methylphenidate for
hyperactivity and aggressive behavior and atropine or
benztropine for sialorrhea, antireflux drugs of gastroesophageal reflux used on an individual basis. There is
no role for so-called brain tonics.
Parental Counseling
Interaction of the doctor with the parents is very important. Ongoing efforts are needed to ensure parental
acceptance of the problem and their participation in
prolonged management programs. Considerable understanding and insight are required for proper counseling.
Simple and honest explanations with emphasis on the
positive aspects of the child should be provided. Parents
also need to be explained about long-term treatment,
along with practical short-term goals. It is also important

to help remove the feeling of guilt, and instill positive
attitudes. As the child grows older, he or she needs
appropriate schooling or special training according to
his or her abilities. Guidance to the parents should be
provided on these issues. The ultimate goal of management is to help the child to achieve his or her optimal
developmental potential and to integrate him or her as a
functional member in the society.
Follow-up and Outcome
Children with CP need regular follow-up to ensure that
they are being benefited by their management plan and
to add new management strategies as the child grows.
Majority of the patients with cerebral palsy live to
adulthood. Life expectancy of severely affected individuals is significantly less than that of the general
population. Prognosis is worst with spastic quadriplegia,
i.e. the more limbs involved, the worse the prognosis.
Prognosis is also determined by the presence of
associated defects, socioeconomic status of the family and
availability of rehabilitative services.
To conclude, cerebral palsy represents a nonprogressive central motor disorder with a wide range and
severity of manifestations. Early diagnosis and intervention, with a team approach and active parental
involvement, can help the child with CP to become a
useful member of the society.
BIBLIOGRAPHY
1. Eicher PS, Batshaw M. Cerebral palsy. Pediatr Clin North
Am 1993;40:537-51.
2. Kuban KCK, Leviton A. Cerebral palsy. New Engl J Med
1994;330:188-95.
3. Mutch L, Alberman E, Hagberg B, Kodama K, Perat MV.
Cerebral palsy epidemiology: Where are we now and
where are we going? Dev Med Child Neurol 1992;
34:547-51.
4. Rosenbloom L. Diagnosis and management of cerebral
palsy. Arch Dis Child 1995;72:350-54.
5. Singhi PD: Cerebral palsy. In Talukdar B (Ed): Essentials
of Pediatric Neurology. New Age International (P)
Limited: New Delhi 1997;114-25.
6. Singhi P. Counseling to parents of a child with cerebral
palsy. Indian Pediatr 1988;25:368-70.
1049
19.3 Attention Deficit Hyperactivity Disorders

Nandini Mundkur
INTRODUCTION
Attention deficit hyperactivity disorder (ADHD) is a
symptom complex characterized by poor ability to
attend to a task, motor overactivity and impulsivity.
These children are fidgety, have a difficult time remaining in their seats in school, are easily distracted, have
difficulty awaiting their turn, impulsively blurt out
answers to questions, have difficulty following the
instructions and sustaining attention, shift rapidly from
one uncompleted activity to another talk excessively,
intrude on others, often seem not to listen to what is
being said, lose items frequently and often engage in
physically dangerous activities. Moderate to severe level
of disorder are accompanied by poor school and social
performance resulting in easy distractability. It is
important to know that the attention span increases with
age. The normal attention span is said to be 3 to 5
minutes per year of age, e.g. a 3-year-old child with have
an attention span of 15 minutes.
Incidence
ADHD affects 3 to 4 percent of children in the USA. Boys
are more affected than girls in a 6:1 ratio. ADHD persists into adolescence and adult life. Age of onset is
usually before 4 years but diagnosis is made around 3 to
4 years of age. Statistical data is not available for the
Indian children, experts agree that it is roughly the same
percentage as in the western population.
Etiology
One of the theories about the cause of ADHD is, that it is
due to minimal brain damage has been disputed. Also,
there is no clear relationship between home environment
and this syndrome. Excess sugar or food additives
believed to make children hyperactive which is true only
in 5 percent of cases. Therefore to summarize, ADHD is
not caused by too much TV watching, or food allergies,
or for that matter excess sugar in the diet or poor home
life or poor schools.
Scientists have used PET (positron emission tomography) scanner to observe the brain at work and have
concluded that brain areas which control attention use

less glucose in children with this syndrome. Medication
used to increase glucose intake in these parts of the brain
which control attention is proved to beneficial in some
children. Therefore, this is probably an acceptable theory
for the cause of ADHD.
Diagnosis
The diagnosis of ADHD is based on the criteria of DSM
IV on hyperactivity, impulsivity and attention deficit
(Table 19.3.1).
Children with a disorder usually have intelligent
quotient at par with age but have difficulties in scholastic performances. Some studies have suggested that
hyperactive children have higher verbal scores than
performance scores on the Wechsler Intelligence Scale
and lower scores on the Attention concentration subtest.
Psychometric tests should cover four essential areas
language skills, visuospatial skills, sequential analytic
skills and motor planning and execution skills.
Educational level, as measured on the Peabody
Individual Achievement test and the wide range
achievement test, may be lower than expected for age
IQ, especially for children who also have learning disabilities. Specific test for learning disabilities should be
administered to pin point areas of difficulty.
Medical conditions like hearing loss, thyroid dysfunction, visual disturbances, some genetic disorders, seizures
disorders and few allergic conditions may be considered
in the differential diagnosis. Mental disorders like
Tourette's disorder, oppositional defiant disorder,
conduct disorder, anxiety and depressive disorders,
pervasive developmental disorder not otherwise specified, obsessivecompulsive disorder and schizophrenio
are to be ruled out.
Very often it is seen that these children get to be highly
sensitive and conscious of their poor performance in
school. Behavioral problems like night terrors and sleep
difficulties, coordination problems, enuresis and
articulation problems may be seen in these children.
1050

TABLE 19.3.1: DSM IV criteria for attention deficit/hyperactivity disorders
A. Either (1) or (2)

1. Inattention: At least six of the following symptoms of inattention leave persisted for at least six months to a degree
that is maladaptive and inconsistent with developmental level:
a. often fails to give close attention to details or makes careless mistakes in school work, work or other activities.
b. often has difficulty sustaining attention in tasks or play activities
c. often does not seem to listen to what is being said to him or her
d. often does not follow through, on instructions and fails to finish school work, chores, or duties at the workplace
(not due to oppositional behavior or failure to understand instructions)
e. often has difficulties in organizing tasks and activities
f. often avoids, expresses reluctance about or has difficulties in tasks that require sustained mental effort (such as
school work or housework)
g. often loses the things necessary for tasks or activities (e.g. school assignments, pencils, books, tools or toys)
2. Hyperactivity-Impulsivity: At least five of the following symptoms of hyperactivity-impulsivity have persisted for at
least six months to a degree that is maladaptive and inconsistent with developmental level:
Hyperactivity
a. often fidgets with hands to feet or squirms in his or her seat
b. leaves seat in classroom or in other situations in which remaining seated is expected
c. often runs about or climbs excessively, in situations where it is inappropriate
d. often has difficulty in playing or engaging in leisure activities quietly
e. is always on the go acts as if driven by a motor
f. often talks excessively
Impulsivity
g. often blurts out answers to questions before the questions have been completed
h. often has difficulty waiting in lines or awaiting turn in games or group situations
i. often interrupts or intrudes on others
B. Some symptoms that caused impairment were present before the age of seven
C. Some symptoms that cause impairment are present in two or more settings
D. There must be clear evidence of clinically significant impairment in social, academic or occupational functioning.
Effective behavioral modification and counseling could

improve all these conditions.
focus of management would be to organize life and

discipline.
Management
Home Management
A description of the problem behaviors in specific

situations and environments should be elicited. A history
of aggression and fears, poor relationships with peers,
academic difficulty, behavioral problems at school and
reaction to authority, define the breath of the problem
and provide useful information about the ADHD.
Improvement and good outcome is possible if their
parents and teachers provide understanding and
direction and preserve the child's self esteem. Many of
these children improve attention span as they grow but
remain restless even in adulthood. Recent research
indicates, that children with ADHD treated with multiple therapies (medication, and parent counseling) are less
likely to present with delinquency in adolescence.
This is a chronic condition and needs special
intervention by parent, school and the doctor. The main
Parent counseling helps them to understand the problem,

accept the child's condition and tell them that the
hyperactive behavior is not intentional, attempts to
change an energetic child into a quiet socially acceptable
may prove to be difficult.
These children need to be provided with outdoor
activities; play with minimal instruction would be beneficial. These children need to organize to get adequate
sleep and rest. A structured home schedule for daily
activities like wakeup time, meal time, bed time, etc.
should be followed with consistency. These children need
a carefully planned discipline to be followed. Aggressive
behavior such as biting, hitting, pushing should not be
tolerated. All risks must be enforced with nonphysical
punishment. Overwhelming situations such as big
gatherings should be avoided till child learns to control
himself.
Structured behavioral modification program for
increasing attention span, proper disciplining should be
adopted. Child on special program in school would be
beneficial.
Methylphenidate (Ritalin), dextroamphetamine,
magnesium pemoline and tricyclic antidepressants are
efficacious in reducing overactivity, increasing attention
span, improving interaction between the child and the
mother. The long-term benefits of these medicines have
not yet been established. Methylphenidate is most
commonly used stimulant, it is efficacious in 75 to 80
percent of patients when administered in a dose ranging
from 0.3 to 1 mg/kg 4 hourly. Dextroamphetamine is
efficacious in 70 to 75 percent of patients. Dose is 0.2 mg/
kg. Magnesium pemoline is used in the dose of 19 mg
stat and later tablet per week. Children on any of these
drugs must have liver functions to be monitored.
1051
Clonidine and tricyclic antidepressants are said to be

effective in some children. Major short-term side effects
include anorexia, abdomen pain and insomnia. Longterm use may result in increased heart rate and growth
suppression. Drug therapy must be planned by only
those who handle child with an understanding of the
condition, and monitored regularly.
Dietary Management
The idea that behavior disorder may be caused by food
is largely suggested by Dr. Feingold. He saw 30 to 50
percent of hyperactive children show a significant
improvement when placed on a special elimination
program of avoiding naturally occurring salicylates and
artificial food additives, particularly in hyperactive
children with a genetically predetermined predisposition. Although this has not been conclusively proved,
it is worthwhile trying a diet based on wholesome food
and avoiding foods with artificial color or flavor.
19.4 Learning Disability

MS Mahadeviah
INTRODUCTION
Classification
Learning disability, scholastic backwardness, school

failure are common terms applied to children who
experience difficulties in coping with academic skills.
Learning disability is popularly known as Dyslexia.
Learning disability is perhaps the most common of
developmental disabilities in children. It is estimated that
5 to 15 percent of all school going children suffer from
scholastic backwardness.
At the outset it is important to classify learning disability as (i) global and (ii) specific.
Global
It occurs when the child has difficulties in all the
subjects which is usually the result of subnormal intelligencemild retardation or borderline range of intelligence.
Early Identification
Early identification of learning disability (LD) is very
desirable for early rehabilitation to help the child to attain
his or her optimum potential. Most of the children with
LD are identified by the teachers in school and not by
the pediatrician.
However children who show developmental delay,
have behavior disorders, early language disorders
including articulation disorders are well known to be At
Risk: for developing Learning Disability.
Specific
Specific learning disability means a disorder in one or
more of the basic psychological processes involved in
understanding or using language, written or spoken
which may manifest itself in an imperfect ability to listen,
think, speak, read, write, spell or do mathematical
calculations. The term includes such conditions as
perceptual handicaps, brain injury, minimal brain
dysfunction, dyslexia and developmental aphasia.
1052
The term Specific Learning Disability (SLD) does not

include children who have learning problems which are
primarily the result of visual hearing or motor handicaps,
mental retardation, or emotional disturbance, or
environmental, cultural or economic disadvantages.
Etiology
There is increasing evidence that genetics plays an
important role. Learning disability is six times more
common in boys than girls.
The vast majority of the children have no neurological
deficits in their physical examination. There is some
evidence that children with SLD have had delay in
speech and language development.
This should include detailed neurological examination.
However in general, children with learning disability
have a normal neurological examination. The presence
of soft neurological signs are controversial. The main
purpose of the examination is to detect sensory
impairments such as hearing loss and visual difficulties.
Investigations
These include screening for hearing and vision, detailed
psychological and psychoeducational evaluations, and
when necessary psychiatric, speech and language
evaluations. Social service intake is necessary to
determine the family dynamics.
Clinical Features
Management
Children with learning disability usually present with

behavioral difficulties, hyperactivity, poor attention span,
day dreaming, fidgety, impulsive distractable, hypersensitive, bed wetting, fluctuating moods and school
failures.
A multidisciplinary approach is necessary with pediatrician, psychologist, educational specialist, social

workers, and when necessary, a psychiatrist and others.
Drugs may be useful to control hyperactivity, enuresis
and emotional difficulties.
As education forms the most important priority of
all parents and educational excellence reaps the rewards,
the future physicians will have their handful to deal with
children who experience school failure.
History
A detailed history should be obtained to focus on various
prenatal, perinatal and postnatal factors contributing to
the central nervous system dysfunction:
i. Prenatal: Bleeding, infections, toxemia, malnutrition
and metabolic disorders (diabetes).
ii. Perinatal: Prematurity, difficult labor, fetal distress,
hypoxia, seizures, jaundice, low birth weight, low
apgar score.
iii. Postnatal: Head injury, meningitis, and encephalitis.
iv. Developmental history: Detailed developmental
history including onset of schooling and onset of
behavioral difficulties.
BIBLIOGRAPHY
1.
2.
3.
4.
Family History
5.
It is extremely important to determine the genetic

etiology. Detailed history should be obtained regarding
the psychosocial aspects of the family such as marital
disharmony, sibling rivalry, preferential treatment,
unrealistic expectations of achievement, and emotional
disturbance.
6.
7.
8.
Cantwell DP, Baker L. Association between attention

deficit-hyperactivity disorder and learning disorders:
Journal of Learning Disabilities 1991;24:88-95.
Kinsbourne M, Kaplan P. Children with learning and
attention problems. Boston-Little: Brown and Company
1979.
Levine MD, Brooks R, Shonkoff JP. A Pediatric Approach
to Learning Disorders.
Mahadeviah MS, Krishna Swamy R. Role of Pediatrician
in learning disability in children. J Practical Pediatr
1997;5(1) Jan-Mar.
Oberklaid F, Levine MD. Precursors of School Failure.
Pediatrics in Review 1980;2:5.
The Pediatric Clinics of North America, Vol 31: Number
2, April 1984.
The Pediatric Clinics of North America, Vol. 39: Number
3, June 1992.
Touwen BCL, Prechtl FGR. The neurological examination of the child with minor nervous dysfunction clinics
in developmental medicine 38.
1053
19.5 Childhood Autism

MS Mahadeviah
INTRODUCTION
Autism and Autistic Spectrum Disorders (ASD) have
caught the imagination also a growing suspicion that the
incidence of Autism and ASD is increasing.
From the last edition of the IAP text book upto the
present it has become necessary to update our present
knowledge.
Autism is a Neurobehavioral and Neurodevelopmental Disorder which was first described by Dr Leo
Kanner in 1943 in a classic paper titled Autistic
Disturbances of Affectile Contact in the Journal Nervous
Child 1943; 2:217-50.
Till recently the incidence quoted was 4-6 per 10000
children. However the present incidence quoted is an
astronomical 160 per 10000.
However it is reasonable to agree the incidence has
increased. The often quoted reasonable figure would be
20-30 per 10000 suffice to say that it is definitely
conceivable that Practicing Pediatrician of today will
definitely be seeing children with ASD and should have
enough knowledge about this condition.
Autism is a Neuro-behavioral Disorder that persists
throughout the life span of the individual whose etiology
is still not definitely known. During the initial period
Autism was felt to be a condition caused by the family
Psychodynamics. This concept was changed after some
of these children were noted to have seizures and
attention was focused on the brain.
During the last decade considerable advances have
been made in Clinical, Epidemiological and Biological
Research and in the field of Neuro-imaging and genetics
which has thrown new light into our understanding of
Autism.
Etiology
Autism is not a disease. It is a well defined Neurobehavioral and Neurodevelopmental Disorder which
belongs to the group of developmental disabilities that
include cerebral palsy, mental retardation, communication disorders, learning disability and attention deficit
hyperactivity disorder.
Although Autism is a well defined syndrome its cause
is still not definitively known unlike other developmental
disorders. Prenatal, perinatal and postnatal factors do

not play a major role. A small number of children with
autism have a known association in conditions such as
fragile X-syndrome, tuberous sclerosis, congenital
rubella, infantile spasms, structural abnormalities of the
brain and metabolic diseases.
As present there seems to be Genetic Factors having a
Significant Role 60 to 90 percent concordance for
monozygotic twins compared to 5 percent for Diztgotic
Twins. There is also finding of deletions and duplication
in chromosome 15. Anomalies have also been reported
in many other chromosomes, however the definitive role
of genetics is still not well understood.
Pathophysiology
The occurrence of seizures more frequently in autistic
children indicates involvement of cerebral cortex.
Neuroimaging and neuropathologic studies have
indicated abnormalities in pre-frontal and temporal lobe
areas. Some studies have indicated increase in brain
volume in children with autism. Other findings include
cerebellar hypoplasis, Purkinje neuronal loss, loss of
cerebellar granule cells.
Neurochemical abnormalities have been implicated
specially dopamine, catecholamines and serotonin
pathways.
Clinical Features
Autism is characterized by a triad of qualitative
impairment in verbal and non-verbal communication,
imaginative play and reciprocal social interaction.
Typical age of presentation is 18-24 months children.
Most of the children present with problems in communication, speech and language delay, impairment in
comprehension and language, fluent but unintelligible
jargon, repetitive and compulsive play activity, lack of
reciprocal smile, gaze avoidance, hyperactivity,
impulsivity, poor attention span, unusual interest in TV
commercials and music, twirling, flapping of hands, toe
walking and behaving deaf.
Many autistic children are irritable, chronically
unhappy, making the parents life absolutely miserable
and unbearable.
1054
Other clinical features are seizures and mental

retardation. The occurrence of seizure is more during
adolescence. Mental retardation is present in the majority
of autistic children (50-70%); some autistic children have
some amazing isolated areas of brilliance.
Mental retardation. The severe type

Autistic spectrum disorders such as Aspergers
And Rett syndrome
Schizophrenia.
Investigations
There are no specific investigations or tests to diagnose
autism.
Speech and language assessment
Psychological and Psychiatric Evaluation
If indicated, chromosomal analysis
EEG
Neuroimaging, Positron Emission Tomography
(PETSCAN).
Management
Autism is perhaps the most severe form of Developmental Disability. There is no specific treatment or a drug
management is by a multidisciplinary team and the most
successful management is behavior modification.
Team should consist of a pediatrician preferably
trained in Developmental Pediatrics, Psychologist with
specialization in behavior modification, Speech Pathologist, Psychiatrist, Social Worker and an Education
specialist parents should become an integral part of the
team.
Drugs
Drugs alone have very limited value in the management
of Autism. Drugs that are commonly used are for
seizures, anti-depressants, stimulants have been used
with some success. Special diets are found to be of no
value. Controversys about MMR vaccine is not valid.
Role of opiates, peptides, gluten is controversial.
Prognosis
Factors favorable for good prognosis are normal
intelligence, good communicative skills to start with,
early diagnosis and absence of seizures. With early
diagnosis, therapy and proper counseling the vast
majority of children with autism can function well in
society.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
6.
7.
8.
9.
An update on autism: A developmental disorder. In

Martha Bride Denckla, Stanley James I (Eds): Supplement: Pediatrics 1991;87(5).
Bauman ML. Microscopic neuroanatomic abnormalities
in autism. Pediatrics 1991;87(Suppl):791-6.
Courchesne E. Neuroanatomic imaging in autism
pediatrics 1991;87.
Folstein SE, Fiven J. Etiology of autism: Genetic influence.
Pediatrics 1991;87(Suppl):767-73.
Leo Kanner. Childhood psychosis: Initial studies and
new insights. VH Winston and Sons INC Publishers 1511,
K StNW Washington DC 1991;20005.
Minshein NJ. Indices of neural function in autism clinical
and etiologic implications. Pediatrics 1991;87(Suppl):
774-80.
Nelson KB. Prenatal and perinatal factors in the etiology
of autism. Pediatrics 1991;87(Suppl):761-6.
Rutter M, Scopler E. Autism and pervasive developmental disorders. Concepts and diagnostic issues. J
Autism and Dev Disorders 1987;17:159-86.
Taft LT, Cohen HJ. Hypsarrhythmia and infantile autism.
J Autism and Childhood Schizophrenia 1971;1:761-6.
1055
19.6 Early Detection and Early Intervention

Therapy for Developmental Delay
MKC Nair, Babu George
INTRODUCTION
Advances in neonatology and establishment of special
care nurseries have improved the survival chances of
many high-risk newborns with prematurity, low birth
weight, birth asphyxia, neonatal convulsions, and
hyperbilirubinemia. Some of the survivors become
handicapped at a later age physically, mentally or both.
Very often these are identified quite late, when little can
be done to improve the situation. Developmental followup and early interventional therapy can help to identity
and institute appropriate therapy.
By early infant stimuli program we mean early
interventional therapy for babies at risk for developmental delay. A team of professionals consisting of
developmental pediatrician, developmental tester,
developmental therapist and developmental teacher
should chalk out programs of various activities including
play, exercise, reflex modification techniques and also
teach the same to the parents to help them to do the
therapy at home. The term early intervention encompasses a wide variety of medical, educational and psychological treatments for an at risk baby or an infant with
neurodevelopmental abnormalities or socioeconomically
disadvantaged children. Objectives range from prevention to complete amelioration, to slowing the rate of
degeneration and helping families to cope.
Communication Stimulation
When children are born, they appear to have an innate
preference for looking at human faces and attending to
human voices over and above other types of stimuli. Such
preferences serve to orient the newborn to their
immediate interpersonal and communicative environment. Newborn children also show a tendency to imitate
the facial expressions they see, which may not be
intentional communicative act on the part of the baby. It
seems likely that the positive attention that children
receive when they copy a smile or gesture eventually
lead them to make these gestures deliberately to the
adults around them. However, it is difficult to know
when this shift from imitation to intentional gesture

actually occurs.
Soon after birth, baby will begin to communicate with
each other by exchanging glances, sounds and by touch.
A newborn is already learning about the world through
his senses. As the days after birth pass, newborn will
become accustomed to seeing the parent and will begin
to focus on his/her face. His senses of touch and hearing
are especially important, though infant will be curious
about noises he hears and the spoken voice. Talk to the
baby, whenever you get a chance. Even though he doesnt
understand what you are saying, parents calm,
reassuring voice is what he needs to feel safe.
Communicating with a newborn is really a matter of
meeting his needs. Always respond to newborns cries
he cannot be spoiled with too much attention. Prompt
response when the baby communicates, will let him
know that hes important and worthy of attention. Baby
is listening to everything the parent says and he is storing
it away at an incredible rate. Instead of using baby
words, teach him the correct names for people, places
and things. Speak slowly and clearly and keep it simple.
An infant may still be communicating with gestures
such as pointing to something he wants. Gestures are
okay, but one should use a running commentary along
with it. Such behavior encourages the baby to respond
and participate in conversations. But dont frustrate the
baby by withholding food or drink waiting for a response.
Between 15 months and 18 months, baby will
probably begin to enjoy language games that ask him to
identify things, such as; wheres your ear? and where
is mummy? His vocabulary will grow quickly, but his
pronunciation isnt likely to keep pace. Resist the
temptation to correct babys pronunciation; most babies
mispronounce their words. Instead, emphasize the
correct pronunciation in response.
Aims of Early Stimulation
The aims of early stimulation are:
1. Stimulating the child through the normal developmental channel
1056
2. Prevention of developmental delay

3. Prevention of asymmetry and abnormalities
4. Detection of transient abnormalities and minimization of persistent abnormalities.
Various easily available age appropriate toys are
advised and the optimum time for stimulation is when
the child is most active and playful. The four major
sensory modalities recommended for neonatal developmental intervention include:
not more than 10 percent of cerebral palsy cases perinatal

asphyxia could be attributed as the true cause.
Visual stimulation: Decoration of surroundings, with

mobiles and brightly colored objects.
Developmental Observation Card (DOC)
Auditory stimulation: Talking, singing, music boxes,

recorded mother's voice, recorded heartbeat.
Tactile stimulation: Non-nutritive sucking, stroking,
flexing, massaging, rubbing, handling, positioning.
Vestibular-kinesthetic stimulation: Rocking, oscillating beds,
e.g. water beds. Development depends on the maturation
of the nervous system and sensory motor abilities to
interpret and use stimuli to change behavior patterns for
more effective functioning in the environment. It is the
product of biological inheritance and environmental
stimulation.
Developmental Delay
Developmental deficits occur among children in four
broad categories of risk for early interventional therapy
programs.
Established risk: These include infants or children with a
medical disorder leading to developmental delay, e.g.
Down syndrome, hydrocephalus, cerebral palsy, hearing
and visual impairment and other congenital anomalies.
Environmental risk: These include infants or children who
are at risk for delayed development because of limited
early environmental experiences, e.g. very young
mothers, extreme poverty, low socioeconomic status,
single parent, etc.
Developmental Assessment
Details of different developmental assessment methods
have been discussed earlier in the chapter on Development. Here some methods for early and quick developmental assessment in field by field health worker and
Anganwadi worker are provided.
This is a self explanatory simple card, that can be used

by the parents. It consists of 4 simple developmental
milestones completed at definitive periods:
1. Completed 2 monthsSocial smile
(Baby smiling back in response to your smile)
2. Completed 4 monthsHolds head steady
(Keeping head steady when baby is held upright)
3. Completed 8 monthsSits alone
(Baby able to sit alone with minimal support)
4. Completed 12 monthsStands alone
(Baby able to stand on both legs with minimal
support).
CDC Grading for Motor Milestones
This is especially useful to follow-up large number of
apparently normal babies in the Well Baby Clinic, at 4, 8
and 12 months of postnatal life, the grading of three
important motor milestones helps to assess developmental status. The CDC grading for motor milestones in
infancy is given below.
Head holding
Grade 0:
No head holding at all
Grade 1:
Head erect and steady momentarily (Fig.
19.6.1)
Biological risk: These include babies with a history of

prenatal, natal or postnatal events, suggestive of
insults to the developing central nervous system, e.g.
prematurity, low birth weight, neonatal hypothermia,
asphyxia, hypoglycemia, hyperbilirubinemia and convulsions.
With no apparent risk: Developmental deficits may also
occur among infants with no apparent biological risk. In
Figure 19.6.1: Head holding grade I
Grade II:
Supinelifts head when pulled up by arms

(Fig. 19.6.2)
Grade V:
1057
Head balanced always (Fig. 19.6.5).
Figure 19.6.2: Head holding grade II
Grade III:
Proneelevates self by arms and chest (Fig.

19.6.3)
Figure 19.6.5: Head holding grade V
Sitting
Grade 0:
Grade I:
Not sitting at all

Sits momentarily (Fig. 19.6.6)
Figure 19.6.3: Head holding grade III
Grade IV:
Holds head steady when moved around

(Fig. 19.6.4)
Figure 19.6.6: Sitting grade I
Grade II:
Grade III:
Grade IV:
Grade V:
Standing
Grade 0:
Grade I:
Figure 19.6.4: Head holding grade IV
Sits 30 seconds or more leaning forward

(Fig. 19.6.7)
Sits with the child's back straight (Fig. 19.6.8)
While sitting, can manipulate a toy (Fig.
19.6.9)
Raises self to sitting position (Fig. 19.6.10).
Does not stand at all.
Stands holding a furniture momentarily
(Fig. 19.6.11)
1058
Figure 19.6.10: Sitting grade V

Figure 19.6.7: Sitting grade II
Figure 19.6.8: Sitting grade III

Figure 19.6.11: Standing grade I
Grade II:
Figure 19.6.9: Sitting grade IV
Takes a few steps, both hands held

(Fig. 19.6.12)
Grade III: Without support, can stand alone [legs
apart] (Fig. 19.6.13)
Grade IV: Stands up, all by himself by throwing weight
on arms (Fig. 19.6.14)
Grade V: Takes a few steps without support
(Fig. 19.6.15).
It would be ideal to have a follow-up at completed 2
months [social smile], 4 months [head holding],
8 months [sitting] and 12 months [standing]. Every baby
should have at least one developmental assessment at
four months. Grades 0 and I are to be considered
definitely abnormal and need a detailed neurodevelop-
Figure 19.6.12: Standing grade II
1059
Figure 19.6.14: Standing grade IV
Figure 19.6.13: Standing grade III
mental evaluation. Grade II needs repeat evaluation after

1 month. Grades III, IV and V are considered normal and
do not require any further follow-up routinely.
Counseling Mothers for Stimulating Infants
with Delayed Development
Head Holding/Neck Control
i. Stimulating the child to hold the head by carrying
the child in an upright position by supporting the
infant's head as and when possible.
Figure 19.6.15: Standing grade V
ii. While playing and talking with the child, lift the
child by supporting his upper arm and chest,
thereby stimulating him to lift and hold his head.
iii. The child must be made to lie on his stomach
and is guided on his elbow (a roll or round pillow
can be used if necessary). Encourage the child
to lift and hold his head by showing a colorful
toy.
1060
iv. Stimulate the child in prone position guiding on his

hands on the surface, encourage the child to lift and
hold his head and then rotate laterally showing a
colorful toy.
v. Encourage the child to lift and hold head by pulling
him to sitting position in a playful manner, and then
gradually put him back to the lying position.
Sitting
i. Encourage the child to sit by putting him in an arm
chair in a sitting position, supporting him with
pillows, as and when possible.
ii. While playing and talking with the child, encourage the child in sitting position with a wide base
(thighs apart), supporting at the pelvis with a
downward force.
iii. During play, the child can be encouraged in sidesitting position on both sides by supporting himself
on the hand to the side which he is sitting.
iv. Guide the child to support on his hands and knees
(four point kneeling/quadruped position) during
play. A roll or pillow can be used, if necessary. Then
slowly guide him to sit on one of his sides, supported by the same hand. Help the child to maintain
this position for a while. Then guide him again on
to his hands and knees and then gradually to side
sitting on the other side.
v. Baby walker can also be used to stimulate and
improve sitting.
Standing
i. Guide the child on to his both knees during play.
Finally support him at the pelvis. If necessary, give
support to the upper part of his body. Gradually
the support can be withdrawn and the child can be
made to support himself by holding on to a low
stool. This position can be maintained by directing
the childs attention to any play activity.
ii. From lying on the back position (supine position),
stimulate the child to sit and gradually to the
standing position during play time.
iii. Firstly, guide the child to his both knees supporting
himself on a low stool with both hands. While
directing his attention to a colorful toy through play,
slowly help him to raise one leg so as to make him
stand on one foot (leg straight), the other on the knee
(half standing position) help the child to maintain
this position while playing and talking with him.
This position can be repeated on other side. Meanwhile depending on the childs ability, stimulate him
to pull to standing position by himself, supporting
on the stool.
iv. Encourage the child in standing position as and
when possible, first with support, gradually withdrawing the support given, as per the childs ability.
A baby walker will also serve the purpose of
developing standing and walking skills.
Trivandrum Developmental Screening Chart [TDSC]
This is a simple developmental screening chart designed and validated at the Child Development Centre, and
is being used in large scale community developmental
screening programs using Anganwadi workers. This can
be applied to children below 2 years of age. The time
taken to administer the test is 5 to 7 minutes.
There are 17 test items in the chart. The range of each
test item is taken from the norms given in the Bayley
Scales of Infant Development. The left hand side of each
horizontal dark line represents the age at which 3 percent
(Fig. 19.6.16) of children passed the item and the right
end represents the age at which 97 percent of the children
passed the item in the Baroda sample. A vertical line is
drawn or a pencil is kept vertically at the level of the
chronological age of the child being tested. If the child
fails to achieve any item that falls short on the left side of
the vertical line, the child is considered to have
developmental delay. Any obvious abnormality or
asymmetry is also considered abnormal.
TDSC is a simple tool that can be administered by
Anganwadi workers or any person with minimal training. Among the 17 tests, items for testing hearing, and
vision are also included.
Neurological Evaluation and Follow-up
A system of neurological examination that allows detection and recording of subtle neurological abnormalities
that may disappear at the end of first year (called
transient abnormalities) or persist even beyond that
(persistent abnormalities) is needed. Amiel Tison has
incorporated many ideas and has provided us with a
comprehensive system of neurological evaluation for the
first five years of life. This system gives us a framework
for instituting physical therapy program. In the Amiel
Tison method of neurological evaluation presence of
hypotonia or hypertonia is identified by measuring
certain angles.
1061
Figure 19.6.16: Trivandrum Developmental Screening Chart (TDSC) (Based on BSID Baroda norms)
MKC Nair, Babu George, Elsie Philip. Indian Pediatr 28: 86972, 1991
Angle Details
Adductor angle (Fig. 19.6.17): With the infant lying supine,
the legs are extended and gently pulled as far apart as
possible. The angle formed by the legs at this point is
called the adductor angle. Asymmetry between the right
and the left leg should be noted.
towards the ear. The pelvis must not be lifted from the
table. The angle is represented by the arc extending from
the infants heel to the table. Increased resistance on one
side is an indication of asymmetry, but it might be
difficult to apply equal pressure to both sides.
Heel to ear (Fig. 19.6.18): With the infant lying supine, the
legs are held together and pressed as far as possible,
Popliteal angle (Fig. 19.6.19): The thighs are flexed laterally

at the hip along both sides of the abdomen. While holding
the infant in this position, the examiner presses the lower
leg as far as possible towards the thigh. The popliteal
Figure 19.6.17: Adductor angle
Figure 19.6.18: Heel to ear angle
1062
Figure 19.6.19: Popliteal angle
angle, which is formed by the calf and the thigh is

estimated in both legs simultaneously. In contrast to the
maneuvers described above, it is easier to apply equal
pressure to both sides when examining the popliteal
angle. Therefore, the estimation of asymmetry is more
objective. Significant asymmetry is indicated by a
difference of 10 to 20 degrees between the right and left
angles.
Dorsiflexion angle of the foot (Fig. 19.6.20): The examiner
holds the infants leg straight and flexes the foot towards
the leg. This is accomplished by applying pressure with
the thumb to the sole of the foot. The dorsiflexion angle
is formed by the dorsum of the foot and the anterior
aspect of the leg.
Figure 19.6.20: Dorsiflexion angle
Scarf sign (Fig. 19.6.21): The infant is held in a semireclining position, supported by the examiners palm.
At the same time, the examiner takes the infants hand
and pulls the arm as far as possible, across the chest
towards the opposite shoulder. Four positions are
possible in describing the position of the elbow in relationship to the umbilicus.
Figure 19.6.21: Scarf sign
i. The elbow does not reach midline (not cross)

ii. The elbow passes across the midline (cross)
iii. The arm encircles the neck and the elbow reaches
axilla.
iv. The arm encircles the neck like a scarf and the elbow
is beyond axilla.
Normal range of angles
Angle
Adductor
Heel to ear
Popliteal
Dorsiflexion
Scarf sign
1-3
months
4-6
months
Angles in degrees
7-9
10-12
months
months
40-80
80-100
80-100
45
Not cross
70-110
90-130
90-120
45
Cross
100-150
120-150
110-160
45
Axilla
130-150
140-170
150-170
45
Beyond
axilla
Therapy based on passive exercises: Out of the items assessed

in the Amiel-Tison method, the angles taken (At risk baby
chart) give an important clue for the therapy and
stimulation part of intervention. A limitation in angles
indicates hypertonia and wide angle indicates hypotonia
in most cases. In such instances, stimulation becomes
effective only after normalizing the muscle tone.
Home-therapy based on Amiel-Tison passive angles
is a simple concept which does not aim to hasten
developmental milestones, but aims to prevent
i. Mental subnormality by better mother-infant interaction.
ii. Joint stiffening by repeated passive movements.
iii. Contractures by repetitive passive movements.
iv. Muscle wasting and fibrosis.
v. Helplessness in parents.
The purpose of passive therapy is essentially to reduce
these deformities by constant effort of the mother in a
playful manner.
APPENDIX 19.6.1
NURSERY EVALUATION SCALE
TRIVANDRUM [NEST]
Most pediatricians face the dilemma as to what to do
when presented with a child with mental subnormality,
studying in a sophisticated nursery school, not able to
cope with school routines with associated behavioral

problems, hyperactivity, etc. We wish if only the parents
had bothered to bring the child much early before all this
problems had set in. The preschool teacher is in a unique
position to observe, interact and encourage a preschool
child leisurely and under more natural setting. Assessment of a child in a clinic setting by a developmental
3rd, 50th and 97th percentile age placements in months for each item of NEST
GROSSMOTOR DEVELOPMENT
Sl. No. Items on NEST
1.
Pedals tricycle-turning corner
2.
Jumps off sideways and backwards
3.
Jumps over a 20 cm rope
4.
Jumps from a height of 15 inches
5.
Broad jump 10 inches
6.
Stands on 1 foot 10 sec
7.
Hops on one foot 1 meter
8.
Catches a ball with arms thrown away from 1 meter
9.
Catches a soft ball with one hand
10.
Dribbles ball 4 times
11.
Heel to toe walk 8 steps
12.
Walks on 20 cm elevated balance beam
13.
Skips 4 times
*age in months
3rd percentile
50th percentile
97th percentile
46*
48
51
50
52
48
49
48
53
58
61
64
65
49*
52
53
54
56
57
58
61
64
68
68
69
52*
54
58
56
60
66
62
65
68
72
72
72
3rd percentile
50th percentile
97th percentile
44
42
49
48
49
50
50
52
51
56
53
53
63
61
47
49
52
53
54
56
57
58
60
61
62
64
66
68
51
51
54
56
62
59
65
61
63
66
64
68
72
72
3rd percentile
50th percentile
97th percentile
43
45
44
46
48
50
48
48
49
52
54
56
50
51
54
65
59
60
FINE MOTOR DEVELOPMENT

14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
Sorts 3 shapes
Builds bridge in imitation
Make a mechanical toy work
Print A,F,E
Complete block pattern
Paints shape
Threads 10 beads in 60 seconds
Uses pencil sharpener
Folds paper sequence 2 times diagonal
Draw a picture with 3 parts (excluding draw a man)
Copies square, rectangle and triangle
Tear simple shape
Copies diamond shape
Prints name
COGNITIVE DEVELOPMENT
28.
29.
30.
31.
32.
33.
Matches one to one

Matches Geometric form
Tells which objects go together
Names position of objects
Put numerical 110 in sequence
Completes a simple maze
1063
1064
34.
35.
36.
37.
38.
39.

Arrange objects according to width and length
Picks specific number of objects (5)
Can add and subtract 2 out of 3
Names days of a week in order
Builds pyramid of 10 blocks
Read 10 printed words
53
55
52
57
54
61
63
64
65
65
66
68
69
66
69
70
71
72
3rd percentile
50th percentile
97th percentile
42
42
43
42
44
45
46
50
53
48
56
45
45
46
47
47
47
52
54
56
58
63
48
48
48
50
49
54
58
60
61
68
3rd percentile
50th percentile
97th percentile
42
49
51
50
52
51
53
47
52
53
54
54
57
60
49
57
59
61
56
60
66
3rd percentile
50th percentile
97th percentile
42
44
45
46
42
44
48
50
51
51
52
58
46
46
48
49
49
51
53
54
57
59
60
68
49
48
53
56
54
54
57
59
62
63
65
72
PERSONAL SOCIAL DEVELOPMENT

40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
Wipes nose when directed

Washes hands and mouth
Follows rules
Undress completely
Plays near and talk with other children
Imitates adult role
Feeds self
Pour from jug without spilling
Hangs up clothes on hanger
Put jumper/shirt
Buttons and unbuttons
EXPRESSIVE LANGUAGE DEVELOPMENT

51.
52.
53.
54.
55.
56.
57.
Tells daily experiences

Name functions associated with 3 body parts
Define 10 words
Answer how questions
Answer what happens if
Answer why questions
Tells materials and objects made up of
RECEPTIVE LANGUAGE DEVELOPMENT

58.
59.
60.
61.
62.
63.
64.
65.
66.
67.
68.
69.
Points to full/empty
Selects open/shut
Carries out a series of unrelated commands
Put together opposite analogies
Points to not shown picture of action
Selects Man/Woman
Points to 16 body parts
Points to more/less
Points to absurdities in a picture
Points to hard/soft, rough/smooth
Points to middle
Put together 5 part picture
Intervention Schedule for Improving the Functional Skills of Preschool Children (based on the items of NEST)
pediatrician or a psychologist is a possibility only for a
selected few and hence the basic screening of preschool
children would be possible only by the preschool teacher,
provided they have a simple screening tool. NEST is one
such simple tool developed and validated at Child
Development Center, Thiruvananthapuram. It consists
of items on areas-like Gross Motor, Fine Motor, Cognitive,
Personal Social, Expressive Language and Receptive
Language. This test is designed for the children belonging
to the age group 4 to 6 years (preschool). Each child must
be assessed in each developmental area and a trained
preschool teacher must do this. When all sections of the
NEST has been completed, an accurate developmental
profile of the childs ability in each area will be obtained
with a record of those skills that the child performed and
those which he is not ready for. Therapy items included
in NEST manual can also be effectively used for special
education at preschool level.
The following table shows the third, 50th and 97th
percentiles of age in months of preschool children who
completed the specific items of NEST. The 50th percentile
value is to be taken as cut off point and intervention has
to be offered as per the guidelines described. If a particular
child cannot complete one item and if his chronological
age in months is more than the 50th percentile value of
the research study, that child needs intervention. (For
example, if a childs age is 55 months and the child cannot
do the item Pedals tricycle-turning corner he needs
intervention as 50th percentile age of the research sample
is 49 months).
GROSS MOTOR DEVELOPMENT
1. Pedals Tricycle-Turning Corner
a. Make the child stand on the mothers feet.
Mother to hold the childs hand and mother to
lift alternate leg in a cycling movement.
b. Sit in a chair holding on to the armrest. Imitate
the cycling movement. Encourage the child to
imitate this movement of legs.
c. Make the child sit on a tricycle and help him
ride it in a straight line and later to turn corners.
2. Jumps Off Sideways and Backwards
a. Make the child stand along side with you.
Demonstrate jumping sideways and backwards.
b. As a game, give opportunity for child to jump
sideways when the mother claps once and to
jump backwards when the mother claps twice.
1065
c. Make children stand in a circle. Give a cloth ball

to the child and ask him to throw it to his
neighbor. If that child is unable to catch it, he
should jump backwards and the person who
stood on his left to jump sideways and occupy
his space.
3. Jumps Over a 20 cm Rope
a. Draw a line and ask the child to jump over the
line. Demonstrate if need arises.
b. Tie a rope, 10 cm above the ground and help
the child to jump over the rope by holding his
hands.
c. Tie a rope 20 cm above the ground and help the
child to jump over the rope by holding his
hands.
4. Jumps From a Height of 15 inches
a. Help the child on to the chair/stool. Help him
down.
b. Stand along with the child on the stool or chair.
Holds his hands and jump down with him.
Make the child stand on the chair or stool. Let
the mother stand down. Holds the childs hand
and help him jump down.
5. Broad Jump 10 inches
a. Make the child stand opposite to mother. The
distance between the mother and the child
should be 5 inches. The mother should hold the
childs hands and make her jump towards the
mother.
b. Keep two chairs on either side of the child and
ask the child to hold on to both the chairs, apply
his/her weight on it and to jump forward.
c. Place a toy 10 inches away from the child. Ask
him to jump towards the toy and get it.
6. Stands on 1 Foot 10 seconds
a. Place a large ball on the floor. Ask the child to
keep one foot over the ball and stand.
b. Give opportunity to him/her to hop and catch
others.
c. Demonstrate standing on one foot. Encourage
him to imitate you (first with support-people,
wall, things, etc. and later without support).
7. Hops on One Foot 1 meter
a. Teach the child to stand on 1 foot with and
without support. Repeat it with the other leg.
1066

b. Encourage the child to hop forward by holding
on to the mother or wall.
c. Draw a large rectangle on the ground and
divide it into 2 by drawing a vertical line in the
middle. Then divide the rectangle into 8 smaller
rectangles. Keep different objects in each of the
rectangles. Ask the child to come hopping into
the first small rectangle and take the object
placed in it. Then hop forward and collect all
the objects placed in the rest of the smaller
rectangles.
8. Catches a Ball with Arms Thrown

Away from 1 meter
a. Mother and child to sit facing each other.
Mother to throw a cloth ball to child and to catch
the ball. Encourage the child to throw the ball
back to the mother.
b. Mother and child to stand facing each other 50
cm apart. Make throwing and catching the cloth
ball between arms and chest a game.
c. Increase the distance between the mother and
the child and also give opportunity to throw and
catch big plastic ball, medium sized plastic ball.
9. Catches a Soft Ball with One Hand
a. Stand facing the child. Throw a cloth ball and
ask him to catch it using both hands.
b. Decrease the distance between the mother and
child and throw a ball to the child let him catch
it using both hands.
c. Increase the distance between the mother and
child. Throw a small rubber or tennis ball for
him to catch using one hand only.
10. Dribbles Ball 4 Times
a. Dribble large air filled balloons.
b. Dribble ball using shuttle bat or wide and hard
board.
c. Demonstrate dribbling the ball using hand.
Encourage the child to dribble the ball once
followed by continuous dribbling.
11. Heel to Toe Walk 8 Steps
a. Arrange children in the form of a trainone
child in front of the other. Each child is to hold
on to the shoulder of the child is front. Imitate
the sound of the train while walking one behind
the other.
b. Draw two lines according to the width of the
childs foot. Child should walk in between these
lines.
c. Show the child how to do the heel to toe

walking. Encourage the child to imitate you.
12. Walks on 20 cm Elevated Balance Beam
a. Help the child to walk on narrow and not so
high surface.
b. Help the child walk on bricks placed in a line.
c. Help the child walk on narrow wooden planks.
13. Skips 4 Times
a. Draw 4 large circles on the ground, encourage
the child to jump forward from one circle to the
other swinging his/her arms in circular motion.
b. Help the child to jump over a rope held in his
hand without swinging his arms in circular
motion.
c. Help the child to coordinate jumping over the
rope held in his hands and swinging his arms
in circular motion and thereby learning
skipping.
FINE MOTOR DEVELOPMENT
14. Sorts 3 Shapes
a. Draw a circle, square and triangle on the paper.
Give each shape different colors. Talk about the
distinct features of each of the shape like triangle
has 3 corners, square has four corners and circle
is round.
b. Draw a picture using shapes already introduced, e.g. ask the child to color the shapes
triangle-red, circle-blue and square-green.
c. Make the shapes from cardboard and ask the
child to sort it.
15. Builds Bridge in Imitation
a. Keep two match boxes a little apart. Make the
child also do this.
b. Take another matchbox and keep it above the
other two. Insert a pencil, or pen into the gap
between the first two-match boxes to get the
childs attention to this gap.
c. Give the match boxes to the child and let him
make his own bridge.
16. Make a Mechanical Toy Work
a. Give the child a bottle with cap to open and
close. Make sure that there are grooves at the
mouth of the bottle.
b. Give a lock and key to the child to use it. Show
him to how to insert the pencil into pencil
sharpener and how to use it.
17. Print AFE
a. Practice pre-writing strokes.
b. Draw large alphabets on the ground and ask
the child to place leaves and flowers on it. Also
allow the child to trace over the alphabet using
his hands and fingers.
c. Teach the child to form alphabets from
semicircles, e.g. CD.
18. Complete Block Pattern
a. Develop the habit of discussing what the child
has done right from morning to night in the
correct order.
b. Teach him after concept using objects, pictures,
and story cards.
c. Make a pattern using leaves and flower and ask
the child to imitate.
After gaining proficiency, give opportunity to
add on to the pattern by placing a flower after
the leaf. Repeat with difficult object and extend
the number of objects to 3.
19. Paints Shape
a. Draw big circles on the ground and ask her to
fill it using saw dust, sand.
b. Once the child can fill it staying in the limits,
offer finger painting to fill in the shape.
c. Offer big crayon to color the picture.
20. Threads 10 Beads in 60 Seconds
a. Large wooden beads, papaya stick cut into small
pieces or small hollow circle from card boards
may be used.
b. Using plastic wire, teach him to string the above
said objects.
c. Using plastic thread, teach him to thread normal
sized beads.
21. Uses Pencil Sharpener
a. Demonstrate pencil sharpener and how to use
it.
22. Folds Paper Sequence 2 Times Diagonal
a. Teach the child to fold the handkerchief into 2
folds and into 4 quarters. Dots can be drawn in
the middle of the handkerchief, which would
serve as guideline for the child. After gaining
proficiency, teach him to fold the handkerchief
twice diagonally.
b. The same to be done using newspaper with
dotted lines to help the child in folding the
paper.
1067
c. After gaining proficiency in this, let the child

fold paper without the help of dotted lines.
23. Draw a Picture with 3 Parts
(Excluding draw a man)
a. Practice 0 1On paper, sand, etc.
b. Make use of each of the above strokes to draw
simple pictures, which the child can learn in
step-by-step manner.
c. Encourage the child to draw and practice the
line drawings.
24. Copies Square, Rectangle and Triangle
a. Using small sticks, used match sticks show and
teach the child how to make these shapes one
by one in a step-by-step manner.
b. Draw the shape on the ground or on paper. Ask
the child to trace over it using his finger and
pencil.
c. Show the child how to draw these shapes using
pencil in a step-by-step manner. Later ask him
to draw the shape from memory.
25. Tear Simple Shape
a. Give paper, plantain leaf and jackfruit leaves to
tear vertically.
b. Draw two vertical lines on a newspaper, ask the
child to tear the paper vertically between the
two lines.
c. Make big holes on a paper in a vertical line and
ask the child to tear the paper along the vertical
line. Reduce the size of the holes and introduce
corners and curves as the child gains proficiency.
26. Copies Diamond Shape
a. Show a child how to make a diamond shape in
a step-by-step manner using small sticks, let the
child imitate this.
b. Keep pre-drawn picture of a kite. Make the out
line of the same picture using dots and ask the
child to complete the picture by joining the dots.
c. Make a cut out of diamond shape from card
board and ask the child to trace along the side
of the diamond shape using pencil.
27. Prints Name
a. Introduce his name written on a small piece of
cardboard. Read it out to him. Stick similar
cardboard slips on his belongings which he uses
daily like his school bag, toys, cupboard, etc.
1068

b. Teach him to sort out his name slips from among
others. Show him how to write each and every
alphabet of his name after reading it out in a
step-by-step manner.
c. Give a pre-written name slip and ask him to
copy his name from it when the slip is in sight.
Later, help him to write his name from memory.
COGNITIVE DEVELOPMENT
28. Matches One to One
a. Introduce the concept of same using object.
b. Give two sets of pictures with only slight
difference and ask the child to find the pair of
each one.
c. Worksheet can be used for this.
29. Matches Geometric form
a. Introduce the concept of same using similar
objects at first, e.g. keys, dolls, and bottles.
b. Introduce the shapes, triangle, circle, and
square. Have two identical sets of shapesone
set for you and the other for the child made out
of cardboard. Point to a shape from your set.
Ask the child to give you the same shape from
his set.
c. Give him the two sets of shapes and ask him to
match the shapes. Worksheets can also be used
for this.
30. Tells, Which Objects, go Together
a. Bring to the childs attention, the relationship
between the objects like egg-hen, bananaplantain tree, book-pen, cup-saucer, etc.
b. Place all the picture cards which are related.
Take each picture card, name the picture and
give clues to find the related objects.
c. Later give the child opportunity to do it on his
own.
31. Names Position of Objects
a. To teach the concept of front and back, make
use of the picture of a cat and say that nose, eyes,
mouth are in the front of the head and tail is at
the back.
b. To teach the concept of top and bottomsay
that the sky is at the top and earth is at the
bottom; head is at the top and feet is at the
bottom.
c. We live inside the house, trees are outside the

house. First introduce the concept of beginning
and end and later the concept of middle.
32. Put Numerical 1 to 10 in Sequence
a. Make 10 circular cards of varying sizes. In the
smallest card write the numeral 1, 2 in the next
biggest one and so on, so that in the biggest card
numeral 10 is written. With the increase in the
size of the card the size of the numeral written
on it should be increased. The child has to
arrange the cards according to the size and also
the sequence of numbers.
b. Draw a picture of an animal on a large paper.
Write the number 1 to 10 horizontally just
beneath the picture by placing the numerals in
the correct sequence.
c. Teach the sequence of numbers through action
songs and rhymes.
33. Completes a Simple Maze
a. Draw a large maze on the floor and make the
child walk through it.
b. Draw a maze on paper or floor and ask the child
to put stones /sawdust /sand along the maze.
c. Draw a maze on the paper and ask the child to
drag his finger through it.
34. Arrange Objects According
to Width and Length
a. Give objects to arrange according to length and
width.
b. Give sticks of different length and ask the child
to take the longest from the lot, then place it
next to the teacher, then the next longest and
continue to do it till the whole set is arranged in
the longest to the shortest sequence.
c. Give blocks of different sizes for the child to
place one above the other so that the biggest is
at the bottom and the smallest at the top.
35. Picks Specific Number of Objects (5)
a. Teach him the quantity of each numeral using
objects whose number does not change, e.g. 1
sun, 1 nose, 2 eyes, 2 ears, 10 fingers, etc.
Likewise teach up to 5 for which action songs
can be used.
b. Puppetsfinger and brown paper bag can be
used to teach him to count the objects.
c. Teach him to associate numeral with the quantity asking him to place 1 bead when you say
one, 2 beads when you say 2 and likewise.
36. Can Add and Subtract 2 out of 3
a. Teach the concept of give and take away using
object.
b. Stories and narrations like I had 3 sweets. I gave
1 to my sister, now how many do I havecan
be used to teach the concept of addition and
subtraction.
c. Action songs can be used to teach this.
37. Names Days of a Week in Order
a. Teach the names of the days of week through
guided play. Make the children stand in a circle
and assign each one the name of each day. When
the teacher gives directions like Monday to
come and mount the table, Tuesday come and
tear the paper the corresponding children will
come forward and do it.
b. Teach him songs on days of week.
c. Make it a habit to tell him the name of each day.
38. Builds Pyramid of 10 Blocks
a. Teach him to build tower using soap cover,
cassette cover, matchbox, etc.
b. Teach him to build pyramid in a step-by-step
manner alongside you.
c. After that allow the child to copy making a
pyramid from the one you have already made
kept in childs sight.
39. Read 10 Printed Words
a. Introduce the habit of reading with the child.
b. Introduce the alphabets and its sounds.
c. Give activities for visual and auditory discrimination.
PERSONAL SOCIAL DEVELOPMENT
40. Wipes Nose When Directed
a. Teach the concepts neat and dirty using different examples and how to clean up the dirt.
b. Develop the habit of using handkerchief especially when one has a cold.
c. Ask him to wipe off the dirt on the dolls face.
41. Washes Hands and Mouth
a. Develop the habit of washing hands using soap
and water before and after meals (Praise him
when he does it on his own).
b. Ask him to wash the dolls face and hands.
1069
42. Follows Rules

a. Develop listening and attention in children
through stories and songs.
b. Give small errands for him to do on his own.
43. Undress Completely
a. Mother can demonstrate undressing a doll.
b. Mother can unbutton the childs dress and child
to take off his clothes.
c. Child to undress on his own.
44. Plays Near and Talk with Other Children
a. Give opportunity for the child to interact with
the elders in the family.
b. Allow him to play with and interact with
children of his age. Do not push him if he is not
willing to take part in games with them. Just be
there, observing them, gradually child will start
playing with other children and will find it interesting to join the group.
c. Do not scold the child if he is not interested and
do not discuss this habit in front of others as
this will help only in further alienating him from
others.
45. Imitates Adult Role
a. Encourage make believe play or role-play. You
can suggest themes or roles like doctor and
patient, teacher and students, police and robber,
etc.
b. Two children to be assigned the same role. On
calling out the role they have to perform the first
person who comes forward is allowed to do the
role.
46. Feeds Self
a. Keep a separate seat, plate, glass and spoon for
the child. This will create an interest for him to
have food on his own.
b. In the beginning, let him have dosa, idly, chapatti,
biscuits and the like which does not crumble.
c. Arrange food items, which he likes in a very
colorful and esthetically pleasing manner.
Praise him when he feeds on his own.
47. Pour from Jug without Spilling
a. Place some dough in a coconut shell and ask
him to transfer or put it into the other shell
without it falling outside.
b. Fill up the jug with sand and ask him to pour it
from the jug into a cup. Little spilling is
accepted.
1070

c. The same to be done without spilling. The same
to be repeated with water-to fill up big and small
bottles with water.
48. Hangs up Clothes on Hanger

a. Teach him how to fold his clothes. Shirt, trousers
and handkerchiefeach has to be folded in a
different way.
b. Give a separate cupboard or basket for him to
keep his clothes.
c. Encourage him to keep his clothes in his cupboard or basket only. This helps to develop in
him a sense of responsibility for his belongings.
49. Put Jumper/Shirt
a. Make newspaper dresses for the doll and ask
the child to dress up the doll.
b. Give easy to wear front open dresses which
children themselves can take it off.
50. Buttons and Unbuttons
a. Pierce a powder tin and help the child to use
this as a piggy bank.
b. Stitch a big button and corresponding buttonhole on a piece of cloth. Help the child to
button and unbutton it.
c. Help the child to button and unbutton dolls
clothes.
EXPRESSIVE LANGUAGE DEVELOPMENT
51. Tells Daily Experiences
a. Find time to talk with the child.
b. Share daily experiences and patiently listen to
what he has got to say.
c. Help him develop a sense of trust in you and
show that you care for him through spending
time together.
52. Name Functions Associated
with 3 Body Parts
a. Teach him the functions of each of the body
parts, e.g. eyesto see, tell him to close his eyes
and ask him if he can see anything? Ask him to
open his eyes and then see. Like wise teach the
functions of other body parts.
b. Action songs can be used for this.
c. Guided play can be used for this.
53. Define 10 Words

a. Introduce objects and tell him the use of each.
b. As a game, say the name of the object and the
child to say its use.
c. Riddles can also be used.
54. Answer how Questions
a. Give opportunity for the child to talk about
things in a very detailed manner.
b. Make use of the opportunity that arises while
doing things together to talk about the ongoing
activity. Introduce new words denoting actions
like bathing, cooking and gardening.
55. Answer What Happens If
a. Tell him the consequences of actions.
b. Stories and songs can be used for the same.
56. Answer Why Questions
a. Introduce the concept of why questions through
stories and songs wherein the character visits
many places like market, shops, hospital,
friends house, etc. After the story ask the child
why the character visited so many places.
b. Use daily experiences to get the child answer
why questions like Why didnt you finish
your tea/milk, Why do you want to go there,
etc.
57. Tells Materials and Objects Made Up of
a. Teach using examples like bottle is made of
glass, which is breakable. Similarly give, e.g. of
tablewood, book-paper, studs-gold, ballrubber.
b. As a game ask the child to say the name of things
made of gold, wood, stone, paper, rubber, etc.
c. Rhymes.
RECEPTIVE LANGUAGE DEVELOPMENT
58. Points to Full/Empty
a. Teach the child to fill up old and empty powder
tins and coconut shells with water, sand, etc.
and to empty it into other bottles. Tell him that
when the bottle is filled with sand /water it is
full and when it doesnt have any sand in it, it
is empty.
b. Take two identical containers and fill up one.
c. Ask the child to fill up a bottle and empty a
can.
59. Selects Open/Shut
a. Train the child to open and close pen, bag,
umbrella, tin, door, books, small bottles,
windows, etc.
b. Introduce the concept of open and shut through
pictures.
c. Ask him to sort the pictures of open and closed
containers, books, and windows.
60. Carries Out a Series of Unrelated Commands
a. Tell the child Crow flew away and sat on the
tree trunk. Ask him to repeat what he heard.
b. Do an action and ask him to repeat it.
c. Ask him to talk about what all he saw on his
way to school.
61. Put Together Opposite Analogies
a. Introduce the concept of opposite through real
life situation and pictures.
b. Stories and riddles can also be used.
1071
beads and to say which is more and which is

less.
66. Points to Absurdities in a Picture
a. Discuss the absurdity of the picture with the
child.
b. Pictures like a cow with wings; zebra with
giraffes neck, etc. can be used.
c. Give a picture an ask him to make it absurd.
67. Points to Hard/Soft, Rough/Smooth
a. Give opportunity for the child to touch and feel
each of the different textures and surfaces.
Table, books, penhard
Clothes, cotton, doughsoft
Coconut shell, sandpaper, bitter gourd, stones
rough
Paper, velvet, tiles, mica table topsmooth.
62. Points to Not Shown Picture of Action

a. While brushing the teeth, mother to ask who is
brushing the teeth and who is not?
b. Preschool teacher to use the naturally occurring
incidents in the classroom to teach them who is
playing, who is not; who is throwing the ball,
who is not, who is jumping and who is not?
c. Pictures can be used to find out the difference.
68. Points to Middle

a. Introduce the concept by telling her that you
have put bindi in between or in the middle of
your eyebrows. Ask him to put a dot in the
middle of your eyebrows. Tell him that the
needles of the clock are fixed in the middle of
the clock.
b. Ask him to put a dot in the middle of the page.
c. Arrange 3 objects in a row and ask him to point
to the one in the middle.
63. Selects Man/Woman

a. Introduce the concept of man-woman through
family members.
b. Pictures can be used.
c. Dolls can be used.
69. Put Together 5-Part Picture

a. In the beginning give 2-part picture to assemble.
b. Later picture with 3 parts can be used.
c. Give 5-part picture to assemble, with and
without support.
64. Points to 16 Body Parts

a. Child to point out 16 body parts of mother as
the mother names each one of it.
b. Child to point the body parts of the doll.
c. Mother and child to stand in front of the mirror.
Child to observe and imitate the mother as she
points each body part.
65. Points to More/Less
a. Introduce the concept of more/less using
dough, water, sand, etc.
b. After that use flowers, wheat grains, green gram
to teach more/less.
c. Ask the child to sort out 2 different colored
BIBLIOGRAPHY
1.
2.
3.
4.
5.
In Amiel-Tison C, Grenier A (Eds). Neurological assessment during the first year of life. New York and Oxford:
Oxford University Press 1986;96-145.
Nair MKC, Babu George, Sabarinathan K, et al. CDC
grading of motor milestones. Indian J Practical Pediatr
1995;3:53-4.
Nair MKC, George B, Philip E, et al. Trivandrum
Developing Screening Chart (TDSC). Indian Pediatr
1991;28: 869-72.
Nair MKC. Nursery Evaluation Scale Trivandrum
(NEST). In: Nair MKC (Eds): Growth and Development,
G and D Chapter of IAP, Calcutta 1996;44-55.
Nelson KB, Ellenberg JHL. Antecedents of cerebral palsy:
Multivariate analysis of risk. N Eng J Med 1986;315:81-6.
1072
19.7 Mental Retardation

Sunanda K Reddy
INTRODUCTION
The term mental retardation and the more acceptable
phrases such as intellectual disability, learning
difficulty, or mental subnormality refer to a significantly subaverage mental development from birth or
early childhood.
Contemporary developmental pediatric approach is
to use the term as a symptom and not a diagnostic entity,
as the condition does not relate to a single cause but
indicates a deficiency or lag in cognitive development,
along with delay or deviant patterns in other streams of
development and adaptive behavior. The degree of
adaptive failure is variable and manifests between birth
and 18 years of lifethe time considered the developmental periodmaking it thus a neurodevelopmental
disability of childhood. The condition represents a lifelong impairment, with the persons affected showing
diminished intellectual capacity throughout their lives.
However, in most individuals, those parts of the brain
that are not damaged continue to develop, resulting in
some acquisition of skills and abilities as they grow older,
albeit slowly (slow learning). Mental retardation (as
abbreviated as MR) is representative of developmental
disabilities in general, in its nature, causation and
management.
Today, professionals are increasingly aware that the
term mental retardation has a derogatory connotation.
However, it continues to be used widely by the common
man as well as by the policymakers to explain the
condition associated with poor or insufficient development of mental functions from birth or early childhood
and we shall, therefore discuss the condition under the
title mental retardation. It is recommended that we learn
to use the term intellectual disability more in keeping
with the current trends.
DEFINITION AND CLASSIFICATION
Definition
Mental retardation is defined as significantly subaverage
general intelligence, with onset during early developmental
period, and concurrent deficits in adaptive functioning
(American Psychiatric Association 2000).
Understanding what sub-average intellectual

functioning is requires a knowledge of normal development and average levels of intelligence. Standardized
tests, popularly known as the IQ tests, are used to
measure intelligence. Not all people have the same level
of intelligence; the expected performance norms for the
tests also vary depending upon innate neurobehavioral
potential, environmental and socioeconomic factors. As
mental retardation broadly implies that the intelligence
is low, learning and performance are sub-average. An
IQ or intelligence quotient of 100 is considered normal
average intelligence and the tests attempt to measure the
percentage of intelligence a person has in comparison to
a normal person from a similar background. Significant
sub-average function, as it relates to one or more
standardized tests, falls 2 standard deviations below the
mean, or at an IQ of approximately 70.
Adaptive behavior provides a more functional
definition in that it is a measure of the degree an
individual meets his social responsibility at a given age
within a specific culture. There is often a demonstrable
relationship between the manifested severity of
retardation and adaptive behavior.
Classification
There is no completely satisfactory classification that can
encompass the wide spectrum of presentation of mental
retardation. The pitfalls in the assessment of IQ in a
young child are many and developmental pediatricians
and behavioral scientists prefer to use the related and
more appropriate measures of developmental quotient
(DQ) or the social quotient (SQ) in which importance is
given to the acquisition of socially relevant skills.
However, the widely accepted medical classification
(ICD-10) and DSM IV of the American Psychiatric
Association (1994) recognize 4 categories of intellectual
disability based on IQ levels as shown in Table 19.7.1.
IQ levels 70-85 are considered borderline; those close
to the lower side of the normal range are evaluated in
different settings with a cautious follow-up to assess their
capabilities and factors contributing to the poor score but
are not categorized as mentally retarded. Professionals
TABLE 19.7.1: Category or degree of mental retardation
according to IQ
Category/degree of MR
IQ
Mild mental retardation
50-69
Moderate mental retardation
35-49
20-34
Profound mental retardation
Below 20
working with children with developmental disabilities

are increasingly opting for a more practical way of
classifying mental retardation, which is to think of only
2 categories: mild mental retardation with an IQ range
of 50-70 and severe mental retardation with an IQ
below 35.
The widely used classification recommended by the
American Psychiatry Association now looks at the added
dimension of functioning and adult attainment in
different categories of mental retardation (Table 19.7.2).
With evidence supporting the knowledge that even those
with severe mental retardation can become at least partly
independent in looking after themselves through early
intervention, special education, loving care, supervision
and training, care providers are averse to accepting the
older functional classification with the categories of
untrainable, trainable, educable and slow learner. The
table here reflects the current thinking that classification
is not to define precise functional entities but to help
1073
understand the special needs and plan an optimal

interventional program.
EPIDEMIOLOGY
Mental retardation is the second most common neurodevelopmental disability in children. The prevailing
controversies regarding terminology, difficulties in
ascertainment due to a misinterpretation of definition
and underreporting due to the stigma attached to the
label in many parts of the world not withstanding, most
available estimates suggest that there will be about 3%
of cases with mental retardation.
A large population study in 2-9 years old Bangladeshi
children found an age-specific prevalence of 2%. Other
age-specific studies report an increasing prevalence from
the pre-school years to adolescence, perhaps due to
additional acquired causes such as trauma, infection. The
relative risk increases with decreasing socioeconomic
status. Studies on determinants and risk-factors are few.
A large community-based study in Pune, India, reported
a 29% low birth weight (LBW) incidence and identified,
among other population attributable risk factors,
malnutrition of pregnant mother adolescent girls as an
important determinant. Data related to prevalence in
Indian population shows much variation from 1.5% to
5% of general population. Further studies are underway
to ascertain the prevalence of intellectual disabilities in
India and other developing countries.
TABLE 19.7.2: Adult attainments in different degrees of MR
ETIOLOGY
Degree of MR
IQ range
Adult attainments
Mild
50-70
Literacy+
Self-help skills + +
Good speech + +
Semiskilled work +
Moderate
35-50
Literacy+/Self-help skills +
Domestic speech +
unskilled work with or
without supervision
The symptom-complex of MR does not relate to a specific

cause and is often attributable to multifactorial genetic
and environmental factors. Anything that damages and
interferes with the growth and maturation of the brain
can lead to MR. The known causes of MR fall into three
broad categories (Table 19.7.3).
Severe
20-35
Assisted self-help skills +

Minimum speech +
Assisted household chores+
Profound
Less than 20 Speech +/Self-help skills +/-
NB: + means attainable; + + means definitely attainable, +/- means

sometimes attainable
NEUROPATHOLOGY
There are no specific neuropathologic correlates of mental
retardation. A variety of changes reflect the heterogeneous nature of the disorder. They include:
Malformation syndromes from failure of induction
of mesoderm and neuroectodern.
Disorders of cell migration, proliferation and
differentiation, dendritic arborization.
Postnatal destructive changes secondary to metabolic
insult, infection, or trauma.
1074

TABLE 19.7.3: Causes of mental retardation
Category
Type
Examples
Prenatal (causes before

birth)
Chromosomal disorders
Down syndrome*, Fragile X syndrome, Prader Willi

syndrome, Klinefelter syndrome
Single gene disorders
Inborn errors of metabolism galactosemia*,

phenylketonuria*, mucopolysaccharidoses,
Hypothyroidism*, Tay-Sachs disease
Neuro-cutaneous syndromes Tuberous sclerosis,
neurofibromatosis
Brain malformations Genetic microcephaly,
hydrocephalus, myelo-meningocele*
Other dysmorphic syndromes Laurence Moon Biedl
syndrome
Other conditions of genetic origin
Rubistein Taybi syndrome

De Lange syndrome
Adverse maternal/environmental
influences
Deficiencies* Iodine deficiency and folic acid

deficiency
Severe malnutrition*, in pregnancy
Substance abuse* alcohol (maternal alcohol syndrome),
nicotine, and cocaine during early pregnancy
Exposure* to other harmful chemicals such as pollutants,
heavy metals, abortifacients, and harmful medications such
as thalidomide, phenytoin and warfarin sodium in early
pregnancy
Maternal infections Rubella*, syphilis*, toxoplasmosis,
cytomegalovirus and HIV
Others excessive exposure to radiation*, and Rh
incompatibility*
Third trimester (late pregnancy)
Complications of pregnancy*
Diseases* in mother heart and kidney disease and
diabetes
Placental dysfunction
Labor (during delivery)
Severe prematurity, very low birth weight, birth asphyxia

Difficult and/or complicated delivery*
Birth trauma*
Neonatal (first four weeks of life)
Septicemia, severe jaundice*, hypoglycemia
Perinatal
(around the time of birth)
Postnatal
(infancy and childhood)
Brain infections tuberculosis, Japanese encephalitis,

and bacterial meningitis Head injury*
Chronic lead exposure*
Severe and prolonged malnutrition*
Gross understimulation*
Note: conditions marked with an asterisk are definitely or potentially preventable
At times the gross accompanying changes may be

obvious as in Lissencephaly, holoprosencephaly, etc.
In a majority, no significant structural changes can be
demonstrated.
Post-mortem studies using special techniques such

as Electron microscopy or Golgi method may reveal
abnormal synaptic development and dendritic
arborisation in a few.
CLINICAL PICTURE
There is no uniform clinical picture as mental retardation
is a symptom or a disability associated with a variety of
conditions as mentioned above. Expected clinical features
include:
Microcephaly or occipitofrontal circumference 2 SD
below the mean.
MR of prenatal causes may be associated with some
of these findings on examination, viz. growth
retardation, cataract, skeletal anomalies, multisystem
involvement (congenital heart disease, seizures,
hepatosplenomegaly, etc.).
Muscle weakness or hypotonia, craniofacial features,
hearing loss, focal neurologic abnormalities and
behavioral alterations are common in both prenatal
and postnatal insults.
A family history of miscarriages or learning difficulties in affected family members may be elicited in
some children with mental handicap associated with
X-linked disorders and autosomal dominant disorders (e.g. neurocutaneous syndromes, Fragile
X syndrome).
DIAGNOSTIC EVALUATION
(Diagnosis, Differential Diagnosis and Investigations)
Establishing an accurate etiological diagnosis is not
always possible, nevertheless the diagnostic process is
absolutely necessary for accurate genetic counseling and
rehabilitative planning. Quite often, a detailed developmental history including prenatal, perinatal, neonatal
history and developmental patterns during early infancy
may be suggestive of diagnosis. In an older, school-going
child, scholastic performance and learning behaviors
must be enquired about. A history of consanguinity,
family history of similar problems and contributory
illness provide clues to the diagnosis.
A diagnostic work-up comprises of the triad of
history, clinical examination including psychological
evaluation and diagnostic investigations.
History
A meticulous history should include:
1. Reasons for parental concern (delayed speech, poor
mobility, bizarre behavior, etc.)
2. Maternal illnesses, obstetric characteristics
3. Status of the infant at delivery and the clinical course
in hospital (apnea? seizures? hyperbilirubinemia?)
1075
4. Milestones of development in the fine motor, gross

motor, personal-social, language and cognitive areas,
evidence of regression and recent patterns of
dissociated development
5. Nutritional history
6. Self-help capability and Activities of Daily Living
(ADL) such as feeding, toileting
7. Behavior (sleep patterns, attention, etc.).
Clinical Evaluation
General physical examination and a standard
developmental screening inventory is a pre-requisite
to further diagnostic developmental evaluation.
One or more standard developmental scales such as
Bailey infant scales, Gessels developmental schedules, Vineland maturity scales, WISC and
Goodenough Draw-a-man test, coupled with
psychological testing may not only help diagnostic
formulation in terms of maturation and development
(IQ/DQ) but also give the levels of function and
adaptation. This evaluation also forms the basis for
the special education needs as well as indicates the
childs social and vocational adequacy to plan
effective management.
Associated impairments such as visual, auditory
problems and seizures may require careful evaluation.
Investigations
These are generally prescribed to elicit etiological
diagnosis. There is a limited role for investigations
beyond infancy. The first contact work-up should ideally
include testing for specific conditions, e.g. T4, TSH
(hypothyroidism), TORCH antibodies, MRI/CT scan of
brain, genetic and metabolic tests for conditions such as
aminoacidemia, chromosome studies (Down and other
chromosomal disorders such as Fragile X, etc.).
The child may, wherever possible, be referred to an
experienced neurodevelopmental pediatrician to
confirm the diagnosis by ruling out conditions such
as autism, attention deficit and hyperactivity disorder
(ADHD) and specific learning disabilities (SLD) such as
dyslexia.
The pediatrician or the primary care physician should
keep in mind the fact that MR is not a mental illness.
1076
The major characteristic of mental retardation is delay

in cognitive development and is present from
childhood, whereas the major characteristic of mental
illness is disturbance in the mental functions of
thinking, feeling and behavior with onset later in life
after a phase of normal development.
MANAGEMENT
The guiding philosophy is that interventions are for
the child and the adult that he or she will become.
Management of children with mental retardation
may have to be individualized as per their special
needs. The variation in the levels of mental retardation viz. mild, moderate, severe and profound
suggests that a variety of approaches need to be used
with these children.
The overall management consists of skill building and
countering undesirable behaviors. Behavioral
management with a consistent approach should be
adopted with meaningful goals and meet the
objectives of effective therapy and educational
programs.
An individual habilitative program is best developed

in an interdisciplinary staffing conference involving
parents, clinical psychologists, social workers,
occupational therapists, speech pathologists and
pediatricians. However, children in resource-poor
settings may benefit from community-based and
family-centric management with the key careprovider approach which is also cost-effective and
sustainable in the developing world.
The common areas for Early Intervention usually
include the following: improving receptive and
expressive language, fine-motor coordination,
promoting activities of daily living (ADL), decrease
manipulative behavior and the management of
seizures with appropriate antiepileptic drug therapy
(AED). A sensitive disclosure of the childs problem
along with parental counseling for optimal care of
the child, followed by a discussion regarding the
prognosis, are important aspects of the early
intervention for the child.
The pediatrician and the primary care physicians play
a supportive role in the long-term management of the
TABLE 19.7.4: Prevention of mental retardation

Level
Approach
Interventions
Primary prevention
(preventing the
occurrence of MR)
Health promotion
Health education, especially for adolescent girls
Specific protection
Improvement of nutritional status in the community, Optimum

health care facilities
Improvements in pre-, peri- and postnatal care
Universal iodization of salt
Rubella immunization for girls and women before pregnancy
Folic acid administration in adolescence and early pregnancy
Genetic counseling
Prenatal screening for congenital malformation and genetic
disorders
Detection and care of high-risk pregnancies
Prevention of damage because of Rh incompatibility
Universal immunization for children
Secondary prevention
(halt disease progression)
Early diagnosis and treatment
Neonatal screening for treatable disorders

Intervention for babies at risk for neurodevelopmental impairments
Early detection of developmental delay and early intervention
Tertiary prevention
(preventing complications
and maximization of
function)
Disability limitation and

rehabilitation
Stimulation, training and education, and vocational opportunities

Mainstreaming/integration
Support for families
Parental self-help groups
[Adapted from: Girimaji S et al. Mental Retardation: From Knowledge to Action (2001), WHO Document]
child with mental retardation. Parental support,
liaison with education services, management of
behavioral problems are some important issues in the
follow-up. Diagnosing the problem, referring the
child for appropriate health services, performing the
preschool assessment and addressing the parents
concerns during the school years and so on, no other
professional is in a better position to actively
participate in the long-term development of the child
with mental retardation. Later, during the adolescent
years, sharing the anxiety about sexuality, or referring
the children to organizations which provide appropriate support for improved quality of life, including
vocational placement, the pediatrician is in a unique
position to guide the child and the family and play a
meaningful role in the lives of the young adults. The
need for primary care always exists, though the
intensity of medical care decreases as the youngster
grows older and habilitation requirements in
educational and vocational areas increase.
PREVENTION
In the field of developmental impairments such as mental
retardation, prevention includes prospective interventions to prevent progression to disabilities. Approaches
and interventions for prevention at various levels are
summarized in Table 19.7.4. Primary prevention
strategies remain the best for developing countries.
Prevention at the primary level is possible by efforts
to reduce the contributory illness and determinants of
mental retardation (Table 19.7.3 also lists some of the
preventable causes of the condition). Good prenatal
services and obstetric care, good nutrition and administering MMR vaccine to all girls, fortification of food with
Iodine, Iron, folic acid, and general awareness campaigns
1077
for promoting health seeking behaviors, as well as

screening for early identification, can go a long way in
decreasing the prevalence of mental retardation in
children.
BIBLIOGRAPHY
1. American Psychiatric Associations: Diagnostic and
Statistical Manual of Mental Disorders, 4th Edition
(DSM-IV, Text Revision). Washington DC, American
Psychiatric Association, 2000.
2. American Academy of Pediatrics, Committee on
Children with Disabilities: Pediatricians role in the
development and implementation of an Individualized
Education Plan (IEP) and/or an Individual Family
Service Plan (IFSP). Pediatrics 1999;104:124-7.
3. Curry CJ, Stevenson RE, Aughton D, et al. Evaluation of
mental retardation: Recommendations of a consensus
conference. Am J Med Genet 1997;72:468-77.
4. Farrell O. Children with emotional and behavioural
difficulties. Famler Press. London 1995.
5. Girimaji S, Zaman SS, Wijetunga PM. Pejara Sangharn
U. 2001. Mental Retardation: From knowledge to action.
WHO document.
6. Nair MKC, Babu G. Monograp on Early Detection and
Developmental Delay 0-5 years, CDC, Trivandrum
Publication 1998.
7. Peshwaria R, Menon DK. Needs of families of mentally
handicapped children Indian Journal of Disability and
Rehabilitation 1991;I:69-72.
8. Shapiro BK, Batshaw ML. Mental Retardation. In Burg
FD, Ingelfinger JR, Polin Ra, Gershon AA (Eds): Gellis
and Kagans Current Pediatric Therapy, 18th ed.
Philadelphia, WB Saunders 2005.
9. Stromme P, Hagberg G. Aetiology in severe and mild
mental retardation: A population based study of
Norwegian children. Dev. Med Child Neurol 2000;42:
76-86.
10. World Health Organization (1992) ICD-10: The ICD-10
Classification of Mental and Behavioural Disorders:
Clinical Descriptions and Diagnostic Guidelines. World
Health Organization, Geneva.
20.1 Basics of Immune System in Children: Keya R Lahiri, Roshani N Taori ........................................................................................ 1080
20.2 Immunodeficiency Disorders: Surjit Singh, H Paramesh ................................................................................................................ 1085
20.3 Allergic Rhinitis: H Paramesh ........................................................................................................................................................... 1087
20.4 Food Allergy and Related Gastrointestinal Tract Diseases: VS Sankaranarayanan ................................................................... 1091
20.5 Value of Allergy Tests in Pediatrics: L George Moses, A Parthasarathy ....................................................................................... 1095
20.6 Allergen Specific Immunotherapy: K Nagaraju ............................................................................................................................... 1099
20.7 Rheumatological Disorders in Children: S Ramakrishnan, A Parthasarathy ................................................................................. 1101
20.8 Antiphospholipid Syndrome: Surjit Singh ........................................................................................................................................ 1112
20.9 Approach to Vasculitis in Children: Surjit Singh ............................................................................................................................. 1113
20.10 Kawasaki Disease: Noel Narayanan .................................................................................................................................................. 1115
20.11 Intravenous Immunoglobulin: Surjit Singh ....................................................................................................................................... 1118
1080
20.1 Basics of Immune System in Children

BASICS OF IMMUNE SYSTEM IN CHILDREN
In a world filled with pathogens and microbes, good
health and resistance to disease is no accident. It requires
a vigorous and vigilant immune system to keep the body
free from pathogens. Immune system is a collection of
mechanisms within an organism that protects against
disease by identifying and killing pathogens and tumor
cells. It detects a wide variety of agents, from viruses to
parasitic worms, and needs to distinguish them from the
organisms own healthy cells and tissues in order to
function optimally.
There are three levels of defense mechanism for
protection against pathogens:
1. The first line of defense mechanism (non-specific) is
the physical barrier (skin and mucous membrane).
2. If a pathogen breaches these barriers, the innate
immune system provides an immediate, but nonspecific response.
3. However, if pathogens successfully evade the innate
response, vertebrates possess a third layer of
protection, the adaptive immune system, which is
activated by the innate response. Here, the immune
system adapts its response during an infection to
improve its recognition of the pathogen. This
improved response is then retained after the pathogen
has been eliminated, in the form of an immunological
memory, and allows the adaptive immune system to
mount faster and stronger attacks each time the same
pathogen is encountered.
such as the tubercle bacillus. It also plays an important

role in protection against tumors.
Components of the Immune System (Fig. 20.1.1)
The immune system consists of T lymphocytes, B
lymphocytes, natural killer (NK) cells, dendritic and
phagocytic cells, and complement proteins.
T Lymphocytes
Cellular immunity is mediated by T lymphocytes which
are derived from the thymus. In the blood, T cells
constitute 60% to 70% of the peripheral lymphocytes.
Each T cell can recognize a specific cell-bound antigen
by an antigen-specific T-cell receptor called as TCR.
Subpopulations of lymphocytes may be identified by
surface markers as well as by functional abilities. Markers
on the surface of the lymphocytes are assigned CD
(clusters of differentiation) numbers on the basis of their
reactions to a panel of monoclonal antibodies.
Acquired Immunity
Acquired immunity has two components: Humoral
immunity and cellular immunity. Humoral immunity is
mediated by circulating immunoglobulin antibodies in
the blood. Immunoglobulins are produced by B
lymphocytes, and they activate the complement system
and attack and neutralize antigens. Humoral immunity
is the major defense system against bacterial infections.
Cellular immunity is mediated by T lymphocytes. It is
responsible for delayed allergic reactions and rejection
of foreign tissue transplants. It constitutes a major defense
against infections due to viruses, fungi and a few bacteria
Figure 20.1.1: Origin of immune cells
Pediatric Immunology, Allergy and Rheumatology

There are three major types of T cells: Cytotoxic T
cell, helper T cells and memory T cells. Most cytotoxic T
cells display the glycoprotein CD8, and the helper T cells
display the glycoprotein CD4. These proteins are closely
associated with the T-cell receptors and may function as
co-receptors. CD4 is expressed on approximately 60% of
the mature T cells, whereas CD8 is expressed on about
30% of T cells. Thus in a normal healthy person, the CD4CD8 ratio is about 2:1. There are two subtypes of helper
T cells depending on the cytokines they produce on
activation. T helper 1 (TH1) cells secrete IL-2 and gamma
interferon which promote cytotoxic T-cell or delayed
hypersensitivity types of responses. T helper 2 (TH2) cells
secrete IL-4 and IL-5 and interact primarily with B cells
in relation to humoral immunity and allergic sensitization. Cytotoxic T cells recognize foreign or self altered
antigen on the surface and destroy them. This mechanism
may play a role in rejection of transplanted tissues,
detection of virus infected cells and surveillance against
malignancy.
Clinical Significance
Normal newborn infants are also capable of mounting
antigen- specific T cell responses at birth, as evidenced
by the vigorous tuberculin reactivity a few weeks after
BCG vaccination even on first day of life.
Patients with severe defects of T lymphocyte number
and/ or function, such as severe combined immune
deficiency and thymic aplasia (DiGeorge syndrome),
show an increased susceptibility to infections due to
candida, cytomegalovirus and pneumocystis carinii.
They also have higher incidence of malignancies if
they survive infections.
HIV selectively binds to the cells expressing CD4
molecules on their surface, primarily helper T cells
(CD4 cells) leading to progressive depletion of these
cells.
B Lymphocytes
In birds, B cells are derived from bursa of fibricus (hence
the name B cells). But in mammals, as there is no bursa,
the transformation occurs in bursal equivalents, i.e., fetal
liver and, after birth, the bone marrow. B lymphocytes
constitute 10 to 20% of the circulating peripheral
lymphocyte population. B cells can bind antigens
directly, but they must contact helper T cells to produce
full activation and antibody production. It is the TH2
1081
subtype that is mainly involved. The activated B cells

proliferate and transform into plasma cells. The plasma
cells secrete large quantities of antibodies into the general
circulation. Circulating antibodies protect their host by
binding to and neutralizing some protein toxins, by
blocking the attachment of some viruses and bacteria to
cells, by opsonising bacteria, and by activating complement.
As with T cells, each B cell receptor has unique antigen
specificity, derived in part from somatic rearrangements
of immunoglobulin genes. Thus the presence of
rearranged immunoglobulin genes in a lymphoid cell is
used as a molecular marker of B-lineage cells. B cells also
possess several other molecules that are essential for B
cell function. These include complement receptors, Fc
receptors and CD19.
B lymphocytes produce five different classes of
immunoglobulins called IgG, IgA, IgM, IgE and IgD. Of
these, IgG is abundant of immunoglobulins found in
plasma and plays a major role in the prevention of
infections. It crosses the placenta and thus is the primary
defense against infections in the first few weeks of life in
the neonate. IgM is the first antibody to be produced after
an antigenic stimulation and is specially important in
the initial period of primary immune response. The fetus
can synthesize IgM in utero starting from 20 weeks of
gestation. IgA is the secretory immunoglobulin which is
secreted by the B cells and protects the mucosal surfaces
of the gastrointestinal, respiratory and genitourinary
tracts and the breast. IgE is found in low concentrations
in the serum. The normal biological role of the IgE
antibody is not clear. It is probably important in defense
against parasitic infestations. Generally, an elevated level
of IgE is found in the patients suffering from atopic
diseases. IgD is found in small amounts in serum and
also on the surface of the lymphocytes.
Clinical Significance
Patients with immune deficiency syndromes involving B lymphocytes, viz., X-linked agammaglobulinemia, suffer from recurrent pyogenic infections
primarily involving the sinopulmonary tract. These
defects usually manifest after the 6 months of life
when the passively transferred maternal IgG
antibodies level begin to decline.
The capacity to produce specific antibodies to protein
antigens is intact at the time of birth. However,
1082
normal infants cannot produce antibodies to polysaccharide antigens until usually after two years of
life. But if the polysaccharide antigen is conjugated
to a protein carrier, as in the conjugate hemophilus
influenzae type b (Hib) and streptococcus pneumoniae vaccines, the child under two years of age can
produce the immune response.
Complement receptor 2 (CD21) is also the receptor
for the Ebstein Barr Virus (EBV) and hence B cells are
readily infected by EBV.
CD19, a signal-transducing molecule, is B-cell
restricted and appears early in B cell differentiation.
It is therefore useful in identification of B cell tumors.
Macrophages
Macrophages are a part of mononuclear phagocyte
system. The functions carried out by macrophages in the
immune response are as follows:
1. They are required to process and present antigen to
immunocompetent T cells.
2. They produce a variety of cytokines such as IL-1 and
TNF- and thus exert modulatory effect on
inflammatory response.
3. They are the effector cells of some forms of CMI e.g.
delayed hypersensitivity reaction.
The enzymes in macrophages include lysozymes,
cathepsins, acid hydrolases and neutral proteases. They
can secrete digestive enzymes, complement component,
arachidonic acid metabolites, enzyme inhibitors,
interferons and chemotactic factors in its environment.
Clinically, the deficiency of phagocyte function is
acquired secondary to systemic illnesses, viz., diabetes
mellitus, malnutrition and neoplasia, in which defects
of chemotaxis may contribute to susceptibility to
infections. The most common congenital deficiency is
chronic granulomatous disease (CGD). Staphylococcus,
gram negative rods and fungi are troublesome for these
individuals who suffer from skin, periorificial and deep
organ infections.
Antigen Presenting Cells (APC)
APCs include specialized cells called dendritic cells in
the lymph nodes and spleen and the Langerhans
dendritic cells in the skin. Macrophages and B cells can
also function as APCs. In APCs polypeptide products of
antigen digestion are coupled to protein products of the
major histocompatibility complex (MHC) genes on the
surface of the cell. The products of MHC genes are called

human leukocyte antigens (HLA). CD4 antigen can
recognize antigen only in context of class II antigen,
whereas the CD8 cells can recognize cell-bound antigens
only in association with class I MHC proteins.
Natural Killer (NK) Cells
Approximately 10 to 15% of the peripheral blood
lymphocytes do not bear TCR or cell- surface immunoglobulins. These cells are endowed with an innate ability
to lyse a variety of tumor cells and virally infected cells
without prior sensitization. Hence they are called as
natural killer cells. Two cell surface molecules, CD16 and
CD56, are widely used to identify NK cells.
Cytokines
These are the substances that regulate the immunologic,
inflammatory and reparative host responses and
comprise of previously designated lymphokines
(lymphocyte derived); monokines (monocyte derived);
and several other polypeptides.
Cytokines mediating natural immunity: IL-1, TNF, type-1 interferon and IL-8 family.
Cytokines regulating lymphocyte growth, activation
and differentiation: IL-2, IL-4, IL-5, IL-12 and TGF-.
Cytokines activating inflammatory cells: IFN-,
TNF- and IL-8.
Cytokines stimulating hematopoiesis: GM-CSF, GCSF.
The Complement System
The cell killing effects of innate and acquired immunity
are mediated in part by a system of plasma enzymes
originally named the complement system. Complement
activation occurs in two phases, viz., activation of C3
component followed by activation of the attack or lytic
sequence. The critical event is a cleavage of C3 by
complement derived enzymes termed C3 convertases.
The major fragment (C3b) of activated C3 mediates a
number of vital biological activities.
Two different pathways or enzyme cascades activate
the system: The classic pathway, triggered by immune
complexes and the alternative or properdin pathway,
triggered by contact with various viruses, bacteria, fungi
and tumor cells. These proteins have two functions:
They help killing invading organisms by opsonisation, chemotaxis and eventual lysis of the cells.

They serve in part as a bridge between innate to
acquired immunity by activating B cells.
Hypersensitivity
Gell and Coombs enunciated a conceptual framework
for immunopathogenic mechanisms of tissue injury.
Type I: To briefly mention here, immediate anaphylactic
or reaginic hypersensitivity is mediated by IgE antibody.
IgE is bound to mast cells and basophils vis the Fc portion
of the immunoglobulin, leaving the antigen combining
site exposed. IgE is found in quantities of ng/ml in the
blood. They are prevalent around blood vessels, mucosal
and serosal surfaces, connective tissue and integument.
Antigens can activate the mast cell when it binds to IgE
molecules on the surface of the cells. This leads to release
of mediators which increase vascular permeability, influx
of inflammatory cell, pruritus, increased mucus
production and contraction of smooth cell. This
mechanism plays a role in anaphylactic type of reactions
due to food, drugs, insect venoms and in the atopic
diseases (asthma, allergic rhinitis and atopic dermatitis).
Type II: This is cytotoxic mechanism of hypersensitivity.
In this, the antibody is usually IgG or IgM which binds
directly to the tissues vis Fab portion of the molecule,
leaving the Fc portion exposed. Damage to the tissues
may occur via activation of complement cascade or via
the activity of Fc receptor bearing phagocytes. The
prototype of diseases involving type II mechanism is
Goodpastures syndrome and autoimmune hemolytic
anemia.
Type III: Here immune complex mediated injury occurs
when antigen- antibody complexes are deposited in
tissues near the walls of the blood vessels. In this type of
hypersensitivity, the effector mechanism is activation of
complement with attraction and activation of PMN to
release inflammatory substances. The type III mechanism
is responsible for the arthus reaction, serum sickness,
collagen vascular disease, late phase reaction of bronchial
asthma and certain glomerulonephritides.
Type IV: This is referred to as delayed or cellular
hypersensitivity, best illustrated in sarcoidosis where
granuloma formation is predominant. Grauloma can also
result as a response to infectious agents, e.g. BCG,
Schistosoma mansoni or as a response to foreign body
irritants. Close proximity of macrophages to T cells in
1083
the granuloma enhances cell to cell interactions and local

production of cytokines that facilitate killing. The T cells
stimulate the monocyte chemotactic factor which recruits
peripheral monocytes at the site. The clinical prototypes
include contact dermatitis and tuberculin response.
Type V: Roitt proposed a fifth immunopathogenic
mechanism in which antibodies to specific receptor in
some tissues causes malfunction, e.g. Graves disease
The Sequence of Events on Exposure to an
Antigen (Fig. 20.1.2)
The ability to recognize the antigen is innate and
develops without exposure to the antigen. Stem cells
differentiate into many million different T and B
lymphocytes, each with the ability to respond to
particular antigen.
In case of T cells, the antigen is taken up by an antigen
presenting cell (APC), processed and presented to the T
lymphocytes by MHC molecules present on the APC.
For the high affinity binding, specific molecules are
required to be present on the T cells and APCs. For
example, the CD4 molecule present on the T helper cell
binds directly to the MHC class II molecules on APCs;
whereas the CD8 molecules on the cytotoxic T cells bind
to the MHC class I molecule on the target cell. Thus both
CD4 and CD8 molecules are directly involved in the T
cell regulation. This antigen binding signals the T cell to
produce cytokines that ultimately result in T-cell
activation and proliferation. The activated T cells secrete
lymphokines which aggregate and activate macrophages
and induce them to phagocytose and destroy the foreign
antigen. They also attract polymorphs and monocytes to
the site of infection. The helper T cells stimulate B cells
to induce humoral immune response.
In the primary immune response, native antigen is
carried to a lymph node and taken up by specialized cells
called follicular dendritic cells (FDCs). Virgin B cells
bearing surface Ig specific for that antigen then bind to
this antigen. This antigenic adherence stimulates the B
cells to differentiate into antibody producing plasma
cells. Initially, these plasma cells produce IgM. Later a
switch over in the production of immunoglobulins takes
place and plasma cells start producing IgG class of
immunoglobulins. When the stimulus is removed, the B
cell division and differentiation stops, but the circulating
pool of B lymphocytes still contains a large population
of memory cells. During re-exposure to the same antigen
1084
Figure 20.1.2: Cellular and humoral immunity
(secondary immune response), immediate and extensive

divisions of the B cells with IgG receptors take place and
large quantity of IgG antibodies are produced. These
antibodies combine with the antigen and render them
harmless. The antigen antibody combination acts as a
trigger mechanism for the activation of complement
which ultimately destroys the foreign cell.
BIBLIOGRAPHY
1. Adleman DC. Functional assessment of mononuclear
cells. Immunol All Clin North Am 1994;14:241-63.
2.
Buckley RH. T Lymphocytes, B Lymphocytes and

Natural Killer Cells, In: Kliegman RM, Behrman RE,
Jenson HB, Stanton BF (Eds). Nelson Textbook of
Pediatrics, 18th Edn, Saunders, 2007.
3. Goodman JW. The immune response. In: Stites DP, Terr
El (Eds): Basic and Clinical Immunology. East Norwalk,
Conn: Appleton and Lange (7th Edn) 1991;34-44.
4. Kumar V, Fausto N and Abbas A. In: Robbins and Cotran
(Eds). Pathologic Basis of Disease. 7th Edn. WB Saunders
Company, 2004.
5. Romagnani S. Human TH1 and TH2 subsets: Doubts no
more. Immunol Today 1993;12:9.
1085
20.2 Immunodeficiency Disorders

Surjit Singh, H Paramesh
INTRODUCTION
Immunodeficiency disorders are not uncommon in
clinical practice but many of them frequently go
unrecognized because of lack of awareness. These can
broadly be divided into two categories: (i) Primary, and
(ii) Secondary.
PRIMARY IMMUNODEFICIENCY
DISORDERS
The immune system can be categorized into the specific
and non-specific components. Each of these two components has a cellular and humoral component as follows:
Specific
1. Cellular: T lymphocyte system
2. Humoral: Antibody system
Non-specific
1. Cellular: Phagocytic system
2. Humoral: Complement system
Primary immunodeficiencies involve a defect of any
one or more of these systems. The incidence of primary
immunodeficiency is about 1:10,000 but this figure
excludes disorders like IgA deficiency and mannanbinding lectin deficiency which are said to be far more
common. Table 20.2.1 shows a simplified classification
of primary immunodeficiency disorders.
When Should One Suspect a Primary
Immunodeficiency?
Immune deficiency disorders should be suspected in a
child who presents with (a) recurrent respiratory infections associated with growth failure, (b) prolonged
diarrhea, (c) chronic otitis media, (d) oral or cutaneous
candidiasis, (e) recurrent cutaneous abscesses, (f) chronic
conjunctivitis, (g) chronic arthritis, (h) infection with
opportunistic organisms, (i) infection of unusual severity
with low response to antibiotics, (j) invasive infection in
more than one system (k) infection in patients with auto-
TABLE 20.2.1: Classification of primary

immunodeficiencies
1. Humoral immunodeficiency
a. X-linked agammaglobulinemia
b. Common-variable immunodeficiency
c. Transient hypogammaglobulinemia of infancy
d. IgA deficiency
e. IgG subclass deficiency
2. Combined immunodeficiency
a. Severe combined immunodeficiency
b. Adenosine deaminase deficiency
3. Defects of phagocytic function
a. Chronic granulomatous disease
b. Myeloperoxidase deficiency
4. Complement deficiencies
5. Miscellaneous disorders
a. Mannan-binding protein deficiency
b. Wiskott-Aldrich syndrome
c. Ataxia-telangiectasia
d. DiGeorge anomaly
e. Hyper IgE syndrome
immune disease (l) unexplained hepatosplenomegaly

(m) greater than one episode of pneumonia
(n) absence of lymphoid tissue. However, one must
realize that most normal children below the age of 5 years
do get 7 to 8 episodes of common cold per year.
Pulmonary infections are frequently the presenting
features of primary immunodeficiency. Infants with
severe combined immunodeficiency often present with
an unremitting bronchiolitic like illness of variable
severity due to viral respiratory infection as well as
pneumocystis carinii pneumonia. Chest X-ray may be
normal, despite the presence of bronchiectasis.
How Common are the Immune
Deficiency Disorders?
a.
b.
c.
d.
Antibody deficiency (Humoral) 50 to 60 percent

Primary T cell deficiency 5 to 10 percent
Combined T and B cell dysfunction 10 to 20 percent
Disorders of granulocytes 10 to 15 percent.
1086
What Would the Physical Examination Show in

Patients with Primary Immunodeficiency?
Most children with major immunodeficiency disorders
would fail to thrive and their heights/weights are below
those expected for that age. Children with X-linked
gammaglobulinemia and combined immunodeficiency
disorders usually do not have any palpable lymph nodes
and the tonsils are either absent or atrophic. On the other
hand, children with common variable immunodeficiency
and chronic granulomatous disease frequently have
enlarged lymph nodes with associated hepatosplenomegaly. Prominent skin infections are seen in patients
with hyper IgE syndrome (Jobs syndrome) and chronic
granulomatous disease. Eczema and prominent bleeding
manifestations (due to associated thrombocytopenia) are
seen in Wiskott-Aldrich syndrome. In children with
ataxia-telangiectasia, the latter component is usually not
present in infancy and only appears after a few years.
DiGeorge anomaly is associated with a typical facies (low
set ears, micrognathia, short philtrum and upturned
nose) and a congenital heart disease.
What are the Common Investigations which are Usually
done in Such Patients?
Based on the history and physical examination, it is
usually possible to correctly suspect which arm of the
immune system is defective. However, a precise
diagnosis can only be made on the basis of laboratory
tests. For the majority of patients with primary immunodeficiency, the following laboratory tests would suffice
in arriving at a diagnosis:
1. Hemogram
2. X-ray chest: Thymic shadow
3. Serum electrophoresis
4. Serum immunoglobulin assay:
IgG, IgM, IgA, IgE
5. IgG subclass assay
6. Nitroblue tetrazolium (NBT) dye reduction test
7. Lymphocyte subsets:
a. Rosetting for T and B lymphocytes
b. FACS analysis using monoclonal antibodies CD2
CD3, CD4, CD8, CD19, CD16.
8. Mitogen stimulation tests:
Phytohemagglutinin response.
It is noteworthy that a simple hemogram can provide
very vital clues to the diagnosis of a primary immunodeficiency. For instance, most patients with combined
immunodeficiency would have significant lymphopenia,

while children with chronic granulomatous disease
would have neutrophilic leukocytosis. Chdiak-Higashi
syndrome is characterized by abnormal granules while
in Wiskott-Aldrich syndrome there is thrombocytopenia
and the platelets are characteristically small in size.
Pneumococcal polysaccharide deficiency is one of the
most common presentations in children below 2 years
of age; most of them cannot make antibody to pneumococcal polysaccharide. Children under five years may
have a delay in making pneumococcal polysaccharide
antibody.
Treatment of Immunodeficiency Disorders
Children with primary immunodeficiency are usually
not given live vaccines. Prompt and prolonged antimicrobial therapy is required for associated infections.
Choice of antimicrobials depends on the type of microorganism most likely to be associated with a given
disorder. For instance, in children with chronic
granulomatous disease, staphylococcal and aspergillus
infections are most common while in agammaglobulinemia pyogenic bacterial infections, e.g. (Pneumococcus, Hemophilus influenzae, Staphylococcus) are usually
seen. Children with combined cellular and humoral
immunodeficiencies, e.g. (severe combined immunodeficiency) can have infections with multiple organisms.
Treatment of X-linked agammaglobulinemia and
major forms of common variable immunodeficiency
involves replacement therapy with intravenous immunoglobulin which is given every 3 to 4 weeks. This
treatment is expensive. Children with IgG subclass
deficiencies usually can be managed with prophylactic
low-dose cotrimoxazole therapy but an occasional child,
specially with IgG 2 sub-class deficiency, would require
support with intravenous immunoglobulins. Majority of
children with IgA deficiency usually do not require any
treatment as they remain asymptomatic.
Chronic granulomatous disease is another immunodeficiency which is readily amenable to therapy. Lowdose cotrimoxazole prophylaxis (23 mg/kg/day of
trimethoprim) should be started as soon as the diagnosis
is made and then continued life-long. Itraconazole is also
given along with cotrimoxazole. This therapy has
virtually revolutionized the management of a condition
which was hitherto considered rapidly fatal. However,
it must be clearly understood that such patients would

occasionally develop serious breakthrough infections in
spite of prophylactic antimicrobial therapy cotrimoxazole. These episodes need to be managed aggressively
with appropriate antimicrobials. Gamma-interferon is
also a very useful adjunct for such patients.
Children with DiGeorge syndrome may benefit from
thymic transplants. However, majority of patients with
combined immunodeficiency disorders need a bone
marrow transplant as definitive therapy. Such transplants need to be carried out very early in life and
preferrably before serious life-threatening infections have
set in.
Children with Hyper IgE syndrome are put on longterm cloxacillin prophylaxis and seem to do well.
For immunodeficiencies like ataxia-telangiectasia, no
therapeutic modality is curative. Management is
restricted to treatment of intercurrent infections.
SECONDARY IMMUNODEFICIENCY DISORDERS
Secondary immunodeficiency states are far more common than primary immunodeficiency disorders. These
can result from drugs (e.g. corticosteroids), malnutrition,
prematurity, metabolic disorders (e.g. Diabetes mellitus,
uremia), nephrotic syndrome, burns, splenectomy and
lymphoreticular malignancies. However, perhaps the
most common cause of secondary immunodeficiency is
related to infectious diseases. These may be bacterial (e.g.
Salmonella), mycobacterial (e.g. Mycobacterium tuberculosis
and Mycobacterium leprae), fungal, parasitic (e.g., Leishmania donovani) or viral (e.g. measles, varicella).
Infection with human immunodeficiency virus (HIV)
is the most common cause of secondary immunodeficiency in many parts of the world. HIV infection is now
increasingly being reported from India. Children can
1087
acquire the infection perinatally from an infected mother,

through breastfeeding, through blood transfusions or
sexual abuse. Of these, perinatal transmission is by far,
the most common route by which children get infected.
At birth, all babies born to HIV seropositive mothers
would test positive for HIV antibodies because of passive
transfer of maternal IgG. However, on follow-up at 15
to 18 months, majority of these babies would serorevert,
i.e. lose their antibodies. Such seroreverters are, for all
practical purposes, normal individuals with no discernible immune dysfunction. A small proportion (15 to
25%) of babies do get infected vertically and they may
become symptomatic in the first year of life itself.
As compared to adults, children with HIV infection
tend to have more secondary bacterial infections and less
opportunistic infection (e.g. toxoplasmosis). Similarly,
Kaposis sarcoma is rare in children. Lymphoid interstitial pneumonia (LIP) is characteristically seen in the
perinatally acquired form of HIV infection and is not a
feature of the disease seen in adults.
BIBLIOGRAPHY
1. AR Gennery, DA Spencer, AJ Cant. Immune deficiency
and the lung current pediatrics 2004,14:115-21.
2. Buckley RH. Immunodeficiency diseases. JAMA 1992;
268:2797-2806.
3. Finn A, Strobel S, Morgan G et al. A working classification of immunodeficiency and associated infections for
the clinician. Immunol Infect Dis 1991,1:247-50.
4. Paramesh H. Practical approach to recurrent respiratory
infections. Ind J Pediatr 1996,63:181-87.
5. Rosen FS, Wedgwood RJ, Eibl M, et al. Primary immunodeficiency diseases: Report of a WHO Scientific Group.
Clin Exp Immunol 1995,1:1-24.
6. Stiehm ER (Ed). Immunologic disorders in infants and
children, (4th Edn). WB Saunders Company: Philadelphia,
1996.
20.3 Allergic Rhinitis

H Paramesh
Definition
Prevalence and Epidemiology
Allergic rhinitis is clinically defined as a symptomatic

disorder of the nose induced after exposure to allergens,
manifested by sneezing, nasal itching, rhinorrhea and
nasal blockage. It is an IgE mediated inflammation of
the nose.
Allergic rhinitis is a global health problem affecting at

least 10 to 25% of the population and its prevalence is
increasing, our study in Bangalore on school children in
the age group of 6-15 years indicates the incidence of
22.5%, in the year 1994 which increased to 27.5% in the
1088
year 1999. 75% of asthmatic children have allergic

rhinitis. Although allergic rhinitis is not a serious disease,
it has an impact on the social and quality of life of patients
and affects school performance and work productivity
and moreover, the economic burden by rhinitis is
substantial. It has link with asthma, sinusitis and other
comorbidities like conjunctivitis.
The onset of allergic rhinitis is highest in school going
children usually before the age of 5 years and is more
prevalent in boys before the age of 10 years and in girls,
between 10-18 years of age.
It takes more than 3 years or more to develop allergic
rhinitis after exposure to allergens to produce tissue
sensitization and onset of symptoms. Seasonal pollen
allergy, therefore, rarely occurs before the age of three
years. The relative prevalence of various allergies in
children is shown in graph 20.3.1
Graph 1
Many children exhibit more than one symptom at the
same time and 75% of the children who have a family
history of allergic rhinitis/asthma in both sides of the
family and 50% of children with single parent having
allergy will develop either allergic rhinitis or asthma.
Mechanism of Allergic Rhinitis
The understanding of the mechanism of the disease
provides a way for rational treatment. Allergy is
classically the result of IgE mediated response to allergens
causing nasal inflammation. The response includes
chemotaxis, selective recruitment and transendothelial
migration of cells, release of cytokines and chemokines,
activation of eosinophils, T-cells, mast cells and epithelial
Graph 20.3.1: The relative prevalence of allergic

symptoms in children
cells and release of mediators by the activated cells

predominantly histamine and cysteinyl-leukotrienes
(Cyst LT).
Non-specific nasal hyperreactivity is an important
feature of allergic rhinitis. Persistent allergic rhinitis is
due to ongoing inflammatory late phase reaction. The
minimal persistent inflammation is an important new
concept where inflammation of the nose persists without
symptoms and without exposure to seasonal allergens.
Triggering Factors
Most of the triggering factors are aeroallergens like
pollens, dust mites, domestic animal saliva and danders,
molds, cockroach and irritants like tobacco smoke and
other smoke from cooking fuel and smoke from mosquito
coil. Atmospheric pollutants like ozone, oxides of
nitrogen, sulphur dioxide, and particulate matters from
diesel may aggravate the nasal systems in patient with
allergy or in non allergic patients. Epidemiological
evidence suggests that pollutants produce and exaggerate rhinitis. Installation of diesel particles in the nose
induced proliferation of IgE secreting B cells in the
mucosa of airway exposure to diesel exhaust for 1 hour
increases histamine, cytokine release and significant
cellular inflammatory response in the airways. There is
also qualitative and quantitative increase in IgE levels
from diesel exhaust on human studies. Polluted pollens
are 50 times more allergenic.
Aspirin and other non-steroidal anti- inflammatory
drugs (NSAIDs) commonly induce rhinitis and asthma
in some adolescents and adults.
Clinical Features and Assessment
The clinical history is essential to establish accurate
diagnosis, type and the severity of the allergic rhinitis.
The typical symptoms are rhinorrhea, sneezing, itching
and blockage of nose. Any child who has two or more of
these symptoms for more than an hour on most days is
enough to diagnose allergic rhinitis. In addition they have
allergic shiners- dark discoloration in the orbital
palpebral grooves beneath lower eye lids, Dennies linewrinkle below lower eyelids, allergic salute upward
thrust of the nostrils by palm of the hand and transverse
line on the nose due to constant rubbing of the nose
(Figs 20.3.1 to 20.3.3).
In addition they also have adenoidal facies, mouth
breathing, flat maxilla, high arched palate, malocclusion
Figure 20.3.1: Allergic salute
1089
of teeth, recessed chin, excess watering of eyes due to

blocked nasolacrimal duct and long eye lashes. Abnormalities of the oropharynx-hypertrophied lymphoid
follicles on posterior pharyngeal wall (cobblestone
pharyngeal wall), geographic tongue is seen more in
children with allergic rhinitis. These children produce
sounds of clearing throat or nose since they have itching
of the palate also.
Allergic Rhinitis is newly classified as sneezers and
runners or blockers as described in Table 20.3.1.
The new classification is based on international
consensus report on diagnosis and management of
rhinitis and based on symptoms and quality of life as
described in Table 20.3.2.
Allergic rhinitis further classified into intermittent
and persistent based on duration of symptoms. Intermittent type is the one where the symptoms are of less
than 4 days per week or less than 4 weeks duration. In
persistent type the symptoms are more than 4 days per
week and more than 4 weeks duration.
TABLE 20.3.1: Classification of allergic rhinitis

Symptoms
Figure 20.3.2: Facial mannerism of allergic rhinitis
Sneezers and
Runners
Blockers
Sneezing
Paroxysmal
Little or none
Itching
Yes
No
Diurnal rhythm
Worse during day

improves at night
Constant, may
be worse at night
Nasal blockage
Variable
Often severe
Conjunctivitis
Often present
TABLE 20.3.2: Classification of allergic rhinitis

Old classification
Figure 20.3.3: Transverse line on the nose due to repeated

upward thrust of the nose
New classification
Based on time of
Uses symptoms and
exposure like seasonal,
quality of life
perennial and occupational
Used to give a hint at possible Based on duration,
triggering agents
subdivided as intermittent
or persistent
But was not entirely
Based on severity, subsatisfactory
divided as mild or moderate
severe (Sleep, activity,
work, troublesome
symptoms)
1090
TABLE 20.3.3: Classification of persistent allergic rhinitis

Symptoms
Mild
Moderate severe
Sleep
Normal
Abnormal
Daily activity, sport, leisure
Normal
Disturbed
School and work
Normal
Disturbed
Troublesome symptoms
None
Usual
The persistent allergic rhinitis again grouped as mild

or moderate-severe type based on symptoms as described
in Table 20.3.3.
Diagnosis
Most often the diagnosis is predominantly based on
history and clinical examination. In ambiguous cases an
increase in the eosinophil count of more than 10 percent,
of total WBC count in the nasal smear is an indication.
The pH of the mucus in allergic rhinitis is alkaline in
comparison to infectious rhinitis, which is acidic.
Peripheral blood counts show eosinophilia of over
10 percent especially during offending pollen season.
Note marked allergic symptoms can occur in the absence
of eosinophilia. Total serum IgE is elevated in allergic
rhinitis in comparison to non-allergic rhinitis. The specific
allergens to which the patient is allergic can be identified
by skin testing or by vitro serum testing, radioallergosorbant test (RAST) or enzyme linked immunosorbent assays (ELISA) are acceptable alternatives.
Although, these techniques are less sensitive to skin
testing, imaging is not usually necessary unless there is
suspicion of sinusitis .The prevalence of sinusitis is 9
cercent and ottitis media is 22.5 percent.
Management
The nasal and the bronchial mucosa have many
similarities. The management includes (1) avoidance of
allergens, (2) environment control, (3) pharmacotherapy,
and (4) immunotherapy.
Avoidance of Allergens
Patients are advised simple avoidance measures, e.g.
staying indoors when the pollens and fungal spores are
high in midday and afternoons and closing the bedroom
windows during specific seasons and at night. Air

conditioners can be advised to some people including
electronic filters. When high allergen exposure is
unavoidable, a mask may be worn to prevent inhalation
of allergens.
Environment Control
This includes use of air tight rexine or plasticcovers for
pillows and mattress, sun dry the beddings and blankets,
avoiding use of carpets, upholstered furniture, stuffed
toys to prevent dust mite allergy. Avoid wet attics ,
basements and wet areas to avoid fungi. Avoid keeping
pets in the bedroom in specific cases. Washing of hands
and face and changing the clothing after outdoor activity.
Avoid tobacco smoke and burning the mosquito coil and
control the cockroach menace.
Pharmacologic Therapy
Antihistaminics are the mainstay for managing seasonal
allergic rhinitis. Antihistamines (H1 antagonists) are safe
and effective medications in controlling the symptoms
of sneezing, nasal pruritis and rhinorhea but generally
not effective for nasal congestion but have sedative effects
for example diphenhydramine hydrochloride (Benadryl)
and hydroxine (Atarax). Newer long acting, non-sedating
antihistamines like cetirizine, levocetirizine, loratidine,
fexofenadine are beneficial. Topical antihistamines
azelastine (Azep) is unacceptable for its very bad taste.
Anticholenergics help only in rhinorrhea. Antileukotrienes help in rhinorrhea, nasal obstruction and eye
symptoms of mild cases. Intranasal corticosteroids
(belamethasone, budesonide, fluticasone and mometasone) are the most affective agents for the treatment of
allergic rhinitis, since they have wide margin of safety,
the adverse reactions are negligible. If there is clinical
improvement in 2 weeks, continue for a month and step
down. They are the first line of therapy of patients with
nasal obstruction and congestion. Oral and intramuscular
glucocorticosperoids should be avoided in young
children.
Immunotherapy
Specific immunotherapy is effective in children, however
it is not recommended to commence the immunotherapy
in children under 5 years of age. Sublingual immunotherapy (SLIT) is very promising in future.

BIBLIOGRAPHY
1. Jain VK. Current trends in allergy research and clinical
practice, Indian J Allergy Asthma immunology 2002;
16(2):77-81.
2. Lund VJ, et al. International consensus report on the
diagnosis and management of rhinitis. International
rhinitis management working group Allergy 1994;
49(suppl 19):1-34.
3. Management of Allergic Rhinitis and its impact on
Asthma. Workshops report W.H.O 2001. Astra Zeneca
Pharma India Ltd. Bangalore-1.
1091
4. Paramesh H, Cherian E. Pediatric allergies epidemiology

and management. Principles and practice of tropical
allergy and asthma. Ed: Wiqar.A.Shaikh. Vikas Medical
Publishers. Mumbai 2006;603-14.
5. Paramesh H. Epidemiology of asthma in India. Indian J
Pediatr 2002;69:309-12.
6. Spector SL. overview of comodial associations of allergic
rhinitis J. Allergy Clin Immunol 1997;99:5763-72.
7. Tuft Muller Allergy in Children. WB Saunders Company
1970;246-247.
20.4 Food Allergy and Related

Gastrointestinal Tract Diseases
VS Sankaranarayanan
Definition
Adverse food reactions are clinical situations of abnormal
responses exhibited by certain individuals after ingestion
of foods that are otherwise tolerated by majority.
Food toxicity is the normal poisonousness resulting from
ingestion of contaminated food and affects all those who
shared the food.
Adverse reactions to food are often categorized into two
types, viz., food allergy and food intolerance and it is
important to distinguish between these two types of
reactions, because the treatment approaches vary.
Food allergy or hypersensitivity is specifically related to
immunologically mediated reaction in the GI tract
secondary to the ingestion of a food product.
Food intolerance often results from non-immunologic
reactions related to various properties and components
of food products themselves or to deficiencies and
abnormalities in the host (e.g. lactose intolerance).
This chapter focuses on the most common and recent
updates on GI food allergies in infants and children:
Cowmilk protein vs lactose intolerance.
Incidence
Food allergy affects 1 to 8% of infants.
Classification
Regardless of the immunologic mechanism involved,
symptoms of GI hypersensitivity are very similar but
generally vary in time of onset, severity and persistence.
Gastrointestinal hypersensitivity to food and other

dietary products
IgE mediated
Non IgE mediated
Food protein induced
a. Immediate GI
hypersensitivity
entero colitis
b. Oral allergy
Proctitis
syndrome
Enteropathy
Celiac disease
Allergic eosinophilic esophagitis, gastritis,
gastroenterocolitis
Pathophysiology
Allergic reaction of food products is the result of
interaction between food allergens, the GI tract and the
immune system. Usual food allergen is the glycoprotein
portion of the food in cows milk protein though there
are over 25 known immunogenic proteins. Betalactoglobulin, the major whey protein and casein have
the highest level of antigenicity. Varieties of allergenic
proteins are found in human breast milk, cow milk, soy,
egg, wheat and peanut.
Development of GI allergic reactions to cow and soy
protein is felt to be related to genetic predisposition (with
no definite molecular basis of inheritance) followed by
sensitization (Table 20.4.1). There is a higher risk of milk
protein sensitivity with the similar history of atopy in
parents or sibs of families having atopy. Sensitization
may occur in utero in less than 5% of infant food allergies
and the risk is higher when genetically predisposed
infants are exposed early to antigens whether it is in
1092

TABLE 20.4.1: Pathogenesis of GI allergy
TABLE 20.4.2: Clinical characteristics of GI allergy and

hypersensitivity
Genetic predisposition (cow milk and soy protein allergy)

Sensitization
in utero
early exposure
Defective mucosal barrier
GI immaturity
infections
infant formula or in maternal breast milk. An intact GI

tract is efficient to form a barrier to most of ingested
antigens, toxins and even intestinal pathogens in older
infants. Unfortunately, this mucosal barrier is immature
in the newborn infants until 4 months of age,
predisposing the child to macromolecular absorption of
a variety of antigens and the risk is more when there is
damage to the intestinal mucosa, e.g. acute gastroenteritis
leading to break in mucosal barrier and ultimate
sensitization to cows milk and resulting in cow milk
protein enteropathy.
Mucosal epithelial cells, the unique mucosal layer of
the gut, gut peristalsis, gastric acid and pepsin,
proteolytic enzymes, gut immune system, viz., mast cells,
macrophage or dentritic cell, the gut associated lymphoid
tissues, secretory IgA and cell mediated immunity are
the components of gut mucosal barrier. A break in any
of the above components may lead to sensitization and
subsequent allergy. The food allergic reaction may be
chemically mediated through cytokines, cellular
memory, histamine release, prostaglandins, leukatrines
and T cell response resulting in local gut reaction (oedema
from increased permeability to antigen and bleeding of
gut mucosa). Repeated ingestion of the antigen results
in sensitization and results in triggering of mononuclear
cells to release cytokines and histamine releasing factor
(HRF). The end result is stimulation of mucus production,
increased muscle contraction and smooth muscle fibre
spasm and stimulation of pain fibres and recruitment
inflammatory cells. Mast cells of mucosa and submucosa
of the gut appear as early as 3rd fetal month and increase
in number until adult life and largely distributed in the
GI tract. Immediate gastrointestinal hypersensitivity and
oral allergy syndrome are results of IgE mediated
gastrointestinal reaction often accompanies allergic
reactions in other target organs (e.g. skin, lungs) and
symptoms are variable.
The clinical characteristics of such reactions and
outline of treatment are summarized and compared in
Table 20.4.2.
Immediate GI
hypersensitivity
Oral allergy
syndrome
Manifestations
Nausea, abdominal pain

and vomiting within 1 to 2
hours. Diarrhea within 2
to 6 hours. Frequently
associated with atopic
disease. Food specific
IgE antibodies
Radiographic gastric
hypotonia and
pylorospasm
Oral
manifestations;
burning, swelling,
itching, erythema.
Immediate onset
of symptoms
Age of onset
Infancy and childhood
Beyond infancy
but typically less
than 5 years
Proteins
implicated
Milk, soy, egg, peanut,

cereal, fish
Heat labile fresh

fruits and
vegetable
allergens. Pollen
and latex cross
reactivity
Pathology
IgE mediated
IgE antibodies
Treatment
Protein elimination
Avoidance
Cooking
Genetics
Familial
associated with atopic
diseases
Familial
Frequent allergic
rhinitis
Natural history
80% cases
resolve after protein
elimination diet (except
peanut and fish)
Unknown
Allergic eosinophilic esophagitis, gastritis and gastroenterocolitis manifest as chronic reflux esophagitis, failure to
thrive, abdominal pain with normal to slightly elevated
IgE. Uncommonperipheral eosinophilia due to cow
milk, wheat, soy, egg, peanut (often multiple antigens).
Diagnosis
Diagnosis by endoscopic mucosal biopsy showing
eosinophilic, poly mononuclear infiltrations of gut
mucosa and submucosa, papillary elongation and basal
zone hyperplasia.
Treatment
Protein elimination. Good response to hydrolysed
protein formula in infants or L-aminoacid formula and

excellent acute response to steroids. 80% of cases of cow
milk allergy induced allergic eosinophilic esophagitis
resolve in less than one year, but cases of soy induced
gastroenterocolitis disorder are of prolonged nature. But
there is a good response to hydrolysed protein formula
in less than 2 years of age.
Non-IgE Mediated Disorders
Allergy to cows milk, soy, rice, poultry and fish can
manifest as vomiting and early diarrhea, anemia,
abdominal distension, failure to thrive with positive
faecal leukocytes and normal IgE. Food challenge with
allergens can induce vomiting in 3 to 4 hours and
diarrhea in 5 to 8 hours of neonate to 1 year of age group.
Biopsy of gut mucosa shows patchy villous injury and
colitis and PMN in biopsy, peripheral blood and stool.
Occult blood positive in stool within 4-6 hours of food
challenge. Good response to hydrolysed casein formula
and symptoms clear in 3 to 10 days. With treatment 50%
resolves by 18 months and 90% by 36 months except soy
protein enterocolitis which may be persistent for a longer
time.
Dietary protein proctitis due to exclusively breast-fed (60%)
or cow milk, egg or soy induced often presents as bloody
diarrhea with positive fecal leukocytes and mild
peripheral eosinophilia. Food challenge symptoms occur
in 6 to 72 hours. Rectal biopsy reveals colitis with
eosinophilic infiltration and nodular lymphoid hyperplasia. Treatment consists of protein elimination. Good
response to hydrolysed formula, breast feeding on
maternal antigen restricted diet and symptoms clear
usually by one year.
Dietary protein enteropathy of children occurs often under
two years of age due to cows milk, soy, cereal, egg and
1093
fish and presents with diarrhea, malabsorption, failure

to thrive, edema, and anemia, protein losing enteropathy
with normal IgE, no peripheral eosinophilia, no food
specific IgE, no increase in atopy, negative anti
endomysial antibody. Ba meal reveals small bowel
edema and malabsorptive state. Food challenge results
in vomiting and diarrhea in 40 to 72 hours. Treatment
consists of elimination of offending antigen (relief in 3 to
21 days). Rechallenge and repeat biopsy is advised at 1
to 2 years. Resolution occurs mostly in 2 to 3 years.
Food Protein induced Enterocolitis Syndrome (FPIES)
It is a recently described symptom complex of severe
vomiting and diarrhea caused by non-IgE mediated
allergy to cows milk and/or soy in infants. Onset of
symptoms in the neonate with failure to thrive and may
progress to hypoalbuminemia, anemia, methemoglobinemia and septicemia and shock. Stool examination
may be positive for occult blood, fecal leucocyte and
reducing substance. Good response to elimination of
cows milk and/or soy and reappearance of symptoms
within two hours on protein challenge and elevation of
PMN in peripheral blood. Negative IgE antibody to milk
and soy (skin prick and/or RAST (Radio allegro sorbent
test). The sensitivity is usually outgrown by three years
of age.
Cows Milk Protein Allergy
(Cows Milk Protein Intolerance)
Cows milk protein allergy is the most common food
allergy in young infants often mistaken as lactose
intolerance by many unless high degree of suspicion is
given. CMA is not equal to lactose intolerance and hence
has to be differentiated from lactose intolerance.
Cows milk allergy (CMA/CMPI)
Lactose intolerance
Incidence: 2-6% in non-breast fed infants and

.5% of breast fed infants
25-67% of recurrent abdominal pain/

irritable bowel syndrome
Clinical presentation:
Immediate: within few minutes, IgE mediated, vomiting,
pallor, shock like state, urticaria, swollen lips
Slow/Late onset reaction: Occurs in few hours or days
T cell mediated diarrhea, failure to thrive, anemia, edema,
sastrointestinal, respiratory and skin manifestations. Skin
manifestations improve possibly after milk withdrawal.
Explosive diarrhea with perianal excoriation, borborygmus,

flatulence and abdominal colic
No extra intestinal manifestations
1094
High risk groups

Atopic child with high IgE and
asthma/rhinitis. Minor immunodeficiency with low IgA
Premature neonates with food intolerance, persistent/chronic

diarrhea with malnutrition frequently seen in adolescents
Diagnosis: High index of suspicion

Family history of atopy and food allergy
Skin prick test > 3 mm is positive
Positive IgE against cows milk
Modified goldmans criteria for diagnosis includes clinical
suspicion of CMA and abnormal histology (small bowel or rectal)
at presentation.
Symptomatic response to milk free diet and repeat biopsy
reveals normal histology after milk withdrawal. A repeat
challenge of milk feeds is given after one year. Depending on
response milk free diet is continued. If not tolerated,
withdrawal and challenges of cows milk annually tried
UGI endoscopy shows lymphonodular hyperplasia,
congestion with aphthoid ulcerations and histopathology
shows villous atrophy with some crypt hyperplasia,
increase in IEL and eosinophils
Often lactose intolerance is diagnosed in a suggestive

clinical setting. Liquid stool pH of < 6, reducing substance of
> 1% in neonate and 5% in older children is diagnostic
of lactose intolerance. HIstory diagnosis with perianal
excoriation and explosive diarrhea after lactose feeds is
more dependable. Lactose tolerance test and breath
hydrogen test are not recommended for routine practice
but may be of academic importance. Clinical response to
lactose free diet is also diagnostic.
Natural history: Most children outgrow the disease by four

years.
There are three types of lactose intolerance: Congenital,

secondary and late onset genetic types. Secondary type is
the commonest following gastroenteritis and many of
these children improve in few weeks after lactose free diet
but the adult late onset type may present with persistence
of symptoms.
Management: Removal of all cows milk and milk products

from diet. Permit soy or hydrolysed formula (not available
in India). 10-15% of children with CMPI have soy allergy
also. Elemental aminoacid formulae (Neocate), home available
vegetable milk like amylase rich feeds, cereals with rice and
dhall are also recommended. Parental counseling and
education are essential.
Milder forms are treated by milk restricted diet (milk

cereals and breast milk-plan A) whole milk is better than
skimmed milk and can be given along with cereals or
in the form of yogurt severe cases of lactose intolerance
need lactose free formulae (plan B)
Parental counseling and education needed.
Celiac Disease
The disease presents as dietary protein hypersensitivity,
reaction to gluten present in wheat, rye, barley and
possibly oats. Often presents typically after 6 months of
age and age on onset depends on timing of gluten
introduction and manifests as chronic diarrhea,
abdominal pain and distension, failure to thrive,
malabsorption with normal IgE and no increased atopy.
IgA gamma endomysial antibodies, IgG/IgE antigliadin
antibodies, confirm diagnosis. Ba. meal reveals malabsorptive state. Small bowel mucosal biopsy reveals
extensive villous atrophy, elongated crypt length (crypt
villous ratio of 1:1 or less), increased intraepithelial
lymphocytes and increased /dT cells. Celiac disease
may be associated with diseases like dermatitis herpetic
formis, diabetes mellitus, thyroid disease, Downs
syndrome, and IgA deficiency. Genetically HLA-DQ2
and DQ8 are associated. Alpha gliadin is considered the
putative protein in wheat which may react with an early

protein of adenovirus 12-being a triggering factor in
susceptible patients suggesting the role of immunologic
basis. Treatment consists of gluten elimination (rotis,
bread, biscuits and cakes) and long term follow up as
the illness is life-long.
Food allergy: Preventive strategy (for high risk infants with
history of family atopy).
Exclusive breast feeds at least six months
Completely hydrolysed formula as alternative
Late introduction of solids after six months
To avoid offending proteins like cows milk or soy
protein or egg for first 12 to 24 months
Monitor to avoid food allergens during pregnancy
and lactation (cows milk and then products, soy, fish,
egg, peanuts, etc.)
Oral sodium chromoglycate and oral ketotifen.

BIBLIOGRAPHY
1.
Jeffrey S Hyams Food Allergy (Food Hypersensitivity)

Nelson Textbook of Pediatrics 18th Ed, 334:1585-87.
2. Philippe A, et al. Food hypersensitivities Annals of Nestle
1999;57:57-67.
3. Sicherer SH. Food protein induced enterocolitis
1095
syndrome: Clinical perspectives. Journal of Ped Gastroenterology and Nutrition 30:S45-49Jan 2000.
4. Srivastava A. Chronic diarrhea and malabsorption
syndrome. IAP Speciality series on Ped. Gastroenterology
2008;6:67-70.
5. Srivastava A. Milk allergy vs lactose intolerance Pedicon.
Selected topics in pediatrics. 2006;3:425-27.
20.5 Value of Allergy Tests in Pediatrics

L George Moses, A Parthasarathy
One in every five children develops an allergic isorder
some time during childhood. Some conditions are shortlived causing mild disturbance while others may be life
threatening. In recent years the understanding of the
interaction between allergens and the human immune
system has improved dramatically. Children with genetic
predisposition towards the development of allergy
(atopic children) often start with sensitivity to food that
exhibits itself as atopic dermatitis during the first two
years of life. After age two, these children often develop
sensitivity to inhalent allergens producing allergic
rhinitis. These children have a increased tendency to
develop asthma as they grow older. Commonly
encountered allergic symptoms among children are:
Anaphylaxis
Rhinitis
Urticaria Angioedema
Sinusitis
Food Allergy
Asthma
Atopic Dermatitis
Otitis Media
Contact Dermatitis
Conjunctivitis
Drug Allergy
First step in the diagnosis of allergy involves
recognition of characteristic symptoms identified from
the clinical history and examination. When tentative
diagnosis of allergic disease can be made out from the
clinical history, many allergic conditions exhibit
symptoms that are hard to distinguish from non-allergic
conditions. Hence the American Academy of Allergy,
Asthma and Immunology (AAAAI) recommends the use
of objective measures to confirm the diagnosis of allergy
in symptomatic patients. The classical diagnostic test
procedures to demonstrate the IgE mediated reactions
includes both invivo and invitro procedures. The invivo
test procedures fall in to two categories:
a. Skin Tests
b. Organ Challenge Tests
Skin Tests
The major methods of skin testing for IgE mediated
diseases are:
a. Epicutaneous (Patch/Photo patch) test
b. Percutaneous (Prick/Puncture or scratch) test and
c. Intracutaneous (Intradermal) test
Of these the Scratch Test is no longer recommended
as a allergy testing procedure due to poor reproducibility
and high incidence of false positive reaction. The
epicutaneous, percutaneous and intracutaneous skin
tests are widely used because of their simplicity,
biological relevance, rapidity of performance and low
cost and sensitivity. A positive IgE mediated skin test
manifests as a wheal and flare reaction.
Epicutaneous Test
Patch Test
Patch Test is used to determine the presence of delayed
hypersensitivity reactions originating on the skin. The
ready to use patch test system coated with the specific
allergens is placed on the upper back and secured with
hypoallergenic tape.
Supplementary tape and the patch test strip is
removed after 48 hours insitu and an initial interpretation
of the result is recorded based on the inflammatory
response and the scores are numbered 1 through 6. Final
reading is taken after 24-96 hours as delayed positive
patch test response are found in about 35% of the patients.
It is primarily used to assess allergic contact dermatitis and
other immunologically mediated skin reactions which are
largely cell mediated but may contain an IgE mediated
component.
1096
Photo Patch Test

The suspected medication or chemical is applied on two
separate areas. One of the areas is exposed to ultraviolet
light. Test is considered positive if only the area that has
been exposed to UV light demonstrates the allergic
reaction.
Percutaneous Test (Prick/Puncture)
A small quantity of the test antigen is applied topically
on the upper back or volar surface of the arm and a
needle/lancet/tines is inserted through the drop into the
topmost layer of the skin. The tip of the device is lifted
so that a tiny needle track is formed through which the
allergen (3 nl) flows into the prick site. The peak wheal
and flare reaction is read usually between 15-20 minutes.
Both erythema and wheal diameter is measured and
recorded in mm. Wheal of 3 mm or more and erythema
of more than 10 mm are the percutaneous cutoff for a
positive test. (Positive control: Histamine and negative
control: 50% glycerine) Percutaneous tests are more specific,
less painful and safe and hence generally accepted as the initial
route for screening for cutaneous allergy. But they are less
sensitive, more difficult to interpret in colored people, and
produce more variable result than intracutaneous tests. Upper
limit of 70 percutaneous tests are recommended.
Intracutaneous Test (Intradermal)
In this test a defined volume (10-50 ul) of allergen is
introduced using a 26/27 gauge needle with bevel down,
at 5 cm interspace on the upper back or volvar surface of
the hand. The erythema and induration is read at 15
minutes with re-evaluation at 25-30 minutes to capture
slower reaction peak. Both erythema and wheal diameter
is measured and recorded in mm. Wheal of 6mm or more
and erythema of 11mm or more are the intracutaneous
cutoff for a positive test. (Positive Control: Histamine and
Negative Control: 0.5-5% glycerine/diluent) Intracutaneous tests are more sensitive than prick test and serve as a
means to find out clinically relevant allergy missed by
percutaneous tests. But more painful and carry more risk than
the percutaneous test. Upper limit of 40 intracutaneous tests
are recommended, tailored to patients allergen exposure.
Late Phase Reaction
Generally the binding of allergens to mastcells allergen
specific IgE result in the immediate release of preformed
mediators leading to triple reaction - erythema, wheal

and itching. A late phase reaction develops in few
persons at 3-4 hrs mainly mediated by basophils,
eosinophils , neutrophils and lymphocytes. Rarely
patients report a late phase reaction to intracutaneous
testing at 24 hours or more after testing. Peak skin
reactivity is observed between 15-50 years. Infants and
older adults show less reactivity.
Medication that intereferes with skin testing:
1. First generation antihistamines 24-72 hours
2. Nonsedating antihistamines
7 days
3. Tricyclic antidepressants
7-14 days
4. Benzodia Zepines
7-14 days
5. Oral corticosteroids
Short term use
Do not affect
High dose long term use
Supress
immediate skin
reactions
6. Topical conticosteroid
2 to 3 weeks
Non-steroid anti inflammatory drugs do not affect
skin reactivity.
Organ Challenge Tests (Provocative Tests)
Organ Challenge Tests are performed when the results
of primary invivo and invitro diagnostic tests (skin test
and IgE antibody serology) do not agree with each other
in case of a strongly suggestive clinical history. This
happens when the circulating IgE antibody has decreased
below the serological assay detection limit, but sufficient
IgE antibody remained attached to the effector cell
receptors to generate positive skin test.
1. Oral Challenge Test: Carried out to confirm or
diagnose IgE mediated hypersensitivity to specific
food.
2. Bronchial Challenge Test: Carried out to confirm or
exclude hypersentivity to certain drugs for which
there is no effective alternative.
These tests should be carried out by experienced
persons for proper testing, interpretation and analysis
and should be avoided in patients who have had a well
documented life threatening reaction to specific food.
Properly performed food challenge test represents the
gold standard for implementing specific diets in food
allergic individuals.

ADDITIONAL IN VIVO DIAGNOSTIC PROCEDURES
Provocative testing procedures whose diagnostic role has
not been established in clinical practice include:
: (Food allergy)
1. Sub-lingual food allergy test
2. Conjunctival Challenge Test
: (Rhinitis and
Conjunctivitis)
3. ProvocationNeutralisation Test : (Food and
(Rinkel-Test)
Inhalent
allergy)
4. Electrodermal Test
(Electro-Occupuncture)
5. Reaginic Pulse Test
6. Applied Kinesiology Test
: (Food Allergy)
: All Allergens
: All Allergens
IN VITRO ALLERGY TESTS

Modern day diagnostic allergy serology began in 1968
with the demonstration that skin sensitizing activity in
the human serum is assocated with IgE antibody.
Demonstration of allergen specific IgE antibody is the
most important serological marker used in the diagnosis
of allergic diseases.
Radioallergosorbent test (RAST) was the first
serological assay developed to detect the allergen specific
IgE antibody in the serum of allergic patients (1968).
Various modifications to RAST have been introduced to
improve the assay performance. In the modified
radioallergosorbent assay (mRAST) different scoring
methods have been devised to assist automation.
In the original and modified RAST procedures the
patients serum sample is added to a known allergen
coated on a solid phase (cellulose solid phase) and
incubated. Non-binding IgE is washed away and a
labelled anti-human IgE is added. This IgE, in turn bound
to the IgE fixed to the coated antigen. The radioactivity
is measured with a gamma spectrometer. The amount
of radioactivity counted is proportional to the amount
of IgE antibody bound. Now 14 different RIA methods
are available to detect the specific IgE level in serum.
The difficulty in automating RIA methods and
reluctance of laboratories to handle radio isotopes led to
the use of different immunoassay methods such as:
1. Enzyme immunoassay (ELISA)
2. Flurorescent immunoassay (FAST)
3. Chemiluminescent Immunoassay (CLIA)
1097
The chemistry of all these tests is similar to RAST but

employs non-isotope labels. Improvements over the years
in assay technology, high binding capacity solid phase
matrices, non-isotope labels for detecting antibodies and
standard calibrated to WHO IgE reference preparation
has led to the evolution in assay methods from the 1st
generationqualitative assays through 2nd generation
semiquantitative assay to 3rd generationquantitative
assay.
In qualitative assay system the specific IgE in serum
is reported as negative or positive. In semiquantitative
assay system the results are recorded in increasing grades
as I - VI or qualitative grading scheme using color chart
or by end point dilution. In qualitative assay the results
are reported in iu/ml.
Two widely used quantitative assays are:
i. Immunocap system
ii. Immulite 2000
As the individual allergen specific tests are very
expensive to perform on a specific allergen basis multiallergen screening system is introduced to measure IgE
antibodies to multiple allergens. Now the following
multiallergen screening tests are available to screen
combination of different
1. Group specific allergens such as dust mite, pet
epidermals, pollens, mold spores, and
2. Species specific allergens such as aspergillus,
penicillium, cladosporidium and alternaria Ex :
Immunocap system and immulite 2000
Though multi-allergen screening technique is fairly
cost effective, it provides only a qualitative result
(positive or negative) and its exact role in clinical
evaluation has yet to be established. Utility of in vitro
tests in clinical practice is slower than the skin test as
they are very expensive to perform and less sensitive
when compared to skin test.
INDICATIONS FOR IN VITRO TESTING
i. Patients with severe dermatographism or generalized eczema.
ii. Patients who cannot be safely withdrawn from
medication that will interfere with the skin testing.
iii. Patient who have a history of previous systemic
reaction to skin testing.
iv. Patient with physical or mental impairment.
v. Pregnant Patients.
vi. Very young or elderly patients.
1098
OTHER IN VITRO TESTS OF PROMISE

Basophil Histamine Release Assay (BHR Assay)
Basophils and mastcells have high affinity IgE receptors
on their surface and they contain histamine. Allergens
added invitro to IgE sensitized basophils in a suspension
of washed leukocytes and calcium ion can cross-link IgE
antibody inducing the release of preformed histamine
and production of mediators such as leukotrines (L TC4).
The release of histamine correlates with the severity of
clinical symptoms. For this reason the BHR assay is
considered as a complementary research assay to IgE
immunoassay and skin test.
Mast Cell Tryptase Analyses
Estimation of tryptase released from the mast cell along
with histamine is a reliable marker of mast cell activation.
Component Resovled Diagnosis (CRD)
In the last decade single allergen molecules have been
identified for many important allergic diseases and the
advent of recombinant DNA technology has led to the
characterisation of many of these allergens at the
molecular level. The component resovled diagnosis
developed based on re-combinant DNA technology
holds good promise in the future.
IN VITRO TESTS WHOSE DIAGNOSTIC ROLE HAS
NOT BEEN ESTABLISHED INCLUDE
1.
2.
3.
4.
5.
6.
7.
Cytotoxic test (Leukocytotoxic testBryans test)

Lymphocyte subset count study
Lymphocyte function assays
Food immune complex assays
Leukocyte histamine release testing
Antigen leukocyte cellular antibody testing, and
Idiopathic environmental intolerance test.
CONCLUSION
The first step in the diagnosis of allergy involves
recognizing of characteristic symptoms identified from
the patients clinical history. Routinely used test
procedures are invivo test procedures like epicutaneous,
percutaneous and intradermal tests and, in-vitro test
procedures like RAST, ELISA and CLIA. Invivo test
procedures are widely used because of their simplicity,
biological relevance, rapidity of performance, sensitivity
and low cost. Invitro test procedures are very costly and
their sensitivity and specificity is compared only with

skin test.
Among the skin test the patch test is widely used in
the study of allergic contact dermatitis. Percutaneous skin
tests are generally accepted as the initial screening tests
for allergy. It can easily be completed on infants. But they
are more difficult to interpret in colored skin, produce
more variable result and less sensitive than the
intracutaneous tests. Intracutaneous tests are more
sensitive than percutaneous tests and serve as a means
to find out clinically relevant allergy missed by
percutaneous test. Intracutaneous tests are more painful
and carry more risk than the percutaneous test. Against
all odds the diagnostic usefulness of this test is evidenced
from the fact that:
i. 85.2% of the practicing allergists in United States
perform intracutaneous test in their clinical practice,
and
ii. The Centre for Biologic Evaluation and Research
USA (CBER) has chosen intradermal skin testing
over prick test for allergen standardization.
Invitro test procedures have a diagnostic role in
patients who are unable to undergo skin test. Multiallergen screen is the useful invitro test for excluding IgE
mediated diseases.
BIBLIOGRAPHY
1. Allergic rhinitis and its impact on asthma an update By
Prof. Dr Ruby Pawankar MD PhD Chairperson, Asia
Pacific affiliate. ARIA WHO Initiative. Member, Board
of Directors, World Allergy Organization (WAO)
Founder President, ISBAAR.
2. American Academy of Allergy Asthma and Immunology: Work Group Report: Allergy Diagnosis in Clinical
Practice, 2006.
3. Barrett JT. Microbilogy and Immunology Concept, 1990.
4. Cheesbrough M. Clinical Laboratory Manual for Tropical
Countries, 1984.
5. Harwanegg C, Hiller R. Recombinant allergen based
approaches for the diagnosis of IgE mediated type I
allergies, 2004.
6. Kemp F, Lockey F. Diagnostic Testing of Allergic
Diseases, 2000.
7. Kuzemco JA. Allergy in Children, 1978.
8. Lockey RF. Allergen and Allergen Immunotherapy, 2004.
9. Spickett G. Oxford Handbook of Clinical Immunology,
1998.
10. Valcour A. Allergy Testing for the 21st Century. Labcorp
(Laboratory Corporation of America).
11. Volcheck GW. Which Diagnostic Tests for Common
Allergies. Post Graduate Medicine, 2001;109(5).
1099
20.6 Allergen Specific Immunotherapy

K Nagaraju
Allergen specific immunotherapy (SIT) is defined as a
gradual immunizing process in which increasing doses
of antigens responsible for causing allergic symptoms
are administered to a patient to induce increased
tolerance to the allergen when natural exposure occurs.
It is also known as hypo sensitization or desensitization.
The dramatic changes in health care delivery in the past
decade have brought a renewed focus on the value of
and indication for many therapies. Among these is
allergen specific immunotherapy. It is one of the
treatment modalities available to medical profession for
IgE mediated allergic disorders. The benefit of specific
immunotherapy is dependent on both the dose and the
route of administration. Although the mechanism by
which this benefit occurs is not fully understood, the
current consensus is that specific immunotherapy works
by inducing allergen-specific T regulatory cells that
reduce the late-phase response to the allergen.
It was introduced by Noon in 1911 by inoculating
pollen extracts in cases of hay fever. Literature reveals that
different methods have been applied from time to time
viz. inhalation method in asthma sensitive to house dust
mite and Rinkle method in pollen hay fever. Later Ohman
and Bousquet et al used the allergen immunotherapy in
asthma and allergic diseases. In India, an array of workers
reported hyposensitization in respiratory allergy and
asthma.
During a period of years, specific immunotherapy
typically induces an allergen-specific IgG response. In
the past, this type of antibody was called blocking
antibody, although there is no evidence that it actually
blocks the allergic response or has any physiologic role.
Immunotherapy is effective in allergic rhinitis, allergic
asthma and insect stinging insect sensitivity, whereas it is
not effective in eczema., Food allergy, latex allergy and
urticaria.
Goals of immunotherapy are complete disappearance
of symptoms with use of medications less or in low doses
with no significant side effects or symptoms should be
at a tolerable level even after completion of immunotherapy.
Indications for Immunotherapy
Insufficient response to pharmacotherapy.
Insufficient response to environmental control.
Significant side-effects to medical therapy.
Patients who have perennial disease.

Poor compliance to medical regimen.
Possible prevention of asthma from allergic rhinitis.
Contraindications for Immunotherapy
Severe asthma FEV1 < 70% with active Rx.

Contraindications for epinephrine (Beta-blocker)..
Immunodeficiency/auto immune diseases.
Pregnancy.
Malignancy.
Psychological.
Mentally impaired patients.
Short expected life span < 5 years.
Non-compliant patient.
Safety and Efficacy of Immunotherapy

When properly administered to an appropriate candidate, it is a safe, effective form of therapy capable not
only of reducing or preventing symptoms, but of
potentially altering the natural history of the disease by
minimizing disease duration and preventing disease
progression. The use of standardized extracts is advised
to get optimal results. Success of immunotherapy
depends on optimal means of allergy testing, quality of
allergen extract, correct initial dose of immunotherapy
and follow-up with maintenance dose. Failure of
immunotherapy is mainly due to inadequate environmental control. Missed diagnosis (non-allergic rhinitis),
failure to include allergen in SIT, exposure to unknown
allergen, inadequate dose of allergen injection, noncompliance of schedule, development of new allergic
sensitivities, unrealistic patient expectations for cure and
some patients may not responded favorably to SIT itself.
Adverse Reactions
Systemic reactions to immunotherapy occur within one
hour usually scattered hives and rarely severe anaphylaxis, whereas local reactions can occur up to 24 hours.
Incidences of fatal anaphylaxis is 1 per 2 million
injections. Common local reactions are wheals, indurations or both mainly due to poor injection technique.
Patient should be under observation for 30 minutes to
monitor allergic reactions. Patient education is essential
especially for delayed reactions. At the first sign of a
systemic reaction, a tourniquet may be applied above
1100
the injection site and epinephrine administered at a

weight appropriate dose preferably by the intramuscular
route. Specific emergency equipment used in anaphylaxis
treatment should be on site at any office administering
immunotherapy. Not even a single case of anaphylaxis
was encountered in authors ten years of practice.
Schedule of Immunotherapy
Schedules of allergen administration are selected based
on the sensitivity of the patient to the allergens in the
extract. Dose ranges from 4-12 ug administered
subcutaneously. Subcutaneous route of allergen
administration is most widely used and documented.
Despite the established efficacy of subcutaneous
injections of causal allergens, the therapy did not gain
popularity due to risk of systemic reactions.
Primary Immunotherapy: To start with low doses are
administered which can be stepped up gradually in
dosage and frequency until maintenance dose is reached.
It has to be given for 3-5 months.
Maintenance Immunotherapy: After attaining adequate
control with twice dose, it can be changed over to once a
month dose. To start with twice monthly until adequate
control and later change to monthly once. To get adequate
response one year of treatment is compulsory .If there is
no response it can be discontinued. Progressive
improvement occurs by 2-3 years. Maintenance immunotherapy is given for a period of 3-5 years. Prediction of
response is difficult. Extracts are stored at 2-8C in the
refrigerator for optimal efficacy.
Future strategies include alum depot preparations

which act as adjuvants, allergoids which are chemically
modified allergens, peptide immunotherapy which uses
allergen derived T-cell peptide epitope, recombinant
allergens and anti-IgE antibodies.
Rush Immunotherapy
The process of inducing adequate immunological
response in an accelerated pace, where in all the doses
could be given within a period of few days is termed as
Rush Immunotherapy. Here the doses are spaced out in
2-6 hourly intervals so that maintenance dose is reached
within few days. The risk of Systemic Allergic reactions
is high. It has to be undertaken where facilities for
intensive care and monitoring are available. Patients
should be pretreated with antihistamines and corticosteroids.
BIBLIOGRAPHY
1.
2.
3.
Alternative Routes
Nasal Immunotherapy is administered as spray allergen
solution into the nose in a phased manner but lack of
significant immunologic response led to discontinuation
of this route.
Sublingual immunotherapy is administered as drops
of high dose allergen solution underneath the tongue
which is then swallowed. It may be started at the full
maintenance dose, without the gradual increase in dose.
The common side effect of sublingual immunotherapy is
local irritation in the mouth and under the tongue (47 to
52%). But it is usually transient and does not progress to
anaphylaxis. This side effect presumably reflects local
allergic reactions to the allergen extract. In the authors
own practice local irritation and even mouth ulcers were
encountered in almost all patients. It has the added
advantage of ease of administration, home based therapy
and avoidance of painful injections. So it can be advocated
for children.
Intrabronchial administration which was advocated
initially is now out of general usage due to untoward
side effects.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Bousquet J, Lockey R, Malling HJ. WHO panel members.

Allergen immunotherapy: The therapeutic vaccine for
allergic diseasesA WHO position paper. J Allergy Clin
Immunol 1998;102(4):558-61.
Bousquet J, Maasch H, Martinot B, Hejjaoui A, Wahl R,
Michel FB. Double blind placebo-controlled immunotherapy with mixed grass pollen allergoids. II comparison between parameters assessing the efficacy of
immunotherapy. J Allergy Clinic Immunol 1988;82:
439-46.
Dan Atkins, Donald YM Leung. Principles of Treatment
of Allergic Disease. In: Behrman R, Kliegman RM, Jenson
HB, Stanton BF(Eds): Nelson Textbook of Pediatrics (18th
Ed). WB Saunders: Philadelphia 2007;947-949.
European Academy of Allergology and Clinical
immunology. Immunotherapy position paper 1988;43.
Gidaro G, Marcucci F, Sensi L, Incorvaia C, Frati F,
Ciprandi G. The safety of sbulingual-swallow immunotherapy : an analysis of published studies. Clin Exp
Allergy 2005;35(5):565-71.
Keenan JP. Management of problems and immunotherapy failures : In Otolaryngic Allergy and Immunology. WB Saunders Co: Philadelphia, 1989.
Lockey, et al. Fatality from immunotherapy. J Allergy
Clin Immunol 1987;79:660-77.
Mark H, Moss MD. Immunotherapy: First do no harm.
Immunol Allergy Clin N Am 2005;421-39.
Norman PS. Safety of allergen immunotherapy. J Allergy
Clin Immunol 1989;84(4):438.
Patterson R. The role of immunotherapy in respiratory
allergic diseases. J Allergy Clin Immunol 1998;101:
L403-4.
Tripathi DM. Principles of successful immunotherapy.
Bom Hosp J 1992;34(4):71-9.
Tripathi DM. Role of Aerobiology in treatment of allergic
patients. Current trends in life sciences 1994;20:291-300.
1101
20.7 Rheumatological Disorders in Children

S Ramakrishnan, A Parthasarathy
INTRODUCTION
Rheumatic diseases are a group of diseases of unknown

etiology involving the joints and multiple organ systems.
These diseases are associated with significant morbidity
and mortality. Since these diseases are chronic in nature
they are among the common causes for physical disability
in children. The commonly encountered rheumatic
diseases in children are described here.
This includes general examination and system examination:

1. General examination.
2. Examination of the joints including the spine.
3. System examination cardiovascular, respiratory
system, central nervous system, gastrointestinal and
cardiovascular system.
CLINICAL APPROACH TO A CHILD

WITH ARTHRITIS
Children with arthritis are encountered in practice. Early
recognition, correct diagnosis and appropriate management will reduce significantly the morbidity and physical
disability seen in arthritic children.
A stepwise approach to children with arthritis is given
in Table 20.7.1.
Clinical History
1. Is there pain in joints or early morning stiffness in
the joints?
2. Presence of swelling, warmth or restriction of joint
movements.
3. Whether the arthritis was migratory or additive?
4. Presence of extra-articular symptoms like fever,
weight loss, skin rash, photosensitivity, oral ulcers,
cough and difficulty in breathing, per orbital swelling
difficulty in swallowing, muscular weakness with
difficulty in standing form squatting posture,
Raynauds phenomenon, abdominal pain, alteration
of bowel habits with passage of blood or mucus,
headache, convulsions or stroke.
5. Presence of family history of psoriasis and inflammatory bowel disease.
6. History of preceding upper respiratory infection,
gastrointestinal or genitourinary infection.
TABLE 20.7.1: Diagnosis of arthritis
Clinical history
Clinical examinations
Laboratory investigations
After clinical examination one should come to the

conclusion:
1. Whether it is arthralgia or arthritis?
2. Whether it is monoarticular, oligoarticular or polyarticular arthritis?
3. Whether there are extra-articular manifestations?
(Table 20.7.2).
All children with arthritis should undergo laboratory
investigations which aid in the diagnosis (Table 20.7.3).
While it is important to do these investigations the
diagnosis of JIA is a clinical one. The importance in doing
these investigations is to exclude other diseases which
present with joint pain.
Hematology
All children with arthritis should have a complete blood
count including erythrocyte sedimentation rate and
peripheral smear. Elevated ESR could suggest inflammatory arthritis. One common fallacy is not to diagnose
JIA if there is no elevation of either ESR or C-Reactive
Protein since it is common to see normal ESR or other
acute phase reactants in monoarticular/oligoarticular
JIA.
Anemia in a child with arthritis could be due to either
anemia of chronic disease, hemolytic anemia, hematological malignancy or NSAID induced gastrointestinal
blood loss. Thrombocytopenia and leukopenia suggest
the possibility of leukemia, systemic lupus erythematosus
(SLE) or drug induced marrow damage. Peripheral smear
examination is a must in all children with arthritis and
constitutional symptoms or anemia to exclude the
1102
TABLE 20.7.2: Polyarthritis with extra-articular manifestations
TABLE 20.7.3: Laboratory investigations
Organ involvement
Suspect
Fever
Systemic JIA
Rheumatic fever
SLE
Inflammatory muscle disease
Vasculitis
Septic arthritis
Leukemia/lymphoma
Serum sickness
Viral arthritis
Kawasaki disease
Systemic JIA
SLE
Dermatomyositis
Psoriatic arthritis
Reiters syndrome
Serum sickness
Henoch-Schonlein purpura
Systemic vasculitis
Kawasaki disease
Iatrogenic (gold, D-penicillamine)
Systemic sclerosis
Systemic vasculitis
Post-diarrheal reactive arthritis
SLE
Systemic vasculitis
Polymyositis
Dermatomyositis
Steriod induced myopathy
SLE
Systemic vasculitis
Wegeners granulomatosis
Microscopic polyarteritis
Rheumatic fever
Systemic JIA
SLE Kawasaki disease
Reiters syndrome
Kawasaki disease
Pauciarticular JIA
Juvenile ankylosing spondylitis
Behcet
Rheumatic fever
Polyarticular JIA
Rheumatoid arthritis
SLE
SLE
Behcet
SLE
Vasculitis
SLE
Scleroderma
Iatrogenic (NSAIDs and DMARDs)
Skin rash
Gastrointestinal
Systemic hypertension
Muscular weakness
Pleuropulmonary
Cardiac
Conjunctivitis
Uveitis
Photosensitivity
Oral ulcers
Alopecia
Renal
Hematology
Biochemistry
Immunology
Microbiology
Radiology
possibility of leukemic arthritis. In a child with suspicion

of hemarthrosis a coagulation profile should be
performed to exclude hemophilia.
Biochemistry
Muscle enzymes like creatine kinase, aldolase, serum
glutamic-oxaloacetic transaminase and lactic acid
dehydrogenase have to be performed in arthritic children
with suspected inflammatory muscle disease. Renal
biochemistry is to be performed in arthritic children with
suspected SLE or vasculitis. Liver function tests are
performed in JIA children on methotrexate.
Immunology
1. ASO: Tests for ASO is performed when rheumatic
fever is suspected. ASO is always expressed in
International Units. An ASO of 400 IU or above 400
IU is considered abnormal and elevated. An elevated
ASO titer is one of the minor criteria for diagnoses of
rheumatic fever. One should interpret elevate ASO
in a child always on the clinical background.
2. Rheumatoid factor: Tests for rheumatoid factor is
performed in children in whom juvenile idiopathic
arthritis (JIA) is suspected. Tests for rheumatoid factor
(RF) are done by latex agglutination or nephelometry.
Rheumatoid factor of 80 IU/ml or above is considered
specific for the diagnosis of rheumatoid factor positive
polyarticular JIA. Other conditions in which RF can
be elevated are infective endocarditis, Sjogrens
syndrome, hepatitis B infection and leprosy.
3. Anti-nuclear antibody (ANA): ANA is a screening test
to diagnose patients with SLE. ANA is positive in
systemic rheumatic disease like SLE, scleroderma,
inflammatory muscle diseases like polymyositis and
dermatomyositis and Sjogrens syndrome. ANA is
positive occasionally in other non-rheumatological
disorders like idiopathic lung fibrosis, Crohons
disease, Graves disease, chronic autoimmune
hepatitis, leukemia, lymphoma and immune hemolytic anemia. One should be aware that ANA may be
positive in 5-10% of normal people in low titre. A
1103
TABLE 20.7.4: ILAR criteria for classification of juvenile idiopathic arthritis

Frequency*
Onset age
Sex ratio
Systemic arthritis
4-17%
Throughout childhood
F-M
Oligoarthritis
27-56%
Early childhood; peak at 2-4 years
Rheumatoid-Factor positive polyarthritis
2-7%
Late childhood or adolescence
Rheumatoid-Factor negative polyarthritis
11-28%
Biphasic distribution; early peak at 2-4 years

and later peak at 6-12 years
F>>M
Enthesitis-related arthritis
3-11%
Late childhood or adolescence
Psoriatic arthritis
2-11%
Biphasic distribution; early peak at 2-4 years

and later peak at 9-11 years
F>M
Undifferentiated arthritis
11-21%
F>>>M
F>>M
M>>F
*Reported frequencies refer to percentage of all juvenile idiopathic arthritis.

Frequency, age onset, and sex distribution of the International League of Associations for Rheumatology (ILAR) categories of
juvenile idiopathic arthritis
positive ANA test should always be interpreted on

the background of the clinical history and clinical
findings. Serial estimation of complement components C3 and C4 is performed to assess disease
activity in patients with SLE.
4. Antineutrophil Cytoplasmic Antibody (ANCA): Tests for
ANCA is performed in patients suspected to have
Wegeners granulomatosis or microscopic polyarteritis.
Microbiology
Throat swab culture for beta-hemolytic streptococci is
performed when rheumatic fever is suspected. Synovial
fluid for gram strain and culture is performed when
septic arthritis is suspected.
Radiology
These include radiographs of the involved joints and
other non-invasive modalities like CT, MRI and radionucleotide bone scan which have to be performed in
relevant situations.
Synovial Fluid Analysis
Analysis of the synovial fluid should be performed when
septic arthritis or crystal induced arthritis is suspected.
Juvenile Idiopathic Arthritis (JIA)

Juvenile Idiopathic Arthritis (JIA) is not a single disease.
The term Juvenile Idiopathic Arthritis encompasses all
forms of arthritis that begin before the age of 16 years,
persist for more than six weeks and are of unknown
cause. Juvenile Idiopathic Arthritis is the most common
pediatric rheumatic disease having arthritis as the
principle manifestation. JIA is one of the chronic diseases
in children leading to physical disability and blindness.
The etiopathogenesis of JIA includes immunogenetic
predisposition, environmental triggering factors,
abnormal immunoregulation and cytokine production.
The International League against Rheumatism (ILAR)
has published the following classification criteria for the
diagnosis of various subsets of JIA (Table 20.7.4) as per
the criteria laid down by ILAR seven disease categories
of JIA were recognized on the basis of features present
in the first 6 months of the disease.
Systemic Onset JIA
Approximately 10 percent of JIA patients belong to this
category. Both sexes are equally affected and the disease
starts at any age. Classical clinical presentation is high,
intermittent spiking fever, rash, lymphadenopathy,
1104
anemia, hepatosplenomegaly and arthritis. The rash of

systemic onset JIA is maculopapular, evanescent and
occurs during the periods of fever. Other extra-articular
manifestations are pleuritis, pericarditis, myocarditis and
hepatic dysfunction.
Laboratory investigations reveal neutophilic leukocytosis, anemia, elevated ESR, negative tests for
rheumatoid factor and ANA and raised serum ferritin
levels Arthralgia and myalgia are common during the
initial stages of the disease and majority of the patients
develop a florid polyarthritis during the first few months
of the disease (Figs 20.7.1 and 20.7.2 JIA arthritis of
hands). Occasionally systemic onset JIA patients develop
a threatening complication known as Macrophage
Activation Syndrome. The syndrome is characterized by
sudden onset of spiking fever, pancytopenia, disseminated intravascular coagulation, hepatic insufficiency,
normal ESR, raised triglyceride levels and increased
ferritin levels. Bone marrow examination will reveal
active phagocytosis of hemopoietic cells by macrophages.
The differential diagnosis of systemic onset JIA includes
bacterial and viral infections, leukemia, lymphoma,
retinoblastoma, systemic lupus erythematosus, Kawasaki
syndrome and inflammatory bowel disease. The
diagnosis of systemic onset JIA is one of exclusions since
there is no specific diagnostic test for the diagnosis.
Figure 20.7.1: Systemic onset JIA
Figure 20.7.2: Systemic onset JIA arthritis of hands
Oligoarthritis JIA
For JIA to be characterized as oligoarticular JIA at least
four or fewer joints should be involved in the first six
months of onset of the disease (Fig. 20.7.3). This is the
commonest subtype and is more common in girls than
boys. This subtype usually has an early onset and is seen
in children less than 6 years of age. The onset of arthritis
is usually insidious and predominantly the joints of the
lower extremities are involved especially the knees and
ankles. It is unusual for the hip joints to be involved at
the time of presentation though they may be involved
Figure 20.7.3: Oligoarthritis onset JIA
1105
later in the course of the disease. Uveitis is an extraarticular manifestation seen in around 20 to 40 percent
and may be silent and lead to blindness. Uveitis is more
commonly seen in girls and these patients are invariably
ANA positive. All oligoarticular JIA children should have
periodic complete ophthalmic assessment including slit
lamp examination to exclude uveitis. Usually the acute
phase reactants are often normal or marginally raised.
ANA is positive in nearly 70 percent of oligoarthritis JIA
and ANA positive patients are at risk for developing
uveitis. There are two categories in the oligoarthrits
subtype, viz., -persistent oligoarthritis and extended
oligoarthritis. In persistent oligoarthritis JIA the disease
is confined to four or fewer joints even after six months
of disease. In extended oligoarthritis JIA the arthritis
extends to involve more than four joint after six months
of the disease. Involvement of the upper limb joints and
elevated ESR are predictors of evolution of oligoarthritis
JIA to extended oligoarthritis phenotype.
Rheumatoid Factor (RF) Positive Polyarthritis JIA
Rheumatoid factor positive polyarthritis JIA is defined
as an arthritis that affects five or more joints during the
first 6 months of onset of the disease with positive tests
for IgM Rheumatoid factor. RF positive polyarthritis
onset JIA usually resembles adult rheumatoid arthritis
in its clinical presentation. The presentation is usually a
symmetrical polyarthritis affecting the larger joints like
the knees, wrists, elbows and ankles with subsequent
involvement of the smaller joints of the hands and feet
(Fig. 20.7.4). The smaller and larger joints of both upper
and lower limbs are involved. This subtype is usually
seen in adolescent girls. Rheumatoid nodules are seen
in nearly 30 percent of patients. Specific articular
complications are cervical spine involvement leading to
atlantoaxial subluxation and temporomandibular joint
involvement leading to micrognathia (Fig. 20.7.5).
Figure 20.7.4: Polyarthritis onset JIA
Rheumatoid Factor (RF) Negative Polyarthritis JIA

Rheumatoid factor negative polyarthritis JIA is defined
as an arthritis that affects five or more joints during the
first 6 months of the disease in the absence of IgM
RF.There is a heterogeneity in this subtype. The first set
is one which resembles oligoarticular JIA in that there is
early age of onset of disease, female predominance,
frequent positive ANA with increased risk of iridocyclitis.
Figure 20.7.5: Polyarthritis onset JIA Micrognathia
1106
The second set is characterized by overt synovitis

affecting the large and small joints, onset in school going
age, negative ANA with variable outcome. The third type
is known as Dry synovitis. In this subset there is
negligible joints swelling, but stiffness, flexion contractures with normal or marginal elevated ESR and C reactive protein levels.
Enthesitisrelated Arthritis
Enthesisrelated arthritis affects mainly male children.
This subtype usually manifests in children after the age
of six years and is characterized by the presence of
enthesitis and arthritis. The commonest sites of enthesitis
are the plantar fascia, tarsal area and the calcaneal
insertion of the achilles tendon the joints of the lower
extremities are commonly affected. Usually the knees,
ankles and even the hips are affected. In some patients
the disease progresses further to affect the sacroiliac and
spinal joints to produce the clinical picture of ankylosing
spondylitis. Most of these patients are positive for HLA
B-27.
Psoriatic Arthritis
The diagnosis of juvenile psoriatic arthritis by ILAR
criteria requires the simultaneous presence of arthritis
and a typical psoriatic rash (Fig. 20.7.6). If a typical
psoriasis rash is absent for a diagnosis of Psoriatic
arthritis the criteria required are the presence of arthritis
and any two of the following: Family history of psoriasis,
dactylitis and nail pitting . Dactylitis is swelling of one
or more fingers that extend beyond the joint margins
(Fig. 20.7.7). Children with Psoriatic arthritis have usually
Figure 20.7.7: Psoriatric arthritis with dactylitis
an oligoarthritis. They are frequently ANA positive and

are at risk for developing uveitis.
Undifferentiated Arthritis
Undifferentiated arthritis includes patients who do not
satisfy inclusion criteria for any criteria or who meet the
criteria for more than one.
Diagnosis of JIA
There is no one pathognomonic test to make a diagnosis
of JIA. The classification criteria (Table 20.7.4) aid in the
diagnosis of JIA and its subsequent classification into the
various onset subtypes (Table 20.7.4). The diagnosis is
also based on a meticulous physical examination that
confirms the presence of inflammatory arthritis. All
children with JIA should have a complete blood count
including ESR and peripheral smear performed. Children
with polyarticular JIA should have tests for rheumatoid
factor performed. Test for ANA should be performed in
oligoarthritis JIA since ANA positive children are at risk
of developing uveitis. The diagnosis of systemic onset
JIA is one of exclusions and detailed laboratory work up
for pyrexia of unknown origin should be performed
when one suspects systemic onset JIA.
Management of JIA
Figure 20.7.6: Psoriatic arthritis with skin lesion
The objectives of management of JIA is to control

inflammation and the disease process so that these
children retain maximum functional capacity and have
normal physical growth (Tables 20.7.5 and 20.7.6). Since
JIA is not one disease, treatment approach differs
between various subtypes.

TABLE 20.7.5: Management of JIA-objectives
Immediate
Control inflammation
Relieve pain and discomfort
Prevent deformities
Preserve function
Control the disease
Minimize side effects of the disease and
treatment
Promote normal growth and development
Minimize impact of chronic illness on family
Educate the child and family
Rehabilitation
Long-term
TABLE 20.7.6: Management of JIA
NSAIDs
DMARDs
Steriods
Rehabilitation
NSAIDs
NSAIDs are analgesics, antipyretics and anti-inflammatory. There is an individual variability in response
to NSAIDs. One should wait for at least for 4 weeks to
assess the therapeutic efficacy of an NSAID. Combination
of NSAIDs does not offer additive therapeutic effects. A
combination of NSAIDs should not be given to the
arthritic child. NSAIDs are contraindicated in renal
failure and in children on oral anticoagulants. An
analgesic like paracetamol can be combined with an
NSAID for additive therapeutic effect. NSAIDs cause
damage to the gastrointestinal mucosa on prolonged
usage. The arthritic child on prolonged NSAIDs should
be monitored for NSAID induced gastropathy. NSAIDs
approved by FDA, USA for use in children are ibuprofen,
aspirin, naproxen and tolmetin sodium (Table 20.7.7).
The COX-2 inhibitor NSAIDs are not being used in
children at present.
1107
Disease Modifying Anti-Rheumatic

Drugs (DMARDs) in JIA
The drugs commonly used in management of JIA are
methotrexate and sulfasalazine.
The indications for DMARDs in JIA are RF positive
polyarticular JIA; RF negative polyarticular JIA and
systemic onset JIA evolving into polyarticular form and
oligoiarticular JIA evolving into extended oligoiarticular
JIA. DMARDs have established the reputation of
decelerating the disease progression in JIA. One has to
wait for four to eight weeks for the therapeutic efficacy
of DMARDs.
Methotrexate has become the DMARD of choice in
the management of JIA. Patients on low dose methotrexate require periodic complete blood count, liver
function tests and serum creatinine to be performed.
(Table 20.7.8). Improvement of patients is seen within 6
weeks to 12 weeks of methotrexate therapy. The supplementation of folic acid could help to prevent the
occurrence of liver enzyme abnormalities with Methotrexate. When patients are not responsive to oral
methotrexate, one can change over to parenteral
methotrexate and wait for a response.
Sulfasalazine confers improvement to a significant
extent on patients with late onset oligoarticular JIA and
on patients with juvenile spondyloarthrits Patients on
sulfasalazine should have their blood counts monitored
frequently (Table 20.7.8).
TABLE 20.7.8: DMARDs in childrenDosage and side effects
Drug
Maintenance dose
Side effects
Methotrexate
10 -20 mg/m2/week
Stomatitis, nausea,
hepatotoxicity,
bone marrow
suppression,
alopecia
Sulfasalazine
50 mg/kg/day
Rash, bone marrow

suppression
TABLE 20.7.7: NSAIDs-drug dosage in children

Drug
Mg/kg/day
Maximum
mg/day
Frequency/
day
Steroids
Diclofenac
Tolmetin
Naproxen
Ibuprofen
Indomethacin
3 mg/day
25 mg/day
20 mg/day
40 mg/day
1 mg/day
1500
1600
750
2400
150
Thrice a day
Twice a day
Thrice a day
Twice a day
Systemic steroids are used in JIA only in certain

situations. Systemic steroids (prednisolone 0.1 to
1 mg/kg/day) are used in systemic onset JIA when the
systemic symptoms are not relieved with NSAIDs or
when they have life-threatening situations like
1108
myocarditis and serositis. Topical ocular steroids are

indicated in JRA children with uveitis. Systemic steroids
have to be used with caution in JIA since their long-term
usage results in adverse effects like retarded physical
growth and osteoporosis. Intra-articular steroid injection
is preferred therapeutically for use in one or two joints
that do not respond satisfactory to a conservative
program with conventional NSAIDs or as a short-term
aid to physical therapy. Intrarticular steroid injection
with triamcinolone hexacetonide (10-40 mg/joint or
1mg/kg/joint) is indicated in oligoarthritis JIA. Intraarticular steroids are rapidly effective and they break the
vicious circle of inflammation that leads to limb length
discrepancy and deformities. Although the effect of intraarticular steroids are not curative, their effect is long
lasting. Intra-articular injections can be given once in 3
months but the same joint should not be injected more
than three times in a year.
Rehabilitation
All children with arthritis should be referred to a
physiotherapist for an effective rehabilitation program.
The parents of children with arthritis should be educated
with respect to the nature of the disease and the need for
compliance with regular treatment. Nutritional impairment is common in children with JIA.The attending
pediatrician should take into consideration the calorific
needs with emphasis on intake of calcium and vitamin
D especially if the arthritic child is on systemic steroids.
Prognosis in JIA
Systemic onset JIA has a variable course. 50% have a
monocyclic or an intermittent course with remissions and
exacerbations with a good long term outlook. In the
remaining 50% the disease follows an unremitting course.
In this group the systemic features may resolve but they
experience a chronic disabling arthritis.
Oligoarthritis JIA generally has a favorable outcome.
The rate of remission in oligoarthritis JIA varies from
23% to 43% after 6-10 years of disease.
Polyarthritis JIA has a variable prognosis depending
on the presence or absence of rheumatoid factor. RF
positive JIA behaves like adult onset rheumatoid arthritis
resulting in progressive deforming arthritis. RF negative
polyarthritis has a variable outcome, which shows the

heterogeneity of the subtype.
The prognosis of psoriatic arthritis, as defined by the
ILRA criteria is not clearly established. In general
children with psoriatic arthritis have a poorer long term
outlook with more frequent involvement of smaller
joints.
Enthesitis-related arthritis has a variable prognosis
with some patients progressing to develop involvement
of the axial skeletal joints.
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Systemic lupus erythematosus is a protype autoimmune
disease with a tendency to involve many organs. The
disease is characterized by the presence of many
pathogenic autoantibodies, formation of immune
complexes with subsequent multiple target organ
damage. The etiopathogenesis of SLE involves a complex
interaction between genetic, hormonal and environmental factors leading to immune dysregulation,
autoantibody formation and immunoinflammation
SLE is unusual in children below the age of 5 years. The
female to male ratio is approximately 8:1. The clinical
presentation of SLE includes constitutional symptoms
like fever, malaise, rash, photosensitivity, oral ulcers,
nonerosive inflammatory polyarthritis and malar rash
(Fig. 20.7.8). This disease has the tendency to involve
many organ systems which contributes to the morbidity
and mortality associated with the disease. The rashes of
SLE are photosensitive. The oral ulcers usually occur on
the palatal and nasal mucosa. The arthritis of SLE is
usually polyarticular and non-deforming. Hepatosplenomegaly and generalized lymphadenopathy are
often seen in lupus patients. Cardiac involvement
presents as pericardial effusion, myocarditis, conduction
disturbances or verrucous endocarditis. Nearly 50
percent of SLE patients have renal involvement which
manifests as fluid retention, microscopic hematuria,
proteinuria, systemic hypertension and abnormal renal
biochemistry. Involvement of the central nervous system
in SLE presents a neuropsychiatric disturbances or
organic brain syndrome. Serositis in SLE presents as
either pleural effusion or pericardial effusion or ascites.
1109
renal biochemistry or systemic hypertension. Laboratory

assessment of disease activity includes serial estimation
of C3, C4 and anti-dsDNA antibody titers. Criteria for
the diagnosis of SLE requires the presence of 4 out of 11
criteria present either serially or simultaneously
(Table 20.7.9).
Management
Figure 20.7.8: SLE Malar rash
SLE patients having positive tests for antiphospholipid

antibodies may experience recurrent arterial or venous
thrombosis due to a hypercoagulable state. Occasionally,
SLE patients may present initially as autoimmune
hemolytic anemia or immune thrombocytopenia. The full
blown picture of SLE with multi-system involvement
may not be seen at the time of initial presentation. The
course of the SLE is unpredictable and is characterized
by remissions and exacerbations.
Diagnosis
Hematological abnormalities are leukopenia, thrombocytopenia and anemia. All patients with SLE should be
assessed for renal involvement. The diagnostic immunological tests are positive ANA and positive tests for antids DNA, anti-Sm, anti-Ro and anti-La antibodies. Anti
dsDNA antibodies and anti-Sm antibodies are positive
specifically in SLE patients. Lupus patients with positive
tests for anti-dsDNA are at risk for developing renal
involvement. Lupus patients presenting with either
arterial or venous thrombosis should be screened for the
presence of antiphospholipid antibodies. Renal biopsy
is performed in SLE patients with either persistent
proteinuria and active urinary sediment or abnormal
The management of SLE depends upon the severity of

the disease and the presence of target organ involvement.
Arthritis is managed with analgesics, NSAIDs and
antimalarials (hydroxycholoroquine 5 mg/kg/day).
Local corticosteriod preparations, sun screeners and
antimalarials (hydroxychloroquine 5 mg/kg/day) are
administered to patients with dermatological problems.
SLE patients are advised with dermatological problems.
SLE patients are advised to avoid direct exposure to
sunlight and wear protective clothing. Serositis is
managed with NSAIDs and/or low dosage steroids. SLE
children with life-threatening organ involvement like
hemolytic anemia, thrombocytopenia, nephritis and
central nervous system disease are treated with high dose
steroids like prednisolone in a dosage of 1 to 2 mg/kg/
day, which is subsequently, tapered depending upon the
clinical response and laboratory indices of disease
activity. Severely ill patients require intravenous pulse
methylprednisolone (30 mg/kg/day) given as an
infusion once a day for three consecutive days. Children
with proliferative lupus nephritis are also administered
intravenous pulse cyclophosphamide (500 to 750
mg/m2 body surface) every 4 weeks for 6 months to
induce remission. The induction phase for 6 months with
cyclophosphamide is followed with a maintenance phase
of either mycophenolate or azathioprine. Intravenous
pulse cyclophosphamide is indicated in lupus patients
with profilerative glomerulonephritis and this treatment
has been found to induce disease remission and preserve
renal function. Other therapeutic modalities include
administration of intravenous immunoglobulin, cyclosprorine, mycophenolate mofetil and plasmapheresis.
Serological tests to assess disease activity are serial
estimation of C3, C4 and anti ds-DNA titer. SLE children
either on steroids or cytoxic drugs are immunocompromised and they should be promptly treated for
infections. SLE children on prolonged steroid therapy
have the risk of developing growth retardation,
osteoporosis and avascular necrosis. SLE children on
1110

TABLE 20.7.9: 1997 criteria for the classification of SLE (American College of Rheumatology)
Criterion
Definition
Malar rash
Fixed erythema flat or raised, over the malar eminences, tending to spare the nasolabial folds
Discoid rash
Erythematous raised patches with adherent keratotic scaling and follicular plugging atrophic scarring
may occur in older lesions
Photosensitivity
Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation
Oral ulcers
Oral or nasopharyngeal ulceration, usually painless observed by the physician
Arthritis
Nonerosive arthritis involving two or more peripheral joints, characterized by tenderness, swelling or
effusion
Serositis
a. Pleuritis Convincing history of pleuritic pain or rub heard by a physician or evidence of pleural
effusion OR
b. Pericarditis-documented by ECG or rub or evidence of pericardial effusion
Renal disorder
a. Persistent proteinuria, greater than 0.5 grams per day or greater than 3+ if quantification not
performed OR
b. Cellular castsmay be red cell, hemoglobin, granular, tubular or mixed
Neurological disorder
a. Seizuresin the absence of offending drugs or known metabolic derangements; e.g. uremia,
ketoacidosis, or electrolyte imbalance OR
b. Psychosisin the absence of offending drugs or known metabolic derangements; e.g. uremia,
ketoacidosis, or electrolyte imbalance
Hematologic disorder
a.
b.
c.
d.
Immunologic disorder
a. Anti-DNA; antibody to native DNA in abnormal titer OR

b. Anti-Sm: Presence of antibody to Sm nuclear antigen OR
c. Positive finding of antiphospholipid antibody based on:
1. An abnormal serum level of IgG or IgM anti-cardiolipin antibodies
2. A positive test for lupus anticoagulant using a standard method, or
3. A false positive serologic test for syphills known to be positive for at least 6 months and
confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody
absorption test.
Antinuclear antibody
An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at

any point in time and in the absence of drugs known to be associated with drug induced lupus
syndrome.
Hemolytic anemia with reticulocytosis OR

Leukopenialess than 4000/mm3 total on two or more occasions OR
Lymphopenialess than 1500 mm3 total on two or more occasions OR
Thrombocytopenialess than 100,000 mm3 in the absence of offending drugs
prolonged steroid therapy should have supplemental

calcium intake and vitamin D intake and adequate
physical exercise to prevent osteoporosis. Significant
mortality is encountered in SLE patients and the common
causes of death are renal involvement, CNS disease,
cardiac involvement and infection. The outlook of lupus
patients is encouraging. The 5-year survival rate is greater
than 90 percent thanks to the progress in early diagnosis
and aggressive management of SLE patients.
JUVENILE DERMATOMYOSITIS (JDM)
Juvenile dermatomyositis is a systemic rheumatic disease
characterized by nonsuppurative inflammation of
striated muscle, skin and gastrointestinal tract. The basic

pathology is an immune complex mediated vasculitis.
JDM is the most common disease of the pediatric
inflammatory myopathies.
The classical clinical presentation of JDM is constitutional
symptoms, rash and proximal muscle weakness. The
symptoms of JDM at the time of diagnosis are usually
rash, muscular pain and weakness, fever, dysphagia,
difficulty in phonation, arthritis and abdominal pain. The
characteristic rashes of JDM are:

a. Scaly erythematous eruptions over the metacarpal
phalangeal or interphalangeal joints (Fig. 20.7.9).
b. Periorbital purplish discoloration (heliotropic rash)
c. Erythematous scaly rashes over the face and neck (V
sign), upper back and arms (shawl sign), and
extensors tendons (linear extensor erythema).
These children present with proximal limb girdle
muscle weakness and their symptoms aredifficulty in
walking, climbing stairs and inability to dress. Neurological examination confirms the presence of proximal
muscle weakness.
Figure 20.7.9: JDMGottrons Papules
Diagnosis
Laboratory investigations confirm the diagnosis.
Biochemical investigations reveal elevated muscle
enzymes viz, creatine kinase, aldolase, aspartate
transaminase and alanine transaminase. Immunological
abnormalities are positive ANA and positive tests for
myositis-associated specific autoantibodies like anti-Jo1
antibodies. Electromyography reveals a myopathic
pattern. Muscle biopsy reveals the characteristic features
of an inflammatory muscle disease. The differential
diagnosis includes SLE, scleroderma, muscular dystrophies and viral myositis.
Management
Skin rash of JDM is managed with topical sunscreens,
topical steroids and oral hydroxychloroquin (5 mg/kg/
day). Steroids have been the traditional mainstay for
therapy in JDM. Muscle disease is managed with oral
1111
prednisolone to 1 to 2 mg/kg/day which is subsequently

tapered depending upon the clinical response and levels
of the muscle enzymes. Intravenous methyl-prednisolone (30 mg/kg/day) given as an infusion once a day
for 3 consecutive days indicated in JDM children when
they have severe disease at onset. Toxicity with chronic
use of corticoisteroid therapy is high and concomitant
therapy with Methotrexate has been found to result in
more rapid withdrawl of steroids in JDM patients.
Methotrexate (15 mg/m 2 body surface/week) in
conjunction with folic acid 1 mg/day is indicated in JDM
children along with steroids. JDM patients refractory to
steroid and methotrexate are administered azathioprine,
cyclophosphamide, cylcoporine, intravenous immunoglobulin, plasmapheresis or extracorporeal photochemotherapy. General supportive care includes
nutrition with special emphasis on protein, calcium and
vitamin D supplementation. Physical rehabilitation is
most important in JDM children. The objectives of the
physiotherapy program are to prevent contractures,
maintain muscle tone and power and maximize range
of joint motion. The outcome for JDM patients has
improved and at present the long-term survival rate
approaches 90 percent and functional outcome has
significantly improved. Important complications in JDM
are calcinosis and vasculitis. The vasculitis affecting the
gastrointestinal tract may lead to gastrointestinal
perforation and bleeding with significant mortality and
morbidity.
VASCULITIS SYNDROMES
Inflammatory vasculitis is a prominent component of
systemic rheumatic disease. The classification of
vasculitis is based on the type of vessel involved, viz.,
large vessel, medium vessel and small vessel involvement. The clinical manifestations depend upon the type
of the vessel involved. The vasculitic diseases are giant
cell arteritis, Takayasu arteritis, polyarteritis nodosa,
microscopic polyarteritis, Wegeners granulomatosis,
and hypersensitivity vasculitis. Henoch-Schonlein
purpura and Kawasaki disease are the commonly
encountered vasculitis in children (Fig. 20.7.10).
CONCLUSION
Children with rheumatic diseases are often encountered
early. Recognition, correct diagnosis and appropriate
1112
Figure 20.7.10: Vasculitis rash on palms
management will reduce significantly the morbidity and

mortality in these children.
BIBLIOGRAPHY
1. Agarwal A, Mishra R. Juvenile Arthritis in India: Is it
different from that seen in western countries? Rheumatol
Int 1994; 14; 53-56.
2. Cassidy JT, Pety RE, Laxer RM, et al. Textbook of Pediatric
Rheumatology (5th Ed). Philadelphia: Elsevier 2005.
3. Cassidy JT. Rheumatic disease of childhood. In: Kelley
WN, Harris ED, Ruddy S, Sledge CB (Eds): Textbook of
Rheumatology (7th Ed). Philadelphia: Elseiver Saunders
Company, 2005.
4. Laxer RM.Pediatric Rheumatology. Rheumatic Disease

Clinics of North America 2007;33(3):365-689.
5. Pachman LM. Juvenile Dermatomyositis: Immunogenetics, pathophysiology and disease expression.
Rheumatic Disease. Clinics of North America 2002;
28(3):579-602.
6. Petry RE, Southwood TR, Manners P, et al. International
League of Associations for Rheumatology Classification
of Juvenile Idiopathic Arthritis: Second revision,
Edomonton, 2001. J Rheumatol 2004;31:390-92.
7. Ravelli A, Martini A. Juvenile Idiopathic Arthritis. The
Lancet. 2007;369:767-78.
8. Ramanan AV, Whitworth P, Baildam EM. Use of
methotrexate in juvenile idiopathic arthritis. Arch Dis
Child 2003;88:197-200.
9. Thomas J, Lehman A. SLE in Childhood and adolescence,
In: Daniel J Wallace, Bevra Hannahs Hahn (Eds). Dubois
Lupus Erythematosus (6th Edn). Philadelphia:
Lippincott: Williams and Wilkins 2002;863-84.
10. Thomas J, Lehman A. Paediatric rheumatic diseases
connective tissue disease. In: Klippel JH (Ed). Primer on
the Rheumatic Disease (12th Ed). Atlanta: Arthritis
Foundation, 2001.
11. Wagner-Weiner L, Pediatric Rheumatology for the Adult
Rheumatologist. Journal of Clinical Rheumatology
2008;14(2):109-19.
12. Koopmam WJ, Boulware LW, Heudebert GR. Clinical
Primer of Rheumatology (1st Edn). Philadelphia;
Lippincott Williams and Wilkins, 2003.
20.8 Antiphospholipid Syndrome

Surjit Singh
THE ANTIPHOSPHOLIPID ANTIBODY (APLA)
SYNDROME
The APLA syndrome can present as a rheumatological
emergency and can have devastating consequences. It is
usually seen in association with systemic lupus
erythematosus but can be an accompaniment of other
rheumatological disorders as well. It presents as a
hypercoagulable state and can manifest with arterial and
venous thrombosis, livedo reticularis and thrombocytopenia. The disorder can be fatal if not recognized
early and managed appropriately. The syndrome can also
arise de novo when it is known as primary APLA
syndrome. Children can occasionally present with the
catastrophic APLA syndrome which is characterized by
widespread thrombosis and multiorgan failure. Laboratory investigations usually show abnormalities in the

coagulation profile with a normal prothrombin time (PT)
and a prolonged partial thromboplastin time with kaolin
(PTTK). Thrombocytopenia is not uncommon. The
diagnosis can be confirmed by the detection of anticardiolipin antibodies (IgM and IgG) and the lupus
anticoagulant test. In our experience almost 25-30% of
children with systemic lupus erythematosus on longterm follow-up have detectable anticardiolipin antibodies and/or the lupus anticoagulant test. Treatment
is with long term oral anticoagulation.
1113
BIBLIOGRAPHY
1.
Ahluwalia J, Singh S, Garewal G. Antiphospholipid

antibodies in children with systemic lupus erythematosus: a prospective study from Northern India.
Rheumatology International 2005;25:530-35.
2. Hughes GRV, Harris EN, Gharavi AE. The anticardiolipin syndrome. J Rheumatol 1986;13:486.
3. Khetarpal R, Goraya JS, Singh M, Singh S, Kumar L.
Pulmonary hypertension as presenting feature of
childhood SLE: association with lupus anticoagulant.
Scandinavian Journal of Rheumatology 1998;26:325-26.
20.9 Approach to Vasculitis in Children

Surjit Singh
Vasculitic disorders are not uncommon in children but
are frequently missed in clinical practice. These should
be thought of whenever a child presents with a
multisystemic disorder. These conditions can be
classified according to the size of the vessel involved:
1. Large vessel vasculitis (e.g. Takayasu arteritis)
2. Medium vessel vasculitis (e.g. Kawasaki disease,
polyarteritis nodosa)
3. Small vessel vasculitis (e.g. Henoch-Schonlein
purpura, Wegeners granulomatosis).
Of these, Henoch-Schonlein Purpura and Kawasaki
diseases are, by far, the commonest conditions seen in
pediatric practice. The classification criteria for the
common types of childhood vasculitis are given in Tables
20.9.1 to 20.9.3.
Takayasu Arteritis
This usually involves the aorta and its major branches.
Four major patterns of involvement are recognized:
Type-1 aortic arch; Type-IIdescending aorta; Type-III
aortic arch and descending aorta; Type IV-aorta and
pulmonary artery involvement. The classification criteria
for childhood Takayasu arteries are given in Table 20.9.1.
In our country many children with Takayasu arteritis
may have a clinical association with tuberculosis and are
frequently Mantoux positive. Takayasu arteritis must be
excluded in children with renovascular hypertension.
Diagnosis can be confirmed by angiography. Treatment
is based on long term immunosuppression with
prednisolone and oral weekly methotrexate. With
TABLE 20.9.1: Classification criteria for

childhood Takayasu arteritis
Angiographic abnormalities (conventional, CT or MR) of the
aorta or its main branches
plus
At least one of the following four features:
1. Decreased peripheral artery pulse (s) and/or claudication of
extremities.
2. Blood pressure difference > 10 mmHg
3. Bruits over aorta and/or its major branches
4. Hypertension (based on childhood normative data)
angioplasty and appropriate stent placement, the longterm prognosis is now reasonable and 5-year survival
rates above 90 percent have been reported from several
centres. Hypertension has to be managed carefully.
Kawasaki Disease (KD)
Refer Page 1115.
Polyarteritis Nodosa (PAN)
PAN is distinctly uncommon in children and can be a
very difficult condition to diagnose in pediatric practice
as the clinical manifestations can be extremely variable.
Usual clinical features include fever, rash (typically
livedo reticularis), hypertension, abdominal pain, joint
pains and myalgia. Neurological involvement can take
the form of seizures, encephalopathy and peripheral
neuropathy. The latter can be very difficult to evaluate
1114
TABLE 20.9.2: Classification criteria for childhood

polyarteritis nodosa
A childhood illness characterized by the presence of either a
biopsy showing small and mid-size artery necrotizing vasculitis
or angiographic abnormalities# (aneurysms or occlusions)
plus
At least two of the following:
1. Skin involvement
2. Myalgia or muscle tenderness
3. Systemic hypertension (based on childhood normative data)
4. Abnormal urine analysis and/or impaired renal function
5. Mononeuropathy or polyneuropathy
6. Testicular pain or tenderness
7. Signs or symptoms suggesting vasculitis of any other major
organ systems (gastrointestinal, cardiac, pulmonary or
central nervous system)
#Should
include conventional angiography if magnetic resonance

angiography is negative.
in young children. Clinical diagnosis is facilitated by

angiography when aneurysms are demonstrable in the
renal arteries or celiac axis. On histopathology there is
fibrinoid necrosis in medium sized arteries typically with
segmental involvement. The diagnostic criteria for
childhood PAN have been recently revised and are given
in Table 20.9.2. Treatment consists of long term
immunosuppression with prednisolone and cyclophosphamide.
TABLE 20.9.3: Classification criteria for childhood

Wegeners granulomatosis
Three of the following six features should be present:
1. Abnormal urinalysis
2. Granulomatous inflammation on biopsy
3. Nasal sinus inflammation
4. Subglottic, tracheal or endobronchial stenosis
5. Abnormal chest X-ray or CT scan
6. Positive C-ANCA staining
Behcets Disease
Behcets disease is an unusual vasculitic disorder
characterized by the following clinical manifestations:
Major features: Aphthous stomatitis, genital ulceration,
cutaneous manifestations and ocular disease.
Minor features: Gastrointestinal disease, thrombophlebitis,
arthritis, family history and neurological involvement.
The disease is characterized by multiple relapses.
Major morbidity is because of the ocular and neurological
manifestations. The pathergy test (i.e., cutaneous pustular
reaction following needle pricks) is virtually pathognomonic in a clinical setting of the disease. HLA B5 and
B51 haplotypes have been associated with this syndrome.
Drug therapy involves use of colchicine and thalidomide.
BIBLIOGRAPHY
Henoch-Schonlein Purpura
Refer Page 733.
Wegeners Granulomatosis (WG)
WG is an uncommon disorder in pediatric practice in
which there is involvement of the respiratory tract and
kidneys. The condition usually has an insidious onset
and constitutional symptoms (for e.g. fever/malaise) are
quite common. Laboratory diagnosis is based on
detection of anti-neutrophil cytoplasmic antibodies
(ANCAs), especially C-ANCA, which are virtually
pathognomonic of WG. The diagnostic criteria for
childhood WG are given in Table 20.9.3. With steroids
and cyclophosphamide, the long-term outlook is
excellent.
1. Cassidy JT, Petty RE. Textbook of Pediatric Rheumatology, 5th Edn. Elsevier Saunders, Philadelphia, 2005.
2. Jain S, Sharma N, Singh S, Bali HK, Kumar L, Sharma
BK. Takayasu arteritis in children and young Indians.
International Journal of Cardiology 2000;75(S):153-57.
3. Kakkar N, Vasishta RK, Banerjee AK, Singh S, Kumar L.
Pulmonary capillary hemangiomatosis as a cause of
pulmonary hypertension in Takayasus Aortoarteritis.
Respiration 1997;64:381-83.
4. Kushner HI, Macnee R, Burns JC. Impressions of
Kawasaki Syndrome in India. Indian Pediatrics
2006;43:939-42.
5. Ozen S, Ruperto N, Dillon MJ, Bagga A, Kamorz K, Davin
JC, et al. EULAR/PreS endorsed consensus criteria for
the classification of childhood vasculitis. Annals of
Rheumatic Diseases 2006;65:936-41.
6. Singh S, Bali HK, Salaria M, Lal S, Pandav SS, Kumar L.
Takayasus Arteritis in young childrena potentially
treatable conditions. Indian Pediatrics 1999;36:291-96.

7. Singh S, Bansal A, Gupta A, Kumar RM, Mittal BR.
Kawasaki diseasea decade of experience from North
India. International Heart Journal 2005;46:679-89.
8. Singh S, Das R. Clinical approach to vasculitis in children.
Indian Journal of Pediatrics 2002;69:27-34.
9. Singh S, Dayal D, Minz RW, Joshi K, Datta U, Kumar L.
Severe Henoch-Schonlein nephritis: Treatment with
azathioprin and steroids. Rheumatology International
2002;22:133-37.
1115
10. Singh S, Gupta MK, Bansal A, Kumar RM, Mittal BR. A

comparison of the clinical profile of Kawasaki disease in
children from Northern India above and below 5 years
of age. Clinical and Experimental Rheumatology
2007;25:654-57.
11. Sood M, Singh S, Khandelwal N, Kumar L. Bilateral
sudden loss of vision: An unusual presentation of
childhood polyarteritis nodosa. APLAR Journal of
Rheumatology 2001;4:187-89.
20.10 Kawasaki Disease

Noel Narayanan
In 1967, Tomisaku Kawasaki described in fifty Japanese
children a distinctive illness characterized by fever,
lymphadenopathy and mucocutaneous inflammation
which he called acute febrile mucocutaneous lymph
node syndrome. This syndrome, now popularly known
as Kawasaki Disease (KD), has surpassed acute
rheumatic fever as the leading cause of acquired heart
disease among children. The etiology remains obscure,
though several compelling evidences support the role of
both infection and immunologic dysfunction in genetically predisposed children. Significant advances are
made in identifying an infectious agent as well as a new
genetic polymorphism that determines a childs risk of
getting Kawasaki disease.
The basic pathology is a necrotizing inflammatory
vasculitis with a striking predilection for the coronary
arteries. All three layers of blood vessels are involved
with destruction of the internal elastic lamina causing
weakness and aneurysm formation, and intimal
proliferation leading to stenosis. The disease is seen
worldwide, across all races, and in recent years the
incidence in India has increased, partly due to heightened
awareness among doctors and the public.
Clinical Features
KD affects predominantly children below 5 years of age
and boys are affected more frequently than girls. The
diagnosis is essentially clinical and is based on presence
of fever of five or more days duration, accompanied by
four of the five principal clinical criteria given in Table
20.10.1; Figure 20.10.3. The fever is usually high,
persistent and does not respond well to antipyretics.
TABLE 20.10.1: Diagnostic criteria

1. Fever lasting 5 days or more
2. Presence of at least 4 of the following 5 principal criteria:
a. Bilateral non-purulent conjunctivitis
b. Redness of the mucosa of oropharynx, strawberry
tongue and dry fissured lips.
c. Changes in extremities, such as edema and erythema
of hands and feet and later periungual desquamation
which may also involve palms and soles.
d. Polymorphous non-vesicular rash.
e. Cervical lymphadenopathy of at least 1.5 cm in size,
usually unilateral.
3. Illness not explained by another known disease.
Many cases are self limiting with acute symptoms lasting

an average of 12 days. Untreated, in some children the
disease can run a protracted course and can cause severe
cardiovascular sequelae. Patients who do not fulfill the
essential four clinical criteria are referred to as incomplete
KD. This is more common in young infants, often difficult
to diagnose and carries a greater risk for coronary
vasculitis. An algorithm showing approach to diagnosis
of incomplete KD is shown in Table 20.10.2. Term atypical
KD is sometimes used for unusual presentation of KD.
Three distinct phases of the disease occur. Acute
phase lasts up to 2 weeks, when most severe clinical
manifestations including fever are present. The sub-acute
phase begins with resolution of fever and goes on up to
4 weeks, while thrombocytosis and the classical
periungual desquamation are evident (Fig. 20.10.1). The
convalescent phase lasts up to 8 weeks. All symptoms
may not develop simultaneously and therefore these
1116

TABLE 20.10.2: Approach to incomplete KD (Modified from Newburger JW et al.
Pediatrics 2004; 114: 1708-1733)
Figure 20.10.2: Irritability, oral and eye changes

(Courtesy: Dr A Santhosh Kumar)
Figure 20.10.1: Characteristic desquamation of hands
patients should be assessed repeatedly. Cardiac

involvement occurs mostly during the acute and sub
acute phase and new lesions beyond 8 weeks are unlikely.
A pancarditis may be evident and coronary arteries are

involved in 20 to 25 percent of untreated children leading
to aneurysm formation (Fig. 20.10.2). Giant aneurysms
can occur rarely, with a vessel diameter greater than 8mm, and these carry a grave risk for thrombosis, rupture
or myocardial infarction. Children who develop coronary
1117
TABLE 20.10.3: Differential diagnosis of KD

Measles
Scarlet fever
Drug reactions
Stevens-Johnson syndrome
Other febrile viral exanthemas
Toxic shock syndrome
Staphylococcal scalded skin- syndrome
Bacteremia and Sepsis
Juvenile rheumatoid arthritis
Leptospirosis
artery abnormalities will require long term follow up.

There is no convincing evidence of any long term
cardiovascular sequelae for those children who do not
develop coronary artery disease within eight weeks of
onset.
Involvement of other arteries occurs infrequently.
Less common findings include extreme irritability,
arthritis, diarrhea, vomiting, aseptic meningitis, hydrops
of gallbladder and erythema and induration at BCG scar.
Perineal accentuation of the rash with desquamation is
frequently seen. About two percent cases may recur.
There are no confirmatory laboratory tests and the
clinician must carefully exclude other diseases that mimic
KD (Table 20.10.3).
Laboratory Tests
In the acute phase a normocytic normochromic anemia
and polymorphonuclear leukocytosis are frequently seen.
Thrombocytosis is evident after the first week of illness
and may be an outstanding feature. Acute-phase
reactants, ESR and C-reactive protein are typically
elevated to high levels. It may take six to eight weeks for
these values to return to normal. Proteinuria and sterile
pyuria can occur. Mild increase in transaminases may
be seen although jaundice is rare. ASO titre, antinuclear
antibodies and tests for various infections are negative.
Chest X-ray is usually normal. Rarely ECG abnormalities
in the form of decreased voltage, ST-T changes and
conduction defects are seen.
Echocardiography will detect coronary artery
involvement in the form of increased echogenicity,
coronary ectasia, aneurysm formation and other cardiac
lesions. This should be done preferably by a pediatric
cardiologist on admission, again during sub-acute phase
and also at the end of 6-8 weeks. A vessel diameter >
Figure 20.10.3: Dry fissured lips and strawberry tongue

(Courtesy: Dr A Santhosh Kumar)
3mm is abnormal for a child below 5 years. Other

abnormalities like valvular leak, pericardial effusion and
left ventricular dysfunction seen in the initial stages will
usually subside without any sequel. In chronic phase,
selected group of children with coronary artery disease
may require specialized investigations like stress test,
perfusion scan, cardiac catheterization, CT or MRI
imaging and coronary angiography.
Treatment
The child has to stay at home from school or day care
until all clinical signs disappear and he or she feels strong
enough to return. Intravenous Immunoglobulin (IVIg)
along with aspirin is the standard treatment for KD.
These should be administered as soon as diagnosis is
made, preferably within 10 days of onset of illness.
Ideally, a single dose of IVIg 2 g/kg is administered over
10 to 12 hours. This will result in rapid defervescence
and resolution of clinical signs in 90% of cases and is a
supportive evidence for the diagnosis of KD. However
ESR may take longer time to settle. Therapy with IVIg
may be repeated in those children, who do not show
adequate response to initial treatment.
Aspirin is given in a dose of 80 to 100 mg/kg daily in
four divided doses during the acute phase and then
continued in a smaller anti-thrombotic dose of 3 to
5 mg/kg daily. At the end of eight weeks aspirin is
discontinued, if cardiac evaluation does not indicate any
coronary artery involvement. Otherwise, aspirin should
be continued until full regression of coronary arteries
occurs, occasionally life-long. Addition of clopidogrel or
1118
rarely warfarin should be considered for children with

large multiple aneurysms. Abciximab, a glycoprotein
inhibitor may be tried in patients with giant aneurysms
to reduce the risk of developing thrombosis. Consideration should also be given for full treatment of
children with incomplete KD and those presenting
beyond 10 days, if coronary involvement occurs or fever
persists along with elevated acute phase reactants.
In IVIg resistant cases, methyl prednisolone 30
mg/kg/day IV for 1-3 days has been shown to alleviate
symptoms and signs, but not coronary artery disease.
Long term follow up of patients with abnormal coronary
arteries is required with echocardiography, lipid profile
and cardiac catheterization. Selected patients with severe
coronary artery stenosis may need coronary angioplasty,
stenting or bypass surgery. Cardiac transplantation has
been done for a few cases.
myocardial infarction at a relatively young age. There

are some reports indicating a tendency for premature
atherogenesis in coronary arteries affected by KD.8 These
children should be monitored periodically for risk factors
for atherosclerosis like hypertension, hyperlipidemia and
counseled on avoidance of smoking and obesity.
BIBLIOGRAPHY
1.
2.
3.
4.
Prognosis
Kawasaki disease is usually a self limiting disease,
although without treatment about 25 per cent children
can develop serious cardiac disease. With early
recognition and adequate treatment, full recovery can
be expected in majority of cases and the risk of coronary
artery disease can be significantly reduced to less than
5%. Similarly, the overall mortality can be reduced from
2% to less than 0.3 percent. Worst prognosis is in children
with the so-called giant aneurysms. Approximately one
half of aneurysms will regress within 5 to 18 months.
Remainder may progress to stenosis, occlusion and
5.
6.
7.
8.
Cheung YF, Yung TC, Tam SC, Ho MH, Chau AK. Novel
and traditional cardiovascular risk factors in children
after Kawasaki disease: Implications for premature
atherosclerosis. J Am Coll Cardiol 2004;43:120-24.
Gupta-Malhotra M, Rao PS.Current perspectives on
Kawasaki disease. Indian J Pediatr 2005;72:621-29.
Ishii M, Ueno T, Akagi T, Baba K, Harada K, Hamaoka
K, Kato H, Tsuda E, et al. Guidelines for catheter
intervention in coronary artery lesion in Kawasaki
disease. Pediatr Int 2001;43:558-62.
Muta H, Ishii M, Egami K, Furui J, Sugahara Y, Akagi T
et al. Early intravenous gamma-globulin treatment for
Kawasaki disease: The nationwide surveys in Japan. J
Pediatr 2004;144:496-99.
Narayanan SN, Ahamed MZ, Safia M. Cardiovascular
involvement in Kawasaki Disease. Indian Pediatr 2005;
42:918-22.
Newburger JW, Takahashi M, Gerber MA, Gewitz MH,
Tani LY, Burns JC, Shulman ST, Bolger AF, et al.
Diagnosis, treatment and long term management of
Kawasaki disease. Pediatrics 2004;114:1708-33.
Onouchi Y, Gunji T, Burns JC, Shimizu C, Newburger
JW, Yashiro M. ITPKC functional polymorphism
associated with Kawsaki disease susceptibility and
formation of coronary artery aneurysm. Nature Genetics
2007;40:35-42.
Rowley AH. Incomplete (atypical) Kawasaki disease.
Pediatr Infect Dis J 2003;53:153-57.
20.11 Intravenous Immunoglobulin

Surjit Singh
Intravenous immunoglobulin (IVIg) is a powerful
therapeutic tool and can be life-saving therapy for several
clinical conditions. It is prepared by fractionation of
pooled plasma obtained from remunerated healthy
donors and consists of normal intact polyspecific IgG.
These donors are subjected to strict screening procedures
and the quality of the end product essentially depends
on the quality of this screening. Each batch of IVIg
represents a donor pool of 4000-10000 individuals. Such
large donor pools serve to ensure that the antibody

reperoire is complete and representative of the population at large. IVIg preparations presently being
marketed contain 90-95% monomeric IgG with only
small amounts of IgA and IgM. The efficacy of IVIg
depends essentially on the IgG subclass distribution of
the given preparation. However, some IVIg preparations
do not contain the IgG3 subclass in adequate quantities.

IVIg is the preferred treatment for several childhood
conditions like Kawasaki disease, autoimmune demyelinating polyradiculoneuropathy (AIDP), and idiopathic
thrombocytopenic purpura (ITP). The recommended
dose is 2 g/kg given as a single infusion or 1 g/kg given
over 2 consecutive days. For ITP, however, doses much
lower than the aforementioned (e.g. 0.5-0.8 g/kg) have
also been found to be equally effective.
IVIg is also used as physiological replacement therapy
in children with hypogammaglobulinemia, where the
therapy has to continue life-long. The recommended dose
is 0.4-0.6 g/kg every 3-4 weeks.
IVIg has also been used in children with autoimmune
haematological disorders (e.g. neutropenia, thrombocytopenia), severe myasthenia gravis, and patients with
life-threatening lupus.
1119
IVIg should be administered under careful supervision as there is a real risk of anaphylactic as well as
anaphylactoid reactions. The infusion must be started
very slowly and the child monitored for any side-effects.
BIBLIOGRAPHY
1. Burnouf T, Radosevich M. Reducing the risk of infection
from plasma products: specific preventative strategies.
Blood Rev 2000;14:94-110.
2. Ochs HD, Smith CIE, Puck JM. Primary Immunodeficiency Diseases: A molecular and genetic approach.
Oxford University Press, London, 1999.
3. Parslow TG, Sittes DP, Terr AI, Imboden JB. Medical
Immunology 10th Edn. New York: Lange Medical
Books/McGraw-Hill Medical Publishing Division, 2001.
4. Singh S, Bansal A. Transient hypogammaglobulinemia
of infancy: twelve years experience from Northern India.
Ped Asthma All Imm 2005;18:77-81.
21.1 Basics of Pediatric Therapeutics: Sandeep B Bavdekar, S Ramesh ............................................................................................ 1122

21.2 Adverse Drug Reactions, Drug Interactions and Therapeutic Drug Monitoring: Archana Kher, Milind S Tullu .................... 1126
21.3 Rational Drug Therapy in Children: Arun Phatak ........................................................................................................................... 1130
1122
21.1 Basics of Pediatric Therapeutics

Sandeep B Bavdekar, S Ramesh
The unspoken assumption behind most medical
behaviors is that every illness should be treated. Although
this principle of therapeutic enthusiasm is clearly
appropriate in severe and life-threatening illnesses, it does
not apply to all clinical situations. Infants, children and
adolescents have intrinsic recuperative capacities. Hence,
therapeutic intervention may not be required in many
conditions. It should be borne in mind that drug therapy
is not synonymous with good health care. There are other
special aspects of drug therapy in children, too. Their
abilities to metabolize drugs mature overtime and their
excretory capabilities reach adult levels during or after
late infancy. Before starting drug therapy following steps
need to be taken:
STEPS IN INITIATION OF THERAPY
Reach an Initial Working Diagnosis
With a provisional clinical diagnosis after initial
assessment, appropriate treatment can be started
depending on the clinical status of the child. One should
not wait for specific confirmation of the etiological agent
as in cases like bronchopneumonia, meningitis, etc. In
such serious and life-threatening conditions, therapy can
be initiated taking into consideration the patients age,
likely etiological agent and the pattern of resistance likely
to be encountered. The treatment can be changed
subsequently on the basis of response to therapy and in
the light of results of laboratory and other tests.
Define Therapeutic Objectives
The next step is to define therapeutic objectives. In this
step the treating doctor should specify what he/she intends
to achieve through therapy and in what time interval. It
might include symptomatic treatment, therapy directed
towards cause of illness and even steps to prevent or
ameliorate complications. For example, when a patient
presents with fever and burning micturition and is
diagnosed to have urinary tract infection, therapeutic
objectives would include symptomatic relief, eradication
of infectious agent, steps to prevent further attacks of
urinary tract infection and preserve renal function.
Defining therapeutic objectives helps the doctor prescribe

minimum number of drugs and also provides a benchmark
for the assessing effectiveness of therapy.
Assess Effectiveness of Therapies
Few therapeutic regimens are completely effective in all
cases. Efficacy is dependent on many factors including
patients own defense, drugs pharmacokinetic properties
and stage of illness. The treating doctor should be aware
of the comparative efficacy of various therapeutic
interventions. If the initial response is good, the treatment
can be continued irrespective of microbiological studies.
At the same time, drug resistance to conventional drugs is
not uncommon. This has been encountered, for example,
in certain illnesses like typhoid fever, urinary tract infection
and malaria.
Assess Risk to the Patient
Most drugs are chemicals and have adverse effects. There
are no completely innocuous treatments. The risk to patient
increases when multiple pharmacological agents are used.
The physician should be aware of drug interactions and
should anticipate them. Every new drug will have its
potential adverse affects not known at the time of
introduction.
Plan Strategies to Ensure Compliance
A patient will not derive benefits from therapy if the drug
is not properly administered. The physician must explain
to the parents the importance of administering drug, the
symptoms it would help control or the manifestations that
it might ameliorate and when this is expected to happen
and the importance of completing the course. The clinician
should be familiar with the available preparations, flavors
and unpleasant characteristics of particular medication.
Frequency of administration either as a single dose, twice
daily or thrice daily will depend on the drugs prescribed,
based on the half-life of these drugs.
Consider Costs Involved
For many families, expenses involved including travel
expenses, cost of drugs, expenses for diagnostic tests and
Therapeutics
professional fees, if any, are some of the important factors
determining compliance. Where oral medications are
sufficient to treat an illness; parenteral drugs must be
avoided. Further, when time honored cheaper but effective
medications are available, one shouldnt push the parents
to buy more expensive drugs.
1123
into the systemic circulation. Premature babies have very

little muscle mass and children in whom perfusion is
diminished; the drug may remain in the muscle and be
absorbed very slowly.
Drug Distribution
Another consideration in choosing a drug is to know what

has failed with this patient in the past. This includes
questions about hypersensitiviry, adverse reaction, noncompliance and non-effectiveness.
Knowledge about drug distribution is important while

designing an optimal dosage regimen. The distribution
characteristics of drugs differ markedly amongst term
infants, premature babies and children as compared with
adults. These differences are a result of much important
age-dependent variables. These include the following:
Special Aspects of Pediatric Pharmacology
Composition and Size of Body Water Compartments
Children develop and grow, and their response to drug

therapy is conditioned by age, size and stage of
development. Physiological processes that influence
pharmacokinetic variables in children change significantly
during the first few months. Pharmacodynamics
differences between pediatric and other patients are
probably small.
Neonates have a higher percentage of their body weight

in the form of water (70-75%) as compared to adults (5060%). Similarly, the extra-cellular water compartment
accounts for 40% of the body weight in neonates compared
to 20% in adults. The volume of extra-cellular water
compartment is important in determining the
concentration of drugs at receptor sites.
Drug Absorption
Protein-binding
Enquire about Previous Experience
Gastrointestinal absorption: Drug absorption in infants

and children follows the same principles as in adults.
The patient and drug characteristics that affect absorption
of a drug from the gastrointestinal tract are, in turn,
influenced by several factors. These include age of the
child, lower secretion of gastric acid, lower concentration
of gastrointestinal enzymes, prolonged gastric emptying
and slower peristalsis in the first few days of life, which
may affect absorption of drugs from the gastrointestinal
tract. For example, plasma concentrations after oral
administration of paracetamol and phenytoin have been
shown to be lower in infants than those in children and
adults. Delayed development of gastrointestinal flora and
its metabolic abilities can influence the absorption of
certain drugs like digoxin.
Parenteral Routes of Absorption
Physiological and physiochemical factors that affect the
rate and extent of logical drug absorption form parenteral
sites. The primary means of extra-vascular drug
administration in infants and children, other than the oral
route, is the intramuscular route. Blood flow to and from
the injection site should be adequate to ensure absorption
Albumin, alpha-glycoprotein and lipoprotein are the most

important circulating proteins responsible for drug
binding in plasma. The concentration of most of these
proteins is low in infancy. These factors will influence the
resultant balance between free and bound drug
concentrations and hence have an affect on drug
distribution.
Membrane Permeability
Permeability of membrane has an influence on the
distribution of the drugs.
Drug Metabolism
Liver is the primary organ for drug metabolism and
different hepatic enzyme systems mature at different ages.
The cytochrome P-450 mono-oxygenase system appears
to mature rapidly, with metabolic activity similar to adults
being achieved by 6 months of age. In contrast, glucuronide
formation reaches adult values between third and fourth
years of life. Although infants are regularly characterized
as being slow metabolizers of drugs, some drugs (for
example, theophylline, phenytoin, phenobarbitone) are
more rapidly metabolized by infants than adults. There
are qualitative differences, too. A drug may be
1124
preferentially metabolized by one pathway during the

neonatal period (e.g. theophylline) as compared to
adulthood. All these have practical implications. While
determining dosages of drugs that undergo hepatic
biotransformation, sequence of maturation of process of
drug metabolism has to be taken into account. The drugs
that are metabolized at a rapid rate are required to be
administered in higher does. Thus, theophylline is
administered at much higher dose and frequency during
infancy than in adulthood.
Drug Excretion
Kidney is the predominant organ concerned with drug
excretion. Drugs are also excreted through the
gastrointestinal tract; biliary tract, respiratory tract and
sweat glands, but these are important routes of excretion
only for miniscule minority of drugs. Renal excretion is
dependent upon glomerular filtration rate (GFR), renal
blood flow (RBF) and rate of active tubular secretion. These
are dependent on age and maturity. A term infant has
GFR and RBF that approximate 30% of adult values. In
premature neonates, these renal capabilities are only 15%
or less, depending on the degree of prematurity. The renal
capacity to excrete solutes improves quickly to reach 50%
of adult value by 4 weeks and equals that of adults by 9-12
months of age. Thus, the dosages in the neonatal period
should be based on age and maturity to avoid
accumulation of drugs.
Pediatric Drug Dosages
Because of the differences in pharmacokinetics in infants
and children enumerated above, simple proportionate
reduction in the adult dose is not adequate to determine a
safe and effective pediatric dose. Formulae or rules
providing calculations based on age or weight of the child
are mere approximations. The most reliable pediatric dose
information is usually that provided by the manufacturer
in the package insert, in the pharmacopia or in pediatric
textbooks. Health care providers should carry them for
ready reference while prescribing drugs for children.
METHODS OF DRUG DELIVERY AND PEDIATRIC
FORMULATIONS
Oral Administration
Depending on age, various drug forms like drops,
suspensions, dry syrups (powder to be mixed with water
before use), dispersible tablets, tablets and capsules are
used for oral administration in children. Suspension
containing sorbitol base or alcohol base provides uniform

drug amount even without shaking but there may be
objections on religious or moral grounds for use of alcohol
as a base. Syrupy suspensions contain un-dissolved
particles of drug and these may not be evenly distributed
throughout the vehicle. Therefore, the bottle should be
shaken prior to administration of each drug dose. Proper
measurement of the drug dose administered is necessary
in terms of ml and not in terms of teaspoonful. The parents
should be advised to use calibrated medicine cups or
syringe for measuring the dose to be administered. Advent
of dispersibie tablets has simplified administration of oral
medicines. As the tablets can be dissolved in small volume
of water, use of dispersibie tablets makes the process
easier. Children over 8 to 12 years can be taught to take
medicines in tablet or capsule form. This avoids inaccurate
measurement, minimizes spills and bypasses bad taste.
Parenteral Administration
This may have to be resorted to in serious illnesses or
when only parenteral form of drug is available or when
compliance has to be ensured. Local application to skin
and mucous membranes is mainly used for treating local
ailments. Drugs administered by subcutaneous route are
slowly absorbed. The drug behaves as if it is in a reservoir
as the subcutaneous tissue has limited blood supply.
Intramuscular injections should be administered in the
antero-lateral aspect of the thigh rather than in the gluteal
muscles. This avoids the risk of injury to the sciatic nerve
and the possibility of a part of the dose getting injected in
the subcutaneous fat that is abundant in the buttocks.
After five years of age, when deltoid mass is generally
well-developed that site can be used for intramuscular
administration.
Intravenous administration of drugs to children requires
certain special considerations. Some drugs have to be
administered as intravenous (IV) push so that the drug is
placed in the circulation with a minimum delay. This is
an important factor when rapid onset of action is essential
(e.g. adrenaline for treatment of anaphylaxis, adenosine
for managing supra-ventricular tachycardia). This method
should, however, be resorted to only by individuals
familiar with acute toxicities of medications. The route
carries the risk of sudden cardiac or respiratory collapse,
severe anaphylaxis due to sudden antigen-antibody
reaction and local venous thrombosis if the drug damages
the vascular wall (e.g. crystalline penicillin, cloxacillin).
Some drugs are required to be administered over a longer
Therapeutics
period to avoid acute toxicities or vessel wall irritation.
The volume of fluid that can be administered to neonates
and young infants or to children with renal failure or
congestive cardiac failure is restricted. Hence, novel
methods of IV administration are used in pediatrics.
Intravenous piggyback (IVPB) route is used to infuse drugs
over a period of 1 to 2 hours. This is common way for
administering anti-microbial agents in children.
The dose of medication is injected into volumetric
chamber inserted between the IV bag and the device
controlling the rate of administration. The method is
simple, does not require costly equipment like syringe
pump and as the medication is diluted in existing IV fluid,
no extra fluid is administered. The syringe pump method
is the gold standard for administration of drugs intravenously as there is absolute control over drug delivery.
But this is not necessary for many medications. The
syringe pumps are expensive and entail administration
of extra amounts of fluid. The retrograde system is a
simpler method mainly used in neonates, as it does not
require injection of additional fluids.
There are only limited indications for administration
of drugs through sublingual, intra-thecal and intraperitoneal routes. For example, sublingual administration
is used for control of severe hypertension with nifedipine
and intra-thecal route is used for administering
methotrexate in the treatment of childhood leukemia. Antidiuretic hormone (ADH) is administered with the help of
a nasal spray for the control of nocturnal enuresis and
diabetes insipidus in selected patients. Use of pulmonary
absorption of aerosolized drugs has revolutionized the
management of childhood asthma. Beta-agonists and
steroids are administered through this route. Advantages
of this route of administration include almost
instantaneous absorption of the drug into the blood,
avoidance of hepatic first-pass loss and direct delivery of
the drug at the desired site of action and lesser chance of
developing systemic toxicity on prolonged use. The
cumbersomeness of method of administration that could
come in the way of its use in young children has been
overcome by using spacer devices or rotahalers.
Drugs and Breastfeeding
When a mother is on medications, many drugs appear in
the breast milk. One must be aware of the side effects of
these medications on the neonate (e.g. chloramphenicol
and phenobarbitone). When a nursing mother needs
1125
medications, the physician must keep in mind the safety

profile of the drugs that need to be administered.
Practical Hints while Prescribing
Drugs for Children
In addition to the usual considerations, it is worthwhile
emphasizing the following points that need to be
considered while prescribing medications for children:
Prescribe drugs only when necessary keeping in mind
the risks, benefits and costs involved. Review therapy
as and when additional information becomes
available.
Rather than rushing to know the latest on every new
drug, one should be more concerned about the use of
proven worthwhile therapies.
Prescribe minimum number of appropriate,
inexpensive drugs of good quality, one is familiar with.
Do not succumb to pressures of prescribing newly
marketed drugs, unless a clear indication exists.
To ensure compliance, explain to parents the nature of
the disease and the likely benefits to be obtained from
the therapy. Give clear instruction, preferably in
writing to avoid misinterpretation, including the need
to complete a given course even if child appears to be
asymptomatic.
Prescribe doses at a frequency as advised in product
insert or as per standard pediatric texts.
Prescribe medications for a complete course in
appropriate formulations, e.g. drops for neonates,
liquid preparations or dispersible tablets for infants
and young children and tablets and capsules for
children older than 8 to 12 years.
Direct parents to discard all remaining doses so as to
protect the child from accidental poisoning or improper
self-medication at a later date.
Explain the adverse effects of the drug, if any, to the
parents: especially when long-term treatment is
suggested. Whenever necessary, explain the need for
periodical clinical and/or laboratory monitoring when
on long-term drug therapy for epilepsy, tuberculosis,
renal diseases, etc. to assess the response and prevent
serious side effects. Ask the parent to report any
worsening, unexplained event or adverse effect
immediately.
Drug combinations must be used with caution, unless
the drugs are in the specified dose requirements (e.g.
1126
sulfonamide plus trimethoprim, amoxicillin and

clavulanic acid, sulfonamide plus pyrimethamine,
isoniazid and rifampicin). Avoid fancy but inappropriate combinations like metronidazole plus nalidixic
acid or norfloxacin, ampicillin and cloxacillin, etc.
Drug interactions between two drugs can happen if
administered simultaneously, e.g. penicillin and
aminoglycoside in the same syringe.
Be conversant with the ongoing developments and
progress in the fields of therapeutics and drug
development. Prescribe drugs in a judicious manner
to ensure that children do not remain therapeutic
orphans and at the same time their safety is not

sacrificed while prescribing newer drugs.
BIBLIOGRAPHY
1.
deVaries TPGM, Henning RH, Hogerzeil HV, Fresle DA.

Guide to Good Prescribing, Geneva, World Health
Organization, 2000
2. Loebstein R, Vohra S, Koren G. Drug therapy in pediatric
patients In: Carruthers SG, Hoffman BB, Melman KL,
Nierenburg DW [Eds.] Melman and Morrellis
Clinical Pharmacology Basic Principles in Therapeutics
4th Edn. New York, McGraw Hill Medical Publishing
Division 2000; 1143-49.
21.2 Adverse Drug Reactions, Drug Interactions

and Therapeutic Drug Monitoring
Archana Kher, Milind S Tullu
ADVERSE DRUG REACTIONS (ADR) IN CHILDREN
The past decade has seen an explosion in the drug market.
Drugs prescribed for a disease can themselves cause a
serious degree of adverse reactions. These may range from
mere inconvenience to severe morbidity and even death. It
excludes adverse reactions due to drug overdose
[poisoning], drug abuse and therapeutic errors.
Drug use in children may be accompanied by different
problems as their growth and development may be affected.
In some cases, somatic and neurologic sequelae result.
Definition
An adverse drug reaction may be defined as any unwanted
consequence of administration of a drug during or
following a course of therapy. These unpleasant effects
occur at doses intended for therapeutic (prophylactic or
diagnostic) effect and which necessitate reduction of dose
or withdrawal of the drug, and/ or forecast hazard from
future administration. Intolerance means a low threshold
to the normal pharmacological action of a drug.
Idiosyncrasy denotes an inherent qualitative abnormal
reaction to a drug.
The administration of a drug may result in the
development of side effects, untoward effects, toxic effects
or allergic and idiosyncratic effects. ADR could be either

local [irritation, necrosis, thrombophlebitis] or systemic.
ADRs are generally classified as:
Type A: These are also known as augmented, attenuated
or quantitative ADR. They comprise a hyper response to
the main action of the drug e.g. insulin hypoglycemia.
Type B: They are also known as bizarre or qualitative ADR.
Unpredictable or unexpected effects are seen. The
mechanism is genetic, immunological or unknown.
Type C: The effect is time and dose related as in analgesic
nephropathy.
Type D: The ADR is time related as in carcinogenesis.
The commonly reported ADRs include:
a. Dermal reactions-erythema multiforme, Stevens
Johnson syndrome, fixed drug eruptions (e.g.
sulphonamides).
b. Gastrointestinal symptoms-nausea, diarrhea,
vomiting (e.g. antineoplastic drugs).
c. Hepatotoxicity (e.g. antitubercular drugs).
d. Neurological-tremors (e.g. bronchodilators), ataxia,
dystonia, pseudodementia, hyperactivity, impaired
cognitive function (e.g. phenobarbitone).
e. Hematological-neutropenia, aplastic anemia (e.g.
chloramphenicol).
f. Anaphylaxis (e.g. penicillin, vaccines).
Therapeutics
Causes of ADRs
1. Non-drug Factors:
a. Intrinsic to the patient: Age, genetics, drug allergy,
disease (factors like sex, personality, habits do
not play a significant role in Pediatric ADRs).
b. Extrinsic to the patient: Prescriber, environment.
2. Drug Factors: Intrinsic to the drug, choice of the drug,
use of the drug, and drug interactions.
Non-drug Factors
In the neonate and infant: Distribution is influenced by
lower proportion of fat and higher proportion of water.
The blood-brain barrier is more permeable. The metabolism of drugs is reduced in the first two weeks of life due to
immaturity of the enzyme systems. They also have inability
to conjugate. Elimination by kidney is also lowered and
some drugs e.g. gentamicin and digoxin have prolonged
half-life. Older children may metabolize some drugs more
rapidly than adults.
Hereditable conditions can cause increased or toxic
drug response, examples being:
a. Methemoglobinemia: Due to deficiency of methemoglobin reductase, methemoglobin is readily formed
with sulphonamides leading to cyanosis.
b. G6PD deficiency: This enzyme is an important source
of non-drug adverse reaction.
Factors Intrinsic to the Drug
Side effects: These are an inevitable part of the
pharmacological action of the drug at therapeutic doses,
but are undesired, e.g. drowsiness with pheno-barbitone.
Secondary effects: These occur due to indirect consequences of a primary drug action, e.g. diuretic induced
hypokalemia leading to digoxin intolerance.
Toxicity: A high dose of a drug can have a damaging
effect on tissues and toxicity, e.g. paracetamol induced
liver damage, 8th cranial nerve damage with gentamicin.
Mutagenicity, teratogenicity, carcinogenicity are special
toxic effects. Inappropriate choice, incorrect techniques of
administration especially of anti-cancer drugs and general
anesthetics can cause adverse reactions.
Allergic reactions to drugs result from an interaction
of drug or metabolite with patient and disease and again
from subsequent re-exposure. Most drugs are simple
chemicals and act as incomplete antigens or haptens.
Penicillin anaphylaxis is rare in neonates and up-to the
age of one year (except when high dose of penicillin is
1127
used in VDRL-positive neonates or leptospirosis, that is

known as Jarisch-Herxheimer reaction). IgE-mediated
immunological reactions are rare in young infants.
The reactions can be classified by time of onset as:
a. Immediate, which typically begin within 30 minutes of
drug administration.
b. Accelerated represent IgE-mediated and begin 2 to 72
hours after drug use.
c. Late reactions occurring 72 or more hours later, are often
unrelated to IgE-mediated mechanisms.
Test dose alone at times will be inadequate to rule out
any ADR. One has to be cautious while using the drug for
the first time in a child with a family history of drug allergy.
The allergic reactions are of the following types:
Type I Immediate (anaphylactic) type. The drug causes
formation of tissue sensitizing antibodies that are fixed to
mast cells or leukocytes. Allergy develops within minutes
and lasts for 1 to 2 hours.
Type II Auto allergy, e.g. penicillin induced hemolytic
anemia. Autoantibodies are formed to the drug and body
protein complex.
Type III Antigen and antibody form large complexes that
activate complement, e.g. serum sickness, vasculitis and
glomerulonephritis.
Type IV Delayed type (cell-mediated) allergy in which
antigen specific receptors develop on T lymphocytes.
Further administration causes a tissue allergic reaction,
e.g. contact dermatitis. Fixed drug eruption to sulfa can
occur after a safe use for more than 2 years as delayed
hypersensitive reaction.
Thus allergic reactions do not have any correlation
with known pharmacological properties of the drug or
any linear relation with the dosage. Reactions include
rashes, angioedema, serum sickness, anaphylaxis and
asthma. There is no induction period on re-exposure and
desensitization is possible.
Drugs also Act on the Embryo/Fetus
Direct action results from thalidomide, anti-cancer drugs
or drugs which affect cell division, protein synthesis or
DNA synthesis. Indirect action may result from drugs
acting on the placenta (e.g. vitamin A), on the uterus
(vasoconstrictors cause fetal anoxia by reducing blood
supply).
Lipid-soluble drugs can go across the placental barrier
and pass into the fetus. Drugs relatively insoluble in lipids
1128
may pass only if present in very high concentration. Drug

kinetics differ in the fetus and the metabolites persist due
to less developed excretory processes. Drugs known to be
teratogenic are warfarin, alcohol, anti-cancer drugs,
steroids, anti-epileptics, etc.
ADR Detection and Monitoring
A greater awareness is necessary to detect ADR in Indian
children. Practicing doctors must detect ADRs and report
to the authorities as a professional responsibility. It may
take some years before the information is pooled by
authorities to declare the drug as unsafe for use in practice.
i. Certain antihistamines (e.g. astemizole, terfenadine).
ii. Promotility drug like cisapride.
Two types of ADR are noted in penicillin allergic
childrenan accelerated reaction which occurs within 1
to 72 hours, and a late reaction after 72 hours.
Risk of combining certain drugs enhances the ADRs,
e.g. vancomycin and gentamicin increases the susceptibility to ototoxicity and nephrotoxicity especially in
preterm and low birth weight infants.
Fixed drug eruption to sulfa can occur even after a safe
use for more than 2 years as delayed hypersensitivity
reaction.
Drug Interactions
Drug interactions result from the use of two or more drugs.
This may lead to an enhanced or a diminished effect. Drug
interactions may be desired or undesired, beneficial or
harmful. Examples of synergistic combinations of drugs
are antibiotics and antihypertensives. Drug interactions
are important in the following situations:
i. Drugs that have a small therapeutic index or exhibit
zero order kinetics.
ii. Drugs that are enzyme inducers or inhibitors.
iii. Drugs used for the same disorder, e.g. theophylline
and salbutamol increase the risk for cardiac
arrhythmias.
iv. Long term use.
v. Presence of multiple pathology or major organ failure.
vi. Use of multiple drugs.
Drug Interactions are of Two Types
1. Pharmacodynamic Interaction: Where both drugs act on
the target site of clinical effect and influence the same
physiological function. They may be mediated through
receptors, transport processes or electrolyte levels, etc.
Potassium depletion enhances digoxin effect.

Interactions may result in antagonism or synergism.
Synergism is of two kinds:
a. Summation or addition takes place when the effects
of two drugs having the same action are used.
b. Potentiation occurs when one drug increases the
action of another, e.g. trimethoprim and sulphonamide. Interactions are termed direct when two
drugs act either at same site or different sites with
the similar net results. Indirect interactions are
those where the end result of an index drug is
altered by a different kind of action of an interacting drug. Some examples of pharmacodynamic
drug interactions are as given in Table 21.2.1.
TABLE 21.2.1: Pharmacodynamic drug interactions
Index drug
Interacting drug
Net effect
A. Direct types
Synergism
Muscle relaxants
Frusemide
Antagonism
Salbutamol
Aminoglycosides, Quinine
Aminoglycosides
Apnea
Ototoxicity
Beta-blockers
Poor asthma
control
Poor clotting
Warfarin
Vitamin K
B. Indirect types
Synergism
Digitalis
Thiazides, Frusemide
K+ supplements
ACE inhibitors,
K+ sparing diuretics
Antagonism
Drugs used in
NSAIDs
CCF, hypertension
Asystole,
Arrhythmias
Hyperkalemia
Control difficult
Combining certain drugs enhances the risk of

developing ADR e.g. vancomycin and gentamicin together
increases the suscep-tibility to develop ototoxicity and
nephrotoxicity in preterm and low birth weight infants.
2. Pharmacokinetic Interaction: They are easy to detect and
quantify and deal with the life of the drug in the body,
absorption, meta-bolism, distribution and excretion.
They can occur outside the body or in the body.
Absorption: Changes in pH (e.g. with antacids) alter the
drug ionization, solubility in lipids and thus alter the rate
of absorption. Chloroquine, ciprofloxacin, and rifampicin
are better absorbed in an acidic pH. These drugs must be
taken an hour before or 2 to 4 hours after the interacting
drug. Direct interaction in the gut affects absorption, e.g.
Therapeutics
liquid paraffin reduces absorption of fat-soluble vitamins.
Change in gut motility and gut flora influence absorption.
Absorption can be altered at other sites, e.g. adrenaline
added to local anesthetics delays their absorption by
causing vasoconstriction.
Distribution: Depends on the protein binding. A second
drug competes with and displaces the first, which is then
free and available to act. This free drug may later be
available for metabolism and elimination, e.g. aspirin,
indomethacin displace and so potentiate warfarin toxicity.
Vitamin K can cause kernicterus in the neonate by
displacing bilirubin. Bilirubin can also be displaced by
sulphonamides.
Metabolism: Drugs can induce increased synthesis of
hepatic enzymes with the result that the rate of metabolism
of the inducing drug and others is enhanced.
Examples are:
Enzyme inducers (stimulants)
Interacting drugs
Barbiturates, Rifampicin
Phenytoin, Carbamazepine
Warfarin
Enzyme inhibitors
Interacting drugs
Cimetidine, erythromycin
Isoniazid, Chloramphenicol
Sodium valproate
Quinolones
Drugs affected
Corticosteroids,
cyclosporin
Thyroxine
Drugs affected
Digoxin, propranolol
Theophylline,
phenobarbitone
Phenytoin, pamotrigine
Carbamazepine
Excretion: Clinically important interactions occur in the

kidney. Lipid-soluble drugs are reabsorbed across the
renal tubular cell membrane. The drug may be ionized
(lipid-insoluble) or unionized (lipid-soluble). The urinary
pH determines the degree of solubility; pH can be raised
by sodium bicarbonate and lowered by ascorbic acid.
Alkalization of urine is useful in phenobarbitone
poisoning.
Interactions that take place outside the body are
physiochemical in nature. Some formulations are stable
only for a few hours on reconstitution, many are
photosensitive, certain combinations, e.g. dopamine with
bicarbonate is not compatible. Intravenous solution must
be checked for visible changes like turbidity, color, and
1129
precipitates. Use of the correct vehicle, and appropriate

pH of the infusion is essential.
Therapeutic Drug Monitoring (TDM)
Therapeutic Drug Monitoring (TDM) can be defined as
the use of drug measurements in biological fluids as an
aid to the management of patients receiving drug therapy
for the treatment or prevention of disease. Measuring the
concentration of certain drugs in plasma assists optimal
individualization of therapy. Genetic variation in
metabolism, elimination rates, disease states, nutritional
deficiencies and interactions with other drugs give rise to
a wide range of plasma levels in patients given the same
dose. Phenytoin concentration can be altered in the
presence of low albumin levels. Presence of AIDS can
reduce the absorption of anti-TB drugs.
Plasma levels serve as a useful guide when there is a
narrow range between therapeutic and adverse effects.
One must also note that there is variability among
individual responses to give plasma levels. A few patients
are sensitive and respond to lower plasma levels.
Interpopulation variations and ethnic differences also
influence plasma drug concentrations.
The actual time that the sample was obtained is
important. The levels can be determined any time during
dosing interval for drug with a long half-life, e.g.
phenobarbitone. For drugs, e.g. aminoglycosides that have
a short half-life, peak and trough concentrations must be
measured at specific times. Concentrations measured
during the distribution phase are variable and do not
correlate with usual therapeutic range. Plasma drug
samples should be procured after 4 half-lives of the drug.
Peak concentrations are observed within 1 to 2 hours after
oral administration of a drug. To ensure proper absorption
concentrations must be measured before the next dose
(trough). Drug levels must be monitored in patients with
chronic hepatic or renal disease to avoid sub-therapeutic
therapy or toxicity. The most useful drugs that have
inhibitory effects on hepatic drug metabolism prescribed
in children are cimetidine, erythromycin, ciprofloxacin,
and omeprazole. Co-administration of these agents with
a medication that has a narrow therapeutic range such as
theophylline can result in increased plasma concentration
and toxicity of the drug. Likewise the promotility drug
(cisapride) when given with theophylline can induce
cardiac arrhythmias. Drug monitoring may be an effective
approach to determine non-compliance in patients. TDM
is commonly carried out for anticonvulsants, theophylline,
1130
digoxin, and salicylates as these are prescribed for chronic

ailments. Appropriate dose adjustments and good
therapeutic concentration can be achieved in 70% patients.
TDM is a useful tool for evaluating therapeutic drug
regimens and minimizing toxicity of certain drugs.
BIBLIOGRAPHY
1. Choonara I, Gill A, Nunn A: Drug toxicity and surveillance in Children. Br J Clin Pharmacol 1996; 42:407-10.
2. Dikshit RK; Nayak UV: Drug Interactions. J Applied
Medicine 1997; 23(1): 61-65.
3. Gogtay N J, Khirsagar N A, Dalvi C S. Therapeutic drug
monitoring in a developing country, an overview. Br J
Clin Pharmacol, 1999; 48: 649-54.
4. Gupta A, Waldhauser LK: Adverse drug reactions from
birth to early childhood. Ped Clincis of North America
1997; 44(1): 79-93.
5. Karande SC, Kshirsagar NA: Adverse drug reactions in
developing countries. The National Medical Journal of
India 1996; 9(3): 218-21.
6. Kshirsagar NA, Karande SC: Adverse drug reaction
monitoring in pediatric practice. Indian Pediatrics 1996;
33:993-98.
7. Kushwaha KP, Verma RB, Singh YD, Rathi AK:

Surveillance of drug induced diseases in children. Ind J
Pediatr 1994; 61:357-65.
8. Laurence DR, Bonnet PN Brown MJ: Unwanted effects
of drugs and Adverse Reactions in Textbook of Clinical
Pharmacology (8th Edn). Section 2,Chapter 8, C
Livingstone 1997;12137.
9. Loobstein R, Keren G: Clinical pharmacology and
therapeutic monitoring in neonates and children. Ped
Rev 1998; 19:423-28.
10. Mellon MW, Schatz NR, Patterson R: Drug allergy. In: GJ
Lawlor, Fischer TJ, Adelman DC (Eds): Manual of Allergy
and Immunology (3rd Edn). Little Brown & Co., 1995;
262--90.
11. Oates J A. The science of drug therapy. In: Goodman and
Gilmans. The Pharmacological Basis of Therapeutics
(11th Edn). Brunton L L [Ed], Lazo JS, Parker KL [Assoc
editors] McGraw Hill 2006; 11736.
12. Satoskar RS, Bhandarkar SD, Ainapure SS: Evaluation of
drugs in man, drug prescribing and drug interactions.
In: Satoskar, Bhandarkar, Ainapure (Eds): Textbook of
Pharmacology and Pharmacotherapeutics. Section 1. 19th
Edition. Popular Prakashan, Mumbai, 2005; 61-75.
21.3 Rational Drug Therapy in Children

Arun Phatak
The word rational is defined as something sensible based
on sound reasoning. Medical practice (any branch) largely
depends on the use of drugs. Having studied pharmacology for a year and a half and having done clinical work
for four years, a doctor is expected to be judicious in the
choice of drugs. Unfortunately, irrationality in drug usage
is not uncommon.
respiratory infections) are examples of the type. Use of unindicated drugs occurs also when fixed-dose combinations are used. Very few such combinations are rational.
Combinations of paracetamol-ibuprofen or paracetamolantihistamine-decongestant are prescribed commonly
when any one of the drugs could suffice. Use of an
unindicated drug, at times, could be hazardous.
IRRATIONALITIES IN DRUG THERAPY
Wrong Choice of Drug
There are four main types of irrationalities in drug therapy:

Use of a drug which is not indicated, wrong choice of the
drug, inappropriate dosing and route, and poorly written
and explained prescriptions.
The drug should not only be effective and safe but it must
be easily available and affordable. Often a new drug is
prescribed with a belief that it is better. The new drug is
usually more costly and its side-effects and adverse
reactions are not fully known.
Use of an Unnecessary Drug

A large number of drugs are prescribed without any clear
indication. Misuse of the so-called tonics (vitamins,
minerals, digestives, appetizers) and antibiotics
(especially in the management of diarrhea and upper
Inappropriate Dose and Route of Drug Therapy

In children, the dose of the drugs is calculated by weight
or by surface area and the dose may be different in
neonates, in infants and in older children. An
Therapeutics
inadvertently given high dose could be catastrophic. The
frequency and route of administration of the drug should
be such that optimal blood levels are reached and
maintained. In emergency situations the drug needs to be
administered intravenously but once the child is stabilized
and can feed orally, one should switch over to oral route
whenever possible.
Poor Prescribing
A prescription has a standard format which must be
followed. It must have:
i. Doctors name, qualification, address and registration number.
ii. Patients name, age sex, weight and date.
iii. The names of the drugs along with the recommended
strengths, form, amount to be bought and if
necessary, the pharmaceutical name.
iv. Clear instructions to the parents and patients about
the dose frequency and duration of medication,
preferably in a language understood by the parents.
But, a number of our patients are illiterate and the
doctor or his assistant/paramedic must take time to
explain and if necessary, to demonstrate how the
various drugs are to be taken.
v. If possible, the common side effects should be
informed to the parents (e.g. black stools/constipation after iron therapy, reddish urine after rifampicin).
vi. The handwriting should be legible. Many drugs have
similar syntax and pronunciation and the chemist
may dispense a wrong drug which would not only
be ineffective but could cause a serious adverse
reaction.
1131
internet. Prescribing information (product insert) provided

with a drug is also an important source of information
about a new drug.
Inappropriate Peer Model
Many freshly graduated practitioners look at their senior
established peers as role models and try to imitate their
manner of patient management without scrutinizing its
rationality.
Undue Pressures
A practitioner in the beginning of his practice feels that
curing the patient quickly will increase his clientele and
tries to treat every possible cause of his symptoms
simultaneously (poly-therapy). Many parents ask for
medicines when not required (e.g. acute gastro-enteritis,
upper respiratory infections, and tonics) or they ask that
an injection be given under the misbelief that injections
give a quicker cure. A doctor should spend some time in
counseling the parents about the management of the
disease and not succumb to undue pressures.
Unfair Practices
The drug industry and the medical profession are both
integral and essential partners in the health care system.
At times, same pharmaceutical companies use unethical
methods and inducements to influence the prescription
behavior of practitioners. These practices have the capacity
to hinder rational use of drugs. It is important that doctors
maintain their integrity and ensure that child-patients
interests are protected at all times.
Personal Ambitions and Life Goals
Not Using an Indicated Drug

This type of irrationality is rare and occurs due to oversight
or ignorance.
REASONS FOR IRRATIONAL DRUG THERAPY
Everybody needs to be financially secure but some aim at

earning a fast buck. All said and done, practice of
medicine has continued to be a profession and not a
business and a doctor with decent rational practice can
certainly be able to enjoy a decent comfortable family life.
Ignorance
Medical education is an ever-expanding, lifetime process.
Every year, new drugs introduced in the market which
were never taught to us. The continuation of medical
education (CME) is essential for implementing rational
therapy. It is provided by the newer editions of textbooks,
review articles in standard journals, by various academic
programs organized by professional bodies and by the
Myths
Two myths prevail in the minds of the fresh graduates:
a. What is preached cannot be practiced. Although the
circumstances and work conditions in the medical
college hospital are different from those existing in
private sector, there is no reason why one cannot be
rational and scientific in private practice.
1132
b. A doctor has clinical freedom. The belief, at best, is a

cloak for ignorance and at worst, an excuse for
quackery. A doctor must be able to justify every aspect
of the patient management on the basis of available
evidence.
ENSURING RATIONAL THERAPY
The rational therapy can be ensured by a variety of means.
Directive Orders
Departments of teaching as well as non-teaching hospitals
canadopt standard management for the common
diseases (protocols) any deviation must be justified by
the doctor in charge of the case and adopt a system of
regular audit of medical and other management.
Legal Back-up
There are acts of the Parliament that prohibit certain
irrationalities (e.g. the Infant Milk Substitutes, Feeding
Bottles and Infants Foods Act) or make irrational treatment
punishable (e.g. Consumer Protection Act). The
administrative set-up under Drug Controller of India can
ban the production or order withdrawal of potentially
hazardous or irrational formulations.
Education
As mentioned earlier, it is necessary for the medical
practitioners to maintain and enhance their knowledge,
expertise and competence throughout their career.
Reading recent editions of standard textbooks and
journals is one way to update. Constitute another
important resource. CME programs organized by the
professional bodies constitute another important resource.
Adult learning is particularly effective when it is problem
oriented. Osler had advised,The important thing is to
make the lesson of each case tell on your education. The
value of experience is not in seeing much but in seeing
wisely. Every time we do anything for the patient, we
must pause and reflect whether it is the best possible under
the given circumstances and in the best interest of the
child and the family. In most of the cases, it is enough to
refer to standard textbooks and guidelines and standard
therapeutic recommendations by the professional bodies.
In some out of way cases it becomes necessary to look into
the recent literature. One therefore needs to learn how to
get the evidence on the internet and how to appraise it
critically.
Medical Audit
Most of the directive orders mentioned above apply to the
doctor in service. There is hardly any supervision or control
over the doctor in private practice. An audit means an
official examination usually of accounts. A medical audit
means a scrutiny of the various aspects of the management
of the patient. There is scrutiny, not only of the drug
treatment, but also of the necessity of hospital admission,
laboratory investigations done, duration of hospital
statistics, the cost of the treatment, etc.
As has been stressed earlier, a doctor must be
accountable to the patient, to the society, to the peers, and
to ones own self.
Audit by peers is the most effective corrective measure
to ensure rational therapy. When small groups formally
review the practice and outcome and keep written records,
the peer pressure on the prescriber can be great enough to
make him/her realize and rectify the shortcomings. Peer
groups can audit individual prescriptions and case
histories or grouped cases from one department or unit.
One must also learn to keep a watch on ones own self
(self-audit). It is not difficult. A doctor could maintain a
register of relevant information of patients and the
treatment. The data can be analyzed and the treatment
compared with the standard recommendations. In this
way one can easily monitor the areas maximum irrational
drug use.
EVIDENCE BASED MEDICINE, GUIDELINES AND
PROTOCOLS
Some information in the latest editions of the standard
textbooks may be 4-5 years old. There are some 5000
medical journals all over the world which publish
thousands of papers every year. Only 10%-15% of these
are of lasting value. So if one wants to know the latest
information, one has to search the recently published
scientific papers (evidence) on the internet. These papers
are graded for their reliability (strength) on the basis of the
design (Table 21.3.1), their methodology and the
applicability of the results to our patients.
Guidelines are systematically developed statements
with an objective of helping the clinician take an
appropriate decision about patient management in the
specified circumstances. They are expressed in terms of
general principles and leave room for judgment within
broad parameters. Protocols, on the other hand, are written
for use in situations with predictable eventualities. They
Therapeutics
leave very little room for individual judgment and variation
(e.g. protocol for neonatal resuscitation).
Guidelines and protocols are usually developed by
expert committees of professional bodies. The Indian
Academy of Pediatrics has published guidelines and
protocols for many conditions. It is better to follow these
guidelines and protocols in clinical practice. There are,
however, many areas where unanimity may not be reached
or there may be some ambiguity or no guidelines may be
available. Sometimes the practitioner may not agree with
the recommendations. Any deviation from the guidelines
and protocols should be based on sound scientific
principles and evidence.
ESSENTIAL DRUGS
Three-fourth of the worlds population lives in the
resource-poor settings while only 15% of the drugs are
available to them. The concept of essential drugs was
first stressed in 1972 in the WHOs action program for
attaining Health for All by 2000 AD. Essential drugs
are those which satisfy the health care needs of the
majority of the population. The Hathi Committee (1975)
had recognized 113 drugs as essential. The Government
of India has, in 1996, prepared a list of 279 essential drugs.
Listing essential drugs does not mean that others are
useless - it means that those listed should always be
available. Obviously, the list has to be adapted to suit the
local requirements.
It is ironical that in a developing country like India,
more than 8,500 pharmaceutical units put into the market
more than 70,000 formulations worth about Rs. 9.2 billion.
Over 10,000 of these are fixed-dose drug combinations
most of which are irrational. A legal ban on the production
of such drugs is an answer to this problem.
DRUGS BY GENERIC NAME
More than 90% of the sales of drugs are by brand names
and the manufacturers resort to irrational promotional
tactics. It has been suggested that use of drugs by generic
names will discourage the promotion and to make the
drug cheaper. The belief that brand name ensures good
quality is not always true. Prescribing drugs by generic
name is possible when single ingredient formulations are
used. It can be implemented in hospital pharmacies which
stock a limited number of essential drugs selected by a
drugs committee.
1133
TABLE 21.3.1: Levels of evidence for

drug therapythe hierarchy
Meta-analysis and systematic reviews of randomized clinical

trials (RCTs) give the best (strong/most reliable) evidence
and the conclusions would be almost always right; while level
5 evidence is very weak and the conclusions may or may not
be right.
Level of
Type (design / nature) of evidence
evidence
1a
1b
2a
2b
3a
3b
4
5
Systematic review with homogeneity of RCTs

Individual RCTs with narrow confidence interval
Systematic review with homogeneity of cohort
studies
Individual cohort studies; Low quality RCTs
Systematic review with homogeneity of casecontrol studies
Individual case-control study
Case series; Poor quality cohort and case-control
studies
Expert opinion without explicit critical appraisal
or based on physiology, bench research or first
principles
SOME EXAMPLES OF RATIONAL DRUG TREATMENT

Two general classes of drugs which are most commonly
misused are cough-cold mixtures and antibiotics. Their
rational use will now be discussed briefly.
Cough-Cold Mixtures
Cough and cold are common symptoms in pediatric
practice. In USA, more than 6 million cough-cold mixtures
are written every year costing 1 to 2 billion dollars. The
drugs used for treating cough and cold may be classified
into four groups: (i) antihistamines, (ii) decongestants,
(iii) antitussives, and (iv) expectorants.
Antihistamines (e.g. chlorpheneramine, diphenhydramine, promethazine) are the most commonly used
medicines for alleviation of the uncomfortable symptoms
and signs of cold.
Decongestants (pseudoephedrine, phenylephrine,
phenyl propanolamine) cause vasoconstriction in
congested areas and are helpful in relieving nasal
stuffiness. Chronic use of topical decongestants (sprays
or drops of phenylephrine, oxymetazoline, naphazoline,
etc.) may cause rebound congestion and precipitate serious
conditions like hypertension and glaucoma. They should
not be used for more than five days.
1134
Antitussives like codeine, noscopine or dextromethorphan are useful in suppressing the troublesome
unproductive cough.
Expectorants (guaiaphenesin, iodides) are expected to
make the secretions thin and flowing. They have a very
limited value and the model list of essential drugs prepared
by WHO does not mention any expectorant or
mucolytic.
Bronchodilators are needed when there is bronchospasm (reactive airway). They cannot be considered as
primary drugs for cough.
A rational cough mixture should have a single
ingredient proven to have the desired effect. In case there
are multiple ingredients, they should not be antagonistic
in their action. A notification of the Central Government
(Ministry of Health and Family Welfare, Department of
Health Notification GSK 996 E dated 11th February 1991)
considers the following combinations to be dangerous:
i. More than one antihistamine
ii. Centrally active antitusive with an antihistamine of
high atropine potency (e.g. chlorpheniramine)
iii. A bronchodilator with an antihistamine or an
antitussive.
Very few (according to one survey only 11 of listed 80
formulations) can be considered to be rational. Local nasal
decongestants can have serious adverse effects. Instillation
of saline drops followed by suction with a bulb syringe is
simple, safe and effective.
Antibiotics
More than a hundred different antibiotics are now
available but only a few (less than a dozen) are required
in day-to-day practice. The clinician should know them
thoroughly. Some general principles dos and donts
governing their rational use are given below:
Use antibiotics only if indicated. Do not use them to

treat viral infections.
Do not use antibiotics as antipyretics.
Give antibiotics prophylactically only if justified. There
are very few conditions where antibiotic prophylaxis
is indicated.
If there is urgency of starting an antibiotic, collect
appropriate body fluids/tissues for culture and
antibiogram before starting therapy.
If cultures are not possible, at least simple laboratory
screening for bacterial infection (CRP, band cells count,
etc.) should be carried out.
Enquire about previous allergies before starting
antibiotic therapy.
Consider special situations (pregnant/lactating
mothers, organ failure) while choosing the drug and
the dose.
Use the right antibiotic in the right dose by the right
route for the right duration.
Avoid fixed-dose combinations (use of only a few
combinations like co-trimoxazole, amoxycillinclavulanate, anti-TB drugs is justified).
Do not rush for a new antibiotic blindly. Old is gold
all its advantages and disadvantages are known. A
new drug is more likely to give unpleasant surprises.
Keep a watch for adverse reactions.
BIBLIOGRAPHY
1. Greenhalgh T. How to Read a Paper. 3rd Edn. Oxford,
Blackwell Publishing Ltd., 2006.
2. Phatak AT, Desai HK. Medical audit for rational
treatment. Indian Pediatr 1987;24:325-29.
3. Straus SE, Richardson WS, Glasziou P, Haynes RB.
Evidence-Based Medicine. 3rd Edn. Elsevier Churchill
Livingstone, 2005
4. World Health Organization. The Use of Essential Drugs.
WHO Technical Report Series 1990; 796.
22.1 The Need and Scope of Intensive Care in Pediatrics: Krishan Chugh ............................................................................................ 1136
22.2 Organization of a Pediatric Intensive Care Unit: Sunit C Singhi ..................................................................................................... 1138
22.3 Cardiopulmonary Resuscitation: Yogesh C Govil ............................................................................................................................ 1141
22.4 Shock: Jayashree Muralidharan ........................................................................................................................................................... 1148
22.5 Acute Respiratory Failure: Uday B Nadkarni ..................................................................................................................................... 1153
22.6 Assisted Ventilation in Children: Suchitra Ranjit .............................................................................................................................. 1156
22.7 Monitoring a Child on Intensive Care: Archana Sathe ..................................................................................................................... 1160
22.8 Interpretation of Laboratory Findings in a PICU: Anil Sachdev ...................................................................................................... 1168
1136
22.1 The Need and Scope of Intensive

Care in Pediatrics
Krishan Chugh
Pediatric intensive care is the branch of medical science
which provides care to most seriously ill children, many
of whom have compromised respiration and circulation
with some of their organs already showing signs of
dysfunction or at risk of functional failure.
Three types of patients are admitted to the pediatric
intensive care unit (PICU):
i. Those who have critical dysfunction of vital organs.
ii. Those who have a high chance of critical
dysfunction of vital organs in the immediate period
ahead.
iii. Those who require extra nursing care.
An analysis of age and sex distribution of children
admitted in PICU shows that maximum children are in
their infancy and males predominate; a trend similar to
that seen in western countries (Table 22.1.1).
Pediatric intensive care provides comprehensive care
to the critically ill child, often integrating a number of
other pediatric subspecialties such as cardiology,
pulmonary medicine, and surgery (Table 22.1.2). The
field of pediatric intensive care encompasses practical
management issues of resuscitation, monitoring,
concentration of resources, and bedside titration of
therapy.
The management of critically ill children in PICU is
extremely expensive as it needs large number of skilled
and trained personnel and sophisticated medical
equipment and costly medicines. Our economic
limitations make it imperative on us to concentrate the
medical equipment and the trained personnel to a
predesignated area, i.e. PICU. Admitting all seriously ill
children into a separately designated area (PICU) ensures
that the medical equipment would not be damaged
frequently, repair will be fast and efficient. Further,
concentration of efforts by the medical team to a
designated area will minimize the number of members
required to provide the care.
In the advanced countries, in a majority of centers
critical care to children in the PICUs is being provided by
pediatric intensivists who have received training and
certification in pediatric intensive care. The pediatric
intensivist must be capable of independent judgement and
TABLE 22.1.1: Age distribution of PICU patients

Age group
(N = 439)
N
< 1 month
1-6 months
7-12 months
1-4 years
5-8 years
9-12 years
> 12 years
14
107
44
125
65
47
37
(2003)
(%)
3.2
24.3
10.02
28.47
14.8
10.7
8.43
Source: Sir Ganga Ram Hospital, New Delhi

TABLE 22.1.2: PICU patients: distribution by
primary system of involvement
System
Respiratory
CNS
CVS
GIT
Renal
Hematology
Infections
Poisoning
Miscellaneous
Vellore
AIIMS
SGRH
(%)
(%)
(%)
26.2
23.4
9.5
7.3
2.2
4.5
9.5
9.3
5.1
13.5
36.0
7.8
13.8
7.0
6.3
14.8
10.2
17.31
23.69
5.92
11.39
4.1
4.1
10.25
0.91
5.47
decisions at times of crises without consultation/

collaboration. He/she must have a thorough
understanding of pathophysiology of life support (i.e.
appropriate treatment of organ systems failure). He/she
must have skills of providing basic and advanced life
support to the critically ill.
Continuing medical education of all members of the
team is mandatory. The trainees, residents, subspecialty
residents and nurses all have to keep up with the latest
knowledge and the pediatric intensivist has to provide
this knowledge to them and encourage them to acquire
it from other sources also.
A certification course of one year has recently been
started in India also for the post-MD candidates. Whether
certified or otherwise trained, the director of PICU and
Pediatric Intensive Care 1137

Ensuring Quality of Care
Figure 22.1.1: PICU management
his whole team are faced with another problem:

acquiring and trying newer technologies, treatment
modalities and drugs in the critically ill children.
Although, many of these do not have any sound scientific
evidence to support their use, the physicians are
pressurized by the industry, colleagues and parents to
try them as the treatment being given is failing. In such
circumstances, two principles must be remembered do
no harm to your patient and follow standard treatment
protocols or consensus guidelines.
Legal and Ethical Issues
Occasionally, legal problems arise in the PICUs in our
country, too. The best way to minimize them is to take
an informed consent from the parents for all forms of
treatment in the PICU and maintain a clear, complete
and honest communication with them throughout the
childs stay in the PICU (Fig. 22.1.1).
Ethical issues crop up in the PICU almost every day.
Both, parents and professionals, have to work together
in a therapeutic alliance to set the goals of treatment in
any individual case. However, it should be left to the
professionals to make decisions about which treatment
modalities are necessary to advance these goals.
Institutional policies have been advocated to help,
prevent or resolve ethical conflicts in critical care.
It is the responsibility of all members of PICU team
to help the parents cope up with a critical situation. They
should try to understand the problems of the family,
show empathy and objectivity, keep them fully informed
about their childs condition but never lose professionalism. Help of a social worker or a psychologist may be
needed.
To ensure optimum outcome in patients being treated in

a PICU, all efforts have to be put into maintain the quality
of care. Several quality management techniques have
been devised and tested. Traditional approaches include:
laying down and following ICU policies and protocols,
quality assurance programs and morbidity and mortality
reviews. However, recently more effective methods of
assessing quality have been introduced. These include
quality improvement techniques, evidence based
standards and critical care clinical practice guidelines.
All along, the mandatory practice standards laid by the
governmental health authorities of the region have to be
followed to avoid getting into legal problems.
A comparison of morbidity and mortality parameters
among different PICUs is inevitable when evaluating the
quality of care being provided in a given PICU. When
doing this, one must take into account the severity of
illness of children treated in that PICU. For assessing the
severity of illness, various scores have been developed,
e.g. Pediatric Risk of Mortality Score (PRISM), Severity
of Organ Failure (SOFA), Physiologic Stability Index (PSI)
and Acute Physiologic and Chronic Health Evaluation
(APACHE) score.
The paradigm of total quality management (TQM)
has supplanted the older narrower paradigm called
quality assurance and quality improvement in some
centers. TQM is a team-based continuous process of
examining and improving all structures and processes
in the PICU. Computerized data and information
systems are key tools in the TQM process.
Cost Issues
An audit of the activities of the PICU on a regular basis
is an essential component of ensuring good quality of
care. In a PICU, more so in the developing countries, a
balance has to obtained between quality of care on the
one hand and cost-effectiveness and efficiency on the
other hand.
Critical care medicine consumes a disproportionately
large fraction of health care resources, of the order of 1
percent of the gross domestic product in USA. There, it
has been estimated that the largest fraction of cost goes
to human resources, principally nurses (42%) and
physicians (10%). These two figures are likely to be
somewhat lower in our country.
1138

TABLE 22.1.4: Duration of stay of PICU patients
TABLE 22.1.3: Profile of PICU admissions
Ventilation required
Yes
No
Survivors/Non-survivors
Survivors
Non-survivors
(N = 439)
N
(2003)
(%)
119
320
27.1
72.9
395
44
90
10
Modern day pediatric intensive care involves giving

ventilatory support (Table 22.1.3) and continuous
vasoactive support to many children. Continuing these
measures during transport, e.g. to the CT scan center,
inside the center and back to the PICU can be hazardous
and requires sophisticated technology. If a decision to
actually transport the child is made quality care before,
during and immediately after transport should be
ensured.
In its relatively short history, pediatric critical care
has accomplished much for gravely ill-infants and
children in the advanced countries. The field is evolving
in our country too. Limitations of resources have put
greater responsibility on us to work out strategies to give
maximum cost benefit ratio. With ever increasing
technological advances and better understanding of
critical illnesses in the future, we need to continue to
strive towards decreasing morbidity and duration of
PICU stay (Table 22.1.4) and mortality and helping
families of the critically ill children to cope with the
Duration of stay
< 1 day
1-5 days
6-10 days
11-15 days
16-20 days
> 21 days
(N = 439)
N
40
311
47
16
10
15
(2003)
(%)
9.11
70.85
10.7
3.64
2.28
3.42
potentially overwhelming stress. There is a great scope

for the services of pediatric intensive care to expand and
to reach out to more and more critically ill children in
centers across the country.
BIBLIOGRAPHY
1. Bongard FS, Sue DY (Eds). Current Critical Care
Diagnosis and Treatment. Tata McGraw-Hill Publishing
Co Ltd: New Delhi, 2003.
2. Fuhrman BP, Zimmerman JJ (Eds). Pediatric Critical
Care, Mosby year book: St. Louis, 1992.
3. Hall JB, Schmidt GA, Wood LH (Eds). Principles of
Critical Care. McGraw-Hill: New York, 1998.
4. Holbrook PR (Ed). Textbook of Pediatric Critical Care.
WB Saunders: Philadelphia, 1993.
5. Murray MJ, Coursin DB, Pearl RG, Prough DS (Eds).
Lippincott Williams and Wilkins: Philadelphia, 2003.
6. Rogers M (Ed). Textbook of Pediatric Intensive Care.
Williams and Wilkins: Baltimore 1997.
7. Todres ID, Fugate JH (Eds). Critical Care of Infants and
Children. Little Brown and Co Boston, 1996.
22.2 Organization of a Pediatric

Intensive Care Unit
Sunit C Singhi
The management of complex life-threatening diseases,
provision to intensive monitoring and institution of lifesustaining therapies in an organized manner to critically
ill children need separate pediatric intensive care unit
(PICU). This chapter provides guidelines to organize and
manage a PICU in our set-up.
The first consideration in establishing a new PICU is
to document the need for such a unit in a given set-up.
An assessment of its need should primarily be based on
the existing patient load and type of illnesses cared for

in that set-up. Availability of committed and appropriately trained staff, and adequate financial resources
are other important considerations.
SIZE
It is felt that a multispecialty hospital requires about
25 percent of beds for critical care, and 1 percent should
be in PICU.

LOCATION
A PICU should be located adjacent to or within direct
access to pediatric emergency room, children wards,
radiology department, and operating and recovery
rooms. Transport of patients to and from the unit for
diagnostic and therapeutic procedures should be
minimum.
SPACE
Approximately 20 m2 space should be available per
patient with 3 to 3.5 meters separating each patient.
Enough floor space should be provided around the head
end of the bed to assemble necessary personnel and
equipment for resuscitation. In addition, space should
be provided for nursing and clerical activity, doctors
duty room, nurses room, conference room, offices of
nursing superivisor and physician, laboratory, storage
area for equipment, supplies, linen and patients
belonging, a clean and soiled work room, and toilets. An
intermediate care area to allow for continuing care of
patients, and waiting room for families should also be
provided immediately adjacent to the unit. The total area
needed is about three times of the size that is needed for
beds alone.
maintenance, calibration and replacement of equipment, organization of educational and research

activities, staff development and improvement in
standrads of care, collection of statistical data
necessary for evaluation of the units effectiveness,
and implementation of policies and procedures.
2. House-staff (resident): For a 24 hours in house
coverage a house staff (resident) is a must. He or she
should be exclusively designated for PICU. He or she
must be trained in cardiopulmonary resuscitation and
intubation.
3. On-call coverage by subspecialty pediatricians,
pediatric surgeons, and anesthetist.
Nurses
Nurses are the most important staff in any PICU for
actual delivery of critical care. The ideal nurse patient
ratio is 1:1, the minimum is one nurse per two patients
in the unit all the time.
Respiratory Therapist
Respiratory therapists are an important part of PICU
team in the developed countries. At least one respiratory
therapist should be available round the clock.
DESIGN/LAY-OUT
Other Members
Provision for adequacy of observation and easy access

to the patient is of pivotal importance in the design of
patient care area. A central station for observation, record
keeping and charting, preparation of medications, and
other functions is necessary. The patient care area may
have an open ward design. For a 6 to 8 bed unit, a big
room serving 4 to 6 patient, and two smaller rooms (25
to 30 m2) serving 1 to 2 patients are adequate. These
rooms are required for isolation and dialysis. An area
for intermediate care may be designed within the PICU
to look after patients who require intensive monitoring
but are not on life supporting therapeutic intervention.
A biomedical and a laboratory technician, a unit clerk to

handle patient and administrative paper work, and a
physiotherapist should be assigned specifically for PICU.
Adequate coverage by a nutritionist should be available.
A social worker is valuable in sociopsychological evaluation and family support.
PERSONNEL
Physician Staff
1. Medical director/consultant incharge: The incharge
should have special training and experience in the
care of critically ill children. He or she must be
available full time for regular clinical, administrative,
and educational activities of the unit. The responsibilities of the incharge includes quality control,
coordination of multiple subspecialty services,
SERVICES THAT SHOULD BE AVAILABLE

Monitoring
An essential part of successful intensive care is the
anticipation and treatment of critical problem. A PICU
must therefore, have capability to monitor on continuous
basis:
i. Cardiac and hemodynamic indices
ii. Respiratory functions
iii. Temperatureincluding core temperature
iv. Cerebral functions.
Therapeutic or Diagnostic Modalities
Besides the usual facilities available in pediatric wards
following specific services should be available.
1. Emergency resuscitation
1140
2. Respiratory support
a. Maintenance of airwayendotracheal intubation
and tracheostomy
b. Mechanical ventilation
c. Tube-thoracotomy, thoracocentesis
d. Bronchoscopy
3. Cardiac support
a. Defibrillation
b. Temporary cardiac pacing
4. Infusion pumps and pressure infusion devices for
administration of life-saving drugs.
5. Desirable
a. Left heart support
b. Intra-aortic balloon assist
c. Extracorporeal membrane oxygenation
d. Hyperbaric oxygen.
TABLE 22.2.1: Specific equipment ideally

required per bed
1. Resuscitation tray with bag and mask for manual
ventilation
2. One oxygen saturation monitor/pulse oximeter
3. One 4-6 channel monitor with following capabilities
i. Respiratory rate and waveform
ii. Heart rate and ECG
iii. Noninvasive BP monitoring
iv. 2-3 invasive pressure lines for CVP, arterial pressures
v. Two temperaturescore and peripheral
vi. End tidal CO2 monitoring
Separate monitors with above capabilities may also be
obtained in phases depending on budget.
4. Infusion pumps, 2-3 syringe pumps, 2 volumetric types
5. One ventilator (preferably with both pressure control and
a volume control capabilities)
6. One EEG monitor.
Desireable: Cardiac output monitor, ICP monitor
Support Services Necessary for PICU

1. Radiodiagnosis and imaging facility:
a. 24 hours coverage for radiographs of chest, and
abdomen
b. Ultrasound
c. CT scan
d. Echocardiography
e. Angiography, lung scan as and when needed.
2. Laboratory service 24 hours a day:
a. Hematocrit, Hb, blood counts,
b. Blood glucose, urea and electrolytes,
c. Prothrombin time, PTT and platelets counts,
d. CSF and urine analysis
e. Arterial blood gases (result within hour)
Other facilities that should be available are:
i. Microbiology
ii. Blood biochemistry (Ca, PO4, Mg, liver functions)
iii. Toxicology and drug level measurements (digoxin, theophylline, aminoglycosides, phenobarbitone, etc).
3. Centralized oxygen, compressed air, and suction facility.
4. Blood bank and pharmacy.
5. Physiotherapy and occupational therapy.
6. Transport systems: An ambulance team with a nurse,
and a resident trained in evaluation and stabilization
of critically ill patient and resuscitation equipment,
drugs and basic monitoring equipment (Table 22.2.1).
7. Equipment maintenance and care: Services of a
biomedical engineer/technician for regular and
frequent servicing of equipment to keep it in good
working order. For costly equipment, regular

maintenance contract should be made with the
manufacturing firm.
Ancillary Services
1. Housekeeping related to cleaning, water, electrical,
air-conditioning, linen-cleaning, central sterilization
services.
2. Communication within ICU and outside through
telephone, paging and intercom system. A direct
outside telephone line should be available in PICU.
3. Computerized record keeping is desirable.
4. Social services.
EQUIPMENT
All monitoring equipment should have high and low
visible and audible alarms for heart and respiratory rates
and all the pressures. It should also be reliable and
electrically isolated from the patient.
BIBLIOGRAPHY
1. Rosenberg DI, Moss MM: Guidelines and levels of care
for pediatric intensive care units. Crit Care Med
2004;32:2117-27.
2. Task Force on Guidelines, Society of Critical Care
Medicinerecommendation for services and personnel
for delivery of care in a critical care setting. Crit Care
Med 1988;16:809.
3. Task Force on Guidelines, Society of Critical Care
Medicine Guidelines for categorization of services for
the critically ill patient. Crit Care Med 1991;19:279-83.
22.3 Cardiopulmonary Resuscitation

Yogesh C Govil
Cardiac arrest is the cessation of cardiac mechanical
activity, determined by the inability to palpate a central
pulse, unresponsiveness and apnea. The commonest
underlying cause of cardiac arrest in children is
respiratory failure. The second commonest cause of
cardiac arrest is circulatory failure. Unlike adults, cardiac
arrests of primarily cardiac origin, for example arrhythmias and pump failure, are uncommon in childhood.
Thus, early diagnosis and aggressive treatment of
respiratory or circulatory insufficiency aimed at avoiding
cardiac arrest is the key to improve survival without
neurological deficit in seriously ill children.
Cardiopulmonary resuscitation (CPR) consists of
measures for establishing and maintaining the airway,
controlling breathing and providing adequate circulation. These measures are commonly known as the
ABC, signifying airway, breathing and circulation, the
goal of which is to maintain adequate oxygenation and
perfusion of blood throughout the body while steps are
taken to stabilize the child and establish long-term
homeostasis.
Basic Life Support
Basic life support (BLS) includes sequential assessments
and skills designed to restore and support effective
ventilation and circulation in the child with respiratory
or cardiorespiratory arrest. In BLS CPR requires skills,
with no devices or with bag-mask ventilation and
automated external defibrillation (AED) and can be
performed even outside the hospital.
Since early effective bystander CPR has been
associated with successful return of spontaneous
circulation and neurologically intact survival, BLS
courses should be offered to target populations such as
expectant parents, child care providers, sports supervisors, and those who regularly care for children.
outside the hospital unless trained personnel who

continue to be trained periodically to maintain their
expertise as a part of an organized system such as the
emergency medical service (EMS) system are available.
It is important to realize that failure of the circulation
for three to four minutes (less if the victim is initially
hypoxemic) will lead to irreversible cerebral damage and
possibly death from multisystem failure. Cardiopulmonary resuscitation therefore, must be begun rapidly
and should follow the recommended sequence of actions.
Sequence of Basic Life Support
Ensure safety of rescuer and child: From nonrespirable
atmosphere, danger of electrocution, traffic, falling
masonry or a burning bulding, etc.
Check the childs responsiveness: The rescuer must quickly
assess the consciousness level by gently pinching the
child and asking loudly Are you alright?
Open the airway: The rescuer should shout for help and
proceed immediately to open the airway. Airway obstruction is common in the unconscious victim because of
relaxation of muscles and passive posterior displacement
of the tongue. Following methods can be used for opening
the airway.
Head till-chin lift (Fig. 22.3.1A): One hand is placed on
the childs forehead and the head is gently tilted back
Pediatric Advanced Life Support

Pediatric advanced life support (PALS) comprises BLS
with the use of other adjunctive equipment and special
techniques to assess and support the pulmonary and
circulatory function and may not be optimally performed
Figure 22.3.1A: Opening the airway head tilt-chin

lift maneuver
1142
Figure 22.3.1B: Opening the airway with

the jaw thrust maneuver
Figure 22.3.2A: Rescue breathing in an infant

mouth-to-mouth and nose breathing
into a neutral or slightly extended position. At the same

time, the fingertips of the other hand are placed under
the point of the childs chin and the mandible is lifted to
open the airway. Closure of mouth and pushing of soft
tissues under the chin should be avoided since such
maneuvers may further obstruct the airway.
Jaw thrust (Fig 22.3.1B): This method is used if cervical
spine injury is suspected. Two or three fingers are placed
under each side of the lower jaw at its angle and the jaw
is lifted upwards keeping the mouth open by depressing
the tip of the chin with the thumbs with the rescuers
elbows resting on the surface. Because maintaining a
patent airway and providing adequate ventilation is a
priority in CPR, a head tilt-chin lift maneuver is used if
the jaw-thrust does not open the airway.
or mouth-to-mouth and nose or mouth-to-mask with a

mask over the victims nose and mouth or bag-mask
respiration. In the event of the non-availability of a bag
and mask, first the rescuer takes a breath. Then, if the
victim is an infant, his or her mouth and nasal apertures
or only the nose if there is difficulty in covering both the
nose and open mouth of a large infant, are covered by
the rescuer with his or her mouth, creating a good seal
(Fig. 22.3.2A). It may be necessary to close the infants
mouth during mouth-to-nose breathing. If the victim is
a large infant or a child, the victims nose should be
pinched with the thumb and forefinger by the rescuer,
keeping the same hand on the victims forehead to
maintain head-tilt, and a mouth-to-mouth seal is made
(Fig. 22.3.2B). The air is blown stadily and slowly over 1
to 1 and seconds thereby avoiding gastric distention
while watching the rise in chest.
A self-inflating bag-valve device with a face mask has
clear advantage over mouth-to-mouth/nose rescue
breathing in that a higher inspired oxygen concentration
can be provided (Fig. 22.3.3). The self-inflating bag should
have a volume of at least 450 to 500 ml to deliver an
effective tidal volume. An oxygen flow of 10 to 15
L/min into the oxygen inlet and a reservoir attached to
the air inlet of the bag is necessary to deliver a high
oxygen concentration (60-95%).
Effective ventilation can be achieved by a single
person; the thumb and forefinger of one hand are used
to create a tight seal between the mask and face while
the remaining fingers of that hand are used to lift the
jaw. The other hand compresses the bag. A two-person
Keeping the airway open, look, listen and feel for breathing:
To determine whether the child is breathing or not, the
rescuer looks for a rise and fall of the chest and abdomen,
listens for breath sounds by placing his or her ears close
to the victims mouth and nose, feels for exhaled air on
his or her cheeks, taking no more than 10 seconds.
If the child is breathing or resumes breathing, the child
should be turned on his or her side into the recovery
position to help maintain a patent airway and to decrease
the risk of aspiration while checking for continued
breathing.
If no spontaneous breathing is detected any obvious airway
obstruction is removed and rescue breathing is provided
while maintaining a patent airway. Rescue breathing
may be provided by mouth-to-mouth or mouth-to-nose

return and cardiac output, distention of stomach
increasing the risk of regurgitation and aspiration, and
barotrauma. If bag-mask ventilation does not provide
adequate ventilation or if prolonged ventilation is
needed, endotracheal intubation is indicated.
Assess the child: Following opening of the airway and
provision of rescue breaths, the need to provide chest
compression is determined by palpating a pulse (the
brachial or femoral pulse) in the child. The presence, rate,
and volume of the pulse is assessed and failure to detect
the presence of pulse within 10 seconds in an unresponsive nonbreathing victim should be taken as an
indication to initiate chest compression.
Figure 22.3.2B: Rescue breathing in a child

mouth-to-mouth breathing
If circulation is adequate: If a pulse is present but

spontaneous breathing is absent, rescue breathing alone
should be provided at a rate of 20 breaths per minute
(once every 3 seconds) until spontaneous breathing
resumes. During delivery of rescue breaths, the pulse is
rechecked every 2 minutes.
If there are no signs of a circulation: (Breathing, coughing,
movement, or pulse) or the pulse rate is less than 60 per
minute, with signs of poor perfusion, chest compression
is started, combining it with rescue breathing. The child
should be placed supine on a hard, flat surface to achieve
optimal compressions. In infants, the chest compression
is done either by a two-finger technique in which two
fingers are placed perpendicularly over the sternum just
below the intermammary line (Fig. 22.3.4) or preferably
the two thumb-encircling hands technique. In this
technique, both thumbs are placed side-by-side over the
same sternal location as described above, encircling the
infants chest and supporting the infants back with the
fingers of both hands.
Figure 22.3.3: Use of a self-inflating bag-valve

device with a face mask
technique may be necessary to provide effective bagmask ventilation when there is significant airway
obstruction, poor lung compliance or difficulty in
creating a tight seal between the mask and the face. One
rescuer uses both hands to open the airway and maintain
a tight mask-to-face seal while the other rescuer
compresses the ventilation bag. It is crucial to observe a
good visible chest rise but excessive chest rise caused by
excessive ventilation may have adverse effects such as
raised intrathoracic pressure compromising venous
Figure 22.3.4: Chest compression in an infant
1144

changes have been caused by the realization that
ventilations are relatively less important during the first
minutes of CPR for victims of a sudden arrhythmiainduced cardiac arrest; but even in an asphyxial arrest, a
minute ventilation that is lower than normal is likely to
maintain an adequate ventilation-perfusion ratio because
of lower pulmonary perfusion due to poor cardiac
output. However, as mentioned above, there is an
overwhelming need to minimize interruptions in chest
compressions. Once endotracheal intubation has been
done, chest compression at a rate of 100 per minute and
ventilation at a rate of 8 to 10 breaths per minute are
performed continuously and simultaneously without a
pause by two providers.
Figure 22.3.5: Chest compression in a child
The area of compression in a child is located by

placing the heel of the hand, one fingers breadth above
the xiphisternal notch, with the long axis of the heel
parallel to that of the sternum (Fig 22.3.5).
In children over the age of 8 years, it may be necessary
to use the adult two-handed method of chest
compression, the site of compression being the same. The
rescuer positions himself vertically above the victims
chest and keeping the arms straight (applicable only
when heel(s) of hand is/are used.
Good chest compressions have the following
characteristics:
i. Push hard, i.e. the sternum should be pushed with
sufficient force to depress the chest approximately
one-third to one-half the antero-posterior diameter
of the chest.
ii. Push fast, i.e. the rate of compression should be
around 100 per minute.
iii. Following each compressing, the pressure is
released completely to allow the chest to fully recoil.
iv. Interruptions during chest compressions should be
minimum as the coronary perfusion pressure drops
with each pause.
Coordination of chest compression and breathing: In contrast
to the previous recommendations of a compressionventilation ratio of 5:1 currently cycles of 30 compressions
followed by 2 effective breaths are advocated for a single
rescuer. A compression ventilation ratio of 15:2 in
recommended if there are two trained rescuers. These
Defibrillation
Continued absence of pulse following 5 cycles of CPR
(one cycle for the lone rescuer being 30 compressions and
2 breaths) should prompt the use of automated external
defibrillator (AED) in children more than 1 year of age.
In view of higher probability of ventricular fibrillation
or pulseless ventricular tachycardia (shockable rhythms),
AED should be used as soon as possible in children with
sudden witnessed collapse. Availability of AEDs that can
recognize pediatric shockable rhythms and can deliver
appropriate energy has made these devices safe and
effective even when used by lay peope.
Sequence of Actions for Foreign Body
Airway Obstruction
In a witnessed or seriously suspected foreign body
aspiration, if the child is breathing spontaneously, he or
she should be encouraged to persist with spontaneous
coughing and breathing efforts as long as the cough is
forceful. Intervention is necessary only if the cough
becomes ineffective, if breathing is inadequate or if the
child loses consciousness.
For an Infant
1. Perform up to five back blows by holding the infant in
the prone position straddling on ones forearm, with
the head being held firmly by holding the jaw in a
position lower than the trunk (Fig. 22.3.6). Back blows
are given using the heel of the hand to the middle of
the back between shoulders blades. If this fails to
dislodge the foreign body, one should proceed to
perform the chest thrusts.
Figure 22.3.6: Performing back blows in an infant
2. Perform up to five chest thrusts at the same location as

for chest compression after turning the infant as a
unit into supine position. The technique for chest
thrusts should be sharper and more vigorous than
compressions and carried out more slowly (5 thrusts
in 15 seconds).
3. Remove the foreign body from the mouth if it is seen.
4. Open airway by head tilt-chin lift maneuver and
reassess breathing.
5. Provide upto 5 rescue breaths if child is not breathing.
6. Repeat five back blows and five chest thrusts and rescue
breathing cycles until the airway is cleared and rescue
breathing successful.
Figure 22.3.7: Abdominal thrusts with victim

standing or sitting
described for infants and Heimlichs maneuver is

repeated as described below.
When the child is either conscious or unconscious: With the
child lying down, the rescuer kneels beside the victims
hips. Both hands are placed on top of each other with
the heel of one hand at the same site as described for
conscious child (Fig. 22.3.8). Rest of the sequence is same
as for conscious child.
For a Child
Abdominal thrusts (Heimlichs maneuver) are used to
generate an artificial cough to clear the airway in the
following sequence.
When the child is conscious: With the child standing or
sitting, one stands behind him and the arms are wrapped
around the child just below the lower margin of the rib
cage placing the flat, thumb side of 1 fist against the
victims abdomen (Fig. 22.3.7) and clasping the hands
tightly together a series of up to five quick upward thrusts
are given over the victims abdomen in the midline
slightly above the navel and well below the tip of the
xiphoid process. The series of five thrusts should be
continued until the foreign body is expelled or the patient
loses consciousness. If the child loses consciousness, the
airway is opened and rescue breathing attempted as
Figure 22.3.8: Abdominal thrusts with victim lying down
1146
Figure 22.3.9: Summary of pediatric basic life support
A summary of sequence of actions for pediatric basic

life support is shown in Figure 22.3.9.
of only one component of PALS, i.e therapies for

emergency treatment of children with cardiac and
respiratory arrest follows.
Advanced Life Support
Maintenance of the Airway
Since detailed description of advanced life support (ALS)

is beyond the scope of the present chapter, a brief account
Insertion of an oropharyngeal (Guedel) airway moves the

tongue from the back of the pharynx and helps in

Intracardiac administration of drugs is not practiced
because of the risks of coronary artery laceration,
pneumothorax, cardiac tamponade, and intractable
arrhythmias.
Drug Therapy
Endotracheal intubation is the method of choice for

guaranteeing the airway. Intubation protects the airway
from aspiration of gastric contents, permits suctioning
of the airway, optimum ventilation and delivery of
adequate oxygen, and enables administration of
resuscitation medications through endotracheal route.
Adrenaline (epinephrine) is the primary resuscitation

medication. It is administered in a dose of 0.01mg/kg
(0.1 ml/kg of 1:10,000 solution) IV or IO or 0.1 mg/kg
(0.1 ml/kg of 1:1,000 solution by the endotracheal route.
For persistent arrest the same dose of adrenaline may be
repeated every 3 to 5 minutes.
While atropine in a dose of 0.02 mg/kg (minimum
0.1 mg; maximum 1 mg in children and 2 mg in
adolescents) is effective for bradycardia or cardiac arrest
induced by increased vagal tonefor example, during
airway manipulation, calcium is no longer recommended
in the treatment of asystole. Sodium bicarbonate should
only be used in the patient with prolonged cardiac arrest
in a dose of 1 mEq/kg IV or by the intraosseous route
and may be repeated every 10 minutes during the arrest.
Lastly, 25 percent glucose in a dose of 2 to 4 ml/kg IV
should be administered during CPR if hypoglycemia is
detected by rapid reagent strips.
Advanced Circulatory Support
Intravenous (IV) Fluid Administration
Good ventilation, oxygenation and effective chest

compressions may be sufficient to restore an adequate
circulation. Those who do not respond will need
medications, to increase vital organ perfusion pressure,
myocardial contractility and heart rate and to treat
arrhythmias.
If the child in cardiac arrest does not respond to initial

resuscitative efforts and adrenaline, a fluid bolus of 20
ml/kg of Ringers lactate or normal saline is useful.
Figure 22.3.10: The oropharyngeal airway
establishing the airway when head tilt-chin lift or jaw

thrust is not effective. The correct size will extend from
the center of the childs mouth to the angle of the jaw
(Fig. 22.3.10)
Vascular Access
Peripheral venous access may be quite satisfactory if it
can be obtained rapidly. If after 90 seconds or three
attempts, venous access attempts are unsuccessful,
intraosseus (IO) route on the anterior aspect of tibia 1 to
3 cm below the tibial tuberosity should be employed for
fluid infusion or drug administration in infants and
young children. In older children, the intraosseous
cannula may be inserted into the distal tibia, anterior
superior iliac spine, distal radius or distal ulna.
Alternatively, cannulation of femoral vein may be tried
as it being a central vein provides a more direct access
for drug administration. Until vascular route is obtained,
drugs may be administered directly into the endotracheal
tube if it is already in place.
Indications for Termination of CPR

The decision to terminate resuscitation efforts is
frequently difficult. The presence of dilated pupils have
in the past been used as a sign of presence of established
brain damage. However, this sign is unreliable and
should not be used to discontinue CPR. The current
recommendation is that in the absence or recurring of
refractory ventricular fibrillation or ventricular tachycardia, history of a toxic drug exposure or electrolyte
imbalance, or a primary hypothermic injury, the
resuscitation team should discontinue resuscitation
efforts after 30 minutes if there is no return of spontaneous circulation.
When resuscitative efforts are successful, the child
should be transferred to a PICU, if available, for repeated
and regular cardiopulmonary assessments and appropriate interventions. A successful CPR outcome is the
discharge from the hospital of a functioning patient with
1148
intact central nervous system (CNS), likelihood of which

is increased when CPR is begun early and pursued
systematically and expeditiously in accordance with the
above guidelines.
BIBLIOGRAPHY
1. Emergency Cardiac Committee and Subcommittees,
American Heart Association. Guidelines for cardiopulmonary resuscitation and emergency cardiac care.
JAMA 1992;268:2251-75.
2. Guidelines for cardiopulmonary resuscitation and
emergency cardiovascular care. American Heart
Association, Pediatric Basic Life Support. Circulation

2005;112:IV-156-IV166.
3. Hickey RW, Cohen DM, Strausbaugh S, Dictrtich AM.
Pediatric patients requiring cardiopulmonary resuscitation in the prehospital setting. Ann Emerg Med 1995;25:
495-501.
4. Mathers LH, Frankel LR. Pediatric emergencies and
resuscitation. In Behrman RE, Kliegman RM. Stanton BF
Jensen HB (Eds): Nelson Textbook of pediatrics (18th
edn). WB Saunders: Philadelphia 2007;387-405.
5. Young KD, Seidel JS. Pediatric cardiopulmonary
resuscitation: A collective review. Ann Emerg Med
1999;33:195-205.
22.4 Shock
DEFINITION
Shock is a state of widespread reduction in effective tissue
perfusion resulting in insufficient or improper delivery
and distribution of oxygen and nutrients. The result is
an altered cellular and subcellular function leading to
anerobic metabolism, accumulation of lactic acid and
consequently cellular damage, multiple organ dysfunction and finally cardiovascular collapse. Clinically shock
is characterized by signs of hemodynamic instability,
tachycardia, hypotension and evidence of organ
hypoperfusion.
PATHOPHYSIOLOGY OF SHOCK
The primary pathophysiological event in shock,
regardless of etiology is tissue hypoperfusion which leads
to tissue hypoxia, acidosis and end organ dysfunction.
Myocardial Dysfunction
Myocardial dysfunction develops in nearly all the
patients with septic shock. This dysfunction peaks soon
after the onset of sepsis and resolves within 7 to 10 days
in survivors. Sepsis stimulates the release of inflammatory mediators that can compromise cardiac
function. Dilatation of ventricles, reduced contractility
and decreased ventricular compliance may be seen. Both
systolic and diastolic dysfunctions are well described in
septic shock. Diminished responsiveness of the myocardium to 1 agonists is secondary to down regulation of
1 receptors, uncoupling of receptors from adenylate

cyclase or depressed generation of cAMP. The myocardium is dysfunctional despite an increase in cardiac
output during the hyperdynamic phase of sepsis.
Mean Arterial Pressure (MAP)
Maintenance of an adequate MAP is fundamental to
ensure adequate perfusion and organ function. When
mean arterial pressure (MAP) falls below the autoregulatory range of an organ, blood flow decreases,
resulting in tissue ischemia and organ failure. Because
the kidney receives the second highest blood flow of any
organ in the body, measurement of urine output (with
the exception of patients with hyperosmolar states
leading to osmotic diuresis) and creatinine clearance can
be used as an indicator of adequate perfusion pressure.
OXYGEN DELIVERY VS. CONSUMPTION
Oxygen delivery is primarily dependent on cardiac output.
Enhancing cardiac output by increasing preload and
contractility or by decreasing afterload will thus increase
oxygen delivery. Contrary to adults, oxygen delivery, not
oxygen extraction, is the major determinant of oxygen
consumption in children. Attainment of the therapeutic
oxygen consumption goal of >200 mL/min/m was found
to be associated with improved outcome. Abnormalities
between oxygen delivery and extraction in patients with
septic shock have been the focus of considerable interest.
In these patients the concept of pathological oxygen
utilization is forwarded to explain dependence of oxygen

consumption on oxygen delivery even at supranormal
oxygen delivery. The goal in such patients is therefore to
increase oxygen delivery and consumption until consumption is independent of delivery.
Etiologic Classification of Shock
The patient with shock has abnormalities of either: (i) the
heart, (ii) the blood volume, or (iii) the blood flow
distribution. Accordingly shock can be classified into
three groups:
1. Hypovolemic (decreased circulating blood volume)
2. Cardiogenic (impaired cardiac function)
3. Distributive (Inappropriate distribution of blood flow).
Several etiologies which fall into these broad groups
are outlined in Table 22.4.1.
children worldwide. It is usually caused by hemorrhage

or dehydration. Relative hypovolemia may occur
secondary to third spacing of fluids (extravascular
fluid) as it may be observed in children with burns or
with sepsis. Depending on the severity and rate of
development of hypovolemia, the shock may appear
abruptly or evolve gradually over several stages. When
cardiac output is unable to meet the demands of the
tissues, compensatory sympathetic activity produces
selective vasoconstriction of the skin and splanchnic
vessels to divert blood flow to vital organs-namely brain,
heart and kidney. Once the volume deficit exceeds 25
percent of the total volume, the compensatory mechanisms fail, and profound reduction of cardiac output and
fall of blood pressure occur.
HypovolemicTABLE
Shock22.4.1: Causes of shock
Hypovolemia
Hypovolemic
shock isloss
the leading form of shock in
1. Fluid and electrolyte
Diarrhea, vomiting
Excessive sweating
Pathologic renal loss
2. Blood loss
External laceration
Internal ruptured visceras, GI bleed
Intracranial bleed (neonates)
3. Plasma loss
Burns
Leaky capillaries sepsis, inflammation
Nephrotic syndrome
Third space loss. Intestinal obstruction, peritonitis
4. Endocrine
Diabetes mellitus
Diabetes insipidus
Adrenal insufficiency
Cardiogenic
1. Myocardial insufficiency
Congestive heart failure (Congenital, or acquired heart
disease)
Cardiomyopathies, myocrditis
Arrhythmias
Hypothermia
Drugs, toxins
Myocardial depressant effect of hypoglycemia,
acidosis, hypoxia
2. Outflow obstruction
Cardiac tamponade
Pneumopericardium
Tension pneumothorax
Pulmonary embolism
Distributive
Septic shock
Anaphylaxis
Drugs/toxin
Tissue injury
Prolonged hypoxia of ischemia
Cardiogenic Shock
Cardiogenic Shock is commonly described as pump
failure. The common causes are myocarditis, dysarrhythmias, drugs with a myocardial depressant action,
acidosis, and sepsis. It can also result from obstruction
to the outflow tracts (increased afterload). Cardiogenic
shock will have low cardiac output, hypotension and
clinical signs of inadequate tissue perfusion. Typically
intravascular volume is adequate or even increased, but
cardiac dysfunction limits cardiac output.
Distributive Shock
The most common cause of distributive shock is sepsis.
The common denominator in this shock is leakage of
intravascular fluid through capillary bed into interstitial
space known as third spacing of fluids because of
endothelial damage. Sepsis is a systemic disease caused
by microorganism or their products in the blood. The
majority of cases of septic shock are caused by gramnegative bacilli but it may be caused by gram-positive,
rickettsial, fungal and viral infections. Early septic shock
is known as warm shock or hyperdynamic phase as it
is characterized by warm extremities, low systemic
vascular resistance, high or normal cardiac output,
normal BP and increased pulse pressure. Low systemic
vascular resistance increases skin blood flow and causes
bounding peripheral pulses. Therefore despite high
cardiac output, shock and metabolic acidosis develop
because blood flow is inappropriately distributed.
Adequate and early treatment at this stage may
prevent progression. The latter phase of cold shock or
1150
hypodynamic phase is characterized by cold extremities,

high systemic vascular resistance, low cardiac output,
narrow pulse pressure and hypotension leading to
hypoxia, acidosis and death.
Clinical Features and Stages of Shock
Shock can progress over a span of few hours or occur
over minutes, e.g. in hemorrhagic shock. The progression
can be arbitrarily divided into three stages:
i. Early compensated shock
ii. Decompensated shock
iii. Irreversible shock.
Early Shock
Early shock refers to preserved vital organ functions
secondary to effective compensatory mechanisms. Blood
pressure is maintained although signs of inadequate
tissue and organ perfusion are observed. The early
physical signs are that of an exaggerated sympathetic
response to stress. Tachycardia and signs of decreased
peripheral perfusion namely cold-clammy skin, capillary
refill time more than 2 seconds and difference between
core and surface temperature of > 2C are the most
important clinical pointers to early shock. Tachypnea
may be seen without evidence of an underlying
pulmonary disease. Blood pressure is maintained within
normal range during the early stages.
Septic shock in the early stages presents with fever,
warm well-perfused extremities, bounding pulses and
wide pulse pressure. As capillary refill time of 3 seconds
are more denotes impaired skin perfusion, it is a valuable
sign during assessment and monitoring.
vasoconstriction. A cascade of anaerobic tissue metabolism and multiorgan dysfunction sets in. Patients
presents with poor pulses, peripheral cyanosis, cold
extremities, hypotension and acidosis due to which the
vital organ perfusion is progressively compromised.
Oliguria or anuria results from diminished renal
perfusion. Diminished cerebral perfusion manifests in
the form of lethargy, confusion and disorientation. Rapid
aggressive intervention is required to halt the progression
to irreversible stage. Table 22.4.2 summarizes the clinical
features in shock syndrome.
Irreversible Stage
Irreversible stage of shock is a progressive reduction in
cardiac output, fall in blood pressure and worsening
metabolic acidosis, and multiorgan failure.
Complications of Shock
Myocardial Depression
Long periods of shock will eventually cause reduced
cardiac function. Products of tissue necrosis have been
implicated as myocardial depressants. This is commonly
seen in hypovolemia and sepsis.
Shock Lung
The capillaries of the lung become leaky after a few days
of persistent shock. Patchy infiltrates start appearing in
the lung fields. Eventually the lung condition worsens
to a full blown ARDS (acute respiratory distress
syndrome).
Decompensated Shock
Acute Renal Failure
In this stage, the blood pressure and cardiac output fall

as they cannot be sustained by the intense peripheral
Renal failure sets in once hypotension has been severe

and prolonged.
TABLE 22.4.2: Clinical stages of shock and physical signs

Clinical
Parameters
StageI
(compensated)
Stage II
(decompensated)
Stage III
(irreversible)
Heart rate
Resp. rate
Blood pressure
Pulse pressure
Skin
Mental status
Urine
Tachycardia
Normal
Normal
Normal
Cool
Anxious
Normal
Marked tachycardia
Tachypnea
Hypotension
Low
Mottled
Obtunded
Oliguria
Severe tachycardia, bradycardia

Tachypnea/apnea
Severe hypotension
Markedly low
Cold and cyanotic
Coma
Anuria

Disseminated Intravascular Coagulation (DIC)
Lowered tissue perfusion produces platelet aggregation
and release of tissue thromboplastin producing hypercoagulable state and DIC.
Laboratory investigations that should be obtained in a
patient with shock are shown in Table 22.4.3.
Management of Shock
The successful management of shock requires treatment
of the cause, optimization of cardiac output and systemic
oxygen delivery and restoration of tissue perfusion. This
requires frequent assessment and monitoring of the
patient.
Oxygen Administration
Oxygen should be administered to all patients in shock
in view of the impaired oxygen delivery to the tissues.
Fluid Therapy
The objective of fluid administration in shock is to rapidly
restore effective circulating volume so as to establish vital
organ perfusion. Optimization of circulating volume with
help of fluids is most important cornerstone of therapy
in shock. An immediate intravenous access has to be
established. In children where IV access is difficult due
to collapsed veins an intraosseous line must be
established instead.
TABLE 22.4.3: Suggested investigations in a child with
septic shock
ECG
Chest X-ray
Echocardiogram
Blood gases
Respiratory system
Blood gases arterial
and mixed venous
Lung function tests
Renal system
Urine Na+/Sp. Gravity/
Sediments
Urine protein/sugar
Serum urea/creatinine
Hematologic system
Hematocrit, TLC, DLC
Coagulation parameters
Platelet counts
Gastrointestinal
Stool occult blood
Gastric pH
Liver function test
Pancreatic functions
Metabolic
Serum Na+/K+/Ca+Mg+2
Phosphorus
Blood glucose
Infection screen
Cultures-Blood CSF
Urine
Stool
Pus
Toxicology screen
Volume expansion should be achieved rapidly with

a crystalloid solution, i.e. Isotonic saline or Ringers
lactate. Volume replacement should begin as 20 ml/kg
IV while one is trying to assess the etiology. Response to
fluid challenge includes an improvement in capillary
refill, decreasing tachycardia, elevation of blood pressure
and maintenance of an adequate urine output (1 ml/kg/
hr). Subsequent choice of fluid may depend on the
etiology, acid-base and electrolyte status, oxygen delivery
and coagulation parameters. The amount of fluid to be
infused depends on the volume status, patients response
and the ongoing losses in the patients. Patients in hypovolemic and septic shock may require up to 60 ml/kg in
first one to one and half hours.
Colloids and blood products may be required in select
situations. Blood as volume expander should be given
for traumatic hemorrhagic shock or bleeding due to
coagulopathies. Even in these situations crystalloids are
the first choice for volume expansion while blood is being
arranged.
Dextrose containing solution should be avoided
during shock resuscitation unless there is documented
hypoglycemia. This is because dextrose containing fluids
cause hyperglycemia and osmotic diuresis which can
further aggravate shock.
Cardiovascular Support
Following adequate intravascular volume repletion,
continued presence of hypotension and /or poor perfusion
warrants the consideration of vasoactive therapy, which
should be goal directed. The vasoactive agents used to
support circulatory function may be classified as
inotropes, vasopressors, vasodilators, and inodilators.
Inotropes increase myocardial contractility and often
increase heart rate as well, e.g. dobutamine, mid dose
dopamine 5-10g/Kg/min, low dose epinephrine
(<1 g/Kg/min).
Vasopressors increase systemic and pulmonary vascular
resistance and are therefore useful in patients with low
systemic vascular resistance. If myocardial function is
adequate, vasopressors will typically increase systemic
and pulmonary artery pressures, e.g. norepinephrine,
high dose dopamine > 10 g/Kg/min, high dose
epinephrine (> 1g/Kg/min).
Vasodilators are designed to reduce systemic and
pulmonary vascular resistance. Although vasodilators
do not directly increase myocardial contractility, they
1152
reduce ventricular afterload, which often improves stroke

volume and cardiac output. Vasodilators are the only
class of agents that can increase cardiac output and
simultaneously reduce myocardial oxygen demand, e.g.
nitroglycerine, nitroprusside.
Inodilators (inotropes + vasodilator) improve cardiac
contractility and reduce afterload, e.g. phosphodiesterase
inhibitors like milrinone and amrinone.
The clinician must determine whether there is
evidence of low cardiac output with high cardiac filling
pressure that requires inotropic support or if hypotension
is accompanied by high cardiac output that requires
presser support. Children with severe sepsis can present
with low cardiac output and high systemic vascular
resistance (SVR) (cold shock) or low cardiac output and
low SVR (warm shock). Accordingly in the cold shock,
inotropic support should be started in case of fluid
refractory shock while a combination of inotrope together
with a vasopressor is warranted in warm shock.
Generally adenergic agents are chosen for support
of cardiac contractility and adenergic agonists for
maintenance of perfusion pressure to maintain flow
distribution to the tissues.
Therapeutic End Points
The therapeutic end points of shock resuscitation are:
Capillary refill < 2 sec
Normal pulses with no difference between central
and peripheral pulses
Warm extremities
Urine output > 1 ml/kg/hr
Normal mental status
Decreased lactate and
Mixed venous oxygen saturation > 70%.
Correction of Metabolic Derangements
Metabolic acidosis: Metabolic acidosis, poor tissue
perfusion and resultant anaerobic metabolism leads to
significant metabolic acidosis. Uncorrected acidosis can
lead to further cellular damage and myocardial
depression. Sodium bicarbonate as a rescue therapy for
acidosis is indicated only in a desperate situation where
imminent myocardial failure secondary to severe and
persistent acidosis (pH is below 6.9-7.0) is suspected. In
all other situations bicarbonate must be avoided and all
attempts must be taken to correct the shock. Overcorrection can be hazardous leading to paradoxic CNS
acidosis, coma and death.
Calcium: Acute hemodynamic deterioration in various

types of shock can lead to decrease in the ionized Ca++
level. This hypocalcemia leads to tachycardia, hypotension, alteration in sensorium and motor nerve
excitability. An intravenous infusion of 1 to 2 ml/kg of
10% calcium gluconate should be given when ionized
Ca++ level falls below 2 to 4 mg/dl.
Acute Renal Failure
Adequate fluid replacement is necessary is prevent
development of renal failure. Dialysis will be indicated
in case of hyperkalemia, refractory acidosis and fluid
overload.
Hematologic Support
Hematocrit needs to be maintained between 35 and 45
percent with the help of transfusions. Bleeding which
complicates shock can be managed with fresh frozen
plasma, vitamin-K, and platelet concentrates.
Gastrointestinal Support
Shock can lead to stress bleeding from upper GIT and
toxic ileus. Prophylactic use of antacids and/or an H2receptor antagonist is recommended to prevent stress
bleeds.
Nutritional Support
Shock leads to excessive catabolism, hence nutritional
support is one of the important pillars in the management. Nasogastric feeding should start as soon as patient
can accept enteral feeds.
Respiratory Support
Respiratory support in the form of mechanical ventilation
is indicated for acute respiratory failure, to improve
oxygenation and to decrease work of breathing.
Antibiotic Therapy
Appropriate empiric antibiotics should be started in
suspected septic shock. It should provide broad spectrum
coverage depending upon site of infection and local
epidemiologic data regarding sensitivity pattern. An
aminoglycoside (gentamicin or amikacin ) and a thirdgeneration cephalosporin (cefotaxime, ceftriaxone)
should be used for suspected gram-negative sepsis.
Combination of cloxacillin and an aminoglycoside
should be used if staphylococcal sepsis is suspected.

Other Adjunctive Therapy
Steroids, opioid antagonists, immunotherapy and
antioxidants are some of the modalities that have been
tested especially for their role in septic shock, but without
much success.
Prognosis
Better outcome depends on early recognition and
aggressive intervention at the stage of compensated
shock. The mortality also depends on the etiology of
shock; septic shock has mortality up to 50 percent.
Hypothermia, decreased cardiac output, decreased O2,
development of multiple organ dysfunctions are poor
prognostic indicators in shock.
BIBLIOGRAPHY
1. Blumer JL. Shock. In Blumer JL (Ed). A practical guide
to Pediatric Intensive Care Mosby Year Book: St. Louis,
1990.
2. Carcillo JA, Fields AI. Task force committee members:

Clinical practice parameters for hemodynamic support
of pediatric and neonatal patients in septic shock. Crit
Care Med 2002; 30:1365-78.
3. Dellinger RP, Carlett JM, Masur H, et al. Surviving Sepsis
Campaign guidelines for management of severe sepsis
and septic shock. Intensive Care Med 2004;30:536-55.
4. Dries DJ. Vasoactive drug support in septic shock. Shock
2006;26:529-30.
5. Fiddian-Green, Haglund G, Gutienez G, et al: Goals for
the Resuscitation of Shock 1993;21:S5-S31.
6. Holmes CL. Vasoactive drugs in intensive care unit: Curr
Opin Crit Care 2005;11:413-17.
7. Jatari HS, McGracken GH. Sepsis and septic shock-a
review for clinicians. Pediatr Infectious Dis 1992;11:
739-49.
8. Mouchawar A, Rosenthal M. A pathophysiological
approach to the patient in shock. Internat Anesthesiol
Clin 1993;31:1-20.
9. Rivers E, Nguyen B, Havstad S, et al. Early goal directed
therapy in the treatment of severe sepsis and septic shock.
N Engl J Med 2001;345:1368-77.
10. Whitle MK, Hill JH, Blumer JL: Shock in the pediatric
patient. Adv Pediatr 1987;34:139.
22.5 Acute Respiratory Failure

Uday B Nadkarni
Definition
Ventilation/Perfusion Mismatch
Acute respiratory failure (ARF) may be defined as a

condition when lungs are unable to deliver sufficient
oxygen to meet the demands of the body and/or to
remove carbon dioxide from the pulmonary circulation,
thereby leading to arterial hypoxemia or hypercapnia or
both.
Hypoxemia results when gas exchange in different

regions of the lungs are poorly ventilated in relation to
their blood flow. Hence, alveolar PAO2 is low and
alveolar PACO2 is high.
Pathophysiology
The basic mechanisms involved are:
i. Alveolar hypoventilation
ii. Ventilation/perfusion mismatch
iii. Presence of a shunt
iv. Limitation of diffusion.
Alveolar Hyperventilation
Alveolar hyperventilation results in abnormal increase
in PCO 2 leading to respiratory acidosis. Arterial
hypoxemia is due to decrease in alveolar oxygen
concentration (PAQ2).
Presence of a Shunt
In a shunt situation, perfusion is maintained, however
there is no ventilation. This causes alveolar to arterial
oxygen difference to increase.
Limitation of Diffusion
Limitation of diffusion is a less important cause of ARF,
however, diffusion limitation is associated with
interstitial fibrosis, alveolar proteinosis due to thickening
of the alveolar capillary membrane.
Type of Respiratory Failure
Type 1: Oxygenation Failure/Lung Failure
Physiologically it is always caused by venous admixture
and is always manifested by elevated alveolar-arterial
1154
oxygen pressure difference P(A-a) O2. Here PaO2 is less

than 50 mm Hg and PaCO2 is low or normal with patient
breathing room air at sea level. Oxygenation failure is
always a manifestation of a pulmonary parenchymal
disease.
Type II: Ventilatory Failure/Pump Failure
The physiological basis for pure ventilatory failure is
decreased minute ventilation and increased dead space
ventilation or combination of both. Herein PaO2 is below
the normal level and PaCO2 is more than 50 mm of Hg
with patient breathing room air at sea level.
Etiology
Predisposing factors: During childhood the airways show
progressive development and increase in diameter in
both the upper and lower airways. The thoracic cage is
soft and complaint, ribs are positioned horizontally and
sternum is softer as compared to the adults. Children
are also at a disadvantage because of poorly developed
intercostal muscles and less curvature of the diaphragm.
Causes
Lower Airways and Parenchymal Conditions
These include pneumonias, bronchopneumonia, status
asthmaticus, bronchiolitis, lobar emphysema, cystic
fibrosis, congenital heart disease, drowning and
diaphragmatic hernia.
Upper and Middle Airway Obstruction
The conditions are acute epiglottitis, vascular ring,
laryngeal and tracheal foreign body.
Conditions causing Neuromuscular Paralysis of
Respiratory Muscles or Failure of Central
Mechanics of Respiration
The common causes are poliomyelitis, polyneuritis,
encephalitis, meningitis, septicemia, Reyes syndrome,
head trauma, myasthenia gravis, dermatomyositis,
muscular dystrophy, and poisoning and drug overdosage.
TABLE 22.5.1: Clinical profile of acute respiratory failure

3 distinct clinical profiles of acute respiratory
failure in children
Control dysfunction
Mechanical
Muscle
Dysfunction
dysfunction
{(Predominantly
Airway
(obstructive)/or
Parenchymal
(Restrictive)}
Manifestations: Increased
Increased Decreased
effort
but ineffecor normal
Dyspnea
tive effort
effort (despite
considerable
blood gas
abnormalities).
Rib cage
Dyspnea
distortion
Accessory Nasal
muscle
flaning
Recruitment
Nasal flaning
Adventitious
Breath sounds
Examples:
Airway
Myopathies Apnea of
(obstructive)
prematurity
HRAD,
Polyneuro- CNS injury
Bronchiolitis
pathies
(Meningitis)
Parenchymal
(restrictive)
Pneumonia
CCF
Child may present with tachypnea/bradypnea

decreased or absent breath sounds, flaring of alae nasi,
retractions of chest wall, or apnea and cyanosis. There
may be fatigue, sweating, bradycardia or tachycardia,
hypo- or hypertension and pulsus paradoxes of more
than 12 mm Hg.
The CNS manifestation of hypoxemia such as
restlessness, altered sensorium, irritability, headache,
mental confusion, convulsions and coma could occur.
Clinical Features (Table 22.5.1)

Early recognition of impending respiratory failure is of
paramount importance and is based primarily on clinical
features. A good history and a thorough physical
examination would arrive at a reasonable diagnosis of
respiratory failure and its cause.
Diagnosis of Respiratory Failure

Clinical
i. Respiratory rate more than 50/min (2 months to 1
year) and more than 40/min (1-12 years).

ii. Decreased/absent breath sounds, inspiratory
retractions
iii. Use of accessory muscles, altered sensorium, apnea
iv. Cyanosis.
Blood Gas Evaluation (ABG)
(Tables 22.5.2 and 22.5.3)
pH less than 7. 25, PaO2 less than 60 mm Hg and PaCO2
more than 50 mm of Hg or increasing at the rate of more
than 5 mm Hg per hour blood gas data is important to
assess the extent of respiratory failure. It provides
information about oxygenation, ventilation and acidbase status.
Other monitoring devices to minimize blood gas
sampling. Pulse oximetry (SpO2), Capnometry (ETCO2).
Radiological Examination
Radiological examination is extremely useful in detecting
edema of the epiglottis, foreign body or pneumothorax.
It may also reveal extensive bronchopneumonia,
atelectasis or pleural effusion. It is necessary to take
posteroanterior and lateral chest views.
Goal of Treatment
Restore adequate gas exchange with minimum
complications (A-B-C)
TABLE 22.5.2: Normal values of blood gases
Age
PaO2
PaCO2
Newborn2 years
2 years and above
6090 mm Hg
80100 mm Hg
3035 mm Hg
3035 mm Hg
TABLE 22.5.3: Types of respiratory acid-base imbalance

Types
pH
PaCO2
HCO2
Uncompensated (acute)
Partially compensated
(sub-acute)
Compensated (chronic)
Uncompensated (acute)
Partially compensated
Respiratory acidosis
Respiratory alkalosis
(sub-acute)
Compensated (chronic)
Eliminate initiating factors as soon as possible

Remember that hypoxemia is more dangerous than
hypercarbia; (a short-term PaCO2 up to 60 to 80 mm
Hg may be tolerable).
Indication for ventilatory assistance in a child with
respiratory failure is usually based on the persistence
and/or worsening of the gas exchange.
The blood Hb level is an important determinant of
oxygenation status.
Management
Managing a case of respiratory failure is a challenging
task, but if done promptly and efficiently can prevent
death and hypoxic brain damage. It starts with ABC of
resuscitation: A-airway, B-breathing, C-circulation.
It consists of ABC approach of CPR (cardiopulmonary
resuscitation), i. e. assessing airway patency, breathing
and circulation. It should commence within half a minute
so as to avoid damage to vital organs viz brain, heart
and kidneys.
A. Airway Patency
Maintaining airway patency is the first step in the
management of respiratory failure. It includes proper
positioning of the patient, avoiding neck flexion, splinting
the chest, clearing of oropharyngeal secretions.
Endotracheal intubation: The indications are: (i) upper
airway obstruction with respiratory failure, (ii) excessive
secretions in the airways, and (iii) clearance of aspirated
material and ventilatory support. It can be performed
either by the orotracheal or nasotracheal route.
Tracheostomy: It is indicated in upper airway obstruction,
excessive secretions in the ET tube, prolonged ventilation
and vocal cord paralysis.
B. Breathing
Note the rise and fall of chest and abdomen and feel and
listen for exhaled air. If there is no breathing or ineffective
breathing, institute: (i) mouth-to-mouth breathing
(ii) bag-and-mask ventilation with added oxygen, and
(iii) if (i) and (ii) are ineffective and airway is obstructed,
one must resort to endotracheal intubation or tracheostomy.
Oxygen therapy: Humidified oxygen may be administered
through mask, nasal prongs, hood or tent. It is necessary
1156
to monitor patients by pulse oximetry to keep the oxygen

saturation of more than 90 percent.
Ventilation: An infant or child whose ARF persists despite
oxygenation and establishment of an adequate tracheal
airway, requires mechanical ventilation. It is necessary
to institute the ventilatory support at the earliest (for
details see the Chapter 22. 6 on Assisted Ventilation in
Children).
Future Prospects
The newer avenues for treating respiratory failure are
nitric oxide inhalation, ECMO (extracorporeal membrane
oxygenation) and lung transplantation.
BIBLIOGRAPHY
1. Debruin W, Notterman DA, Magid M, et al. Acute
hypoxemic respiratory failure in infants and children.
clinical and pathologic characteristics. Crit Care Med
1992;20:12223.
2. Guillemin K, Krasnow MA. The hypoxic response:
Huffing and Hiring, Cell 199;89:89.
3. Khilnani P. Mechanical ventilation in pediatrics. Indian
J Pediatr 1993;60:10917.
4. Singh M, Kumar L: Management of respiratory failure.
Indian J Pediatric 1996;63:5360.
5. Third European Consensus conference in Intensive Care
Medicine: Tissue hypoxia: How to detect, how to correct,
how to prevent. Am J Respir Crit Care Med 1996;
154:1563.
22.6 Assisted Ventilation in Children

Suchitra Ranjit
Ventilation may be defined as the movement of air in
and out of the lungs. Respiration is defined as the process
of gas exchange within the lungs (external) or at the tissue
level (internal). It may be spontaneous (patient breathing
for himself) or assisted. Assisted ventilation involves an
external device connected directly to the patient which
provides the movement of air in and out of the lung.
This device may be a resuscitative bag or a mechanical
ventilator.
and, access to the patient is limited. Both techniques may

be used in pediatric ventilation although PPV is more
common by far.
Assisted Ventilation
Frequency/ventilatory rate: The rate that is initially set

depends on the indications for ventilation and the
physiologic norm for the patients age.
Mechanical ventilation may deliver a volume of gas to

the patients lungs in one of two ways.
Positive-pressure ventilation (PPV): Positive pressure is
applied directly to the airway which forces air down the
airways and into the lungs.
Negative pressure ventilation: Negative pressure applied
externally to the chest cage which will change the
pressure dynamics so that gas flows from the relatively
positive atmosphere to the relatively negative air spaces.
Negative pressure ventilators range from tank ventilators
(iron lungs) to abdominal and thoracic cuirasses.
Although these ventilators are more physiological and
avoids many of the complications of endotracheal
intubation and PPV, the apparatus is more cumbersome
Basic Terminology
Tidal volume (VT): This is the volume of gas that flows in
and out of the chest during quiet breathing. In adults,
the normal tidal volume is 500 ml. In children the tidal
volume is 6 to 10 ml/kg.
Minute ventilation(MV): This is the product of the tidal

volume and the ventilatory rate and is expressed in
liters/minute.
Peak inspiratory pressure/pressure limit (PIP): This is the
highest pressure during the inspiratory period. The PIP
level is usually kept as low as possible since it has been
implicated as one of the causes of barotraumas.
Positive end-expiratory pressure (PEEP): It is designed to
keep alveoli from collapsing at the end of expiration. The
technique is very useful when lungs are stiff and
noncompliant and has become the mainstay of treatment
of acute respiratory distress syndrome (ARDS) and

pulmonary edema. Normal levels of PEEP (physiological
PEEP) is 3 to 5 cm H2O. Higher PEEP (10-15 cm H2O or
even greater) may be used with caution. Adverse effects
of PEEP are ventilator induced lung injury (VILI), fall in
cardiac output, and increased intracranial tension. The
optimal PEEP must be a balance between maintaining
adequate oxygenation at safe levels of FiO2 (see later)
while maintaining adequate tissue perfusion.
Inspiratory time and I:E ratios: The I:E ratio refers to the
relationship between inspiratory time (I) and the
expiratory time (E). The normal I:E ratio is usually 1: 1.5
to 1 :2. Adjustment of the inspiratory time is the primary
method by which the I:E ratio is altered.
FiO2: It stands for fractional inspired oxygen concentration where 100 percent oxygen is represented as 1.0,
oxygen in room air (21%) as 0.21 and so on.
Mean airway pressure (MAP): It is a measure of average
positive pressure generated in the lung throughout the
respiratory cycle. It is not a ventilator setting. MAP is
critical factor in determining both oxygenation and the
potential for barotraumas. It is determined by several
factors including PIP, PEEP, inspiratory time, ventilator
rate and flow rate. Many ventilators have the ability to
continuously monitor and display MAP allowing the
clinician to see the effects of ventilatory adjustments on
this value.
Sensitivity/trigger: This refers to the ease with which a
ventilators can sense the patients demand for a breath
and is usually expressed as the amount of negative
pressure (pressure trigger) of change in flow (flow
trigger) that a patient must create in order for the
ventilator to respond. Setting the sensitivity too high may
increase the work of breathing (the patient must create a
higher intra-thoracic negative pressure in order to get
assistance from the ventilator). Setting the sensitivity too
low may lead to over-triggering and the potential for
ventilatorpatient dyssynchrony.
Modes of Ventilation
This may be broadly classified as:
i. Controlled mechanical or mandatory ventilation
(CMV)
ii. Assist modepatients effort is assisted by the
ventilator
iii. Spontaneous modepatient is breathing on his or
her own.
Controlled Mechanical Ventilation (CMV)

In this mode, all breaths are initiated, sustained and
terminated by the ventilator with the patient taking no
active role in the ventilatory cycle. In general, this mode
is reversed for patients who have insufficient/absent
ventilatory drive (either from the disease process or
iatrogenically due to sedative and/or paralytic agents).
CMV may be volume controlled where a preset tidal
volume is delivered during a set inspiratory time at a
set frequency and constant flow irrespective of the
peak pressure generated. Here volume is guaranteed
but pressure is variable depending on the lung
mechanics.
In pressure-controlled or pressure-limited time cycled
CMV, the ventilator delivers a positive pressure up to a
predetermined pressure limit (PIP) above PEEP during
a preset inspiratory time at a set frequency. Here, while
the clinician has guarantee over the preset pressure,
delivered volumes may be variable and depend on the
mechanics of the patients lungs, airways and ventilator
circuit.
Assisted Modes
Assist-control ventilation: It is essentially identical to

the respective controlled modes except that the
patient plays a significant role in initiating the breath.
The patient performs only the triggering work, while
the ventilator completes the remaining limiting and
cycling work.
Intermittent mandatory ventilation (IMV) and SIMV:
Intermittent mandatory ventilation was developed
as a method of partial ventilatory support to
facilitate liberation from mechanical ventilation.
In this mode, the patient can breathe spontaneously while also receiving mandatory breaths.
As the patients respiratory function improves, the
number of mandatory machine breaths may be
decreased, until the patient is breathing unassisted
on CPAP.
For the spontaneous breaths, the ventilator simply
acts as a source of humidified gas flow.
Unfortunately, there were two problems with this
system: (1) It was possible for the patient and the
ventilator to inspire in series, thusstacking one
breath on top of another, leading to high airway
pressures. (2) The workload of spontaneous
breaths remained quite high-remember that the
patient still has to inspire without assistance
1158

through an endotracheal tube and ventilator
circuita difficult prospect with normal lungs, a
serious burden with an acute lung injury.
A variation of this mode, (Synchronized IMV =
SIMV) allows the mechanical breaths to be given
on patient demand. The issue of stacking breathes
is solved by an inbuilt sensor that synchronizes
the patients spontaneous breaths up to the set
rate.
However, most infant ventilators deliver IMV, not
SIMV as developing appropriate sensitivity and
rapid response times to an infants efforts is
technically more difficult.
The problem of the excessive effort of the spontaneous efforts was solved by introducing an
assisted spontaneous breathing modepressure
support (PS) ventilation. PS is described in more
detail in the following section.
The combination of SIMV-PS remains a popular
weaning mode in pediatrics.
Spontaneous Modes
Pressure support ventilation (PSV):

Here all the patients sensed ventilatory efforts are
supported (boosted) by the ventilator to various
degrees determined by the operator (Table 22.6.1).
The patients spontaneous inspiratory effort is
sensed and gas flows until a preset pressure is
reached which is actively sustained until the end
of inspiration.
The patient controls the breathing rate and the
length of inspiration and expiration.
PSV has been shown to decrease inspiratory work,
abolish diaphragmatic fatigue and has emerged
as an important weaning mode, both as a standalone mode or in conjunction with SIMV.
Weaning is facilitated since the level of pressure
support may be adjusted from full to partial to
none in a gradual fashion.
Continuous positive airway pressure (CPAP):
CPAP is usually defined as positive pressure
maintained in the airways throughout the
respiratory cycle during spontaneous respiration.
Technical considerations: Many devices have been
developed to deliver CPAP. All work on the same
principle, using a continuous gas flow, a reservoir
bag, a valve to maintain positive pressure above
atmospheric and a humidification device
TABLE 22.6.1: Indications for intubation and ventilation

Indications for intubation of the trachea
To provide an airwayfunctional or anatomic airway obstruction
To protect the airwayloss of protective reflexes (cough/gag)
For institution of PEEP or positive pressure ventilation
Tracheal toiletingin patient with copious tracheal secretions
and poor spontaneous cough.
Indications for Ventilation
Patients with respiratory failure severe enough to cause hypoxia
(PaO2 < 60 in FiO2 0.6) or hypercapnia acutely (pCO2 > 55 to
60 with pH < 7.2) may need assisted ventilation. This often
occurs in the following conditions.
1. Inadequate CNS control of ventilation
Apnea
Head and spinal cord injuries
Mass lesions-intracranial
Abnormalities in breathing control
Infectionintracranial
Drug effect
2. Inadequate chest wall function
Neuromuscular disease with respiratory muscle
involvement (Guillain-Barr, Polio)
Chest wall trauma with flail chest
Resp. muscle fatigue, - work of breathing
3. Parenchymal conditions
Alveolar diseaseARDS, pulmonary edema, severe
pneumonias
Interstitial disease
Airway diseasebronchiolitis, asthma
4. Circulatory disorders
Cardiac arrest
Severe shock syndromes
Pulmonary artery hypertension
5. Surgical
After cardiac surgery
After extensive abdominal surgery
Need for high dose analgesia
Trauma
(Fig. 22.6.1). CPAP is most commonly applied to

the patients airways via an endotracheal tube.
Other modes of application include face mask,
nasal prongs or nasopharyngeal tube.
Indications and applications of CPAP: The primary
indications are in acute lung injury, e.g. ARDS and
HMD. Other conditions in which CPAP is useful
include apnea, tracheobronchomalacia and
weaning from mechanical ventilation.

Monitoring of the Ventilated Patient
Figure 22.6.1: Apparatus for setting up CPAP
Care and Monitoring of the Ventilated Patient:

Considerations
Whenever mechanical ventilation is initiated, the
caregiver has to undertake tremendous responsibility
since the potential for disastrous consequences of this
life support technique is enormous. Close monitoring
of the patients condition is therefore essential.
Nutrition: A ventilated child with an endotracheal
tube cannot be given direct oral feeds, since the tube
interferes with normal swallowing. However, the
majority of ventilated children may be fed enterally
via a nasogastric tube. The few patients in whom
enteral feeding is not possible because of ileus or
abdominal pathology should receive parenteral
nutrition. Whichever the route chosen, an attempt to
meet calorie and protein requirements must be made,
however, excessive carbohydrates should be avoided
as it may result in increased CO2 production
Indications for sedation: Intubation and ventilation are
uncomfortable, painful and fear provoking and most
patients receiving this therapy will require some form
of sedation. The current trend is to avoid muscle
relaxants as far as possible.
Prior to the use of medications to sedate the patient,
it should be ensured that the ET tube is patent, in good
position and well-secured and the ventilator settings are
appropriate and no complications (see following section)
have occurred.
Clinical assessment may provide valuable information:

Assess frequency and strength of spontaneous
breathing
Synchronization with the ventilator
Chest wall excursion and frequency of air entry/ exit
Circulationpulse, BP, systemic perfusion
Abdominal distension, feed tolerance
Neurobehavioral activity
Readiness for weaning.
Radiological assessment: Radiographs should be done at
least once daily in the acute phase and whenever acute
deterioration occurs. The following should be looked for:
Position of ET tube and nasogastric tube
Overall lung volume, evidence of hyperinflation
Air leak syndromesinterstitial emphysema,
pneumothorax, etc
Presence of atelectasis, pneumonia, pulmonary
edema
Heart size.
Arterial blood gas: Within 20 to 30 minutes of initiating
ventilation, after altering ventilatory settings, and every
4 to 6 hours thereafter, unless there is a marked change
in condition. Chronic patients need gases less frequently.
The goal should be to maintain PaO2 60-90 mm Hg, PCO2
35-45 mm Hg, pH 7.35 to 7.45.
Others: Complete blood counts, electrolytes, and renal
function tests daily, culture of ET tube secretions once in
3 to 4 days.
Causes of Deterioration in Ventilated Patients
Acute Deterioration
D-Displaced tubein esophagus, or slipped down
in right main bronchus
O-Obsstructed tube
P-Pneumothorax, pneumopericardium
E-Equipment failure, disconnection.
Gradual Deterioration
Partial tube occlusion
1160
Sepsis, pneumonia
Myocardial dysfunction, pulmonary edema
Biochemicalglucose, electrolyte disturbances,
metabolic alkalosis.
Complications of Assisted Ventilation
Numerous complications may contribute to patient
morbidity and mortality.
Related to Increased Airway Pressures and
Lung Volume
Ventilator Induced Lung Injury (VILI): VILI may be
multifactorial ranging from barotrauma, volutrauma,
atelectrauma and biotrauma. End results may be in the
form of pulmonary interstitial pneumonia, pneumothorax, penumopericardium penumoperitoneum,
subcutaneous emphysema.
Pulmonary parenchymal damage, chronic lung
disease
Decreased cardiac filling and poor perfusion
Other organ dysfunction, renal, hepatic, CNS.
Related to Endotracheal/Tracheostomy Tube
Tracheal mucosal damage
Sinusitis/middle ear infection (nasal ET tubes)

Laryngeal edema, subglottic stenosis.
Nosocomial Infections
Ventilator-associated pneumonias
Sepsis.
Mechanical Operational Problems
Mechanical failure
Alarm failure
Inadequate humidification.
BIBLIOGRAPHY
1. Esteban E, Frutos F, et al. A comparison of four methods
of weaning patients from mechanical ventilation N Eng
J Med 15;332:118-23.
2. Heffner JE: Airway management in the critically ill
patient. Crit Care Clin 1990;6:533.
3. Martin LD, Bratton SL, Walker LK: Principles and
practice of respiratory support and mechanical ventilation. In: Rogers Textbook of Pediatric Intensive Care
(3rd ed). William and Wilkins: Baltimore 1996;265.
4. Venkataraman ST: Mechanical ventilation and Respiratory Care. In: Pediatric Critical Care. Fuhrman and
Zimmerman (Eds).3rd ed. Philadelphia, PA. Mosby
Elsevier, 2006;683-719.
22.7 Monitoring a Child on Intensive Care

Archana Sathe
Goals of this chapter are:
Acquisition of substantial understanding and logistics
required for care of critically ill children.
Understanding theoretic and practical aspects of
invasive and non-invasive monitoring.
Cooperation and collaboration with nursing staff and
physicians from other specialities and health care
disciplines.
Development of understanding of the ethical
principles, social factors and legal concerns relevant
to providing intensive care to children.
Monitoring is the activity of continuously, or nearly
continuously, evaluating the physiologic function of a
patient by invasive or non-invasive techniques. Noninvasive monitoring is usually employed for continuous
monitoring of heart rate and rhythm or respiratory rate
whereas non-continuous monitoring measures blood
pressure (BP) and lab values, e.g. arterial blood gases
(ABG). Intermittent measurements of physiologic
parameters therefore provide information at only one
point of time. The fluctuating status of critically ill
children makes real-time or continuous monitoring more
desirable. The goals of any monitoring system are to aid
in diagnosis and prognosis, guide and assess therapy,
alert caregivers to alterations in status and detect
complications early.

It is important to remember that unlike the advanced
intensive care units where several monitoring devices
are available, we simply cannot ignore the need for
continuous close observation of vital signs by the vigilant
caretakers. Because of the cost constraints of the
monitoring systems and the relative lack of monitor
trained personnel involved in the care of sick children,
clinical monitoring is equally or perhaps more important
in our intensive care units. Ideally bedside monitors in
all PICUs must have the capability for continuously
monitoring heart rate and rhythm, respiratory rate,
temperature, hemodynamic pressure, oxygen saturation,
end-tidal CO 2 and arrhythmia detection. Bedside
monitoring in level 1 PICUs must be capable of simultaneously monitoring systemic arterial, central venous,
pulmonary arterial and intracranial pressures. Monitors
must have high and low alarms for heart rate, respiratory
rate, and all pressures with settings according to the
childs age and clinical condition. Hard copy and
trending capability for all monitored variables is
desirable. All monitors must be maintained and tested
routinely.
Although all organ systems deserve monitoring in a
sick child, the four vital areas that need our constant
attention are (i) the cardiovascular, (ii) respiratory, (iii)
neurological, and (iv) renal systems.
CARDIOVASCULAR MONITORING
Knowledge of cardiovascular/hemodynamic monitoring
and timely evaluation is mandatory for all personnel
involved in the care of a sick child. This is typically
indicated in the critically ill child admitted to the PICU
in shock, respiratory failure or with acute neurological
insult. Traditionally, heart rate and blood pressure
monitoring is included as well as central venous pressure
(CVP) and pulmonary capillary wedge pressure (PCWP),
occasionally. In postoperative cardiovascular patients
simultaneous right and left atrial pressures are often
monitored with surgically placed RA and LA lines. In
children with septic shock it is important to monitor the
adequacy of cardiac output and oxygenation and the
ability of oxygen delivery to meet the metabolic demands
of vital organs. The goals of hemodynamic monitoring
are to aid in diagnosis, guide therapy, provide warning
of physiological deterioration and predict outcome.
Noninvasive Monitoring
Low cardiac output states as well as structural abnormalities can be detected by physical examination. The
signs of low output state typically include weak
peripheral pulses, cool extremities, pallor, decreased
capillary refill, tachycardia and hypotension. However,
estimates of cardiac output based on physical examination are not always accurate when compared to more
reliable estimates on thermodilution method. Physical
examination appears to be better for judging relative
changes in cardiac output rather than isolated measurements in time.
Heart Rate
Rhythm abnormalities causing low cardiac output state
should be readily detected on clinical examination.
Tachycardia may have a number of causes fever, pain,
hypoxia, hypoventilation, inadequate cardiac output,
seizures, and drug induced accurate diagnosis is
essential for appropriate treatment. Sometimes it may
be difficult to be sure whether tachycardia is a sign or
the cause of the low output state. Bradycardia is an
ominous sign and a predictor of imminent cardiac arrest.
Bradycardia from complete heart block is also easily
diagnosed rate less than 60/min with associated signs
of congestive heart failure should suggest the diagnosis.
Perfusion
In states of shock, blood flow is diverted from the less
vital tissues to the heart, brain and lungs. Monitoring of
perfusion in less vital tissues such as skin therefore may
provide useful early indication of tissue hypoperfusion.
A widened gradient between the surface temperature of
the great toe and ambient temperature is a more sensitive
marker of severe systemic hypoperfusion than conventional hemodynamic parameters and even arterial lactate
concentration. With the onset of peripheral hypoperfusion toe temperature decreases and approaches
ambient levels. Patients recovering from shock have
demonstrated widening of the toe ambient gradient to
> 4 degrees C whereas gradient remained < 1-2 degrees
1162
C in patients who ultimately died from shock. Although

core peripheral skin temperature gradients do not
always predict cardiac output (CO) or systemic vascular
resistance (SVR) in children, they are routinely performed
around the world. Previous studies have reported
increased mortality in post-cardiac surgical children
where peripheral temperature of the toe failed to increase
in other words the core peripheral gradient remained
wide.
In some centers gastric intramucosal pH (pHi), is
advocated as a way of evaluating splanchnic perfusion
and an index of systemic hypoperfusion. Titration of
therapy aimed at normalizing pHi may be associated
with improved survival.
Traditionally the capillary refill has been used as a
simple bedside tool to assess perfusion both by doctors
and nurses alike. However, there are definite limitations
to this method under different clinical situations.
Electrocardiography (ECG)
When cardiac function appears abnormal due to
structural defect or electrolyte abnormality, it is
important to obtain a proper 12-lead ECG. Rate, rhythm,
axis, intervals (PR, QRS, QTC) and chamber size as well
as patterns of ischemia should be identified on careful
examination. Correct diagnosis of rhythm abnormalities
often requires recording from multiple leads. All
pediatric intensive care patients must be under
continuous electrocardiographic monitoring because
tachycardia or bradycardia or other arrhythmias may be
the first sign of a change in the patients status. Atrial
enlargement or ventricular hypertrophy is often first
suspected on examination of a 12-lead electrocardiogram.
Sometimes the ECG is recorded invasively in
postcardiac surgical children using the transesophageal
lead.
Echocardiography
The most complete noninvasive assessment of both
cardiac structure and function is possible with echocardiography in an intensive care setting. Echocardiography is useful in children with sepsis. It is noninvasive,
easy to perform and repeatable. It assesses the contractile
state of the heart, whether the heart is adequately filled or
dilated and if a pericardial effusion is present. Two-
dimentional echocardiography not only visualizes the

cardiac defect in a child with congenital heart disease
(CHD), but also in combination with pulsed Doppler
mode can determine the presence, timing and direction
of shunting of blood, as well as the pressure difference
between the cardiac chambers. Cardiac ultrasound has
tremendous utility both as a diagnostic and monitoring
tool in the intensive care environment by virtue of its
portability, safety and patient comfort. All of these
findings have major therapeutic implications.
Radiographic Evaluation
Radiography has always played a vital role in intensive
care units. Important information is obtained on a chest
radiograph about presence of lung fluid, lung expansion,
heart size and position of intravascular catheters and
endotracheal tube in the ventilated child. The abdominal
exposure in appropriate position will often diagnose
pneumoperitoneum. Barium swallow esophagograms
remain an important investigation in children with
vascular rings causing airway and esophageal symptoms.
Invasive Hemodynamic Monitoring
Despite limitations in technology to accurately monitor
critically ill children, particularly neonates, where
physical limitations are more challenging, both invasive
and noninvasive methods are used widely.
Although all pediatric patients deserve to benefit from
less invasive monitoring, small neonates with an
immature immune system and a low tolerance for stress
make an ideal case for noninvasive technology. A
noninvasive measurement of a physiological parameter
may not provide the same accuracy as the direct invasive
method.
Invasive pressure monitoring provides us with direct
and continuous hemodynamic information as well as
patient access. To achieve this, a variety of catheters in
specific sizes and configurations are available for
peripheral arterial, central venous and pulmonary
arterial pressure monitoring. Additionally, umbilical
arterial and venous lines are sometimes used for
monitoring sick newborns in early neonatal period. The
indwelling catheter provides the input signal to a
transducer the pressure waveform displayed on the
monitor will depend on the site of the catheter. The
further the site of the catheter tip from the heart the more
dramatic the difference will be. The systolic pressures

are greater peripherally due to summation of reflecting
waves as well as the upstroke is sharp with a narrow
peak. The arterial waveform may be useful in diagnosing
hypovolemia, determining severity of cardiac dysrhythmias and dysfunction (pulses alternans) and evaluating
effect of respiration (air trapping) or high pericardial
pressure on blood pressure (pulsus paradoxus).
In addition to catheter site, hemodynamic variables
are continuously altered by the changing condition of
cardiovascular physiology, e.g. in shock which is a state
of inadequate tissue perfusion, regardless of the cause.
In children, though the absolute volume of blood is lower
than adults, the relative proportion to weight is greater
hence adverse effects of fluid loss are apparent much
earlier the blood pressure may become variable, the
left and right atrial pressures may decrease or increase
and reflexly the heart rate may increase. Cardiac output
is then altered according to the precise cause of shock.
Cardiac output is difficult to measure accurately in
children and the main issue is not what the numeric value
of cardiac output is but whether it is adequate for the
condition. The focus is therefore usually directed towards
perfusion assessment and not the absolute value of
cardiac output. Noninvasive Bio-impedance and Doppler
ultrasound provides simple, safe and repeatable
measures of cardiac output; unfortunately there are wide
limits of agreement. Invasive methods availableFick,
Dye dilution and Thermodilution measurements of
cardiac output are considered more reliable, albeit with
limitations specific to each method.
It is very important to remember that several errors
can occur in the pressure recording arising from
obstruction or kinking of catheters/lines air bubbles,
clots, catheter tip against the vessel wall all leading to
a damped waveform. Leveling of the transducer to
heart level (with the exception of ICP which is leveled to
middle ear) is mandatory for hemodynamic accuracy. If
the transducer is physically above the heart level, a lower
than the true value is displayed and conversely if the
transducer is wrongly leveled below the heart level, a
higher value will be obtained. The other important source
of error is the motion artifact resulting from movement
of the child or the tubing system. Respiratory movement
artifacts need to be remembered for assessment of central
venous pressures and manual measurements can ensure
accuracy in these situations. Several complication can
occur with the placement of invasive central lines
requiring constant vigilance and monitoring for the
prevention of serious infections, bleeding or thrombosis,

pneumothrax, hydrothorax as well as injury to the vessel
accessed.
RESPIRATORY MONITORING
The major function of the respiratory system is that of
gas exchange. Two important respiratory variables that
need to be monitored are oxygenation and carbon dioxide
removal by ventilation. The less distinct but perhaps
more important variable include the respiratory center
function and the respiratory muscle function and
mechanics. It is important to remember that a monitored
variable cannot replace and should be used in conjunction with careful and repeated physical examination and
bedside evaluation of the child.
Despite the availability of various respiratory monitors
their clinical use is often limited by lack of patient
cooperation. Hence, careful clinical examination still
remains the mainstay in the areas of respiratory
evaluation. Usually the chest examination focuses on
auscultation. Careful observation of the pattern of
breathing is considerably more informative about
adequacy of respiratory muscle function. Monitoring the
respiratory rate is the simplest and perhaps the most
predictive of all the respiratory variables monitored.
Tachypnea is an early marker of respiratory compromise.
Another very simple marker for the work of breathing is
the degree of suprasternal and intercostal retractions as
well as the use of accessory muscle groups. With some
experience, it is possible to appreciate such signs of
distress in intubated children on mechanical ventilation
as well. This can be very useful in assessing whether the
ventilator settings are adequate for that childs requirements.
In conjunction with sound physical examination, the
availability of methods to monitor respiratory mechanics
that can measure vital capacity and functional
residual capacity at the bedside have added to the
intensivists assessment of respiratory function. There are
limitations in their application in children who cannot
comply with instructions for these tests. Point of care
testing in the PICU and NICU is more expensive, yet
more expedient and provides valuable information in
minutes at the bedside. Hand held devices are used that
are particularly useful in the transport of critically ill child
in areas where patient is distant from the PICU but must
1164
have a blood gas analysis performed. These simple

devices may also perform a number of other analysis such
as measuring serum electrolytes, glucose, creatinine,
urea, ionized calcium and hematocrit.
Respiratory variables commonly monitored in the
intensive care as required for routine care of sick/
ventilated patients are as follows:
Oxygen Level
Arterial oxygen content is determined by the saturation
of hemoglobin and the oxygen dissolved in plasma (CaO2
= Hb SaO2 1.34 + PaO2 0.003). Peripheral oxygen
delivery is defined as the product of cardiac output and
arterial oxygen content (VO2 = Qt CaO2). The ability to
monitor PaO2 and SaO2 is crucial for ensuring optimal
oxygen delivery for cellular respiration.
Arterial oxygen tension or PaO2 is the partial pressure
of oxygen in arterial blood. PaO 2 must always be
evaluated with respect to the oxygen concentration of
inspired gas (FiO 2normally 0.21 in air). Various
oxygenation indices have been used to assess gas
exchange:
i. Alveolar - arterial oxygen tension difference:
PAO2 - PaO2 and
ii. Arterial/alveolar oxygen ratio: PaO2/PAO2
Normal PAO2 - PaO2 difference is 5 to 10 mm Hg in
room air. Pulmonary dysfunction leads to an increase in
this difference. However, this index changes unpredictably with changes in FiO2. Hence, the PaO2/PAO2 ratio
is better as an index of oxygenation because it is
independent of changes in FiO2. A value less than 0.75
signifies pulmonary dysfunction.
Pulse oximeter readings of SaO2 (oxygen saturation)
have a predictable relationship with partial pressure of
oxygen (PaO2) as shown in Figure 22.7.1. It must be
remembered that the relationship is not linear. Large
changes in the PaO2 above 60 would result in only small
changes in SaO2 while below PaO2 of 50 the fall in SaO2
is also steep. This means, while a SaO2 value of 90 on the
pulse oximeter may appear very reassuring, it actually
corresponds to a PaO2 of only 60 which is quite close to
respiratory failure (PaO2 of 50 or less corresponding to
approximately 85 percent SaO 2 value on the pulse
oximeter).
Transcutaneous Oxygen Tension
Special electrodes can measure the skin capillary oxygen
tension which has good correlation with arterial oxygen
Figure 22.7.1: Relationship among arterial PO2 (PaO2 horizontal axis), oxyhemoglobin saturation (SaO2, left vertical axis) and
arterial O2 content (CaO2, right vertical axis). As PaO2 falls,
both SaO2 and CaO2 diminish rapidly once the shoulder of
the curve is reached, at PaO2 values below 50 to 60 torr. This
phenomenon is the basis for defining hypoxemic acute respiratory failure in terms of a PaO2 value in this range or below
tension particularly among neonates with thin skin. The

results are erroneous when tissue perfusion is low. This
method has fallen out of favor in pediatric and neonatal
units as well because of the need for frequent calibration
and change in probe site to prevent local skin damage.
Arterial Oxygen Saturation (SaO2)
Pulse oximetry utilizes the principle of differential light
absorption spectra for saturated oxyhemoglobin
compared with reduced hemoglobin. The device consists
of a probe and a microprocessor display unit.
The probe is placed around a finger or toe tip. A light
source beams red and infrared light through the
pulsating arteriovascular bed to a detector placed on the
opposite side. The changing ratio of absorbed to
transmitted light is measured and microprocessor unit
calculates and displays the SaO2. Under steady state
conditions pulse oximeters measure saturations within
95 percent confidence limits of 4 percent when the SaO2
is more than 70 percent. It is a good idea to compare the
heart rates on the pulse oximeter and the heart rate
monitor. A discrepancy is an indications of a probable
false SaO2 value. Other situations where the oximeter
gives false values include methemoglobinemia and

carboxyhemoglobinemia where the oximeter overestimates the true SaO 2 because difference from
oxyhemoglobin is not detectable.
The most common source of error is from motion
artifact particularly in the agitated neonate and infant.
Carbon Dioxide Level
Arterial Carbon Dioxide Tension
Measurement of PaCO2 in blood serves as a measure of
ventilation function of the respiratory system. Elevation
of PaCO2 above 65 mm Hg (with pH < 7.20) is an
indication for mechanical ventilation support as it
signifies acute respiratory failure.
As with arterial oxygen tension measurement this
parameter also requires invasive peripheral sampling
drawn intermittently for arterial blood gases or an
indwelling arterial catheter, and thus may miss sudden
changes. Transcutaneous CO2 measurements suffer from
the same drawbacks as with transcutaneous oxygen level
discussed earlier.
Capnography
A device that measures the breath-to-breath level of
carbon dioxide in the airway and displays the waveform
of the values during the respiratory cycle is called a
capnograph. The device works on the principle that CO2
absorbs infrared light.
In healthy subjects the PetCO2 (end-tidal CO2 at
proximal airway) should be similar to PaCO2. However,
this requires normal metabolism, V/Q matching and
cardiac output which is often not the case in a sick child.
In these situations end-tidal CO2 may give readings
different from the arterial PaCO 2 . Nevertheless,
measurement of end-tidal CO2 is regarded as the most
reliable method of detecting esophageal intubation and
circuit disconnections during ventilation.
CENTRAL NERVOUS SYSTEM
EVALUATION AND MONITORING
spectroscopy or invasive catheters are placed to monitor

intracranial pressure (ICP). Currently, acute neurologic
deterioration represents a significant number of
admissions to a PICU. Trauma, tumors, infections,
seizures, vascular malformations, strokes, hypoxia or
various metabolic disorders may produce serious
neuroligic injury.
Evaluation of the Pediatric Neurosurgical Patient
An experienced PICU nurse should be able to perform
careful serial clinical neurological examination, e.g. of
the cranial nerves, especially the papillary reflexes and
score a modified Glasgow Coma Scale (GCS). A complete
history has no substitute with relevant points including
exact timing of events, velocity in the case of road
accidents, immediate neurological response including
seizure activity. Many children arrive in altered mental
state with inadequate medical background.
Glasgow Coma Scale (GCS)
The most commonly used scoring system quantifies
injuries or disease states of the brain on a certain scale
with the goal of comparing disease severity and deciding
thresholds for treatment and monitoring. The score at 6
and 72 hours also has a limited degree of prognostic
value. The score consists of ascribing points to certain
patient behaviors in three areas:
i. Motor responses to stimuli.
ii. Eye opening.
iii. Voice/verbal responses.
The GCS is simple to use and does not require
extensive understanding of neuroligic procedures. The
scores range from 3 to 15. Most patients with scores < 12
should be observed in the PICU. The score is remarkable
reproducible both in the field as well as in the emergency
room. Although initially adapted from observations in
adults with head injuries, the GCS has been widely used
in pediatrics. Some adjustments have been made in
infants and children to cope with differences in verbal
response.
Neurophysiologic Monitoring
A variety of pathological conditions of this system demand
close monitoring by trained personnel in an environment
with specific equipment for neurological assessment in
addition to cardiopulmonary monitoring. Highly
technical noninvasive devices, e.g. electroencephalography (EEG), evoked potentials, near- infrared
Electrophysiologic Monitoring
Information regarding cerebral function is equally
important and of greater prognostic significance. Specific
information regarding cerebral function is possible with
electroencephalography (EEG) and evoked potentials.
Continuous EEGs enable monitoring of the brains
1166
electrical activity. In a recent reports a combination of

two or more predictive EEG features as analysed by
cerebral function monitors demonstrate more than 90%
specificity of poor outcome. Managing a child with severe
status epilepticus helps determine if anticonvulsant
drugs are affecting both the clinical as well as electrical
seizures activity. Refractory seizures may require
Barbiturate Coma. With the common usage of paralytic
(muscle relaxant) and sedative drugs in the ICU settings,
EEG monitoring assumes greater importance for
detecting seizures. Careful data interpretation must
ignore the artifacts produced from various monitors or
ventilators. VIDEO EEG allows correlation between
recorded EEG and the clinical picture.
Evoked Potentials
Enable evaluation of a variety of sensory pathways that
include visual evoked responses (VEPs), brainstem
auditory evoked potentials (BSAEPs) and somatosensory
evoked potentials (SSEPs). These are not affected by
sedatives which may produce an isoelectric EEG. The
brainstem and somatosensory tests are the most
commonly performed evoked potential studies.
The Bispectral Index (BIS) score can be used to
monitor the neurologic status of both sedated and
unsedated critically ill patients ranges from 0 to 100
and is a reliable index of state of consciousness. Scores
> 95 indicate full consciousness. BIS has been proposed
as a guide to prevent oversedation in the critically ill and
potentially assist in the monitoring of barbiturate induced
coma in children.
Radionuclide Imaging
Using a portable Gamma Camera, though rarely
performed in the PICU may provide some useful
information regarding cerebral blood flow as to confirm
brain death at the bedside.
INVASIVE NEUROLOGIC MONITORING
Monitoring of Increased Intracranial Pressure (ICP)
Raised intracranial pressure is the common denominator
in most children admitted to the ICU with neurologic
symptoms. The resultant drop in cerebral perfusion is
thought to be the major factor involved with adverse
outcome in terms of morbidity and mortality. Because
the skull is a closed cavity, the three compartments
namely brain, CSF and cerebral vascular bed are

minimally compressible. Addition of volume in this
closed space results in an immediate rise in the ICP unless
a parallel decrease in one of the compartment occurs.
Since the neural tissue cannot contract (unless edematous), reduction in CSF volume or cerebral blood volume
is the only way to maintain normal ICP. Usually, acute
traumatic events with a GCS < 8 will require a monitoring
device for ICP measurement.
Methods for ICP Assessment
Unfortunately the well-documented findings of raised
ICP such as rise in blood pressure, bradycardia, change
in breathing pattern and consciousness and bulging
fontanels/papilledema rarely correlate with the direct
intraventricular measurements the gold standard of ICP
monitoring.
ICP monitoring devices include transducers for
various compartments on the assumption of equal
pressure transmission within the cranium. The ventricular pressure can be measured reliably by ventriculostomy, brain tissue by a fiberoptic transducer and
the subarachnoid and subdural spaces by a specially
designed catheter or the bolt. Ventricular catheter also
allows removal of CSF if necessary, thereby providing a
therapeutic option. ICP should be < 20 cm H2O. Simultaneous determination of mean systemic arterial pressure
is imperative and its difference from ICP should normally
exceed 50 in older and slightly less in younger children.
All currently available ICP monitors require access
to the intracranial space. Thus, patients who have not
undergone craniectomy for their initial problem are
subjected to an invasive procedure. Review of recent
literature strongly supports the use of ICP monitoring
and control in pediatric head trauma, metabolic
encephalopathies and infectious processes (especially
bacterial meningitis) in improving outcome significantly.
Jugular Bulb Monitoring
Jugular bulb catheterization enables one to obtain
continuous oxygen saturation (JSaO2) measurements
using an indwelling catheter placed in the jugular vein
and advanced cephalad to the level of the jugular bulb.
Values obtained correlate with the jugular PaO2 content
that allow the clinician to determine how well the injured
brain is utilizing oxygen. Knowledge of the arterial
saturation allows calculation of the arterio jugular

difference for oxygen. AJDO2 this is normally 4 to 9
mg/dl. Levels below this indicate cerebral hyperemia
requiring therapies for decreasing cerebral blood flow
levels > 10 mg/dl indicate cerebral ischemia.
MONITORING RENAL FUNCTION
Although several biochemical parameters need to be
measured to ascertain normal renal function, the
monitoring of urine output alone conveys important
information about the adequacy of kidneys in addition
to cardiovascular sufficiency at the bedside. This
information has great practical value in ongoing clinical
decisions made in the intensive setting from hour to hour.
Normal urine output is 2 to 3 mls/kg/hr. A urine output
of > 1 ml/kg/hr is taken as an indicator of adequate perfusion of the kidneys and < 1 ml/kg/hr implies hypoperfusion.
LABORATORY DIAGNOSIS AND MONITORING
Hematology
The optimal hemoglobin (Hb) threshold for erythrocyte
tranfusions in critically ill children is unknown. Recent
trials indicate that restrictive transfusion strategy using
Hb threshold of 7 gm% can decrease overall transfusion
requirements significantly without increasing adverse
outcome such as multiple organ dysfunction syndrome
(MODS). Neutrophilia (>15000) and neutropenia (<1000)
are suggestive of infection: an increase in the immature
to total neutrophil ratio (ITR) is strongly suggestive of
sepsis. Thrombocytopenia may suggest the diagnosis of
sepsis or be associated with disseminated intravascular
coagulation (DIC). DIC with low fibrinogen and elevated
fibrin degradation products is common in septic shock.
Blood Chemistry
The most frequently performed and most valuable
laboratory investigation is the arterial blood gas and acidbase analysis. Arterial oxygen and carbon dioxide
tensions aid in evaluation of the adequacy of oxygenation
and ventilation and pH and base deficit provide
information regarding the adequacy of tissue perfusion.
Serum lactate is very useful to monitor efficacy of
treatment failure of lactate to decrease with therapy is
predictive of a fatal outcome. Ionized hypocalcemia and
hypomagnesemia are common. Hyperkalemia is not
infrequent, especially if renal failure is present. Urea,
creatinine and liver function tests are measured
frequently.
CONCLUSION
Our smaller and younger patients require larger
monitoring continuously throughout 24 hours by
qualified and specialized nursing staff with intermittent
visits by parents who should share the experience of
watchful monitoring in order to feel involved with their
childs care.
Bedside monitoring has experienced tremendous
changes over the past 3 to 4 decades. Fortunately, the
pediatric patient has carved a niche in the world of
corporate attitudes among manufactures and there is a
boom in availability of devices that are reliable, user
friendly, physically compatible to the PICU setting,
accurate and above all cost efficient however, equal or
greater responsibility rests with us as doctors and nurses
who apply the technology. We have no right to abuse
the available technology, if we are unable to understand
or lack the enthusiasm to understand the limitations of a
device and the potential inaccuracies that arise. We
should always question the values displayed on the
monitor in terms of clinical appropriateness instead of
accepting information at face value.
Above all there is a need to use locally available
resources both technical as well as a team of committed
and trained nursing personnel, social workers suitable
to the level of intensive care required, coupled with the
guidance and judgment of experienced clinicians.
BIBLIOGRAPHY
1. Anthony Slater. Monitoring outcome in pediatric
intensive care . Pediatric Anaesthesia 2004;14(2):113-16.
2. Deborah ME, Darowski M, Livingston J. Cerebral
function monitoring in pediatric intensive care: useful
features for predicting outcome. Dev Med and Child
Neurol 2001;43:91-96.
3. Grindstaff RJ, Tobias JD. Applications of bispectral index
monitoring in the pediatric intensive care unit. J Intensive
Care Med 2004;19:111-16.
4. Lacroix j, Hebert P, Hutchison J, et al. Transfusion
Strategies for Patients in pediatric intensive care units.
NEJM 2007;356(16):1609-19.
5. Nadkarni UB, Shah AM, Deshmukh CT. Non-invasive
respiratory monitoring in pediatric intensive care unit.
Review article Journal of Post Graduate Medicine
2000;46:149-52.
6. Nelson Textbook of Pediatrics 17th Edition. Monitoring
Techniques for the Critically Ill Infant and Child.
2004;272-77.
7. Sandra A, Matthijs de H, Joleen HB, et al. Continuous
noninvasive monitoring of barbiturate coma in critically
ill children using the Bispectral index monitor. Critical
Care 2007;11:R108.
1168
22.8 Interpretation of Laboratory Findings in a PICU

Anil Sachdev
Hospital clinical laboratories get a major share of their
work from the intensive care units. Sick neonates and
children on life-support measures in pediatric intensive
care units (PICUs) need repeated laboratory investigations to maintain internal milieu (Table 22.8.1). But
certain investigations are occasionally required for
diagnostic and monitoring purposes (Table 22.8.2). The
concept of acute care laboratory is developing which is
located within or nearest to PICU. Nearer is the
laboratory to the unit, prompt is the sample transportation. Delays in sample transport may result in
inaccurate results.
BLOOD GASES
Acidic ions are produced by normal metabolism in the
tissues. These are transported to the organs or excreted
in a buffered state so that acids do not alter the body
functions. Excretion is carried out by the lungs (CO2) and
the kidney (bicarbonate). Excess production or impaired
excretion of acids can result in collection of these ions in
the body and a fall in pH. This can be dangerous. Hence,
TABLE 22.8.1: Tests most commonly asked for by PICU
Metabolic tests
Blood gas analysis (ABG)
ElectrolytesNa, K, Cl
Calcium, magnesium, phosphorus
Lactic acid
Glucose
Kidney function tests
BUN, creatinine
Urine-routine, microscopy
Osmolality
Bilirubin
SGOT, SGPT
Proteins, albumin
Coagulation profile
Drug levels monitoring
Hematology
Hemoglobin
Hematocrit
Total/differential counts
Cerebrospinal fluid
Radiology, imaging
TABLE 22.8.2: Uncommon investigations in PICU
Hematological
Leukemia panel
Specific coagulation
factor assays
Protein C and S
Antithrombin III
Antiphospholipid
Antibodies
Biochemical
Serum ammonia
Lipid profile
Immunoglobulin levels
S cortisol
Urine electrolytes
Microbiology
Inflammaory markers
Complement levels
Hepatitis viral markers
Genetics
Chromosomal analysis
Specific enzyme tests
Serum aminoacidogram
Sweet chloride level
CD4 and CDS counts

Bone marrow
Homocysteine
Lupus anticoagulant
Factor V Leidin
CPK, CPK (MB)

S amylase, S lipase
S osmolality
S ferritin
Drug levels-CPZ, phenytoin,
digoxin, vancomycin,
amikacin, vitamin B12
C reactive proteins,
procalcitonin, interleukins
Tumor-necrosis factor-alpha
Tropinin-I along with CPK,
CK-MB
Antiviral antibody markers
IgG and IgM
Torch titers
DNA analysis
Urine aminoacidogram
Serum ceruloplasmin
Nuclear Medicine
Gastroesophageal reflux study
Ventilation and perfusion scan
DTPA scan
measurement or acid-base status in the blood is often

required in the PICU. Normal blood acid-base gas (ABG)
values are listed in Table 22.8.3. Evaluation of oxygen
and carbon dioxide values are shown in Table 22.8.4.
Hypoxemia
Whenever the PaO2 values are lower than expected for
the age, hypoxemia exists. Hypoxemia is defined as a
decrease in the oxygen content of the arterial blood. Most
of the oxygen content is dissolved with the hemoglobin;
thus, the relative contribution of the dissolved portion is

TABLE 22.8.3: Normal blood gas report - FiO2, 0.21 (room air)
Arterial Blood
pH
PCO2
PO2
BE
HCO3
Newborn
7.30
33
68
6
20
(first 24 hr)
Infants
7.40
34
90
3
20
Child
7.39
37
96
2
22
Adult
7.40
40
100
0
24
Primary Acid-base Disorder
pH < 7.30 Acidemia (Metabolic and/or Respiratory)
pH >7.50 Alkalemia (Metabolic and/or Respiratory)
pCO2 > 50 Alveolar hypoventilation (Respiratory acidosis)
pCO2 < 30 Alveolar hyperventilation (Respiratory alkalosis)
increased, the minute ventilation may be markedly

elevated while the alveolar ventilation may be normal
or decreased. Therefore, while an increased minute
ventilation may be detected by physical examination
alone and may be assessed without an arterial puncture
(by measuring tidal volume and multiplying it by
respiratory rate), documentation of disorders in alveolar
ventilation requires a PaCO2 determination.
Whenever a state of abnormal ventilation (hypo or
hyper) exists, it must be correlated with the pH and the
clinical importance assessed.
TABLE 22.8.4: Evaluation of PaO2 and PaCO2room air
Mixed Venous Blood Gas
Mild hypoxemia
Moderate hypoxemia
Severe hypoxemia
PaCO2 < 30 mm Hg
Mixed venous gas sampling is upcoming in pediatric

intensive care units. Ideally it is to be taken from the distal
part of a pulmonary artery catheter but it is mostly not
possible in pediatric patients because of uncommon use
of pulmonary artery catheter in pediatric patients. The
alternative method is to take the sample from a correctly
placed subclavian catheter (placed at the junction of SVC
and right atrium). The normal values in a mixed venous
gas sample are pH 7.327.41, PCO2 4252 mm Hg, PO2
3540 mm Hg, HCO3 2428 mEq/L and SaO2 6575
percent. Various causes of changes in mixed venous
oxygen saturation above 70% in patients septic shock are
PaCO2 3050 mm Hg
PaCO2 > 50 mm Hg
PaO2 < 80 mm Hg
PaO2 < 60 mm Hg
PaO2 < 40 mm Hg
Alveolar hyperventilation
(respiratory alkalosis)
Acceptable alveolar ventilation
Ventilatory failure
(respiratory acidosis)
small. Nevertheless, the PaO2 is a critical measurement

because it is the most important factor determining the
proportion of hemoglobin saturated with oxygen.
Therefore, in the absence of an abnormality of hemoglobin (e.g. anemia or carbon monoxide poisoning), the
PaO2 is an accurate indicator of hypoxemia.
Evaluation of Ventilatory Status
The PaCO2 is a measurement of the amount of carbon
dioxide dissolved in the plasma of arterial blood. Carbon
dioxide (CO2), an end product of aerobic metabolism, is
produced continuously by the tissues and excreted by
the lungs. The level of CO2 in the arterial blood reflects
the relationship between CO2 production and excretion.
For practical purposes CO2 production remains constant,
so the PaCO2 reflects excretion. Since CO2 excretion and
alveolar ventilation are inversely related and the
relationship is nearly linear, the PaCO2 is a reflection of
alveolar ventilation. Therefore, alterations in ventilation
are defined in terms of the PaCO2. Hyperventilation is
said to occur, when the PaCO2 is lower than normal;
hypoventilation occurs when the PaCO2 is higher than
normal.
These designations refer to alveolar ventilation rather
than to overall (minute) ventilation and minute ventilation depends on the amount of wasted ventilation
(dead space). In diseases in which the dead space is
Metabolic Acidosis
Metabolic acidosis occurs either due to decrease of
extracellular HCO3 or addition of strong acids.
Etiology
Hyperchloremic
Diarrhea
Small bowel, biliary, pancreatic tube or fistula
TABLE 22.8.5: Causes of changes in mixed venous
oxygen saturation
High SvO2
Low SvO2
Tension pneumothorax
High FiO2 concentration
Ventricular septal defect
Acute hemorrhage
Cirrhosis of liver
Septic shock with lactic
acidosis
Acute respiratory distress
syndrome
Cardiac tamponade
Anemia of chronic renal

failure
Aspiration of blood from a
wedged PA trace
1170
Ureteral diversion
Total parenteral nutrition
Carbonic anhydrase inhibitors
Mineralocorticoid deficiency.
Normochloremic
Ketoacidosis
Diabetes mellitus
Starvation
Glycogen storage disease-1
Inborn error of amino acid or organic acid
Lactic acidosis
Bronchospasm
Pneumonia
Chronic lung disease
Interstitial lung disease
Pulmonary edema.
Impaired lung motion
Pleural effusion
Pneumothorax
Thoracic cage abnormalities.
Neuromuscular disorders
Poliomyelitis
Guillain-Barr syndrome
Brainstem or spinal cord injury or tumor
Myasthenia gravis
Muscular dystrophy
Botulism
CNS depressants
Pickwickian syndrome.
Respiratory Alkalosis
Whenever there is a primary decrease in PCO2 leading
to blood pH greater than 7.50, respiratory alkalosis exists.
The kidney provides compensation by decreasing blood
HCO3 levels.
Causes
Anxiety
Fever
Sepsis
Pneumonia
Pulmonary emboli
CHF with hypoxemia
High altitude
CNS disorder
Liver failure
Hyperthyroidism
Salicylates
Mechanical ventilation.
ELECTROLYTES
Imbalances in fluid and electrolytes are common sequelae
in critically ill patients.
Exogenous toxins
Salicylates
Methanol
Ethylene glycol
Paraldehyde
Renal failure.
Metabolic Alkalosis
Metabolic alkalosis may be due to various mechanisms:
i. Increase in extracellular HCO3 concentration
ii. Loss of H+
iii. Loss of extracellular fluid with more Cl than HCO3.
The causes of metabolic alkalosis may be divided
into two groups depending on urinary chloride
level.
1. Urinary chloride (< 10 mEq/L)
Gastric loss
Diuretic therapy
Low chloride intake
Posthypercapnia state
Intestinal losses (laxative, chloride losing diarrhea)
Cystic fibrosis.
2. Urinary chloride (> 10 mEq/L)
Normotensive
Bartters syndrome
Gitelmans syndrome
Recently ingested diuretics.
Hypertensive
Renal artery stenosis
Renin secreting tumor
Cushing syndrome
Primary aldosteronism
Congenital adrenal hyperplasia
Exogenous mineralocorticoid.
Respiratory Acidosis
Blood pH < 7.30 and a primary increase in PCO2 due to
ineffective alveolar ventilation leads to respiratory
acidosis.
Causes
Acute and chronic lung disease
Acute airway obstruction
Aspiration.

SODIUM
Hypokalemia
Hyponatremia
Causes
Hyponatremia is defined a serum sodium concentration

of less than 130 mEq/L. But it is the concentration less
than 120 mEq/L that is usually associated with serious
clinical symptoms and must be corrected immediately.
Hyponatremia is generally a secondary manifestation of
another primary disease and may occur in association
with hypovolemia, euvolemia and hypervolemia states.
Excessive Renal Loss

Tubular diseases (drugs, cystinosis)
Steroid (aldosterone, glucocorticoids)
Diuretics
Nonreabsorbable anions (e.g. penicillin, bicarbonate).
Hypernatremia
Nonrenal Loss
Vomiting
Diarrhea
Laxative abuse.
Under normal conditions, serum sodium is tightly

regulated between 135 mEq/L and 145 mEq/L. When
serum sodium level exceed 150 mEq/L, hypernatremia
is present, but serum levels above 160 mEq/L have
serious clinical consequences.
Shift from Extracellular to Intracellular Fluid

Insulin
Beta-2 catecholamines administration
Alkalosis.
Causes
Hyperkalemia
Sodium Excess
1. Improperly made oral rehydration solution (ORS)
2. Excessive NaHCO3 administration
3. Ingestion of sea water.
Causes
Water Deficit
1. Central diabetes insipidus
2. Nephrogenic diabetes insipidus
3. Diabetes mellitus
4. Excessive sweating
5. Increased insensible water loss
6. Inadequate access to water
7. Lack of thirst (adipsia).
Water Deficit in Excess of Sodium Deficit
1. Diarrhea
2. Osmotic diuretics
3. Diabetes mellitus
4. Obstructive uropathy
5. Renal dysplasia.
Limited Intake
Altered Renal Excretion

Oliguria
Chronic hydronephrosis
Potassium sparing agents.
Impaired Extrarenal Regulation
Diabetes mellitus
Adrenal insufficiency
Drugs (beta-blockers, converting enzyme inhibitors,
heparin).
Shift from Intracellular to Extracellular Fluid
Rapid cell breakdown (trauma, cancer chemotherapy)
Acidosis
Hypertonicity
Succinylcholine.
POTASSIUM
Increased Intake
IV solutions
Potassium containing salt substitutes.
Hypokalemia occurs when the plasma potassium is less

than 3.5 mEq/L and hyperkalemia is present when
plasma potassium level exceeds 5.5 mEq/L.
Spurious Hyperkalemia
Thrombocytosis (> 500,000 mm3)
Blood hemolysis.
1172
ANION GAP
Estimations of serum electrolytes including sodium,
potassium, chloride and bicarbonate are needed to
calculate the anion gap, which helps in the differential
diagnosis of metabolic acidosis.
Gap = (Na + K) (Cl + HCO3)
Normal value = 12+/ 2 mEq/L
Causes
Increased Anion Gap
1. Increased unmeasured anions
Lactic acidosis
Ketoacidosis
Organic acidemia
Renal failure
Toxinsmethanol, ethylene glycol
Drugssalicylate, penicillin.
2. Decreased unmeasured cations
Hypocalcemia
Hypomagnesemia.
Decreased Anion Gap
Analytical error
Pseudohyponatremia
Hypoalbuminemia
Myeloma proteins
Hypercalcemia
Hypermagnesemia.
Osmolality
Serum osmolality may be determined directly using
osmometer or by calculation.
Glucose
BUN
Osmolality (mOsm/kg) = 2 Na + ___________ + ________
18
2.8
CALCIUM, MAGNESIUM, PHOSPHORUS
The total circulating calcium consists of a physiologically
active free calcium fraction (45%) and a fraction either
bound to albumin or complexed (55%). The precise ratio
of ionized to bound calcium is pH dependent. Many
instruments are available which can measure ionized
calcium using ion-specific electrodes. These instruments
also measure pH and can correct the ionized calcium for

pH 7.4. This may result in misinterpretation of actual
clinical condition. The samples should be drawn
anaerobically, prolonged venous stasis should be
avoided and over-heparinization of sample might induce
problems.
Monitoring of serum magnesium in the critically ill
has increased significantly in the recent years. Decreased
magnesium may lead to increased neuronal excitability
and enhanced neuromuscular transmission. Magnesium
monitoring is required in patients on parenteral nutrition,
refractory hypocalcemia and status epilepticus.
Phosphorus is a critical constituent of body tissues
and is central to the energy metabolism of all tissues.
Phosphorus deficiency may result from hyperalimentation, burns, antacid abuse and recovering from diabetic
ketoacidosis. Severe hypophosphatemia (level less than
1.0 mEq/L) can lead to muscle weakness, respiratory
failure and difficult weaning from ventilator/support.
Lactic Acidosis
Lactic acidosis is a common metabolic derangement in
PICU patients.
Causes of Lactic Acidosis
Increased Oxygen Demand
Generalized seizures.
Tissue Hypoxia
Hypotension
Cardiac arrest
Left ventricular failure
Low cardiac output.
Reduced Arterial Oxygen Content
Asphyxia
Hypoxemia
Anemia.
Drugs and Toxins
Salicylates
Phenformin.
Lactic acidosis occurs when more lactate is produced
than oxygen-starved tissue can use as a source of energy.
Homeostasis is impaired, plasma bicarbonate falls and
lactate accumulates in the circulation. Increasing levels

of lactic acid in a shock patient is a bad sign. Lactate levels
can be measured in plasma serum, or whole blood.
Autoanalysers are used to check lactate levels in citrated
blood and sample should be transported on ice to the
laboratory as early as possible. The normal lactate levels
in different sources of blood are given in Table 22.8.6.
TABLE 22.8.6: Normal lactate levels
Source of blood
Capillary blood
Newborn
Child
Lactate level
Lactate level
(mg/dl)
(mmol/L)
< 27
0.03.0
520
0.562.25
Venous
520
0.52.2
Arterial
514
0.51.6
BIBLIOGRAPHY
1. Goldsmith DI, Nevelloa AC. Clinical and laboratory
evaluation of renal functions. In Edelmann CM (Ed):
Pediatric Kidney Disease. Little Brown and Co, Boston
1992;1:46174.
2. Hurst WJ. Altherosclerotic coronary heart disease. In
Hurst WJ (Ed): The Heart (7th edn). McGraw-Hill: New
York 1990;9611003.
3. Kauflman WM, Bulas DI, Sivit CJ, et al. In Todres, Fugate
Jh (Eds): Radiologic Imaging. Little Brown and Co,
Boston 1996;97113.
4. Krunn VL, Nachyba C. The Harriet Lane Handbook. A
Manual for Pediatric House Officers (16th edn). Mosby
Yearbook; Missouri 2002.
5. Lente FV, Pippenger CE. The pediatric acute care
laboratory. Pediatr Clin North Amer 1987;34: 23146.
6. Mowat AP. Liver Disorders in Childhood. Butterworth,
Oxford 1987;36684.
23.1 Introduction: Why Adolescent Care? MKC Nair, SS Kamath ........................................................................................................ 1176
23.2 Adolescent Care and Family Life Education: Manorama Verma ................................................................................................. 1178
23.3 Adolescent Nutrition: Jugesh Chhatwal ........................................................................................................................................... 1180
23.4 Adolescent Psychology: Jugesh Chhatwal ..................................................................................................................................... 1183
23.5 Identity Crisis and Adolescents: Shrikant W Chorghade ............................................................................................................... 1186
23.6 Adolescent Sexuality: Jugesh Chhatwal .......................................................................................................................................... 1189
23.7 Common Health Problems in Adolescents: Manorama Verma, Jugesh Chhatwal ..................................................................... 1192
23.8 Polycystic Ovarian Syndrome: MKC Nair ........................................................................................................................................ 1200
1176
23.1 Introduction: Why Adolescent Care?

MKC Nair, SS Kamath
Adolescence is that period in our life where nothing seems
to go smoothly, yet our best memories are about those
wonderful days. The present day adolescent is considered
to be more knowledgeable about world affairs, thanks to
the onslaught of the media, so much so, many questions
the need for any special program for adolescents. On the
other hand, some feel disillusioned about the way things
are going and hence, point out the futility of any
intervention program at this level.
Scientists working in the field of HIV/AIDS are
convinced that today's youngsters have totally lost the
traditional moral values that we talk about, and it is high
time that we accept the ground reality and go all out to
prevent HIV infection among this vulnerable group. But
still the society does not accept this view and hence, is
unlikely to cooperate with any drastic program. No parent
is likely to accept the view that their own little one is at
high-risk of HIV infection, even if hard data are to the
contrary. Yet, everybody is convinced about the need to
do something before things go out of hand, particularly
looking at the experience of many other countries.
For the parents of today at least, what comes to their
heart is academic performance of their children. Studies
have conclusively proved that birth weight is the single
most important factor that determines the mental
development of the young child and that a baby with
normal birth weight has a sure edge over the low birth
weight (LBW) baby at least to start with. Now it is also
very clear that the most important community factor that
predicts LBW is the poor nutritional status of the mother
reflected as a pre-pregnancy weight of less than 40 kg and
height of less than 140 cm. The Action Plan for the Child,
Kerala, has stipulated that all girls in Kerala on completion
of 18 years should aim to have 45 kg weight and 145 cm
height. Hence, nutritional monitoring should form part
and parcel of any adolescent program.
Adolescence is also that period in our lives where
contradictions are the rule and not the exception. A period
when they demand independence, yet are mostly
dependent, a period when maximum hostility is shown
to the parents, but they want to be loved and cared for, a
period with maximum rebellion shown, yet want to be the
pet baby of their mother, a period when they reject advice
outright, yet love to be guided through difficulties. Surely

any conventional approach is likely to fail with this group.
Then what do we do? This reminds the authors of a story.
An ardent devotee of God complained to him, "God, you
told me that you would walk beside me always, then why
is that whenever I am in trouble I see only one pair of foot
prints?, why is that You leave my side when I need You
most? God smiled and said, Son, when you were in
trouble I was carrying you on my shoulders. There is
thus always a way of guiding adolescents without hurting
their huge ego.
All of us have fond memories of our adolescence. Still
at least some were not very fortunate to have had a smooth
go at it and always wished if only he/she had some guide
and philospher to get him/her through the difficult years.
Traditionally, in the joint- family system children imbibed
a lot of understanding and skill without even realizing
that they were receiving family life education. The societal
norms were such that mostly we tried to limit our activities
within the acceptable norms of the society. Our parents
and teachers tried to instill in us the correct moral values
as was thought appropriate for the day. Time has changed.
Very little societal control is preceived now and whatever
is still left is not appreciated. Present day parents
themselves often feel inadequate to cope with the fast
changing norms of society and hence, are not sure how to
guide the youngster. Teachers, our traditional source of
wisdom, are often confused about their role in society at
least vis-a-vis the problems of adolescence. Yet, they have
the best opportunity to guide the destiny of millions of
youngsters, if only we could empower them their legitimate
role in society.
To reach out to the maximum number of adolescents,
Family Life Education for adolescents should be imparted
through high schools and through the anganwadis for the
school dropouts. Family Life Education is a more
preferable term than sex education, so as to avoid undue
anxiety among parents. Following are the components of
family life education for adolescents.
Adolescent nutrition: Dealt in detail later.
Personal hygiene: Drinking lots of water and passing
urine frequently at school reduces silent urinary tract
infection and proper menstrual hygiene reduces
Adolescent Care 1177
reproductive tract infections.The adolescent girls

should be made aware that some amount of pearly
white vaginal discharge and discomfort or mild pain
during menstruation are within normal limits.
Understanding ones emotions: A person with a
wholesome personality is the one who has strong
mental, physical and cognitive skills, which enable
him to behave, relate to and act effectively in the family
and the society at large. The family stands for all the
basic human values necessary for living meaningfully.
Adolescents need to be told that all of us constantly go
through the dilemma of deciding right and wrong and
the best way to make an informed decision would be
to keep in mind the philosophy Do not hurt anyone if
possible and do not hurt yourself ever.
Awareness on ones own sexuality, HIV/AIDS and substance
abuse: For the early teenagers, sexual matters should
be presented in such a way that are acceptable to the
local community, especially parents and teachers,
emphasizing on dangers of irresponsible sexual
behavior. Family Life Education Sessions for older
children and young adults should be given adequate
emphasis on issue of understanding and appreciating
ones own sexuality.
The medical and psychosocial needs of
adolescents have to be addressed. Just as we have
established under-five clinics at places where underfive mortality and morbidity are high, setting up
Teenage Care Clinics at Primary Health Centres
(PHCs) with adequate referral support facilities at
District Hospitals once a week is essential for
establishing teenage care services. The objectives of
Teenage Care Clinic should be:
Nutritional status assessment and appropriate education.
Rubella vaccination to future teenage mothers.
Gynecological services preferably by a Lady Medical
Officer.
Eye care services and assessment of vision.
Blood grouping services for the teenage population.
Managing specific medical problems.
Referral services to First Referral Units (FRUs) Taluk
Hospital, District Hospital, Private Hospitals and
Various Specialty Departments of Medical Colleges
including Psychiatry, Internal Medicine, Endocrinology, Dermatology and Venereology, and Obstetrics
and Gynecology.
Psychosocial guidance to tackle the teenage identitycrisis, emotional instability, depression as well as
counseling on dealing with educational and social
problems identified through a network of Teen Clubs
in the community.
Opportunities for the all-round development
should be made available to the adolescents. Teen clubs
could be a solution. The objectives should be:
To discuss about the personal, familial, social and
medical problems.
To improve the personality, leadership qualities,
cultural and athletic spirits.
To promote legal awareness and understanding of right
issues.
To teach how to face gatherings, crowds and thus
overcome shyness.
To identify adolescents having problems and give them
group and individual counseling thereby helping them
to cope with the actual life situations.
Activities that can be included in the Teen Club are:

1. Awareness/Orientation Program: Health awareness
programs by the public health nurse attached to each
PHC and Anganwadi workers of the same PHC area
on various topics can be conducted for both the
adolescents and their parents.
2. Medical check-up camps through schools, tutorial
colleges and teen clubs.
3. Personality Development: The teen club members
should be motivated to organize meetings in the club
independently. Some experts could be invited to give,
lecture demonstration classes on personality, skill
development, and coping-up strategies.
4. Family life education: Factual and scientific information regarding family life will help the teenagers to
change their misconceptions and develop a positive
attitude towards their future life.
5. Career guidance: Adolescence is a phase in which most
of them choose their future career and hence through
career guidance they may be helped to explore career
prospects and job opportunities.
BIBLIOGRAPHY
1. Nair MKC. Adolescent Care 2000 and beyond. Pejwar
RK (Ed). Published by Prism Books (P) Ltd, 1865, 32nd
Cross, 10th Main, BSK II-Stage, Bangalore; 2000.
2. Nair MKC, Elizabeth KE, et al. Defining under weight
using the ELIZ Health Path for Adolescents and Adults
1178
(EHPA). Journal of Teenage care and Premarital

Counseling-Teens. Published by Child Development
Centre, Medical College, Trivandrum, 2001;1(5):89.
3. Nair MKC, Mini KP, Padmamohan J. Scholastic
performance of adolescents. Indian J Pedtr 2003;70:629
30.
4. Nair MKC, Resmi VR, Mini G. Module for Adolescent
Care. Published by Indian Academy of Pediatircs, Kailash
Darshan, Kennedy Bridge, Mumbai, 2004.
5. Nair MKC. Editorial, Perspectives in Adolescent Care
IAP Journal of Practical Pediatrics, 1998;6(1):710.
6.
Nair MKC, Mini K Paul, et al. Effectiveness of counseling

in improving the scholastic performance of adolescents,
Journal of Teenage Care and Premarital CounselingTeens. Published by Child Development Centre, Medical
College, Trivandrum, 2004;3(17 and 18):7986.
7. Nair MKC, Babu George, et al. Self-esteem and academic
achievement of adolescent girls. Journal of Teenage care
and Premarital Counseling-Teens. Published by Child
Development Centre, Medical College, Trivandrum,
2004;3(17 and 18):96102.
23.2 Adolescent Care and Family Life Education

Manorama Verma
As per estimates of World Health Organization (WHO),
there are nearly 1.2 billion adolescents in the world. In
India, about 21% of the population is in the age group of
10-19 years. Adolescence is a unique phase of life during
which a child goes through tremendous physical,
emotional and social changes. With these, arise a lot of
problems because the child who till now was quite
comfortable with his/her body and dependent both
psychosocially and economically upon the family, starts
feeling relatively independent but is not capable of coping
with the situation. The protective environment, especially
of a joint family system that previous generations had,
has eroded and the adolescent is exposed to an onslaught
of new information and experiences. Parental guidance is
frequently lacking due to various reasons and
unfortunately, schools and colleges fail to impart a proper
education about the growing self to these adolescents.
Most of them do not feel comfortable and confident to
discuss their problems with their parents. Hence, they
depend mainly on their peers who themselves may be
ignorant or use various other unsuitable sources like
media for gaining knowledge about their biological
changes and social values. In a study on over 3000
adolescents, majority (79%) had mentioned television and
movies as the source for information with only 11-12%
from doctors or teachers. The information gathered from
these sources rather confuses the young minds and is not
always in conformity with the socio-cultural milieu of the
family system contributing to a dissociation of their
personality. Conflicting messages may put them at risk of
making choices or decisions which can change the course
of their life or even be a threat to life.
The developmental changes that occur in adolescents

cause varying degrees of disturbances in them. One of the
most difficult tasks for the young adolescent is the
acceptance of his/her changed body and physique. The
changes in body size and shape bring along with an
alteration in the sexual drive which exposes the adolescent
to dangers to which they are hitherto unexposed, and hence
vulnerable. He/she is sexually potent now and feels a
surge of sexual interest and excitement as a result of
hormonal rush which disturbs and causes anxiety in the
adolescent.
With little or inaccurate knowledge, these young
people engage in sexual activities, rendering themselves
vulnerable to sexually transmitted diseases and teenage
pregnancies. Not many studies have been done about
sexual activity of unmarried young people in India.
Available data, drawn from small studies, are incomplete
and unrepresentative. According to National Behavior
Survey 8-10% of 15-19 years old had reported to have
indulged in casual sex in the past one year. The risk of
sexual abuse is also there for adolescents. Adolescent girls
are particularly vulnerable and neglected. Unwanted
pregnancies and unsafe abortions, particularly among
urban adolescent girls, are increasing in India.
Adolescent Services
Provision of adolescent friendly services has been lacking
at almost all levels in our country. Most of the morbidity
and mortality among adolescents is preventable.
Adolescents tend to avoid visiting physician and will seek
care when really sick. In addition to curative services there
is a great need for preventive services or anticipatory
guidance to adolescents. To encourage teenagers to utilize

health services, the health professionals should have the
sensitivity and skills to deal with them. They should be
approachable and provide confidentiality. Family
involvement at the visits should be encouraged.
Family Life Education
Sex education or family life education has been a subject
of controversy for long. It has been felt that providing the
information on safe sex, contraception, etc. may increase
promiscuity. In the absence of parental guidance and
formal education, the incorrect knowledge may actually
be more dangerous. The beliefs and practices formed
during adolescence can have far reaching effects. Family
life education is one of the means of providing the much
needed information and guidance to the desperately
seeking teenagers. Brindis (2006) have observed that
comprehensive family life education along with other
policies and measures has resulted in delayed sexual
debut, less pregnancies and abortions and a higher
contraceptive use across all ethnic and racial groups.
Building an Awareness
Creating awareness in various groups of persons involved
is an important and necessary step. Mere provision of
services is unlikely to lead to any change in the scenario.
Various stakeholders who need to be sensitized and made
aware can be:
1. Adolescents themselves: Awareness regarding need
for guidance and appropriate sources as well as
making the right choices.
2. Among the health professionalsthat adolescents
require special health care as their problems are
different from those of children or adults. The doctors
and other health professionals are often ignorant and
untrained to tackle this segment of the population.
Indian Academy of Pediatrics (IAP) has taken a major
step in this direction. A training program to acquaint
the pediatricians with adolescent issues and health
needs has been started. Adolescent friendly health
services (AFHS) are spreading. Government of India
has also introduced adolescent services in RCH II.
Other health professional organizations are also
involved in planning and delivering services to this
hitherto unserved segment of population.
3. Among the educationists: A scientifically planned
curriculum of family life education addressing the
needs of adolescent should be introduced in schools.
Adolescent friendly school initiative is another step in
this direction. At the national level, a population
education program (NPEP) with a significant
adolescent component has been formulated.
4. Among planners and the government that by taking

care of the young, the future resources of the nation, they
will have less problems in controlling population,
epidemics of STDs, etc. Although a number of programs
especially by non-governmental organizations are
targeting youth in smaller populations but still a lot
needs to be done.
TRAINING
Training of a wide group of people like doctors, social
workers, teachers, parents and most importantly, the youth
peer groups to provide proper orientation in reproductive
health is needed. There can be no better person than a
youth peer group leader to properly indoctrinate the group,
as this is the time when adolescent would go to any extent
to be identified with a peer group.
To conclude, family life education should be imparted
with the following themes in minds.
1. Personality developmentso that the adolescent is
able to cope better with emotional turmoil which
accompanies pubertal changes.
2. Human sexualityadolescent should be made aware
of the sexually transmitted diseases and unwanted
pregnancies so that they protect themselves against
exploitation and maintain their physical, mental and
social health.
3. Preparation for future parenthoodphysiology of
human reproduction and other aspects of family life
should be dealt with in detail so that they can decide
about their family size and the quality of family life.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
6.
7.
Adolescent Health and Development. World Health

Organization Fact sheet - India. Adolescent Health
Document. Accessed May-2008.
Adolescent in India - a Profile UNFPA. For UN system in
India. 2003.
Brindis CD. A Public Health Success: Understanding policy
changes related to teen sexual activity and pregnancy.
Annual Rev Public Health 2006;27; 277-95
Jenkins RR Delivery of Health Care to Adolescent in
Nelson Textbook of Pediatrics (18th Edn). Kliegman RM,
Behrman RE, Jenson HB, Stanton BF (Eds). Elsevier: New
Delhi 2007;816-19.
Marcell VA. Adolescent in Nelson Textbook of pediatrics
(18th Edn). Kliegman RM, Behrman RE, Jenson HB,
Stanton BF (Eds). Elsevier: New Delhi, 60-64
Reproductive and child health II. National program
implementation plan. Ministry of Health and Family
Welfare, Govt of India . accessed from http:www.whoindia.org/ May 2008.
Toor TK. Knowledge, attitude, beliefs and practices
regarding AIDS, STDs and sexuality among adolescents
in Ludhiana. Thesis for MD (Ped). BFUHS, Faridkot 2002.
1180
23.3 Adolescent Nutrition

Jugesh Chhatwal
Adolescent is a phase when there is a surge in growth
and development. Almost 20% of adult weight and up to
20% of adult height may be added during adolescent years.
About 40-50% of skeletal muscle mass is attained during
and after the adolescent growth spurt. The composition of
weight gain differs in girls and boys. Girls put on more of
fat while boys gain more muscle mass. This rapid increase
in weight and height puts a great demand for nutrients on
the adolescent body. Growing from a child whose nutrition
demands were overseen by parental supervision, the
adolescent is at a stage when they want dietary
independence. Increasing physical independence and
mobility allows for increased exposure to foods outside
the home environment and dietary experimentation. The
hormonal and psychological changes going on in the
adolescents body make them more prone to erratic dietary
habits. All the given factors can be responsible for causing
nutritional disorders in adolescents and therefore it is
imperative for the concerned physician to be aware of these
problems.
Iron
During adolescence, rapid growth leads to expansion of
blood volume. In boys there is marked increase in lean
body weight which is secondary to increased muscle mass.
In post-menarcheal girls, the menstrual losses add to the
iron requirement. Iron is required for not only building
hemoglobin but also for the muscle protein myoglobin.
An increased intake of iron is essential for adolescents.
Iron rich foods such as dark leafy green vegetables, nuts
and cereals along with better absorbed forms of iron like
lean meat and fish (if possible) should be included in the
diet. The Table 23.3.2 shows the daily requirement for
different age groups. As the bioavailability is only 10% for
iron, the actual iron intake is higher.
TABLE 23.3.2: Iron requirement at different ages
Sex
Age group
Iron requirements
(mg/day)
Boys
11-14
15-17
18+
11-14
(Non-menstruating)
11-14
(Menstruating)
15-17
18+
1.2-1.5
1.5-1.9
1.1-1.4
1.2-1.4
NUTRIENT REQUIREMENTS
The calories and protein intake has to be carefully
balanced during adolescent to match with growth and
physical activity. A physically active adolescent should
not restrict calories intake, else he or she will burn up
energy derived from proteins which is required for growth.
On the other hand, an inactive teenager can become rapidly
obese even with suboptimal dietary intake. Adequate
intake of minerals is also important to ensure growth
especially iron, calcium and zinc.
The recommended dietary allowances for adolescents
for various nutrients are given in Table 23.3.1.
TABLE 23.3.1: Recommended dietary allowances for
adolescents
Group
Age
Calories (kcal)
Protein (g)
Boys
Girls
Boys
Girls
Boys
Girls
10-12 yrs
Do
13-15 yrs
Do
16-18 yrs
Do
2190
1970
2640
1970
2640
2060
54
57
70
65
78
63
Girls
1.7-3.3
1.6-3.1
1.5-2.9
Calcium
About 45% of the adult skeletal mass is formed during
adolescence. Calcium is essential for the increased skeletal
growth during adolescent and all of it has to be derived
from diet. During peak adolescent growth calcium retention
on average can be 300 mg/day for boys and 200 mg/day
for girls. The calcium absorption efficiency from gut is
about 30% only, hence adequate calcium intake must be
ensured to allow appropriate development of bone mass.
Zinc
Zinc is another dietary component which is essential for
growth. It also plays a vital role in sexual maturation. An
intake of 15 mg daily is expected to meet the growth needs

while intake less than two-third of recommended may
pose a health risk. Zinc deficiency has been associated
with growth retardation and delayed sexual development.
DIETARY PROBLEMS DURING ADOLESCENCE
Adolescent Undernutrition
The increased dietary requirements of growing adolescent
if not met adequately can lead to under nutrition. The
psychosocial stresses, body image concerns or eating
disorders can also contribute to under nutrition. Poor
socio-economic status in developing countries would be
a major cause of adolescent under nutrition. An adolescent
with a BMI less than 5th percentile for the age is considered
undernourished. In India, according to a survey by
National Nutrition Monitoring Board (NNMB), 39% of
adolescent girls and boys were stunted and thinness
ranged upto 77.6%. The daily intake of calories, proteins
as well as other nutrient was below the recommended
daily allowances, lower for girls. Ensuring adequate
dietary intake and tackling underlying condition if any
are the necessary steps in undernourished teenagers.
Iron Deficiency Anemia
Iron deficiency anemia is the commonest deficiency disease
in teenagers. As mentioned earlier, there is an increased
body requirement of iron. This is often inadequately met
due to various dietary problems. There may even be a
carried over deficiency of iron from childhood. Hence iron
deficiency with or without anemia is common. The
prevalence of anemia during adolescence has been a
subject of concern especially among girls. An anemic
adolescent girl is likely to grow up as an anemic woman
and have poor growth as well as other related problems.
In India, prevalence of anemia ranges from 11% to 97%
depending on the socio-economic group and gender. Even
in developed countries, iron deficiency can be seen in 9%
of adolescents. Iron supplementation not only treats
anemia but also improves growth, physical and scholastic
performance. A national program to prevent anemia in
adolescent girls is ongoing.
Eating Disorders
Teenagers are uniquely predisposed to develop eating
disorders. The hormonal shifts, changing social
interaction, the preoccupation with body image, the
irregular eating habits along with the impact of the media
generated visions of perfect bodies and beauty make an
adolescent more likely to develop eating disorders. Two
of the disorders, i.e anorexia nervosa and bulimia nervosa
have been reportedly increasing in teenagers. The
frequency has been much more in girls with few reports in

boys. Adolescent with eating disorders are over concerned
about body image and imagine themselves to be obese.
They either starve (anorexia) or eat and then get rid of the
consumed food by induced vomiting or purging (bulimia).
They present with extreme weight loss, electrolyte
abnormalities, decreased growth and may develop
secondary amenorrhea. These teenagers become obsessive
with weight loss and dieting and continue to loose weight,
become thin and cachectic. Many of these teenagers are
psychologically immature and struggling for independence. Management of such adolescents requires a joint
effort by a physician who has to exclude organic causes of
weight loss, monitor the nutritional status and weight
gain while the psychiatrist will take care of the conflicts
and psychological problems and involve the family of the
child as well.
Obesity
Adolescent obesity has been a cause of concern in developed
nation and is also emerging as a significant problem in
developing countries. The diagnosis of obesity in teenagers
is based on measurement of body mass index (BMI). It is
recommended that age and gender specific percentiles be
used. A BMI of > 85 percentile is defined as overweight
whereas > 95th percentile is obesity. Adolescent obesity is
highly likely to track into adult obesity. Several associated
features of obesity can complicate the health of a teenager
(Table 23.3.3). Adolescence is an age particularly prone to
obesity. The hormonal changes, the growth spurt, the erratic
dietary habits and the psychological conflicts associated
with this period of life make the adolescent highly
susceptible to obesity. Obese teenagers have a difficult time
as they have to face ridicule and constant admonishing from
peers as well as family members. This causes them to feel an
outcast and also lonely which further makes them turn to
food for solace and also makes them physically inactive. The
first step in managing obese adolescents is to motivate him/
her for weight loss. Without motivation, treatment of obesity
is almost futile. Decreasing caloric intake and increasing
physical energy expenditure are the basis for management.
It is recommended that obese adolescent should have at least
60 minutes of physical activity daily. The teenager should
be encouraged to join some group activity to help in the
above. Family involvement and participation in the
management is much more likely to lead to success.
Modalities like pharmacological interventions, severe
caloric restriction or Bariatric surgery may be considered
only in severe obesity (BMI > 99th percentile) and always
along with dietary and activity management.
1182
TABLE 23.3.3: System review in obesity and possible causes

Symptom
Possible causes
Anxiety, school avoidance,

social isolation
Severe recurrent headaches
Shortness of breath, exercise
intolerance
Snoring, apnea, daytime sleepiness
Depression
Pseudo tumor cerebri

Asthma, lack of physical
conditioning
Obesity hypoventilation
syndrome
Sleepiness or wakefulness
Depression
Abdominal pain
Gastro-esophageal reflux
disease, constipation,
gallbladder disease, NAFLD
Hip pain, Knee pain, Walking pain
Slipped capital femoral
epiphysis,
Foot pain
Musculoskeletal stress from
weight
Irregular menses (<9 cycles per yr) Polycystic ovary syndrome;
may be normal if recent
menarche
Primary amenorrhea
Polycystic ovary syndrome
Polyuria, polydipsia
Type 2 diabetes mellitus
Unexpected weight loss
Type 2 diabetes mellitus
Nocturnal enuresis
Obstructive sleep apnea
Extremities
Slipped capital femoral
epiphysis
Blount disease
Athletic Adolescent
Adolescent who are active athletes need added attentions
to their diets. Their protein requirement is higher, i.e. 2
mg/kg/day, also they need to have adequate intake of
carbohydrates, the main body fuel. In a planned,
nutritionally adequate diet, additional vitamins and
minerals are not required except for girls who will need
iron supplements. Adequate intake of sodium, potassium
and water must be ensured.
Snacking
Snacking is the term used to describe the intake of small
meals in between the regular meal times. Teenagers tend
to have food fads, some of them carried from childhood
and also slimming trends and as a result tend to skip

meals or have irregular dietary habits. Also often teenagers
do not eat at one sitting and become hungry quickly.
Snacks intake fulfills the hunger need in between meals.
As a result, the intake of adequate regular meals is
declining and the high carbohydrate and fat containing
snack foods are becoming the staple diet. Majority of the
ready-made snacks have very little of vegetables and fruits
and thus do not provide adequate balance of nutrients.
Snacking as a habit may not be all that bad but what needs
to be encouraged is the intake of nutritious food items
containing fruits, vegetables, cheese, nuts, etc. for inbetween meals. The correlation between excessive snacks
and obesity must be considered in an overweight
adolescent and due attention given to the total caloric
intake.
BIBLIOGRAPHY
1. Barlow SE and the Expert Committee. Expert Committee
Recommendations Regarding the Prevention, Assessment and Treatment of Child and Adolescent
Overweight and Obesity: Summary Report PEDIATRICS
Supplement December 2007;120:S164-S192 (doi:10.1542/
peds. 2007-2329C).
2. Chhatwal J, Verma M, Riar SK. Prevalence of obesity in
Preadolescent and adolescent in a developing country
(India). Asia Pacific Journal of Clinical Nutrition 2004;13:
231-35.
3. Food and Nutrition Board, Govt. of India UNICEF office
of south East Asia-A collaborative Study, 1989
4. Garrow JS, James WPT, Ralph A. Human Nutrition and
Dietetics Elsevier (10th Edn). 2000;177- 210.
5. National Nutrition Monitoring Board (NNMB). Diet and
Nutrition status of rural population. National Institute of
Nutrition, Hyderabad 2002;39-55.
6. Toteja GS, Singh P.Micronutrient Profile of Indian
Population. New Delhi. Indian Council for Medical
Research, 2002.
7. Venkaiah K, Damayanti K, Nayak MU, Vijaraghavan K.
Diet and nutrition status of rural adolescent in India.
European journal of clinical nutrition 2002;56:119-25.
23.4 Adolescent Psychology

Jugesh Chhatwal
Adolescence is a unique developmental period during
which major physical, psychological and social changes
occur. It is an approximately 10-year span wherein
important developmental tasks have to take place. The
physical changes in the body during adolescence are more
evident but the psychosocial changes intertwined with
the physical development make it a complicated period.
This bio-psycho-social process involves completion of
certain tasks, viz. emancipation from family and formation
of self identity, sexual identification, achievement of
intimacy, future orientation and career choice. There may
be many differences on when and how these changes take
place during adolescence and are closely related to race,
sex, ethnic background, socio-economic class and family
value system. The changes are summarized in Table 23.4.1
Identity Formation
One of the main developmental tasks of adolescence is the
formation of the identity. The identity encompasses
physical appearance, feelings about self and sexuality,
cognition and the ability to communicate sufficiently,
social status, value system, relationship with others and
independence. During the early adolescence, the tasks
normally accomplished are physical maturation in the
peer group and beginning of interest in hetero-sexual
relationships. In middle adolescence, there is a significant

movement away from the family and parents with
development of stronger opposite sex friendships. During
later adolescence, the tasks include autonomy from
parents, sex role identity, morality and choice of a career.
If these tasks are not achieved and properly resolved, role
confusion results this may cause problems like mood
changes, personality disorders and inability to take on
mature roles in society.
Another important part of individual development is
self- esteem. Self-esteem plays a significant role in
motivation and performance, in school and sports, the
quality of peer relationships, the abuse of drugs and
alcohol, teenage pregnancy, the willingness to persevere,
resilience and capacity to bounce back from failure, etc.
Self-esteem reflects how children feel and think about
themselves and how they view their competencies. It
develops as an interaction of inborn temperament and
environmental forces. Conflicts in development of selfesteem can also lead to psychological problems in
adolescents.
Relationships with Parents
As a part of growing up, the adolescent moves from the
family to the social groups outside. Although parents look
TABLE 23.4.1: Summary of adolescent development
Typical age span (years)

Physical development (Tanner)
Body image
Peer relationship
Family relationships
Identity formation
Early adolescence
Middle adolescence
Late adolescence
12-14
II-V
Preoccupied with own body
and changes
Same sex groups, interest in
opposite sex at a distance
14-16
II-V
Concerns of appearance
16-18
V
Acceptance to a certain
extent
Heterosexual contact
individual level
Strong peer ties with groups/

Individuals with which they
identify
Beginning of turmoil conflict with
Peak of turmoil, questioning of
parents, esp. same sexed parents authority
more argumentative
Increased need for privacy, lack
Feeling of omnipotence and
of control on feelings, idealistic
risk taking behavior
and have fantasies
Beginning of return to family,

less conflict with parents
Refinement of values and
able to accept and
compromise
1184
forward to the adulthood of their child, at the same time

there is a fear of losing control. The growing identity and
independence of the adolescent, the tendency to question
authority and sometimes different level of morality causes
a conflict with parents. Adolescent moodiness and
irritability along with mood swings are common. Many
teenagers during mid adolescence have larger issues of
concern like political, moral or environmental. They may
have role models or heroes far different from their
immediate environment. It is important for parents to
recognize and accept the individuality of their child. The
ability of the parents to communicate, a willingness to
listen and an ongoing affection and acceptance will help
the adolescent to adapt and grow. Negotiating with the
adolescent rather than authoritative or permissive
approach is more likely to lead to a balanced teenager.
Even in sexual matters, it is important for parents to have
a confidential and non-judgmental approach.
Relationships with Peers
The middle years of adolescence are closely related to peer
pressures. The need to join a peer group, conform to their
standards, and popularity are very important issues for
an adolescent. At this stage, the peer groups are the most
dominating forces moulding the personality of the
teenager. If the connectedness with the family is
maintained through this phase, the adolescent is able to
have a balance in his relationships.
The emotionally turbulent phase of adolescence
predisposes to some psychological problems; few of them
are discussed here.
Depression
Teenage depression is not an uncommon problem. The
growing conflicts with parents, the confusion of identity
establishment, and the stress of academic achievements,
career concerns, the need to conform and peer popularitytogether, these impose a considerable strain on the
adolescents mind. Depression is often a result of
significant personal loss, a feeling of helplessness. It often
indicates poor self-image and identity .To counteract these
feelings, many teenagers become engaged in delinquent
activities, alcohol and drug abuse.
Depressed adolescents usually do not present the same
way as adults and the diagnosis may be missed quite
often. The symptoms may vary according to the
developmental age. In early adolescence, the young person
often lacks the insight to recognize his sad feelings.
Depression in this age group may take the form of
depressive equivalents such as falling school grades,

running away, disruptive behaviors at home and school,
somatic symptoms such as headaches or abdominal pain
and unwed pregnancy.
Most depressed teenagers need an understanding
adult with whom they can communicate their feelings of
anger and sadness. Routine health check of teenagers
should include questions about moods, social and home
life, school performance and few screening questions for
depression. Youngsters who are very depressed and in
whom there is a suspicion of psychosis should be seen by
a psychiatrist.
Suicidal Attempts and Suicide
Suicide is one of the major causes of deaths among
adolescents. Suicidal attempts are more frequent among
girls while suicides are more among boys. Depression often
precedes suicidal behavior. It usually indicates that the
adolescents psychological defenses have been stressed
to the limit and coping mechanisms have failed. Suicide,
therefore, often represents the last attempt of an adolescent
to gain control over a situation in which he or she feels
powerless, helpless and lost. The physician must
recognize the depressed teenagers cry for help and a
psychological evaluation must be done for further
management.
School Problems
The major school problems during adolescence include
school truancy or absenteeism, academic failure and
behavioral problems in the classroom. The learning
disabilities like Dyslexia or Attention deficit hyperactivity
disorder seen during childhood are carried to adolescence
and can become more prominent due to the various
psychological stresses of adolescent years. School
problems are frequently masked by some somatic
symptoms such as headache or abdominal pain.
Juvenile Delinquency
Delinquency can be defined as criminal offence committed
by juveniles. Juvenile delinquents can be three major
categories: Sociological delinquents have usually adaptive
rather than maladaptive behavior. Usually, the
delinquency is performed in the context of a supportive
group like a gang. They frequently have close, supportive
ties within the home, but as they reach adolescence they
lack appropriate supervision. Participation in social

action programs or group activities with supervision may
provide the young person to develop more socially
acceptable behavior.
Characteristically, delinquents may have antisocial
personality orientation. These young persons have no
loyalties and trust no one. They may be lonely, guiltless,
and care little for the hurt they impose on others. Often
these adolescents have long-standing histories of
behavioral problems. They need intensive, long term
psychotherapy and should be referred by the primary care
professional to an appropriate mental health facility.
The neurotic delinquents make an attempt to
communicate feelings and needs that they are unable to
in other ways to their environment. These youngsters
usually make sure that others will identify them as the
perpetrators, because they want to 4be identified and
helped. Frequently, these youngsters have no previous
history of behavioral problems and are depressed when
seen after the delinquent episode. These teenagers need
short-term psychotherapy.
Risk Taking Behavior
Risk taking behavior is a normal experience for adolescents. The psychological and emotional turmoil predispose
the teenager to experiment and explore the world and life
experiences. The need for independence and increasing
physical mobility also add to above. Also the teenagers
tend to think that This (untoward incidents/accidents)
cannot happen to me or the magical thinking. With this
backdrop, they are inclined to take risks and indulge in
risk taking behavior. Adolescent boys are more likely than
girls to engage in risky behavior. Risk taking behavior can
be in the form of substance abuse, dangerous driving,
sexual activities, etc. School and family difficulties, low
self-esteem, mental health problem, peer pressures and
access to above situation increases the risk taking behavior.
Healthy family relationships and school dynamics as well
as religious affiliations may be protective factors. Family
physicians must understand and screen for risk taking
behavior in teenagers under their care.
Violent Behavior
Teenagers may indulge in violent behavior or may be the
victims of violent acts. Increasing independence and
mobility outside the home and the mood swings of
teenagers make them susceptible to commit violent acts.
Violent behavior in teenagers may be associated with
certain clinical psychological entities, e.g. oppositional
defiant disorders or conduct disorders. It may occur
without these conditions and in such cases there can be

certain risk factors like socio-economic environment,
substance abuse, fire arms availability. Allowing teenagers
to have access to fire arms or carrying them can be a risk
for use as seen in recent spate of shoot out incidents in
schools. For managing teenagers with violent behavior,
multiple treatment modalities including psychotherapy,
pharmacotherapy and family interventions are required.
Effect of Media
Media in the present times has emerged as a powerful
influence. It has been said that media is the most important
and most understated influence on children and
adolescents. Adolescents are at a stage when they want to
know more about the world and media, both audio-visual
and print, become a very easily available and captivating
source of information. In the absence of parental support
in the quest for information, media becomes surrogate
parents. Internet and television with their restraint free,
colorful virtual world are greatly appealing to teenagers.
The impact of visual media on teenagers cannot be denied
especially, in context of violence, smoking and alcohol
use and sexual experiences shown. In addition, media
displaces other activities especially outdoor physical play
and these contribute to a poor lifestyle and obesity. With
the visual images of perfect bodies, the young adolescent
are likely to develop a distorted body image. To decrease
the influence of media on teenagers, it is recommended to
monitor closely the screen time and allow 1-2 hrs of daily
viewing of television/computer screen/video games.
BIBLIOGRAPHY
1. Brisbon N, Chambers CV. Neurocognitive development
in adolescent males or adolescent boys are from Pluto.
Prim Care Clinics in office practice 2006;33:223-36.
2. Greydanus DE, Rimsza ME, Newhouse PA. Adolescent
sexuality and disability. Adolescent medicine 2002;13:
223-47.
3. Jenkins RR. Adolescent MedicineViolent behavior in
Nelson Textbook of Pediatrics 18th edition. Kliegman
RM, Behrman RE, Jenson HB, Stanton BF (Eds).
Elsevier: New Delhi 2007;820-24.
4. Noble J. Adolescent health issues in Noble: Textbook of
primary care medicine (3rd ed). Mosby, Inc. USA. 2001;
62-71.
5. Rakel RE. Adolescent health care in Rakel. Textbook of
family Medicine (7th ed). Saunders Elsevier: Philadelphia.
2007;597-607.
6. Sharma R, Grover VL, Chaturvedi S. Suicidal behavior
amongst adolescent students in S.Delhi. Indian J
Psychiatry 2008;50:30-33.
7. Strasburger VC. Adolescent, Sex and the media - 00000,
baby, baby - a, Q and A. Adolescent Med Clinics 2005;
16:269-88.
1186
23.5 Identity Crisis and Adolescents

Shrikant W Chorghade
Adolescence is the gift of 20th century. Before 20th century
there was no concept of adolescence. The children used to
enter adult world when they matured physically or when
they began vocational apprenticeship. It was usually the
vocation of father which was pursued by boys and the
girls used to learn skills of housewives from their mothers
and/or grandmothers.
Today the children have to pass through a long period
of education or vocational training before a person can
take adult responsibilities and this is period of
adolescence-gift of 20th century.
Identity crisis is a word coined by a clinical
psychologist Erik Erikson (1902-1994) in his Theory of
Personality . The word identity stands for ego identity.
In his opinion the adolescents have to search a rational
answer to questions such as Who am I? And What am I
going to be? in context of a variety of alternatives and
confusing choices before them. The word crisis does
not connote catastrophe or a threat, but it means a turning
point in the life of an individual.
Adolescents are neither children nor adults. They are
in a transitional phase when size and shape of the body
changes fast. They feel grown up, but parents and seniors
refuse to accept it. During this period adolescents get a
feeling that the parents are asking probing questions.
Parents restrict them to mix with children of opposite sex.
Their movements and activities are questioned. Their talks,
mannerisms are criticized. If their parents praise their
obedience and docility, the peers ridicule them for being
shy and conservative for the same pattern of behavior.
The teachers and others, i.e. adults outside family circle
may be having still different opinions. Thus, they get
confused over their own behavior and body images.
Their own friends who were very much like them now
start appearing in different shapes, sizes and behavior.
They take time to get used to the changing body shape of
themselves and that of peers. Sexual development also
starts appearing at different ages and at a different pace.
The peers who experience variety of body changes, feelings
and emotions may share them with each other to increase
the confusion. Adolescents thus have a confused identity
of their own body and causes changes in emotions and
behavior.
The hormonal changes during adolescence lead to
heightened emotions. Adolescents become more emotional
and sensitive. Casual comments by parents or others may

make them cry or go into fits of anger without understanding why it happens.
Their own emotions confuse them. Childhood
dependencies are abandoned but financially adolescents
have to depend on their parents. Television, radio,
magazines, newspapers display in front of an adolescent,
an information explosion. Rapid social, political and
technological changes, display of values and cultures of
other countries increase confusion as to an adolescents
own place and status in the world as individual.
Traditional value which they have learnt as children may
be in total contrast to what is displayed before them by
peers and the media. These differences result in total
confusion over value system and ideological clashes with
parents, teachers and elders around them.
This is the age when the adolescents have to make a
choice of their career. Their scholastic performances may
not be proper to pursue career of their choice. They do not
have a proper assessment of their own qualities or liabilities
and assets in their personality. They are not sure about
job opportunities.
All these things together lead the adolescent to a state
of utter confusion. Each adolescent has to find own
identity, own place in relation to work, culture,
citizenship. Adolescents have to learn to deal with people
around them including relatives and mends. They have
to fulfill their own moral social and spiritual commitments.
Each adolescent gradually has to learn the intimacies of
love and how to love and being loved in preparation of
adults roles of a husband and wife. An adolescent has to
decide his or her duties to people around. They have to
decide priorities in life. Progression through all these
growth tasks is necessary for healthier adulthood and
personal maturity. This progress does not occur in straight
line there are peaks, valleys and plateaues. Progress in
one area influences progress in other areas.
Obviously, the adolescents success or failure as well
as ease or tension in handling his or her problems will be
determined to large degree by the socio-psychological
forces to which he or she is subjected during this time.
And these may be significantly related to his or her
maturation. Thus, physical status during adolescence,

mediated through the socio-psychological environmentmay exert profound and lasting influences on personality.
For this reason, many aspects of the adults behavior and
personality seem consistent with his or her adolescents
adjustments, attitudes and motivations.
Havighurst had theorized a concept of developmental
tasks for different phases of life span. The specific tasks
arise at about specific period of life of an individual.
Successful fulfillment of these tasks leads to happiness
and success with the tasks assigned for later phase in life.
Some tasks arise out of physical maturation, like
learning to walk. Some tasks develop due to cultural
pressures, like learning to read and write. Some tasks grow
out of personal values, aspirations like choosing a career
or vocation. These three forces work together and decide
the development tasks for the individual for the specific
period of life.
These tasks in his opinion are the guidelines which
enable an individual to know what the society and the
people around him or her expect from him/her during
specific phases in life.
The development tasks assigned for adolescents on
the following lines:
1. Achieving satisfactory relationship with age-mates of
both sex.
2. Behaving as per masculine or feminine role assigned
by the society and culture.
3. Accepting ones body physique as it is and use it
effectively.
4. Thinking and behaving as per social, cultural and
moral norms prevalent in the society.
5. Achieving independent emotional existence leaving
behind attachment behavior and dependencies of
earlier life.
6. Thinking, planning and achieving future training and
career.
7. Developing ones own values, ethics and philosophy
of life and learning to be happy over the life being lead.
Failure to master these development tasks can lead to
frustration and feeling of inadequacy in adolescents. This
may heighten in severity of identity crises. Erikson
identified the crucial task of adolescence as the
establishment of a stable sense of identity including
physical and emotional separation trom family of origin,
initiation of intimacy and realistic planning for economic
independence. The parent to child relationship should
change to adult relationship. Continued difficulty in any
of these areas may warrant need for counseling.
Theorists from a variety of perspectives have described

adolescence as period of questioning, reappraisal and of
diminished well being. While dealing with their own
special concerns parents during middle age have to cope
daily with adolescence who are undergoing great physical
emotional and social changes. It is ironical that people at
two different ages in life linked with emotional crisis often
live in the same household where parents are themselves
in crisis of midlife and their children passing through
adolescence crisis.
A PROBLEM ADOLESCENT
A distressed adolescent may be labeled as problem
adolescent by the parents or the teachers. What is needed
is probing into the history and an attempt to find out
relevant causes for maladjustment. Parents should be
considerate, reasonable and consistent while dealing with
adolescents. If the parents are not reasonable and
understanding or the child is being brought up by a single
parent or in a maladjusted home, the child may show
signs of stress.
Before an adolescent experiences distress and shows
disturbed behavior or goes to the extent of committing
suicide, he or she is likely to show some indications of his
or her disturbed mind through his or her behavior. As the
parents are emotionally close to the adolescents they are
the ones who can detect the earliest indications of
disturbed mind.
The behavioral problems which indicate a disturbed
adolescent include:
1. Changed behaviorshy disobedient, rowdy,
irresponsible, disrespectful patterns of behavior,
scholastic backwardness.
2. Psychosomatic problemsheadache, poor appetite,
backache, stomachache.
3. Organic problemse.g. bed wetting, encopresis,
stammering, stuttering.
4. Addiction to smoking, alcohol, drugs.
5. Antisocial behaviorvandalism, violence sex crimes
6. Neurotic problems, e.g. hysterical symptoms,
depression, anorexia nervosa.
7. Psychotic symptoms-schizophrenia.
Severely distressed adolescent may require a
psychiatrists help. If not detected or treated, the
adolescents may indulge into destructive behavior or
suicide.
1188
Indications of a Disturbed Adolescent

Persistently depressed or disappointed mood.
Eating and sleeping disturbance.
Declining school performance.
Gradual social withdrawal and increasing isolation
from others.
Breakdown in communication with parents and other
important persons around.
Attempt to suicides.
Self-destructive behavior-alcohol and drug addiction,
reckless driving.
Statements like I wish I was dead or What is there
to live for?
Inquiries about lethal properties of medicines and
drugs.
Any recent obvious stressful event, viz. death of a near
one, failure in examination, break up of love affair, etc.
society who, in turn, react to the adolescent because the

pattern and of behavior of the adolescent arouses
discomfort and concerns. The reactions of parents disturb
the adolescent further.
Parents should be counseled to adopt discipline
measures according to changing abilities of adolescents
who are learning to think through problems and solve
them.
Parents who use negotiating techniques are more
successful in getting positive outputs than authoritarian
or permissive techniques of parenting.
The pediatrician who is trying to help an adolescent
in identity crisis and his or her parents must be aware of
this vicious cycle. They should interview the parents
together and separately and also the adolescent alone.
While counseling the parents following precautions are
necessary:
Assurance about Behavioral Difficulties
ROLE OF THE PEDIATRICIAN

The pediatrician needs to help parents to identify and
differentiate between normal discomforts of adolescents
and concerning behavior which need attention.
Bids for autonomy, avoiding family activities, demand
for privacy, excessive tendency to argue are the behaviors
which should not cause concern to parents. Risk taking
in early adolescence is normal. Escalation of this behavior
in late adolescence needs attention.
A pediatrician should interrogate the parents individually and the adolescent separately. The interrogations
may reveal the troubled spots in the childs psychosocial
environment. In the course of evaluation, the pediatrician
should be able to establish a trusting relationship with
the child and the parents. During management the
pediatrician will have to take the help of other disciplines,
viz. psychology and child psychiatry. After identifying
the causal factors the parents will have to be counseled on
the problems of the adolescents, rearing and disciplining
practices of the parents and home environment, etc.
The parents should not be blamed or labeled guilty for the

behavior of their adolescents. They should be assured that
many adolescents have behavior difficulties and such
difficulties are indication of stresses in them, and they
need help.
Strengths of the Adolescents
Every adolescent has some strengths or positive points in
his or her personality. The parents should be made aware
of them and should be advised to reinforce these positive
qualities by verbally mentioning them or by rewarding
them, e.g. a child may be exceptionally intelligent, attractive
to look at, well coordinated, have aptitude towards art
and games etc.
Difficulties
The parents should be explained about the difficulties
which adolescents are finding in adjusting with the
persons around and environment and the ways in which
the adolescents can be helped in adjustment.
GUIDANCE AND COUNSELING TO PARETNS
Reassurance about Positive Points
The adolescent who is disturbed and disturbs his or her

parents by his or her behavior is not behaving in a void.
He or she behaves in the context of his or her family and
Parents should be reassured of positive points in their

behavior and personality and good things they have done
for their adolescents.

The parents should be made aware about the
expectations which adolescents are likely to have from
their parents. This will help the parents to understand
their own behavior which might have disturbed the
adolescent.
If the pediatrician is close to the family where an
adolescent is shaping up, the parents can be counseled
and made aware of likelyhood of the identity crisis and
advised suitable measures in their parenting techniques.
This is called Anticipatory Guidance, tackling the problem
before it arrives.
The counseling to parents during Anticipatory
Guidance should be on the following lines:
1. Understand impending identity crisis.
2. Show your love to your children in words and action
and by spending time with them exclusively and trying
to know their problems and letting them know that
they love them and will stand by them in period of
difficulty.
3. Use of physical touch, hugging, kissing, etc. suitably
to convey love.
4. Reinforcing positive desirable behavior by words of
appreciation and gifts in cash or kind.
5. Getting familiar and be mendly with mends of their
adolescent children.
6. Helping adolescent to pursue hobbies and organized
games and constructive activities.
7. Making the parents aware of ideal ways of parenting.
Summary
In modern industrial societies, passage from childhood to
adulthood is marked by long transitional period known
as adolescence. It is considered to begin with puberty, the
process that leads to emotional maturity and sexual
maturity or fertilitythe ability to reproduce. It begins

from age 10 to 12 until late teens or early twenties.
A vast number of complex interacting factors which
include genetic qualities, the parental attitudes, family
atmosphere, the peers and friends and the effect of
environment decide the personality of adolescents. Each
adolescent has his or her unique personality structure in
the process of development. The type of personality is
decided by the way the adolescent resolves the identity
crisis. Most adolescents seem to have little trouble coming
to a satisfactory resolution of identity crisis. Each
adolescent has to resolve his or her own identity crisis.
His or her parents, the family, the peers the friends, the
family physician, the pediatrician and many others can
offer their support and help them in the process.
BIBLIOGRAPHY
1. Berk E Laura. Child Development~ Prentice Hall of India.
(VI Edition). New Delhi 2002;456.
2. Hurlock Elizabeth B: Developmental Psychology- A life
span approach Tata Mc Graw Hill Publishing Company,
New Delhi 1981;30th reprint 2004;10:222-59.
3. Kliegman Robert M, Behrman Richard E, Jenson Hal B,
Stanton Bontita F. Nelson Text Book of Pediatrics Volume
I Part I to XVI, Saunders an imprint of Elsevier
Philadephia, Indian reprint, First printed in India, 2008;
65.
4. Papalia Diane E, Olds Sally Wendkos Felfman Ruth
Duskin. Human Development Tata McGraw Publishing
company Limited: New Delhi, Tata McGraw Hill Edition
2004;588.
5. Passer Micheal W, Smith Ronald E. Psychology-Frontiers
and Application. McGraw Hill Higher Education. New
Delhi, 2001.
6. Sigelman Carol K, Shaffer David R. Lifespan Human
Development Cole Publishing Company. Pacific Grove,
California USA (2nd edn). 1995.
23.6 Adolescent Sexuality

Jugesh Chhatwal
For the infant and toddler, exploration of ones own sex
and sexuality is part of the myriad learning experiences
like tasting a new food item or learning to walk. The
adolescent has grown up from these experiences and
stands at the thresholds of emerging adult sexual
functions. Sexuality can be defined as a complex
phenomenon of interaction between biological sex, gender
identity and gender role behavior. Due to the various

physiological hormonal influences, sexual functions and
sexuality become a very important part of adolescence.
The adolescent is still a child in many ways and yet has
attained the physiological functioning of the fully grown
adults. Added to this are the influences of the mass media
on the sexually mature adolescent faced with a long
1190
premarital period of lack of sexual gratification. The

massive exposure to explicit sexuality through media
modifies the adolescent sexual behavior to a great extent.
The interaction with peers who may be at a later stage of
maturation also easily influences the immature.
Considering all these, adolescence is a period of anxiety,
confusing and conflicting responses and interest in sex
and sexual anatomy. Understanding these is necessary
for the physician who wants to guide and help the child
through this turbulent phase.
During adolescence there are three main areas of
development viz. physical, cognitive and psychosocial.
Adolescent sexuality development is a part of psychosocial
development and the following four tasks need to be
completed.
i. Effective independence from family of origin
ii. A vocational goal
iii. A positive self-image and personal identity
iv. Mature sexuality.
Formation of personal identity is a critical task of the
adolescent period. By identity, it is implied the individual
or the personality of the person. In relation with sexuality,
it is the sexual identity which is to be considered. The key
components of this are gender identity and sex roles. Both
these components are well in place much before
adolescence and believed to be formed by 2 to 3 years of
age. During adolescence, the hormonal influences further
refine the sexual identity on which the psychosocial factors
play their part resulting in the maleness or femaleness
of a person or being masculine and feminine. Development
of this gender identity influences the sexual behavior also.
In establishing their gender identity, the adolescents
experiment in interpersonal relationships.
The social interactions of the adolescents are modified
by their developing sexual roles not only in relation to
friends and peers but also in the family. The parental
responses towards regulating the adolescent behavior are
also influenced by the growing sexual identity of their
child. The prevalent cultural values and social practices
too modify the adolescents sexual behavior. As a result,
the responses in interpersonal relationships during
adolescence are a mix of the roles played by sexual identity,
parental as well as peer pressure and the sociocultural
values. Sexuality is an important determinant of selfesteem especially during the adolescent years. The way
an individual perceives him or herself in the eyes of the
opposite sex significantly contributes to the self image.
The perceived image of self also affects other spheres of
behavior and social interaction. From this self-centered,
sexually oriented confused individual, the mature adult
has to emerge.
The role of the physicians and parents is important in

presenting a balanced view to the teenager and help him
or her engage in healthy physical and academic activity
and channel his or her sexuality.
PROMISCUITY AND PREMARITAL SEX
The onslaught of western culture through the visual media
has changed the social pattern dramatically in urban as
well as semi-urban areas of our country. In rural areas
also the impact of these changes is slowly becoming
evident. The result of these is the growing promiscuity of
teenagers which is being taken as acceptable. An
unwelcome fallout of increasing marriage age and
increasing literacy is the prolonged period of sexual
nongratification with a higher risk of premarital sexual
encounter.
There are few surveys on adolescent sexuality in our
country. The WHO fact sheet on adolescents for India
reports that about 10% of girls and up to 30% of boys have
indulged in pre-marital sex. The figures may vary
according to the region and socio-economic status. Most
of the sexual encounters for boys are with sex workers.
With increasing permissiveness come the problems of
sexually transmitted diseases (STDs) and pregnancies.
Considering these, anticipatory guidance to adolescent
regarding contraception and prevention of AIDS and STDs
becomes a necessity.
CONTRACEPTION
Unmarried sexually active adolescents are unlikely to use
contraception due to various reasons like ignorance,
problems of accessibility and availability, bravado or just
lack of planning of the sexual act. Even married
adolescents use less contraception as compared to adults.
Providing contraception to the adolescent age group has
been a contentious issue. There is a long standing deeply
entrenched view that provision of contraception
encourages promiscuity. But on the other hand is the
spectre of unwanted pregnancies leading to septic illegal
abortions, abandoned babies and maternal deaths.
Teenagers are ignorant of reproductive physiology and
tend to have a number of misconceptions regarding the
need and methods of contraception. According to a WHO
report, although the awareness of condoms is high (7090%) but the use ranges from 34-64%. Only 8% of 15-19
year old admitted to use of safe method of contraception.
Very few (1.3-1.4%) reported use of pills or condoms. The
physician dealing with adolescents must be aware of these
problems and keep the patients welfare in mind. The
subject of sexual activity needs to be broached with great
deal of sensitivity and taking the teenager in confidence
in a non-judgmental manner. Contraceptive advice must

be given to a sexually active teenager. The issue of
informing or involving parents needs to be tackled with
due consideration of the family interactions.
All types of contraceptive methods can be safely used
by adolescents. Condoms have an additional advantage
of protecting against STDs. Oral contraceptive for
adolescent use should preferably have 50 mg or less of
estrogen. Girls on contraceptive pills must have regular
gynecological check-up. Intrauterine devices are better
avoided in adolescents with or at risk for sexually
transmitted infections.
Emergency Contraception
In situation of coercive sex or otherwise, emergency
contraception is an effective method of preventing an
unwanted pregnancy. There can be side effects like
nausea/vomiting and repeated use should be avoided.
TEENAGE PREGNANCY AND ABORTION
In our country average age of marriage continues to be low
despite the legislation to the contrary. According to National
Family Health Survey, the median age at marriage is about
16 years, and at first birth 19.2 years. The age old beliefs and
traditions remain the most important influence in these
matters. Consequently, in contrast to western countries, most
of the teenage pregnancies in India occur among married
girls. With increasing permissive-ness and premarital sex,
the unwed teenage pregnancies are also increasing.
Most of the unmarried pregnant teenagers are likely to
terminate the pregnancy due to the social and parental
pressures. About 10% of the abortion seekers are
adolescents and about half of unmarried women seeking
abortions are adolescents.
MASTURBATION
Most of the adolescents have false ideas and beliefs about
masturbation. The growing sexual desires in the teenagers
very often culminate in masturbation. As a practice, it is
much more common among boys than girls. Due to the
myths attached to this act, majority of the adolescents and
even adults, indulge in the practice but are left with a
feeling of guilt. As a source of release of sexual energies,
masturbation is a much safer and physiological practice.
The teenagers need to be reassured on this aspect. Similarly,
nocturnal emissions in an adolescent boy are a normal
phenomenon of growing up. The guilt feelings and myths
should be dispelled, and the teenager should be
encouraged to avail proper sex education.
HOMOSEXUALITY
During early adolescence, strong friendship with same
sex and lack of interest in opposite sex is natural. Very
often it is an attempt to experiment and soon the adolescent

switches to heterosexual behavior. Persistence of such
behavior beyond adolescence may indicate a more fixed
identity problem and needs intervention.
ANXIETIES OF SEXUAL INADEQUACY
Self doubts regarding penile size, erectile function,
nocturnal emissions, hair growth and other secondary
sex characteristics, and capacity to attract or interact with
the opposite sex are a continuous source of anxiety to the
adolescent, often requiring reassurance and counseling,
even professional medical help in a minority.
SEXUAL ABUSE
Any sexual activity in which there is no consent given by
the adolescent is considered sexual abuse. Any act which
involves sexual contact including commercial exploitation
like prostitution or use in making pornographic materials
are also considered sexual abuse. The age of consent in
India is 16 years and below this age any sexual act even
with consent is considered an offence. Few studies have
looked at sexual abuse of adolescents in India. In a report
from schools in Goa, 6-18% adolescents reported some
form of nonconsensual sexual activity including sexual
coercion and violence.
Adolescent sexual abuse can happen within the family
or social circle or with a stranger. Such adolescents suffer
from emotional trauma, may have interpersonal difficulties,
run away or fall prey to substance abuse. Many will require
psychological rehabilitation and support. Increasing the
awareness among teenagers and their families is an
essential step for prevention. Education on life skills for
teenagers on how to avoid or deal with abusive situation is
also important.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
Abraham L, Kumar SA. Sexual experiences and their correlates among college students in Mumbai city, India. International family planning perspectives 1999,25:139-46.
Brown RT, Brown JD. Adolescent sexuality. Primary care
clinics in office practice. 2006:33;373-90.
Ganatra B. Abortion research in India: What we know
and what we need to know. In Womens reproductive
health in India. Eds. Jeejeebhoy SJ, Ramasubhan R. Jaipur,
Rawat publications. 2000;186-235.
Jeejeebhoy SJ. Adolescent sexual and reproductive
behavior: A review of evidence from India. In Womens
reproductive health in India. Eds. Jeejeebhoy SJ,
Ramasubhan R. Jaipur, Rawat publications. 2000;186-235.
Patel V, Andrew G. Gender, sexual abuse and risk
behavior in adolescent - A cross sectional survey in
schools in Goa. National Medjoumal ofIndia, 2001;14:
263-67.
1192
23.7 Common Health Problems in Adolescents

Manorama Verma, Jugesh Chhatwal
Adolescence is generally considered a healthy period. In
addition to the usual morbidities, the adolescent period is
particularly susceptible to some health problems. These
include psychosocial problems, gynecological disorders,
sexually transmitted diseases, pregnancy, breast disorders,
hirsutism, acne vulgaris, urological problems in males
and substance abuse. History taking or interview in
adolescents should, in addition to routine questions,
include these areas. An acronym for the assessment of
psychosocial problems and sexual health has been
devised as HEADS/SF/FIRST (Table 23.7.1). Psychological health issues including violence, depression, eating
disorders etc have been dealt with in section on Adolescent
psychology.
TABLE 23.7.1: HEADS/SF/FIRST
H-Home,
E-Education
A-Abuse
D-Drugs
S-Spirituality
S-afety
F-family
F-friends
I-Image
R-Recreation
S-Sexual health
T-Threats and violence
TABLE 23.7.2: Appropriate history to evaluate adolescent

gynecological problems
Age of menarche
Menstrual history
Last menstrual period
Use of tampons or sanitary
napkins
Presence of abnormal
vaginal discharge, abdominal
pain, urinary tract infections
History of sexual activity

Contraceptive use
History of STDs/ vaginitis
History of abnormal pap smear
History of sexual abuse or rape
Dysmenorrhea
Primary dysmenorrhea is the commonest menstrual
disorder in female adolescents. It manifests as lower
abdominal cramps or back pain during menstruation.
Nausea, headache or diarrhea may occur along with pain.
Severe impairment of daily activity can occur during these
painful episodes. It becomes more common as age
increases. Psychological problems like sexual abuse, rape,
school phobia, personal or family problems may also
contribute to increased threshold of pain. Dysmenorrhea
can range from mild, moderate to severe.
GYNECOLOGICAL DISORDERS
Primary Dysmenorrhea
More and more adolescents in India are becoming sexually

active due to a variety of reasons. Gynecological history
and examination is an important part of the medical care
of adolescent females. Pediatricians are not very
comfortable and feel hesitant to go into the details of this
aspect of adolescent care especially in an unmarried girl.
With changing social scenario and increased sexuality in
teenagers in India, it has become necessary for the
pediatricians to familiarize with adolescent history and
examination especially in context of sexual issues. Some
important points in history are provided in Table 23.7.2.
Primary dysmenorrhea is associated with ovulatory

menstrual cycles. There is increased synthesis of
prostaglandins and other hormones like vasopressin,
which cause excessive uterine contractions due to increase
in the tone of myometrium resulting in uterine ischemia
and dysmenorrhea.
.
COMMON MENSTRUAL DISORDERS

Three common adolescent menstrual disorders are
dysmenorrhea, premenstrual syndrome and dysfunctional uterine bleeding.
Secondary Dysmenorrhea (Table 23.7.3)

A pathological process must be excluded in severe
dysmenorrhea. Endometriosis should be suspected in
older adolescents with chronic history of increasingly
painful menstrual periods. The pain begins several days
before the bleeding and becomes quite severe. It responds
to treatment for primary dysmenorrhea but not completely.
Congenital malformations of the genital tract cause severe
pain often at the very first menstrual period due to

obstruction to blood flow unlike primary dysmenorrhea
and endometriosis. A pelvic mass can be detected on
physical examination as well as by ultrasonography. A
recto abdominal examination is sufficient to diagnose the
underlying conditions in severe dysmenorrhea in majority
of cases.
Treatment
For mild cases hot fomentation and analgesics are helpful.
The following non-steroidal anti-inflammatory drugs
(NSAIDs) which inhibit prostaglandin synthetase activity
can also be used:
1. Ibuprofen 10 mg/kg/dose po
2. Naproxen sodium 5-7 mg/kg/dose po
3. Mefenamic acid 5-8 mg/kg/ dose po
Oral contraceptives in low dose combination suppress
ovulation and decrease menstrual pain. They induce
endometrial hypoplasia and decreased menstrual flow
probably due to a decrease in production of prostaglandins. It takes about 2 to 3 months for them to have
maximum effects. Hence, NSAIDs should also be given
initially.
TABLE 23.7.3: Conditions associated with secondary
dysmenorrhea
Genital tract infections
Salpingitis
Congenital malformations of the genital tract
Bicornuate uterus
Rudimentary uterine horn
Endometriosis.
Intrauterine device
Genital tract cysts and neoplasms
Complications of pregnancy
Threatened abortion
Ectopic pregnancy
Premenstrual Syndrome (PMS)

This is not very common in adolescents as it occurs in
ovulatory cycles. It is characterized by physical and
psychological symptoms which occur 7 to 10 days prior
to onset of periods and disappear within the first day or
two of menstrual flow. These include weight gain,
abdominal bloating, breast engorgement and pain,
constipation, peripheral edema, headache, irritability,
anxiety, depression, tension, fatigue, lack of concentration,
increased appetite. There are many proposed theories for
PMS but exact pathophysiology is not clear. Management
includes reassurance, exercise and dietary modifications.

Sometimes medications like magnesium, diuretics or
vitamin E may help.
Dysfunctional Uterine Bleeding (DUB)
This is characterized by irregular, excessive, prolonged
painless uterine bleeding where no organic cause
(systemic, hematologic or pelvic) can be detected. The
nature of bleeding is one of menorrhagia, polymenorrhea,
metrorrhagia and continuous bleeding, preceded by
amenorrhea.
It is usually a result of anovulatory cycles due to
developmental immaturity of the hypothalamo-pituitaryovarian axis. Sometimes polycystic ovary syndrome can
also be the cause. It is common in very young adolescents
between 9 to 13 years of age during the first two years of
menarche. DUB is diagnosed after excluding other causes
of abnormal menstrual bleeding.
1. Pelvic conditions: Small fibroid, Abortion, Endometrial
TB, Infections.
2. Endocrinopathy: Thyroid dysfunction, PCOS, Adrenal
disorders.
3. Hematological: Leukemias, platelet and coagulation
disorders
4. Medications
Management
A careful history and physical examination to rule out the
other causes must be done. A menstrual calendar is helpful
in assessing the pattern. If no evidence for an underlying
causes found then following guidelines are helpful:
Medical treatment to regulate menstrual cycle prevents
excessive bleeding and anemia as a result of continued
blood loss.
Iron supplementation and reassurance alone is needed
in mild cases where hemoglobin is more than 12 gm/
dl.
In moderate cases, where hemoglobin is between 10 to
12 gm/dl, low dose combined estrogen and synthetic
progesterone are used daily for 21 days followed by a
short withdrawal bleed during 7 days of placebo pills.
Three to six cycles of hormonal therapy are given till
menstrual maturity occurs.
In severe cases, when hemoglobin is less than 10 mg/dl,
additional treatment like blood transfusion or hospitali-
1194
zation may be required. Dilatation and curettage is rarely

needed in adolescents.
offered. Only in severe cases or with significant

psychological issues, surgical treatment is indicated.
BREAST DISORDERS IN ADOLESCENTS
Premature Thelarche
For most of the adolescent females, the breasts are a focus

of sexuality. Any deviation in the size and shape of the
breasts from her peers may be a cause of worry for her.
When the breasts are fully developed before the age of 8

years without other signs of puberty or as a part of
precocious puberty. It requires a detailed history and
examination to identify the possible cause. If there is no
cause, reassurance and regular follow-up should be done.
Physiology of Breasts
At puberty, breasts undergo major structural and
functional changes. The whole process is usually
completed by 20 years of age. Girls showing no breast
development by 14 years of age are considered to have
delayed puberty. With the onset of menstruation, the
breasts undergo cyclical changes and may be very painful
during pre-menstrual phase. This may require analgesics
and reassurance. Breast examination should be an
integral part of general physical examination.
Congenital anomalies like polythelia (supernumerary
nipples), amastia (absence of breast) or athelia are rare.
Breast Asymmetry
Unilateral asymmetry could be pseudo- asymmetry
because of scoliosis or rib cage abnormality or true
asymmetry as a result of past infection, trauma or surgery.
In initial stages of thelarche, some asymmetry is common
and usually disappears with growth. A surgical
correction, a reduction or enchancement mammoplasty
may be done for unilateral asymmetry if the adolescent
desires.
Hypoplasia
Bilateral hypoplastic breasts are seen in tall, thin females,
in ovarian dysfunction like in Turners syndrome or
adrenal hyperplasia, preadolescent hypothyroidism, and
androgen producing tumor. Endocrine and genetic workup is necessary to evaluate bilateral breast hypoplasia.
Breast Enlargement
Breast Infection
Lactation mastitis can occur from breast engorgement or
cracked nipples. Non-lactational mastitis occurs
secondary to ductal trauma (e.g. in handling of breast)
mammary duct ectasia, local skin infections, epidermal
cysts, etc.
Breast Cancer
Rare in adolescents under the age of 20 years. The
incidence is less than 1 percent of all breast cancers.
Teaching regular self-examination of the breast and
providing regular physical examination to the adolescent
making them aware of the risk factors, might go long way
in prevention and early recognition of breast cancer which
presents as a hard, nontender, indurated, solitary mass
with indistinct margins.
Gynecomastia
Any visible or palpable development of the breast in boys
or men is called gynecomastia. It is attributed to transient
hormone imbalance i.e. a decreased ratio of testosterone
to estradiol and when testicular function becomes
dominant the hypertrophy resolves. This may take up to 2
years. Sometimes it causes considerable loss of self-esteem
in the boy and requires reassurance and psychological
support. In persistent gynecomastia, surgical intervention
is indicated.
Mammary Hyperplasia (Virginal Hypertrophy)

Breast hypertrophy in girls can occur during puberty. This
is usually symmetrical and may be familial. Tissue
sensitivity to estrogen may be the cause. Occasionally,
massive breast enlargement (macromastia) can cause
complications like pain, dermatitis, tissue necrosis.
Conservative management and reassurance should be
Galactorrhea
It is persistent breast discharge not caused by pregnancy
or lactation. The discharge contains fat globules. The
causes may be neurogenic, hypothalamic, pituitary tumor
(prolactin secreting), endocrine, or drug induced
(marijuana, heroin, codeine, amphetamines), or idiopathic.

HIRSUTISM
Hirsutism is excessive hair in a male pattern in woman. It
should be differentiated from hypertrichosis and
virilization. Hypertrichosis is generalized excessive hair
growth whereas virilization has features of androgen
excess such as change in voice, acne, increased muscle
mass and clitoromegaly. Hirsutism occurs due to
interaction between the circulating androgens and the hair
follicle sensitivity. Excess androgen production is often
due to Poly Cystic Ovary Syndrome (PCOS). This is usually
accompanied with other features like menstrual
irregularity, obesity and insulin resistance.
Frequently hirsutism is idiopathic. Some other causes
seen infrequently are androgen secreting tumors, nonclassic congenital adrenal hyperplasia, hyperprolactinemia, Cushings syndrome, Thyroid dysfunction.
Use of certain medication like anabolic steroids, danazol,
valproic acid may also cause hirsutism.
It has been recommended that only females with
moderate or severe hirsutism or rapid progression or
associated with features of PCOS should be investigated
for androgen levels. Treatment modalities include
removing the source of androgen excess if possible or antiandrogenic therapy. For existing hair, various methods of
removal and reduction are there and depending on severity
and economic costs the choice can be made. Photoepilation with laser and non-laser devices have been
reported to have better results.
PREGNANCY IN ADOLESCENTS
The problem of adolescent pregnancy is a worldwide
phenomenon. Both developed and developing countries
face this problem. The difference lies in the socio-cultural
factors that are responsible for it in the two settings.
Magnitude of the Problem
The rates of adolescent pregnancy, child bearing and
abortion in USA are considerably higher than those of
most European countries. In USA 5% of 15-19 years olds
give birth each year. Asian countries have a wide range of
1 % in Japan to 18% in Pakistan. In India, usually
adolescent motherhood is the result of early marriage. Early
pregnancy following marriage is the norm in majority of
the households. The social pressures of the family
sometimes press the young couple to go ahead to start a
family. The incidence of child marriages has definitely
declined in the last 30 years, but adolescents are still
marrying at the same rate especially in certain parts of the

country. Literacy and early marriages are negatively and
highly correlated.
The Consequences and Risks of
Adolescent Pregnancy
The potential risks to both mother and child are multiple
and tend to be greater for the young mother and her infant.
The younger the mother is at the time of birth of baby, the
greater is the chance of an overall poor outcome of birth.
The risks for adolescent pregnancy are attributable to
biology as well as the social environment. The high risks
are associated through all phases of pregnancy and
childbirth. During antenatal period, adolescents have a
higher incidence of hypertensive diseases, anemia and
obstructed labor. They are also less likely to receive any
antenatal care, tetanus toxoid and iron, supplements.
Adolescents are at a greater risk for premature labor and
delivery. The delivery is also more likely to be attended by
an unskilled person and have consequent complications
for both mother and child. During post partum period, the
young mother has higher likelihood of having depression.
A higher maternal mortality has been reported in
adolescent pregnancies; 645/100,000 live births in 15- 19
years olds as compared to 342 in older age groups. In
addition to the antenatal problems mentioned this could
also be because of poor diet, inadequate psychosocial
maturity, motivation and experience and possibly even
drug abuse in teenaged mothers. The social ostracization
and economic drawbacks in an unmarried teenage mother
further add to the problems.
The babies born to adolescent mothers are likely to be
preterm or low birth weight. There are increased perinatal
and neonatal mortality rates as compared to older
mothers. The babies are at a greater risk for inadequate
care and complications thereof.
Prevention Programs
1. Provision of family-life education in schools, with more
stress on the wisdom of responsible sexual behavior.
2. Increasing the awareness through improved literacy
statusespecially female.
3. Strengthening positive family interaction - openness,
emotional guidance and support.
4. Educational reforms to enhance self-help and selfemployment (e.g. cottage industry) skills of girls thereby
facilitating economic stability, adequate delay in
1196
marriage, better home management skills and maturity.

Parents can help significantly by example and
guidance.
5. Educating adolescent married girls about the health
hazards to both mother and child from early and
successive child bearing with short birth interval.
6. Providing easy access to family planning services
counseling, contraceptives, increasing awareness,
emergency contraception.
ACNE VULGARIS
Acne is a common problem during adolescence. The
condition may be very mild, clearing up with time but can
be disfiguring in a few cases. Acne occurs as a result of
blockage of sebaceous gland ducts and bacterial action
on the accumulated sebum. The inflammatory response
generated causes skin lesions varying from few papules
or pustules to large nodulocystic lesions. Treatment
includes application of keratolytic agents like benzoyl
peroxide and topical antibiotics if required. Rarely referral
to a dermatologist is needed in severe cases where
permanent scarring and disfigurement seem likely to
occur. Psychological support and counseling is also
important.
SEXUALLY TRANSMITTED INFECTIONS

Adolescents are at a greater risk of sexually transmitted
infections due to certain behavioral and physio-anatomical
characteristics. Younger the adolescent at initiation of
sexual activity, higher is the risk. Ectopy of cervix, small
introitus, delayed care seeking, sexual abuse and lack of
adolescent friendly services all contribute to higher risk.
World Health Organization has devised a syndromic
approach to diagnosing and managing STIs. Box given
shows various syndromes for a simplified approach. The
management of these syndromic conditions is given in
flow charts by WHO (Table 23.7.4).
Vulvo-vaginitis
A vaginal discharge may be physiological or pathological.
Physiological leucorrhea is normal vaginal discharge due
to estrogen stimulation in adolescents. Leucorrhea starts
weeks to months before menarche, may decrease or stop
with the onset of menses or may continue for several years.
Staining of the undergarment is due to protein in the
discharge. A good personal hygiene including cotton
undergarments should be advised. A proper history,
thorough physical examination and few laboratory tests
will make a precise diagnosis. Foul odor, abnormal
bleeding or pruritis indicate the presence of infection.
TABLE 23.7.4: Syndromic approach to STIs

Syndrome
Symptoms
Signs
Most common causes
Vaginal discharge
Unusual vaginal discharge

Vaginal itching
Dysuria (pain on urination)
Dyspareunia (pain during sexual
intercourse)
Abnormal vaginal discharge
Urethral discharge
Urethral discharge
Dysuria
Frequent urination
Genital sore
Urethral discharge
(if necessary ask patient to milk
urethra)
Genital ulcer
VAGINITIS:
Trichomoniasis
Candidiasis
CERVICITIS:
Gonorrhea
Chlamydia
Gonorrhea
Chlamydia
Lower abdominal pain
Lower abdominal
pain
Dyspareunia
Scrotal swelling
Inguinal bubo
Scrotal pain and swelling

Painful enlarged inguinal lymph nodes
Vaginal discharge
Lower abdominal tenderness on
palpation
Temperature >38C
Scrotal swelling
Enlarged inguinal lymph nodes,
Fluctuation
Abscesses or fistulae
Genital ulcer
Syphilis
Chancroid
Genital herpes
Gonorrhea
Chlamydia
Mixed anerobes
Gonorrhea, Chlamydia
LGV, Chancroid

Etiology
a. Candidiasis: Candida albicans is the most common
fungus responsible for 85 to 95 percent of cases.
Menstruation, wearing of tight nylon undergarments,
obesity, diabetes, corticosteroid therapy, causes
whitish cheesy discharge with pruritis and erythema
is seen.
b. Trichomonas vaginalis: A flagellate protozoa,
trichomonas is a common cause of vulvo - vaginitis
and cervicitis. It causes a profuse, greenish, frothy,
malodorous discharge with pruritis. Bacterial
vaginosis, foreign bodies like a forgotten tampon, bits
of toilet paper, masturbation aids and allergic or
contact vulvoginitis induced by various physical,
chemical or allergic substances also produce excessive
vaginal discharge. Diagnosis can be made by
microscopy of a simple saline or 10- 20 % KOH wet
mount of discharge.
Treatment
Broad spectrum antifungal imidazoles like miconazole
and clotrimazole or a topical or intravaginal antifungal
agent like clotrimazole for 1, 3 or 7 days for candidial
vaginitis. Metronidazole 2 gms orally as a single dose or
250 mg orally three times a day for 7 days is recommended
for treatment of trichomonas or gardnerella vaginitis.
Cervicitis
Cervicitis is a sexually transmitted disease which can
extend proximally resulting in endometritis and
salpingitis. Also, it can complicate pregnancy causing
chorioamnionitis, premature rupture of membranes,
premature delivery and neonatal sepsis. An adolescent
having cervicitis is a potential source of infection to the
sexual partner and prone to infertility later on. The
common infectious agents are chlamydia trachomatis,
neisseria gonorrhea and herpes simplex virus type 2.
Treatment consists of erythromycin - 500 mg 6 hrly
7 days or Doxycyline - 100mg bd x 7 days. If gonorrhea is
present then in addition to the above, give Amoxicillin or
ampicillin 3 to 3.5 gm orally with probenecid 1 gm orally.
One of them is PID, an infection of uterus and fallopian

tubes. Most PID patients are nulliparous and young.
Almost one third are under 19 years of age. Risk factors
are multiple sex partners, intrauterine devices and young
age. C. trachomatis and N. gonorrhea are common
causative agents.
The classic symptoms of PID are lower abdominal
pain, fever, increased vaginal discharge, irregular vaginal
bleeding and adnexal tenderness. However, these
symptoms may occur in other diseases of reproductive
systems as well as of the urinary and gastrointestinal tract.
Early diagnosis and appropriate treatment are essential
to prevent complications like tubal block, infertility, ectopic
pregnancy, DUB and dysmenorrhea.
Management
The main goal should be prevention of STDs which are
associated with the development of PID. Many therapeutic
options are available for treating PID. Outpatient treatment
with combinations of fluroquinolones or metronidazole
or cephalosporins have been found to be effective. Sexually
active boys should also be screened for STDs to break the
link to their partners.
UROLOGIC PROBLEMS IN THE ADOLESCENT MALE
The common genitourinary conditions encountered
during adolescence are penile problems, scrotal problems,
voiding dysfunction, and infections.
Penile Problems
Anomalies
Phimosis, hypospadias/epispadias with chordee,
normal/abnormal curvatures (e.g. Peyronies disease)
hypoplasia, erectile/ejaculatory dysfunction (real or
perceived) may all be a physical and for psychological
handicap eroding the adolescents self-esteem or may
draw attention to an underlying internal pathology
requiring correction. In obese teenage boys, penis is usually
buried in the pubic pad of fat giving an appearance of
micropenis. Careful examination and reassurance are
helpful.
Pelvic Inflammatory Disease (PID)

An increase in sexual activity in the adolescent with
unprotected sexual intercourse predisposes them to the
serious consequences of sexually transmitted diseases.
Infections
Balanitis and balanoposthitis are infections of the glans
and foreskin. The foreskin or prepuce is phimotic in
1198
majority of such cases. The warm, moist area of the

preputial sac offers an excellent culture medium to
organisms, usually gram positive and negative bacteria
and candida. Treatment includes daily personal hygiene,
antibiotics according to culture and sensitivity, and
circumcision if phimosis is severe.
Treatment
Penile Skin Lesions
Chancroid
Condylomata acuminata or venereal warts are small,

papillary lesions caused by a virus, seen on moist areas of
penis or beneath the preputial sac, sometimes within the
distal or proximal urethra. The urethral lesions present
with bloody discharge or bleeding during voiding.
Treatment
1. Application of 25% solution of podophyllin in tincture
of benzoin to the lesions only.
2. In intra-urethral lesions 5% solution of 5-fluorouracil
cream.
3. Excision and fulguration for large meatal or glandular
lesions if no response to the above two.
4. Circumcision if recurrences of condyloma.
Chancroid is caused by hemophilus ducreyi, a gram

negative bacillus and is acquired by sexual contact. An
erythematous area appears on the penis which becomes a
papule within 24 hours, pustule in 96 hours and then
ulcerates. The ulcer is very painful but unlike in syphilitic
chancre, the edges are not indurated. Treatment consists
of sulfonamides, tetracycline orally and local application
of chloramphenicol or erythromycin.
Genital Herpes Simplex

This painful venereal viral infection is due to HSV-2, less
commonly HSV-l, produces an edematous wheal followed
by appearance of tiny vesicles. It causes severe itching.
Treatment
1. Oral Acyclovir therapy to shorten duration of
symptoms and shedding of virus and prophylactic
suppression therapy in recurrent cases.
2. General therapy in terms of prevention of secondary
infection and trauma to the parts.
Syphilitic Chancre
Usual sites- glans and prepuce. Initially, there is an
erythematous spot followed by desquamation,
indurations and papillae / ulcerated lesions, the whole
process takes about a week.
Diagnosis
1. Demonstration of Treponema Pallidum from fresh
exudates under dark field illumination.
2. Fluorescent treponema antibody absorption test (FTAABS) in serum.
Treatment consists of one of the following:

1. Benzathine penicillin 2 to 4 millions units IM once.
2. Tetracycline hydrochloride 500 mg 6 hrly 15, days.
3. Erythromycin 500mg 6 hrly 15 days.
Scrotal Conditions
1. Hydrocele: It is almost always of communicating type
and hernial sac is present. The size becomes less in
lying down position.
2. Crytorchidism or undescended testes could be due to
retractile testis, ectopic testis, Absent testis and truly
cryptorchid testis.
Therapy should be instituted as early as possible
in a cryptorchid child because of the psychological as
well as physiological risks. Untreated, there is a risk of
infertility and testicular malignancy.
3. Varicocele occurs due to dilated, tortuous pampiniform
plexus. It carries a risk of sterility due to impaired
testicular thermoregulation in long standing cases.
Voiding Dysfunction
Normal bladder function in a male adolescent is defmed
as the ability to be aware of the state of his bladder at all
times, to be receptive to the sensations of filling and the
desire to void, to suppress when necessary until it is
convenient to do so, to void voluntarily when desired/
necessary, recognize when/if the bladder is empty and
have no incontinence. Any deviation from this description
is a form of bladder dysfunction which may vary from
increased urinary frequency to overt urinary incontinence.
A proper history and physical examination are
mandatory. In adolescents, bladder dysfunction is rarely

caused by serious lesions. Most of the cases have some
psychological basis. Before going on to invasive
investigations, the pediatrician should look into this
aspect.
Enuresis can be a distressing condition in adolescents
and may have a psychological basis, but organic causes
such as urethral stricture/valves and occult spina bifida
should be ruled out first. A voiding cystourethrogram is
helpful in confirming the diagnosis of urethral stricture/
valves, and any vesicoureteral reflux.
SUBSTANCE ABUSE
The substance abuse problem is becoming progressively
worse and the number of addicts are increasing
phenomenally. Adolescent is the primary risk period for
initiation into substance use. The WHO fact sheet on
adolescent health states that tobacco use in 13-15 years
age group in India ranges between 5 -63% . This includes
tobacco smoking in the form of cigarettes or bidis as well
as chewing. Alcohol use is reported as 12.7%. The use of
tobacco and other substance is higher in street children
and includes inhalants, alcohol and other drugs. Drug
abuse during adolescence is a major problem. The process
of adaptation to various changes associated with
adolescence, increasing academic and financial
responsibilities, conflicts with parents and peers makes
an adolescent vulnerable to emotional stresses. They seek
an easy solution to these problems. Use and abuse of
alcohol and other channels provide instant release from
the pressures of life. Encouragement by peer groups, the
lure of popularity and conforming to certain patterns and
easy availability of any such substances like alcohol,
cigarettes and even drugs make a teenager an easy prey.
Parental drinking and any other substance use may also
contribute significantly to the adolescents habits. Parents
and siblings also have a strong impact on cigarette
smoking habits. The type of drug users have been classified
as:
1. Experimenters those who will try drugs because of
curiosity or group conformity.
2. Recreational users have a social pattern and may
overindulge.
3. Compulsive users have a physical or psychological
dependence on a drug. They may seek to relieve
routineness or boredom through euphoria.
4. Ritualistic users are those believing in a spiritual
experience as a result of drug use.
Any of the above can progress to dependence. Usually

the progression occurs from curiosity to experimental
stage, followed by early and late regular use finally to end
stage where newer and more intoxicating substances are
sought. The initial gateway substances used are tobacco,
alcohol, marijuana.
Dealing with an adolescent substance abuser requires
sensitivity and an understanding of the adolescents
problems. The teenager very rarely will bring up this area
on his own unless he is frightened or unable to function
or has been referred. Therefore history has to be obtained
by casual nonjudgmental questioning. Once positive
history is elicited, a detailed evaluation needs to be done
to plan further management which can be decided in
consultation with physicians trained to handle drugs
users, social workers and the family members.
BIBLIOGRAPHY
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Adolescent Health and Development. WorId Health

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Benegal V, Bhushan K, Seshadri S, Krott M. Drug abuse
among street children in Bangalore - A monograph. 1998.
Dias P. Adolescent substance abuse-assessment in the
office. Pediatric Clinics of North America 2002;49:269300.
Greydanus DE. Menstural disorders in the adolescent in
Course Manual for adolescent Health Part-I. Greydanus
DE, Patel DR, Pratt H, Bhave S (Eds). Cambridge Press:
Delhi, 2002;354-69.
Greydanus DE, Patel DR. Substance Abuse in course
manual for adolescent health. Part I. Greydanus DE, Patel
DR, Pratt H, Bhave S (Eds). Cambridge Press: Delhi,
2002;480-509.
Greydanus DE. Sexuality transmitted diseases in Course
manual for adolescent health Part I . Greydanus DE, Patel
DR, Pratt H, Bhave S (Eds). Cambridge Press: Delhi, 2002;
337-53.
Jenkins RR. Sexuality transmitted infections in Nelson
textbook of Pediatrics (18th edn). Kliegman RM, Behrman
RE, Jenson HB, Stanton BF (Eds). Elsevier: New Delhi,
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Martin KA, Chang RJ, Ehrmann DA, et al. Evaluation
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Sanfillipo JS. The Breast in Nelson textbook of Pediatrics
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Training Modules for the Syndromic Management of
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1200
23.8 Polycystic Ovarian Syndrome

MKC Nair
INTRODUCTION
Poly Cystic Ovary Syndrome (PCOS) is the most common
reproductive endocrinopathy among women of
childbearing age. It is a heterogeneous condition characterized by menstrual irregularities (persistent anovulation,
oligomenorrhea or amenorrhea), features of hyperandrogenism (hirsutism, acne, male type baldness) and
central obesity, in association with multiple small follicles
in ovary. The condition was first described in 1935 by Dr.
Stein and Dr. Leventhal and hence, also the name SteinLeventhal syndrome.
IMPORTANCE OF PCOS IN ADOLESCENCE
PCOS is reported to be a growing problem with adolescent
girls. It is very difficult to diagnose PCOS in teenage girls
as they may normally also experience irregular or absent
menses and acne. Onset of PCOS is usually at puberty
and the hyperandrogenic effects usually progress slowly
over time. Adolescence is often the age when the first
clinical manifestations of this syndrome are found.
Adolescent girls diagnosed with PCOS, who had a history
of precocious pubarche also developed ovarian
hyperandrogenism and insulin resistance. Prevalence of
polycystic ovaries detected on ultrasound scan in various
studies have varied from 10 to 33%. Prevalence of PCOS
in adolescents is comparable to that in adults, it is found
in 45% of patients who present with oligomenorrhea as
against only 9% of patients with normal menstrual cycles.
Symptoms
While the pattern of irregular menses is often seen as the
first sign of PCOS in adolescents. Obesity, hirsutism, acne
and other symptoms like acanthosis nigricans may soon
develop. Adolescents with PCOS are at increased risk for
impaired glucose tolerance and diabetes mellitus. PCOS
is believed to be strongly associated with insulin resistance
and this has a pre-menarcheal onset. While young girls
may have any or all of the above symptoms, it is possible
for just one of the symptoms to be present leading to the
suspicion and diagnosis of PCOS in adolescents. It seems
that one of the major factors resulting in the transition of a
symptomless young woman with PCOS into a patient with

PCO, is the development of insulin resistance. This causes
great concern among clinicians, due to the potentially
serious complications associated with this condition.
Etiopathogenesis
PCOS is now considered more as a syndrome than as a
disease. The exact cause of PCOS is unknown, though
there are several factors thought to play a part. It reflects
multiple potential etiologies and variable clinical
presentations. The exact pathogenesis is still unclear.
Evidence suggests that patients have functional
abnormality of cytochrome P450c17, the 17-hydroxylase,
which is the rate-limiting enzyme in androgen biosynthesis. PCOS appears to run in families and autosomal
dominant inheritance has been suggested. Full expression
of the syndrome may require an insulin abnormality and
a defect in androgen biosynthesis, but exact gene (or genes)
has not been identified.
In polycystic ovarian syndrome, the normal hypothalamo pituitary cycle is disturbed. Evaluation of blood
serum levels typically reveals elevated LH levels and
normal or low FSH levels. Patients also have increased
levels of free estrogen, primarily estrone and estradiol.
Estrogens exert a complex feedback effect on the pituitary
gland that results in the suppression of FSH secretion
and the increased release of LH. Thus, the production
and release of androgen precursors by ovarian theca cells
is increased. The peripheral conversion of androgens to
estrogens, primarily estrone, strengthens the feedback
effect on the pituitary gland.
The same androgens also inhibit the production of sex
hormone-binding globulin in the liver, indirectly
increasing levels of free estrogen in the bloodstream as
well. Locally, elevated androgen levels in the ovary exert
a direct inhibitory effect on follicular maturation. In
conjunction with the diminished but steady presence of
FSH, the follicles continue to develop without ever
maturing. Thus, numerous follicles are present in the
polycystic ovary and show varying phases of development
and atresia.

Long-term Effects of PCOS
Infertility
Chronic anovulation results in abnormal folliculogenesis
resulting in infertility.
Endometrial Hyperplasia and Cancer
Endometrial cancer has been alleged to be at least four
times more common in women with PCOS and may appear
in women as young as the early 20s.
Impaired Glucose Tolerance and Type 2 Diabetes
In obese women with PCOS, progression from normal
glucose function to impaired glucose tolerance or diabetes
mellitus is more rapid than in women without PCOS.
PCOS and the Metabolic Syndrome
Features of the metabolic syndrome, including obesity,
insulin resistance and dyslipidemia, are common in
women with PCOS.
Cardiovascular Disease
The metabolic features of PCOS have led to wide-spread
concern about the risk of cardiovascular disease.
Diagnosis
Diagnosis is made, based on Rotterdams criteria, requiring
the presence of any two of the following three: (i) Polycystic
ovaries; (ii) Oligo/anovulation; and/or (iii) Clinical or
biochemical evidence of hyperandrogenism, excluding
other related disorders like thyroid dysfunctions,
hyperprolactinemia, adult onset congenital adrenal
hyperplasia and virilising tumors.
Pelvic Ultrasound Examination
Transvaginal ultrasound is the best imaging mode, but
for adolescent girls only transabdominal ultrasound
examination is to be done. Criteria for polycystic ovaries
include bilateral ovarian enlargement, 10 or more follicles
2-10 mm in diameter per ovary, peripherally arranged
(necklace pattern) with an increased density of the central
stroma and volume of the ovary considered as >10 cubic
mm. Endometrial thickness should always be assessed to
exclude significant endometrial hyperplasia.
Glucose tolerance test
Fasting levels of FSH, LH, prolactin, TSH; testosterone.
FSH levels usually low or normal and LH levels

generally high and the LH/FSH ratio is usually greater
than 3.
Androgen (testosterone) levelshigh. Total testosterone is elevated in women with PCOS; however, total
testosterone levels greater than 200ng/dL, is
suggestive of an androgen-producing tumor of the
ovary or adrenal gland.
Free testosterone levels are sensitive for ovarian
hyperandrogenism and are elevated in patients with
PCOS.
Management
1. Obesity: Lifestyle modification by diet and regular
moderate intensity exercise is a must. Weight loss can
cause spontaneous resumption of menses and lower
the androgen levels and even 5% weight loss can result
in these changes.
2. Irregular period: Combined estrogen - progesterone pill
regularizes periods and combats mild hirsutism.
3. Hirsutism/Acne/Seborrhea: Oral contraceptive (ethinyl
estradiol) with anti-androgen (cyproterone acetate 2
mg) to be given for 6 -12 cycles only at a time. Cosmetic
therapy may also be required in more severe cases.
4. Obese with acanthosis nigricans: Insulin sensitizing
agents (metformin 1 gm daily), helps the body utilize
insulin in a more efficient manner by their effects on
glucose metabolism, bring in normal menses and
marked improvement in insulin sensitivity, all the
effects being independent of change in body weight.
BIBLIOGRAPHY
1. Barne RB, Neithardt AB, Kalra SK. Hyperandrogenism,
Hirsutism and Polycystic Ovary Syndrome 2003.
2. Buggs C, Rosenfield RL. Polycystic Ovary syndrome in
adolescence. Endocrinol Metab Clin North Am 2005;34:
677-705.
3. Kandarakis DE, Kouli CR, Bergiele AT, et al. A survey of
the polycystic ovary syndrome in the Greek island of
Lesbos: Hormonal and metabolic profile. J Clin
4. Marcel Ha, et al. Polycystic Ovaries in adolescents and
the relationship with menstrual cycle patterns. Fertility
and Sterility 2000;74:49-57.
5. Nair MKC. Prevalence of Polycystic Ovary among higher
secondary school girls in Trivandrum. An INCLEN Study,
2005.
6. Polson W, Adams J, Wadsworth J, Franks S. Polycystic
ovaries-a common finding in normal women. Lancet
1988;1:870-72.
24.1 Injuries in Children and Injury Control: CG Wilson .......................................................................................................................... 1204

24.2 Poisoning in Children: KS Rao, B Ravichander ................................................................................................................................. 1207
1204
24.1 Injuries in Children and Injury Control

CG Wilson
Accident denotes a random event that cannot be
prevented whereas most injuries occur under fairly
predictable circumstances to high risk children and
families. The term injury promotes awareness, based
on which preventive strategies may be adopted.
The Burden of the Problem
In many countries around the world, injuries are the
leading cause of death accounting for 44% and 65% of
death in the 1-4 year and 5-19 year age groups respectively. In India there is a paucity of data, however,
The National Crime Records Bureau (NCRB) is the
principal nodal agency under the Ministry of Home
Affairs, Government of India, and is responsible for the
collection, compilation, analysis and dissemination of
injury-related information. The injury mortality rate was
40/100,000 population during 2000. The mortality rate
among children <14 years was 8.2%. In India, injury
accounts for the second most common cause of death in
the age group 5-14 years (16.2%). In India as in most other
countries, road traffic injuries and drowning are the two
major cases of fatal unintentional injury (21% and 19%
respectively) other being fire and burns, and intentional
injuries. The circumstances of non-fatal injury are
mainly related to falls mostly from bicycles and
staircase.
Risk Factor for Injury in Children
Apart from age, sex, and ethnic factors, the childs
environment and the socio-economic conditions of the
family also determine the nature and frequency of
injuries in childhood. It is estimated that 98 percent of
all childhood unintentional injuries occur in low-andmiddle income families. Children with ADHD are at risk
for repeated injuries which may be fatal. The childs
environment has a major role to play in injury causation.
Social stress factor like single parent, unemployment of
parent, poor education status, and size of family
contribute to injury causation. Poor housekeeping and
lack of awareness of safety precautions are important.
Road-related injuries are higher in urban areas than in
rural areas. Walkers are a common cause of fall injury in
infants. Walkers are not proven to promote early walking
but those with a faulty design and can easily trip over
and lead to injury. Besides they give the child mobility
at an age when they cannot recognize danger and sustain
falls from staircases, etc. Toys can cause problem in the
form of aspiration of loose parts, electrical shock or burns,
entrapment injuries, laceration, punctures and piercing
injuries, projectile injuries, and explosion. Bicycles are
common cause of injury in the age group of 6 to 12 years.
Management
Management consists of preventing further injury during
transport, maintenance of vitals, and advanced management of the injury. The victims neck should be
immobilized with a semi-rigid cervical collar or
sandbags. The patients clothing is removed so that access
is available for interventions. The patients respiratory
and cardiovascular status is assessed. Emergency
treatment may need to be provided in case of respiratory
or cardiovascular compromise. Following transfer to the
hospital, accurate evaluation of the injuries needs to be
done.
Prevention
The approach to injury prevention involves determining
the magnitude, scope and characteristics of the problem,
identifying the risk factor that are potentially modifiable,
accessing what measures can be taken to prevent, and
implementing the most promising interventions in
community-based approaches. Important elements of
community-based approaches are long-term strategy
effective, focused leadership; multi-agency collaboration;
involvement of the local community; appropriate
targeting; and time to develop a range of local networks
programme to educate and spread awareness in the
community. Community education forms an active
intervention, whereas product modification (seat belts,
air bags etc) and environmental modification (locked
cabinets, fire alarms etc) are passive interventions, which
must also be given due importance. Creation of healthy
environments for children is to be pursued with a
missionary zeal incorporating the raising of awareness
of the risks to childrens health in the setting where they
live, learn, and play, based on a solid foundation of
Accidents and Poisonings

scientific evidence. The following are a few specific
modification which may prevent injuries in children:
Home Environment
Protection of staircase by non-collapsible gates, smooth
flooring, and electrical outlets properly secured with
circuit breakers, keeping hot appliances away from reach
of children and safe housekeeping of medicines, insecticides and household cleaners are important.
Playground
Play areas should have energy-absorbent material like
sand, rubberized surface of coir mats so that children do
not sustain severe injury. Swimming pool should be
properly secured and protected. Adequate protective
gear should be used in games, which can cause injury.
Road Safety
Children need to be taught about road safety by means
of demonstration in the form of traffic parks. Children
less than 5 years of age should not cross roads without
supervision. Motor vehicle accidents can be reduced by
ensuring the age limit for driving. Speed restriction and
proper training must be ensured.
Drowning and Related Injuries
Drowning is the death from asphyxia which occurs while
submerged or within 24 hours of submersion. Severe
drowning is said to occur when death due to submersion
occurs after 24 hours. Drowning occurs more often in
fresh water than in sea water. Though the pathology is
almost the same in both types, the increased salinity of
sea water can lead to hypovolemia, electrolyte disturbances and pulmonary edema.
Drowning result in hypoxia with concurrent disturbances in other systems. The three direct effects of
aspiration of water are hypoxia, aspiration pneumonia,
and hypothermia. Hypoxia for more than 5 minutes
results in neurological damage. The brain is to a certain
extent protected from neurologic damage by extreme
hypothermia. Aspiration pneumonia is characterized by
alveolar collapse, hypoxemia, pulmonary dysfunction
and acute respiratory distress syndrome (ARDS). The
changes that occur in the lung are almost similar in both
fresh water and sea water aspiration. Patients of sea water
1205
drowning may show hypernatremia. Myocardial dysfunction, arrhythmias and infarction, acute tubular
necrosis in the kidneys and hepatic and pancreatic
dysfunction is also reported.
Management
The initial management consists of resuscitation by a
trained attendant at the site of drowning. Oxygen
inhalation should be instituted as early as possible.
Patients who are alert with no neurological dysfunction
should be admitted for observation for 24 hours. Patients
with confusion, amnesia or stupor or those with
respiratory distress need close monitoring of their
respiratory and neurological status. Management
includes oxygen by hood or mask and intermittent
positive pressure ventilation (IPPV) if required. Sodium
bicarbonate may be administrated for metabolic acidosis,
furosemide for pulmonary edema, and antibiotics if
infection is suspected. The temperature should be
monitored. Improvement in neurological status follows
oxygenation and is a good guide of recovery. Children
who are comatose or those with apnea require intensive
care management. These children require intubation and
IPPV to keep the blood gases at an acceptable limit of
PaO2 of 100 mm Hg and PaCO2 of 20 to 30 mm Hg.
Pulmonary edema, pneumonia, pneumothorax and
ARDS should be managed if present. Routine use of
corticosteroids is not indicated. Intravenous fluids and
inotropic drugs may be indicated in children with shock
and myocardial dysfunction. Hypo- or hyperglycemia
should be avoided. Fever and seizures are controlled.
With optimal neurological management many of the near
drowning victims. Particularly those with rapid onset of
hypothermia, make good recovery in the first 24 to 72
hours. The prognosis depends on the duration of
immersion and if hypothermia occurred before hypoxia
had set in. Children with no alteration of consciousness
show complete recovery. Patients with deep coma or
apnea generally have a poor prognosis.
Prevention
Accidental drowning can be decreased if children are
given training in swimming skills at a young age. The
children must swim under supervision. Infants must also
be supervised by a caretaker during time of bath or use
of tub. Teenagers should avoid drugs and alcohol during
swimming, sense of bravado should be held in check.
1206
Burns and Scalds

Scalds are due to wet heat most often following a spill of
hot milk, water or oil being handled by the mother.
Immersion scalding can occur inadvertently when child
trips into a tub of hot water. Intentional scalding, as seen
in child abuse, can lead to a sharply demarcated scald
injury of the limbs or the gluteal region. Flame burns
result from exposure to heat of high intensity as in
building fires and clothes catching fire. These produce
full thickness burns distributed over a larger area and
may have associated pulmonary complications.
Chemical burns result from contact with corrosives.
These involve limited area and severity of injury is
dependent on the strength of the corrosive. Electrical
injury is usually localized. High-voltage electricity is
however potentially lethal. Burns in infant and children
are different from adults in that for a given body weight
they have a larger surface area. The skin is much thinner
and injury is more severe. The water loss due to normal
metabolism and burns is more in children, needing larger
amounts of fluid for resuscitation. Thermal regulation is
more difficult, the healing process takes longer, and there
is a greater chance of scar hypertrophy. The body surface
area in children 0 to 14 years is shown in Table 24.1.1.
TABLE 24.1.1: Body surface area in children aged 0-14 years
Age
(Years)
Head
(%)
Thunk
(%)
Upper Limbs
(Rt & Lt) (%)
Lower Limbs
(RI & Lt)(%)
Newborn
4-6
7-12
12+
18.0
15.0
12.0
6.0
40.0
40.0
40.0
8.0
8.0+8.0
8.0+8.0
8.0+8.0
9.0+9.0
13.0+13.0
14.5+14.5
16.0+16.0
19.0+19.0
First Aid
In case of flame burns, the fire is put off by the patient
rolling on the ground or covering the patient with noninflammable material like a blanket. In cases of chemical
burns, the burnt area is washed with copious amount of
water. Constricting pieces of jewellery are removed. The
burnt area should be covered with clean dry sheet and if
burnt area is less than 15 to 20 percent, cold wet
compresses may be applied. Colored antiseptics like
gentian violet and mercurochrome should not be applied,
blisters should not be punctured. Cardiovascular and
pulmonary status should be examined carefully.

Children with burns greater than 10 to 15 percent need
to be hospitalized and treated with intravenous access,
nasogastric aspiration and appropriate antibiotics, In case
of perineal or genital burns, an indwelling urinary
catheter is placed. If transportation of the patient is going
to be delayed by more than 30 minutes, small quantity
of oral fluids can be permitted. The severity of the burn
is assessed and graded from 1 to 3. Grade 3 burns are the
severest and usually due to immersion injuries or
electrical and chemical burns. Standard charts are
available for infants, children and adults which grade
the extent of burns. Patients with more than 30 percent
burnt area, inhalation burns or third-degree burns need
to be referred to a special care burn unit. Intravenous
fluid may be started and oxygen administered in case of
inhalation burn injury. Burns other than those needing
hospitalization can be managed in the outpatient. The
burnt area should be dressed with a bacitracin,
nitorfurazone, or silver sulfadiazine cream twice a day.
Hospital Management
As soon as patient arrives, an intravenous access is
secured, and assessment of severity and depth of burn is
done. An indewelling catheter is placed if burnt area is
more than 15 percent or patient is in shock. The
respiratory status is monitored closely. One hundred
percent oxygen should be administered where carbon
monoxide poisoning is suspected. Fluid resuscitation for
moderate and severe burns is important. The 24-hour
fluids to be infused are calculated using the formula:
(4 mL/Kg body weight X % body surface area burnt)
+ Maintenance requirement of 1500 mL/m2. Of the total
requirement 50 percent is given within the first 8 hours,
and the rest over the next 16 hours. Ringer lactate is the
preferred fluid for the first day, subsequently fluids may
be given as N/2 saline in 5 percent dextrose. The fluids
should be reduced to 50 percent after the first day. Colloid
can be administered if the serum albumin levels are less
than 2 g/dl, or fluid requirement is in excess of 30 ml/
m2/hr. The burn wounds are an ideal site for bacterial
growth due to the presence of necrotic tissue. Barrier
nursing, early excision of eschar and provision of
adequate skin cover are useful in preventing infections.
Antibiotics need to be given in the presence of active
infection (erythema, purulent discharge, black or green

discoloration). Surface swabs from the wound will
indicate the flora. A combination of an antistaphylococcal
penicillin and an aminoglycoside can be started pending
sensitivity results.
Phychosocial Consequences of Injuries
Children and their family members who survive near
fetal injuries suffer intense psychological stress and are
prone to Post Traumatic Stress Disorder (PTSD) which
may hamper their development. Studies have revealed
that 10-40% of hospitalized survivors of near fatal injuries
have PTSD. Standardized questionnaires to these at risk
children and their families may help to identify the
problem early and take remedial measures. Injuries
increase the economic burden on the family and the
country not only during hospitalization and treatment
but also in the event of survival with permanent
disability. The adage prevention is better than cure
holds true in case of injuries.
1207
BIBLIOGRAPHY
1. Baker S, ONeill B, Ginsburg M, Li G. The Injury Fact
Book. (2nd ed). New York: Oxford University Press, 1992.
2. National Crime Records Bureau. Accidental Deaths and
suicides in India. New Delhi: Ministry of Home Affairs,
Government of India; 2001b.
3. Di Guisseppi C, Roberts I. Individual-level injury
prevention strategies in the clinical setting. Unintentional
injuries in childhood: The Future of Children. In Los
Altos, CA: The David and Ludile Packard Foundation
2000; 10(1):53-82.
4. Finkelstein J. Pediatric burns. An overview. Pediatr Clin
N Am 1992;39:1145.
5. Grossman B, Rivara F. Injury control in childhood.
Pediatr Clin N Am 1992;39:471.
6. King E. A leading cause of the global burden of disease.
WHO (World Health Organization Advisory Group)
Geneva, 1999.
7. Rivara FP and Grossman D. Injury Control. In: Behrman
RE, Kleigman RM, Jenson HB, Stanton BF (eds.). Nelson
Textbook of Pediatrics. 18th ed. Philadelphia: Saunders
2008;366-74.
24.2 Poisoning in Children

KS Rao, B Ravichander
Ingestion of toxic substances is a common problem in
the Pediatric age group. Though poisoning could be accidental, homicidal or suicidal, accidental poisoning is one
of the most common in this age group. The inherent
curiosity and tendency for exploration in children
contributes to the high incidence of accidental poisoning
in children below five years and is most common in the
age group of 1-3 years.
Diagnosis
The diagnosis and treatment depends upon the type of
poisoning and its severity and the latter depends on the
amount ingested and the age of patient. A good detailed
examination and urgent management and life saving
measure take precedence
Examination and History
Common Poisons
Most cases of poisoning are due to substances available in the
home environment and occur due to easy accessibility and
poor housekeeping routine at home. Substances commonly
causing poisoning at home are given in Table 24.2.1
TABLE 24.2.1: Substqnces commonly accounting for
poisoning in children
Medications
Insecticides
Hydrocarbons
Aspirins, Iron, Paracetamol

Kerosene Oil, Solvents
History and circumstances in which the ingestion/

inhalation occurred may give a clue to the type of poison.
A proper clinical examination paying attention to the
vital parameters (Pulse, Respiration, Temp, BP),
consciousness levels, breath odor, pupil size and reaction,
skin (colour, sweating, excoriation etc) and any marks
of injury may give clue to the type of poisoning. Most
poisons may produce clinical signs which may fit into
one of the group of signs and symptoms called the
toxidrome syndromes as given in Table 24.2.2.
1208

TABLE 24.2.2: Features of common poisoning
Features
Sympathomimetic:
Excitability,Tachycardia,Hypertension, dilated pupils, sweating
Sympatholytic
Depressed consciousness, bradycardia, hypotension,
constricted pupils
Cholinergic
Agitation, anxiety, constricted pupils, bradycardia,
increased sweating
Anticholinergic
Tachycardia, hot dry skin, dilated pupils, decreased
peristalsis, urinary retention
Withdrawal
Tachycardia, hypertension, mydriasis, diaphoresis, agitation,
restlessness, seizures, hyperreflexia, piloerection, yawning,
abdominal cramps, lacrimation, hallucinations
Principles of Management
The lab investigations are carried out to confirm the
poisoning for forensic purposes as well as estimate level
of drugs for prognosis. Serial estimation may be useful
for poisons which are slowly absorbed both for prognosis
and to note efficacy of intervention. Estimation of other
biochemistry in terms of liver functions, renal functions,
serum level of enzymes will be based on specific poisons
and their pharmacokinetics in the body. Radiological
investigation have limited role in poisons which are radio
opaque like Iron tablets ingestion or where possible
inhalation/aspiration of the poison is suspected.
Immediate management/first aid.
1. Ensure Airway, breathing and circulation are
stabilized
2. Surface decontamination of poisons which are
absorbed from the skin e.g. Organophosphorus
3. Decrease poison load of ingested poisons. Emesis
induction by physical/chemical means is no longer
recommended as a first aid measure.
4. Transport to nearest medical care facility if poisoning
is suspected for more specific management.
Treatment
The initial treatment consists of managing and protecting
the airway, breathing and circulation. If the patient has
altered sensorium or if the poison is likely to be aspirated
during emesis, Endotracheal intubation (ET) should be
done and the airway secured. In a comatose child an
emergency IV access is secured and a bolus of 2 ml/Kg
Substance
Amphetamine, Ephedrine
Opiates, Barbiturates, phenothiazines, alcohol
Organophosphorus, Nicotine, Carbamates
Antihistamines, Atropine, Belladonna alkaloids (Dathura),

Mushrooms (some), Psychoactive drugs (many) Tricyclic
antidepressants
Alcohol, Barbiturates, Benzodiazepines, Opioids, Sedatives
of 25% Dextrose is given and a bedside blood sugar is

checked. In adolescent and malnourished children a
Thiamine dose of 50- 100 mg is given IM/IV to avoid
precipitating Wernickes encephalopathy.
In a comatose child if the respiration is shallow,
IV Naloxone in dose of 0.2 mg/Kg is given IV to reverse
the effects of Opiate induced respiratory depression. Any
other emergencies in the form of shock, seizures,
arrythmias and hypothermia are managed concurrently.
The most important part of management consists of
decontamination both surface and internal followed by
the use of Specific antidote if available. The list of
antidotes available are given in Table 24.2.3
TABLE 24.2.3: Summary of antidotes
Drug/poison
Antidote
N Acetyl cysteine(Mucomist)
Physostigmine
Atropine and Pralidoxime
Atropine
Flumazenil
Oxygen
Amyl Nitrate inhalation/ Sodium
Nitrite
Digitalis
Fab antibodies (Digibind)
Arsenic
Dimercaprol(BAL)
LEAD
(BAL, EDTA(+ Pencillamine),
DMSA
Mercury
BAL, DMSA
Iron
Desferroxamine
Isoniazid
Pyridoxine
Methanol and ethylene glycol
Ethanol
Opiates
Naloxone
Phenothiazines
Diphenhydramine
Acetaminophen
Anticholinergics
Acetylcholinesterase
Carbamate
Benzodiazepines
Carbon mono oxide
Cyanide
1209
Decontamination
SALICYLATES
Eye: exposure of eyes to toxic fumes or accidental

exposure should be managed with adequate flushing of
eyes with saline. After flushing flouroscein staining of
the cornea to be done for signs of any corneal injury and
appropriately managed .
Skin: Poisons which can be absorbed from the skin
like Organophosphorous, acid burns should be adequately decontaminated by bathing the surfaces with
plain water.
Salicylate poisoning was earlier common in children and

with increasing awareness of its association with Reyes
syndrome and change in its formulation strength the
incidence has decreased. Aspirin usage is less frequent
except in Rheumatic fever and Juvenile idiopathic arthritis.
GI Tract
Gastric lavage may be useful if emesis has not occurred
. The contraindications are corrosives/caustics, comatose
patients and hydrocarbon ingestion., Comatose patients
in whom if the airway is protected by a ET tube, lavage
can be done satisfactorily. Lavage may not be successful
in children particularly if the material is particulate due
to the small size of the lavage tubes that can be used in
children. Just before removal of the tube a bolus of
activated charcoal slurry can be placed in the stomach
which can adsorb the remaining poison in the stomach.
Cathartics in the form of Magnesium sulphate or
Polyethylene glycol have very limited role in GI tract
elimination of the poisons.
Blood: Removal of the absorbed poisons from the
blood may have to be resorted to in certain poisons which
are usually in ionized form in which case methods like
forced alkaline diuresis, peritoneal/hemodialysis/
hemoperfusion could be done.
Supportive Care
Other supportive care in the form of adequate hydration,
sedation if required, maintenance of vital parameters and
psychological support should be given till discharge from
the hospital. Management of specific symptoms like
seizure, arrhythmia, hepatic dysfunction and acidosis
will be on standard lines for that symptom.
Prevention
Primary prevention could to a large extent prevent
poisoning in the pediatric age group. Simple measure
like good house keeping, preventing children access to
medicine or poison containers, institution of child proof
containers for medication, appropriate labeling of
containers, prescribing limited quantity of medication
per prescription etc would minimize the chance of
household poisonings.
Clinical Features
Initial clinical features of toxicity are vomiting, dehydration, tinnitus and hyperventilation. Further stages are
characterized by hyperpnoea, hyperpyrexia, restlessness,
delirium and convulsions. Lethargy drowsiness and
coma may supervene. Chief metabolic features include
metabolic acidosis, hypoglycemia and ketonemia. The
urine Ferric chloride test may be positive. Serum
Salicylate level at time of admission and serial evaluations may indicate the severity of toxicity which is
said to be present when levels exceed 30 mg/dl and levels
above 100mg/dl are potentially lethal. Other biochemistry of LFT, RFT, acidosis and coagulation
anomalies may be present.
Treatment
For recent ingestion stomach wash should be done with
normal saline or weak Soda bi carb solution. Activated
charcoal (1gm/Kg) should be given as a bolus orally to
decrease Salicylate absorption and may be repeated based
on serum levels done sequentially. Forced alkaline
diuresis enhances Salicylate excretion by the urinary
route. Hyperthermia is to be managed with surface
cooling of body. A suitable infusion fluid of N/5 saline
with Soda bicarb added at the rate of 1-2 meq/kg every 12 hours with aim of maintaining urine pH above 7.5 to 8
and urine output of 1-2 ml/kg will enhance excretion.
Vitamin K may be administered if alteration of Prothrombin
time is prolonged. Supportive management of renal and
hepatic failure is necessary. Hemodialysis results in
satisfactory Salicylate clearance and indicated with serum
levels above 100 mg/dl. Patients with hypoglycemia,
seizures or visceral bleeding have poor outcome.
Toxic dose:
Symptoms:
Treatment:
150 mg/Kg
Hyperapnoea, Hyperpyrexia,
vomiting, tinnitus
General measures, Activated charcoal,
forced alkaline diuresis, cooling of body,
Hemodialysis
1210
IRON
Iron is an important toxicological hazard because of easy
availability and bright coloured formulations. Ingestion
up to 25 mg/Kg of elemental iron does not cause any
problem. Higher ingestions are potentially serious.
Clinical Features
The earliest symptoms of Iron ingestion are nausea,
vomiting and diarrhea with onset within 30 min and up
to 6 hrs post ingestion. Following this is a quiescent
phase. Subsequently, GI losses due to increased capillary
permeability and systemic effect in tissues causing
metabolic acidosis and myocardial dysfunction lead to
circulatory failure characterized by shock. Thrombocytopenia and hypoprothrombinemia may also occur.
Hepatocellular necrosis leading to hepatic failure is a
significant cause of mortality. The corrosive effect of iron
leads to gastric scarring causing outlet obstruction as a
late feature of the poisoning.
or 100 ml of Soda bi carb may be left in the stomach after

lavage. Bowel irrigation with Polyethylene glycol may
be useful in Iron elimination from the GI tract.
The excretion of free circulating iron can be enhanced
by chelating with Desferroxamine, the complex of
Desferroxamine-Iron being more water soluble gets
excreted by the kidney. Desferroxamine is added to
normal saline and infused at the rate of 15 mg/Kg/hr.
The Desferroxamine-iron complex colours the urine a
distinct pink(vin-rose) hue to the urine. The infusion is
continued for a period of 24 hrs after the urine becomes
clear or the serum Iron level is below 300 mcg/dl.
The child may require supportive therapy in the form
of IV fluids, inotropic support, maintaining glucose levels
and correction of the metabolic acidosis. Gastrostomy
may be required if radiological visualization confirms
persistence of large number of radio opaque shadows
even after lavage. Hemodialysis is not useful unless
associated renal failure is present.
BARBITURATE
Toxic dose:
Symptoms:
Management:
Antidote:
More than 25 mg/Kg or serum levels

above 300 mcg/dl
GI symptoms (Vomiting & diarrhea),
shock, hepatic failure
General measures-lavage, bowel wash,
IV fluids, Inotropes
Desferroxamine
Poisoning is likely to occur in children who suffer from

epilepsy or where a family member is on such medication. Ingestion of over 1 gm of any barbiturate should
be viewed with concern and over 3 gm is potentially
lethal.
Clinical Features
Lab Investigations
Serum level of iron greater than 300 mcg/dl are
associated with toxicity and levels greater than 500 mcg/
dl are considered severe poisoning and levels above 1000
mcg/dl are invariably fatal. Blood glucose may be
elevated and liver functions may be deranged. X-ray
abdomen may be valuable prior to and after lavage to
see the quantum of radio opaque tablets if ingested.
Treatment
Ingestion up to 25 mg/Kg of elemental iron need not be
treated. Children if symptomatic or with serum levels
above 300 mcg/dl may be managed with specific
antidote. All other children should receive general
measures of poison management.
Lavage is indicated even if emesis has occurred
though the iron tablets may have become a gel in the
acid medium of the stomach and not likely to be fully
removed even with lavage. 100 ml of Milk of Magnesia
The clinical features are characterized by CNS

depression. The respiration may be shallow and progress
to respiratory arrest. Hypotension occurs with severe
poisoning and the pupils are constricted but later dilate.
There is loss of light and corneal reflex. The bullous
lesions on the skin are more due to pressure effects on
the skin rather than toxicity due to the drug. On recovery
there is headache, dizziness, diplopia, ptosis and ataxia.
Cause of death in barbiturate poisoning is due to
respiratory arrest. Serum levels of barbiturate are useful
in confirming toxicity with levels more than 10 mg/dl
for long acting, 7 mg for intermediate acting and more
than 3 mg for short acting drugs considered to be in the
toxic range. EEG changes correlate with severity with
fast activity in mild poisoning to slowing and progressing
to flat EEG with severe poisoning.
Treatment
Gastric lavage is useful if done within 6 hours of
ingestion. Activated charcoal adsorbs barbiturates and
1211
is used as slurry after the lavage. Supportive treatment

for respiratory failure, hypotension and hypothermia is
to be provided. Forced alkaline diuresis enhances drug
excretion.
esophageal reconstructive surgery with a jejunum or

colonic segment. Recent methods involve placement of
stent and allowing the esophagus to heal over the stent
so that a functional esophagus is available.
CAUSTIC INJURIES
HYDROCARBONS
Caustic injuries to the esophagus and stomach result due

to the easy availability of household detergents and
cleaning agents in the home environment.
Clinical Features
Vomiting, drooling, dysphagia and abdominal pain are
common symptoms of all caustics. Involvement of the
glottis leads to stridor and shock. The oral cavity may
show edema, ulceration, pseudo membrane and excoriation at the vermillion skin border. The child may have
fever and leucocytosis. Some children may not have
immediate symptoms but may present later with
strictures of the esophagus or stomach.
Household Cleaning Agents
Symptoms
: GIT symptoms, local lesion in mouth and pharynx
Management : No emesis, Nil orally, Steroids, antacids and H2
antagonist, Fibreoptic endoscopy for evaluation
and dilatation.
Management
Vomiting is contraindicated in such ingestion. The child
with dilute ingestion may be observed at home but those
with symptoms or concentrated caustic should be
admitted even if asymptomatic. The child is kept nil
orally and the inability to predict esophageal injury by
oral examination makes it mandatory for examination
by Fibreoptic endoscopy in the first 24 to 48 hours.
Patients with first degree injury to the esophagus do not
need any specific therapy. The child is advised oral fluids
and subsequently normal diet. Children with second
and third degree injuries require intensive therapy.
Steroids are given to prevent stricture and antibiotics
administered to prevent secondary damage. Antacids
and H2 antagonists are given to suppress acid secretion
which should be continued for 6 to 8 weeks. Child should
be allowed to drink fluids as soon as possible. Endoscopy
evaluation is repeated after 2 to 3 weeks for any stricture
which if found are managed by reverse dilatation
through a Gastrostomy. If strictures are severe they may
not respond to dilatation and these children will require
Accidental ingestion of kerosene, petrol and diesel is a

common poisoning due to its ready availability in the
home environment. Their taste prevents children from
ingesting a large amount and rarely is the amount more
than 30 ml. Amongst the hydrocarbons kerosene is the
most frequent accidental ingestion.
Though ingested the pathology of hydrocarbons is
due to their aspiration into the respiratory passage
resulting from its volatility and low viscosity which
enables its aspiration during ingestion or during
vomiting. On aspiration hydrocarbons cause bronchospasm, atelectasis, emphysema, pulmonary edema and
inflammation. Secondary infections of the lung can occur.
Pathological changes that occur in other organs are
secondary to hypoxia.
Clinical Features
The patient presents with vomiting followed by onset of
respiratory distress. There may be variable degree of
tachypnoea, cyanosis, tachycardia, nasal flaring, grunting
and intercostal retractions. Rales and rhonchi are
commonly heard. The symptoms usually have their onset
within 6 hours of aspiration though occasionally could
be delayed to as much as 24 hours. Radiograph of chest
shows punctate opacities in the perihilar and midfield
zones which coalesce to form areas of consolidation.
There may be areas of atelectasis, emphysema, pneumothorax, pneumatocoeles, pneumo-mediastinum and
subcutaneous emphysema.
Somnoloscence, convulsions and coma are attributed
to hypoxia. Fever is commonly seen in children with
pneumonia. Rarely hemolysis, cardiac arrhythmia and
hepato-splenomegaly can be seen. Most children recover
in 3 to 8 days.
Treatment
Treatment is essentially supportive. If the amount of
ingestion is small and the child asymptomatic for a period
of 6 hours post ingestion, the child can be observed at
home. Children with symptoms need to be hospitalized
and managed with oxygen, positive pressure support
and if required ventilation.
1212
Emesis is contraindicated for fear of aspiration.

Prophylactic antibiotics are useful only if there has been
a preexisting respiratory illness, malnourished children
or those with pneumonia. Steroids have no role in the
management of Hydrocarbon aspiration. The majority
of children recover. Death is usually due to respiratory
failure. Hydrocarbons are usually used as diluents of
other chemicals and hence harbour a suspicion of other
poisoning if the child has additional manifestations.
Hydrocarbons:
Symptoms:
Inv:
Treatment:
Kerosene, petrol, diesel

Odour, vomiting, respiratory symptoms
X ray for pulmonary involvement
Supportive, Oxygen, Resp support
ORGANOPHOSPHOROUS COMPOUNDS AND

CARBAMATES
Organophosphorus compounds and Carbamates are
used as insecticides in agriculture and in domestic usage.
Some of the commonly used compounds are
Organophosphosohates: Tetraethyl pyrophosphate
(TEPP), Ethyl parathion,
Dichlorofos, Fenthion (Baytex),
Malathion, Temephos (Abate),
Endosulphan (Endrin)
Carbamates:
Methocarb(Nudrin), Propoxur
(Baygon), Carbaryl (Sevin)
Poisoning due to these toxins is most often intentional
particularly in the adolescent age group though
accidental ingestion due to inadvertent exposure to
household insecticides may occur.
Pathophysiology
Organophosphorus compounds and Carbamates inactivate the cholinesterase so that the acetylcholine that is
secreted at axonal ends does not get inactivated.
Organophosphorus compounds inhibit this enzyme
irreversibly so that the normal activity can be resumed
only on generation of new enzymes or if the enzyme is
reactivated by drugs like Pralidoxime. Carbamates
inactivate cholinesterase temporarily.
Clinical Features
These substances mediate their effects by accumulation
of acetylcholine at various receptor sites. These
substances are well absorbed through the skin, gastro

intestinal tract and respiratory routes.
Muscarinic effect: This is characterized by excess
salivation, lacrimation, urination and diarrhea. The
pupils are pinpoint and there is marked bradycardia. GI
symptoms consist of nausea, vomiting, pain abdomen
and diarrhea. Tightness of chest , bronchospasm,
wheezing and pulmonary edema may occur.
Nicotinic effects: These are seen in severe poisoning
chiefly causing muscle twitching, fasciculations, and
cramps followed by muscle weakness and paralysis
particularly of the respiratory muscles.
Central effects: These are seen in severe cases and
include restlessness, confusion, headache, slurred speech,
ataxia, seizures and coma.
The signs and symptoms of Carbamates are similar
except that they are milder and of short duration.
Diagnosis
The diagnosis is based on the history and typical clinical
findings. The RBC cholinesterase level is less than 50%
in cases where exposure has occurred and less than 20%
in case symptoms are present. X-ray chest may be
required to document the presence of pulmonary edema.
Treatment
Further exposure to the insecticide must be avoided by
moving to a safer environment. The clothes to be
removed and skin to be washed with adequate amount
of soap and water. If ingested, gastric decontamination
should be done. If conscious, by vomiting followed by
lavage, and if unconconcious by lavage after protecting
the airway with a ET tube. Activated charcoal slurry can
be left in the stomach after lavage.
Atropine is the specific antidote which neutralizes
the CNS and Muscarinic effect but not the Nicotinic effect.
It is given in a loading dose of 0.02 to 0.05 mg/Kg
followed by maintenance dose of the same dose every
10-30 min. Child should be watched for signs of
Atropinisation in the form of dryness of mouth, dry skin,
decrease in bronchial secretions, pupillary dilatation and
tachycardia. The patient is kept Atropinised till the
enzymes regenerates or is reactivated.
Pralidoxime, a cholinesterase enzyme reactivator is
a specific antidote for Organophosphorus compounds.
Enzyme activation occurs most rapidly at the neuromuscular junction with rapid restoration of skeletal

muscle response. The Muscarinic or central effects are
not significantly reversed with this drug and hence
concomitant use of atropine is essential. The dose of
Pralidoxime is 25-50 mg/Kg for a child less than 12 years
and for children above 12 years adult dose of 1-2 gm is
given over 15 to 30 min IV followed by repeat dose after
1-2 hours.
Following recovery the child should be observed
closely for 24 to 48 hours to ensure that cholinergic signs
do not recur as Pralidoxime and Atropine effects wear
off. Intermediate syndrome can develop 24 to 96 hours
after Organophosphorus poisoning which is characterized by weakness in the proximal motor muscles,
motor cranial nerves, neck flexors and respiratory
muscles. A combination of pre-synaptic and post
synaptic impairment of neuromuscular transmission
probably causes this syndrome. Enzyme activation has
no role in Carbamates poisoning and may be harmful.
Symptoms
Management
: Muscarinic- Skin, Resp, Pupils, GIT, Urinary

Nicotinic- Skeletal muscles, Resp muscles
CNS- Confusion, coma
: Decontamination of Surface and GIT
Atropinisation, Pralidoxime
ANIMAL ENVENOMATIONS
Scorpion Bite
Scorpion bites are common in tropical countries particularly rural areas Though there are many species of
scorpion only two species Viz Mesobuthus tamulus and
Palamneus swammerdami are of medical importance.
Scorpion bites are common in summer and rainy seasons
and more so in rural areas. The toxic effects of scorpion
are species specific but the common scorpion bites in this
country cause cardiotoxicity. The toxicity of their poisons
is by their effects on the various ion channels in the body.
Clinical Features
The local effect consists of pain in the local area which
on tapping causes a shock like pain(Tap test) but no other
sign of inflammation. Following pain the child may have
general symptoms like irritability and vomiting. These
symptoms are followed by various cholinergic and
adrenergic symptoms in form of salivation, sweating,
bradycardia/tachycardia, hypotension/hypertension
and pulmonary edema and shock. Investigation like ECG
may show T and ST changes and rhythm disturbances.
1213
Management
The major clinical manifestations are due to autonomic
dysfunction and hence drugs like Prazosin which causes
alpha blockade work as an antidote in scorpion
envenomation. It can be given regardless of the blood
pressure record in the dose of 30 mcg/Kg/dose. If there
is evidence of dehydration IV fluids and inotropic agents
in form of Dopamine/Dobutamine is used. Pulmonary
edema is managed with diuretics, Oxygen and Dobutamine support. Local pain may be relieved with local
infiltration of lignocaine/dehydroemetine/ice packs. In
case of ECG changes, combination of Insulin and alpha
blockade with Prazosin helps in reverting the changes.
Use of Anti-scorpion venom has not been found
useful in studies due to the rapidity of action of the
venom. Lytic cocktail, steroids, Morphine and Atropine
have not been found useful and may be detrimental in
some cases.
Snake Bite
Out of the known species of snake worldwide only 300
of them are poisonous and in India out of the 216 species
only 52 are poisonous. The common poisonous snakes
of India are Common Krait, King cobra, Common Cobra,
Russells viper and Saw scaled viper. Snake poison is a
mixture of enzymatic and non enzymatic toxins
mediating their effect on the neurological, hemopoietic,
cardiovascular and renal systems. The contents of the
venom of various species differ in the quantity of the
various enzymatic and non enzymatic constituents and
thereby have more effect on one particular system. The
effect of envenomation depends on amount of venom
injected, site of bite, body weight, bite through clothing,
exercise, exertion etc.
Clinical Features
The effect of envenomation leads to local and systemic
effects. Depending on the quantity of venom and the
species, the local effects consist of pain and erythema at
bite site followed by edema and blister formation. This
may progress to extravasations, petechial/purpural rash
and the area may get devascularised with features of
necrosis predisposing to onset of gangrene. Secondary
infection including tetanus and gas gangrene may occur.
The systemic effect depends on the species. Cobra
bites are associated with predominant neurological
symptoms with cranial nerve involvement in the form
1214
of ptosis and opthalmoplegia as early manifestation

followed by paralysis of other cranial nerves and the
motor system. Reflexes are preserved till the last stage
and respiratory muscles are almost the last to be affected.
Viperine bites are associated with severe local
manifestations with systemic involvement in the form
of hematological manifestations in form of bleeding from
multiple sites and coagulation abnormalities. They may
be associated with hemolytic changes and also DIC may
be a terminal feature.
Sea snake bites are associated with severe myalgia
and myoglobinuria leading to renal failure.
Management
Snake bite causes a lot of apprehension and fear in the
victim which may increase his activity and thereby
enhance venom absorption. So first aid measures in the
form of rest, reassurance and immobilization of the part
are important. If the bite is over a limb a tourniquet
applied proximal to the bite just to occlude the lymphatic
flow may be beneficial. There is no role for incision or
suction of the bite site with any device.
Specific and supportive therapy: specific therapy with
poly valent anti-snake venom is indicated only if there
are signs of envenomation in form of any local or systemic
signs and symptoms. The severity of the bite can be
classified for purposes of quantity of antivenin administration into mild, moderate and severe. In mild envenomation there may be only local effect in the form of
swelling and erythema involving around the bite area
with no systemic signs or symptoms, in moderate
envenomation there is spread of the edema and swelling
with other manifestations of systemic signs and
symptoms, and in severe systemic signs like DIC,

paralysis and renal failure are present. Dose of anti snake
venom is 50 ml for mild, 100 ml for moderate and 150 ml
for severe bites. Since this is equine derived product a
test dose in the skin has to be done before administration.
The anti-snake venom is diluted in saline and infused
slowly about 20 ml over 30 min and if there is no reaction
the rest of the antivenin is infused in the next 1 to 2 hr.
The response to antivenin administration is quiet
dramatic and repeat doses of antivenin may be required
if signs of poisoning persist. In case of skin showing
positive reaction, slow desensitization should be done
to enable anti-snake venom administration with
adequate precautions for managing anaphylaxis.
Supportive therapy in the form of IV fluids, infusion of
blood/blood products for bleeding manifestations/DIC
will be required. Ventilatory assistance may be required
in respiratory paralysis and cholinergics in reversal of
neuroparalysis. Peritoneal/Hemodialysis are used as
supportive care in presence of renal failure.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
6.
Bryant S, Singer J. Management of toxic exposure in

children. Emerg Med Clin North Am 2003;21(1):
101-19.
Bryant SM, Leikin JB, Iron. Critical Care Toxicology.
2005;687-93.
Chyka PA, Erdman AR, Christianson G, et al. Salicylate
poisoning: an evidence-based consensus guideline for
out-of-hospital management. Clin Toxicol (Phila).
2007;45(2):95-131.
Mahadevan S. Scorpion sting. Indian Pediatr 2000;27:
504-14.
Mathew JL Snake bite. Pediatrics Today 1999;II:36-44.
Wax PM, Beuhler MB. Hydrocarbons and Volatile
Substances. Tintinallis Emergency Medicine: A Comprehensive Study Guide (Sixth Edn). 2004;1124-29.
25.1 Child Psychiatry: Manju Mehta .......................................................................................................................................................... 1216

25.2 Child Guidance Clinic (CGC): T Ravikumar .................................................................................................................................... 1229
1216
25.1 Child Psychiatry

Manju Mehta
Recent epidemiological study of child psychiatric
disorders in urban and rural areas conducted by ICMR
(2001) indicated the overall prevalence of mental and
behavioural disorders in children to be 12.5%. In an earlier
study by Mehta et al 1990, 13% of children were found
suffering from emotional disorders. With the changing
socio-cultural scenario child psychiatric disorders are on
increase. Thus, the pediatrician needs to be familiar with
the developmental and emotional problems of children.
The reasons for this need are as following:
Firstly, it has been estimated that approximately onethird of the children attending a pediatric clinic suffer not
from physical but primarily from psychological illness. In
case of the rest, the illness may have a significant emotional
content and psychological aspect, which will have to be
handled.
Secondly, the family doctor is the most important
person upon whom the parents depend, not only for
treatment of their childs illness, but also for overseeing
their psychophysical development. Many times, parents
approach the doctor for minor developmental problems
like eating problems, problems relating sphincter control
and learning problems and to advise them correctly on
these matters. Pediatricians would require a thorough
knowledge of normal development and common
deviations.
Finally, a general knowledge of child psychiatry is
also necessary for the pediatrician to be able to identify
the more serious emotional and psychiatric disturbances
in the child so as to correctly refer him to a child
psychiatrist.
from multiple sources (e.g. parents, peers and teachers

etc.)
A childs behaviour and cooperation may vary from
time to time. A child may have his good days and his bad
days. A comprehensive assessment would therefore
require observing the child serially over several sessions
(three sessions on an average).
Two types of interviews are used for children, a
conversational and a play interview and they are often
combined in a single interview. A play interview is
essential when examining a child who is less than 7- yearold. The behaviour of a child can be assessed in different
ways. However, it is useful to generally distinguish
between two methods of assessment - direct and indirect.
Direct Assessment Methods
Direct assessment procedures typically allow for the
assessment of clinically relevant behaviours at actual time
and place of occurrence. However, direct assessment
procedures are often difficult to implement due to time,
cost and practical constraints. The various methods are
as follows.
Naturalistic Observations
Naturalistic observation is the systematic monitoring and
recording of a representative sample of childs behaviour
in the environment where the behaviour has been
identified as being problematic. Examples include
observation of a child in a classroom or observing a childs
interaction with peers on a playground.
BEHAVIORAL ASSESSMENT OF A CHILD

Examination of the child consists of interviewing the child
as well as his/her family. The child does not seek help by
self. Often a childs understanding of what troubles him/
her may be at variance with the reports of his parents and
teachers. Also, many behaviour problems are situationspecific. For example, a child may have severe temper
tantrums only when he is with his parents, or a child who
is obedient at home may be disruptive in the classroom.
Therefore as a general rule, information should be gathered
Analogue Observations
This involves the observation of a childs behaviour in
settings, which are designed to increase the chance of
occurrence of specific target behaviour. This method is
particularly useful when the target behaviour is of low
frequency. Example of analogue observation is a parentchild interaction in a structured setting in which specific
instructions are given (e.g. having a parent request the
child to clean up the playroom).
Child Psychiatry
Participant Observations
This involves an observer who is normally a part of the
childs everyday environment, such as a parent, teacher,
or even another child (such as a sibling), who monitors
and records selected behaviours exhibited by the child.
1217
developmental trends (e.g. being rebellious as an

adolescent). Third, there can be behaviors that interfere
with normal developmental processes (e.g. extreme
aggressiveness or shyness that interferes with the
development of friendships).
Self-observations
INTELLECTUAL ASSESSMENT
A child may require observing his/her own behaviour

and then recording its occurrence. This obviously requires
a motivated subject who has the ability to discriminate
between the presence or absence of specific target
behaviours.
Standardized tests of intelligence are employed routinely

as a part of clinical assessment and for educational
purposes. There are three reasons for including a measure
of intelligence as part of routine clinical assessment:
First, there are several specific diagnoses of children
and adults that require a standardized measure of
general intelligence. These include the diagnoses of
mental retardation, specific learning disorders and
developmental language disorders (American
Psychiatric Association, 1993).
Second, intelligence is perhaps the most predictive
single measure of an individuals ability to adapt and
integrate in society. Also, low intelligence may increase
vulnerability with respect to the development of
specific psychiatric disorders, e.g. schizophrenia.
Third, intelligence is important in the complete
assessment of a subjects personality .
Standard measures of intelligence ( e.g. Wechslers
intelligence scale for children, WISC; Malins intelligence
scale for Indian children, MISIC) provide 3 scores.
Indirect Assessment Methods

These procedures collect information about relevant
behaviours that are obtained at a time and place different
than where the actual problematic behaviours occur.
Examples of indirect methods are the most commonly
employed clinical interview, use of rating scales, checklists
and self-report instruments. Two well-known checklists
for children are - Child Behaviour checklist (CBCL;
Achenbach and Edlebrock, 1979) and Conners Teacher
Rating Scale (CTRS; Conners, 1969). Examples of selfreport instruments are Child Depression Inventory (CDI;
Kovacs, 1981) and Perceived Competence Scale (PCS;
Harter, 1982).
Special Considerations in the Behavior
Assessment of Children
All clinical assessments require the examiner to make
distinction between what is normal and what is abnormal.
Making such decisions in the case of a child is often
difficult as behaviours considered normal at a particular
age (e.g. temper tantrums at age 4) would be considered
abnormal at another age (e.g. age 10). Obviously,
knowledge of the normal development of children is a
necessary prerequisite for making clinical decisions. This
interface between abnormal psychology and normal
development has been termed as developmental
psychopathology.
Clinically, three definitions of abnormal behaviors
have been described in the context of the above discussion
(Garber, 1984). First, they can be viewed as deviations
from age-appropriate norms (e.g. a 4-year-old who never
had a temper tantrum). Second, they can be exaggerations
(either in frequency or intensity or duration) of normal
Verbal Intelligence Quotient (VIQ)

The verbal subtests are dependent on verbal comprehension and expression, general awareness, and calculation.
The scores on subtests are age-corrected and summated to
give the VIQ.
Performance Quotient (PQ)
The performance subtests are dependent on visual
analysis, visual motor integration, and motor speed. PQ
is calculated in a manner similar to that of VIQ.
Global or Full Score IQ
The global or full score IQ is obtained as the mean of VIQ
and PQ. Full scale IQ is examined for a general placement
of the person on the continuum of intellectual ability. On
most scales the mean score in any general population
sample is 85+15.
1218
Intellectual Assessment in Pre-school Children

However, the above mentioned standard scales cannot be
applied to infants and toddlers, and there is a different set
of scales to assess the developmental trends for these age
groups.
Examples of such scales are:
Gessells Developmental Schedule (4 weeks - 3 years)
Bailey Scale of Infant Development (< 2 years)
Vineland Social Maturity Scale (from birth to
adulthood)
Seguin Form Board Test (< 10 years)
Despite these attempts, tests for infants and toddlers
are unsatisfactory, as intelligence testing requires certain
receptive and expressive capacities, which this age group
lacks. The scales used for this age group test the
development of motor, communicative and social skills
rather than cognitive skills.
DESCRIPTION OF THE DISORDERS
Some of the common disorders in child psychiatry are
described in the subsequent section.
ATTENTION DEFICIT HYPERACTIVITY
DISORDER (ADHD)
This is discussed in Chapter 19.3.
CONDUCT DISORDER
Conduct disorder is defined as persistent antisocial
behaviour of children and adolescents that significantly
impairs their ability to function in the social, academic or
occupational area. Youngsters with the disorder
repeatedly violate the age-appropriate rules of society,
displaying a lack of concern for the rights and feelings of
others. The rate is much higher among boys than the girls
(Richter and Cicchetti, 1993).
Etiology
It is widely accepted that multiple influence and factors
contribute to the development and maintenance of child
conduct disorder. Studies of adoptees and twins have
suggested the presence of a genetic component for
aggression even if not always for delinquency (aggression
and delinquencies are two dimensions of conduct
disorder). The risk for conduct disorder is increased among
offsprings of parents who had conduct disorder, antisocial
personality disorder or substance abuse disorders.
Other postulated biological factors include high

testosterone levels. This theory was put forward due to the
high male to female ratio for the disorder, but there is no
conclusive evidence in favour of this theory. Possible
deficiency in the serotoninergic and adrenergic systems
are suggested by reports of decreased cerebrospinal fluid
5-hydroxyindoleacetic acid (5- HIAA) which is a metabolite
of serotonin. There seems to be an association between
decreased serotonin and impulsive aggression. But as yet
the role of serotonin in conduct disorder is not clear.
Conduct disorder is strongly associated with abusive,
chaotic and neglectful family environments. Several
specific risk factors have been identified, including
exposure to marital conflict and physical aggression,
maternal depression, large family size combined with
lower socioeconomic status, and early loss of father due
to divorce. Parental psychopathology, such as antisocial
personality and substance abuse may contribute both
genetically and environmentally towards manifestation
of conduct disorder in the offspring.
On the whole, conduct disorder possibly develops in
a biologically predisposed individual on exposure to any
or several of the above mentioned environmental stressors.
Clinical Features
There is evidence for two clusters of symptoms in conduct
disorder, aggressiveness and delinquency. Aggression
may be directed towards people (e.g. peers) or animals
(cruelty towards animals) or objects (destruction of
property). Delinquencies, on the other hand, includes
antisocial behaviours, such as lying, stealing, running
away and truancy that do not primarily involve physical
attack on others. The onset of these symptoms may be
preceded by the presence of a difficult temperament and
high level of physical aggression in preschool years.
While evaluating a child for conduct disorder, one
must consider whether the reported behaviour is
appropriate, developmentally, for the age of presentation.
Defiance, and temper tantrums are often used by children
between 1.5 and 3 years of age when frustrated. This often
resolves with time. Similarly, lying is often used by 2 to 4
year olds as a method of playing with language. By
observing the reactions of parents and caregivers,
preschoolers learn about expectations for honesty in
communication. Almost all children steal something at
some point in their lives. It becomes a problem when it
happens more than once or twice. Thus, certain behaviours
become a symptom only when they occur at a greater
frequency or persist beyond a developmentally
appropriate age.
Child Psychiatry
Unlike the previous behaviours, however, truancy, runaway behaviour, destruction of property (e.g. through firesetting), and repeated aggression against animals or
others are never developmentally appropriate.
Treatment
There is not much data on the pharmacotherapy of conduct
disorder. Stimulants (like methylphenidate and
d-amphetamine), lithium carbonate, carbamazepine, and
antipsychotics have all been tried without any proven
efficacy.
Many different nonpharmacological treatments have
been used in the management of conduct disorder. These
include individual therapy based on alliance building
and behavioural principles. Family therapy designed to
improve communication among family members and to
elicit underlying conflicts is somewhat effective.
Correctional schools can address the educational needs
of juvenile delinquents.
Prognosis
Childhood conduct disorder often persists into
adolescence and predicts antisocial behaviour and alcohol
or substance abuse in adulthood. In general risk factors
for poor prognosis are childhood onset (10 years age),
high level aggression, low intelligence, early court
involvement and peer rejection.
OPPOSITIONAL DEFIANT DISORDER
This disorder is defined by behaviour, which is less severe
than those seen in conduct disorder; temper tantrums.
This disorder is common in adolescence period, more boys
show signs of continuous arguing, defiance of rules,
continual blaming of others, and frequent use of obscene
language. It has a better prognosis than conduct disorder.
A variety of treatment approaches are commonly employed
including behaviour therapy, family therapy and parent
management training.
SUBSTANCE ABUSE
Substance abuse and alcohol are increasing like an
epidemic in our children and adolescent population. The
abuse is often by inhalants - thinner, white fluid, cough
syrups, tobacco/gutka and charas and ganja. 20% of
children and adolescents start experimenting with alcohol
and drugs by 11 years of age (rapid assessment survey,
1219
2004). There are other psychosocial factors which lead to

addiction namely, change in life style, low frustration
tolerance, easy availability of drugs and peer pressure.
The clinical manifestation of substance use in children
are - decline in academic performance, change in
behaviour, irritability, decreased interaction with family
members, lying and stealing and changes in eating and
sleeping behaviour. These children can be assessed on
detailed case history, mental status examination and
standardized psychological rating scales such as CAGE,
Teen - addiction severity index, Fagerstrom test for nicotine
dependence. Management is primarily by cognitive
behavior therapy.
PERVASIVE DEVELOPMENTAL DISORDERS
The pervasive developmental disorders are also known
as Autistic Spectrum disorder. These are a group of
disorders that classify children presenting with
impairments and deviances in social interaction, language
and communication and play. Conditions included under
this category are autistic disorder (infantile autism),
Aspergers disorder, and Retts disorder.
Autistic Disorder
This is discussed in Chapter 19.5.
Aspergers Disorder
This is characterized by impairment in social interaction,
restricted behaviour and interests as seen in autistic
disorder, but there is no evidence for clinically significant
delay in language, cognitive functioning or ageappropriate self-help skills (Tantum, 1988). In fact, the
language of the subjects is highly grammatical.
There are quantitative as well as qualitative differences
from autism in impairment in social interaction and in
restriction of interests and behavior. Impairment in social
interaction is less affected. Also, Aspergers subjects
develop adequate attachment with parents, a feature never
seen in autism. Similarly imaginative play is present in
Aspergers syndrome, which is deficient in autism.
The reported prevalence of the disorder is 1 in 10,000
with a male to female ratio of 9: 1, and the disorder is
frequently not recognized until after age 3. Etiology of the
condition is unknown.
No specific treatment has been developed for
Aspergers syndrome and there have been no studies
addressing its outcome. It is believed that like autism,
Aspergers disorder is a life long condition.
1220
Retts Disorder
First described in 1966 by Andreas Rett, the disorder is a
progressive encephalopathy that develops between 5 and
48 months age in female children and is characterized by
deceleration of head growth (leading to microcephaly),
abnormalities of gait, loss of various functions and skills
including language and social relatedness. There is also
a loss of purposeful hand movements and midline hand
stereotypes including hand wringing and hand wetting
with saliva.
The cause of the disorder is unknown. It has an
estimated prevalence of 1 in 10,000 to 1 in 15,000 females
or even lower. Mental retardation is severe to profound
and MRl reveals significant reduction in overall brain
volume.
There is no specific treatment and the course is one of
progressive irreversible loss of motor function and
cognitive functions.
SPECIFIC DEVELOPMENTAL DISORDERS
Specific developmental disorders refer to a group of
disorders characterized by severe deficiencies in the
development of skills in the academic, language and motor
domains. The term does not include children who have
learning problems primarily as a result of visual, hearing,
or motor handicaps or mental retardation or emotional
disturbance, or of environmental, cultural, or economic
disadvantage. It is estimated that 3-15 percent of schoolage children have some learning disability (Hersen and
Ammerman, 1995). Clinic based studies from India report
a prevalence of 1.1 (Lal et al, 1976) to 3 percent (ICMR
Study, 2001).
Etiology
Academic Skills (or Learning or Scholastic Skills)

Disorder
This includes:
1. Developmental arithmetic disorder: Marked impairment
in arithmetic skills hindering achievement or living
skills
2. Developmental reading disorder: Significant impairment
in skill development related to reading such as word
recognition, decoding skills, and comprehension
3. Developmental expressive writing disorder: There is severe
impairment in such skills as spelling, grammar and
punctuation skills, and poor paragraph organization.
Language Disorders
This includes four subcategories
1. Developmental articulation disorder (phonological
disorder) involves errors in sound production,
substitution of one sound for another (e.g. use of sound
t for target k sound) or omission of final
consonants
2. Stuttering or stammering
3. Developmental expressive language disorder includes
limited vocabulary, delayed speech development and
idiosyncratic word ordering.
4. Developmental receptive (mixed receptive-expressive)
disorder inadequate development of the ability to
comprehend language
Motor Skill Disorders
It includes the developmental coordination disorder. Child
has significantly impaired coordination which interferes
with daily living activities
Management Strategies
Factors which have been implicated include:

Perinatal trauma or neonatal trauma
Low birth weight
Maternal smoking and alcohol consumption during
pregnancy
Elevated lead levels (50% of children with elevated
lead levels have a reading disorder), etc.
In addition, genetic factors have also been implicated,
as a high familial incidence of specific developmental
disorders has been reported.
The management strategies include education of the child

and the family regarding the exact nature of the disorder
after a detailed assessment has been done. The child must
be encouraged to follow the treatment plan. Punishment
of the child for mistakes has to be avoided. The child is
placed in a structured program of tasks, which are graded
on a continuum of increasing difficulty. Behavioral
principles of operant conditioning are used to mould
behaviour (Levine, 1996).
Clinical Description
ANXIETY DISORDERS
Three main categories are recognized each of which further

subsume other categories.
Anxiety fearfulness, and worrying are regularly

experienced as a part of normal development. When they
Child Psychiatry
become disabling to the point that they negatively affect
social interactions and development, they are pathologic
and warrant intervention. Separation anxiety disorder,
overanxious (generalized anxiety) disorder, obsessivecompulsive disorder, phobias and post-traumatic stress
disorder are all defined by occurrence of either diffuse or
specific anxiety related to predictable situations. Of these
the former two are more specific in their onset at any age.
The prevalence of anxiety disorders has been reported to
be 6.8 percent. About one-third of these children were
overanxious, and another third had specific fears or
phobias. .
Separation Anxiety Disorder
The main characteristic of a child with separation anxiety
disorder is excessive anxiety (beyond expectation for
developmental level) concerning separation from home
or a primary attachment figure. The antecedents of
developmentally normal anxiety initially presents at 7 to
8 months of age. As infants begin to differentiate from
their primary caregivers, they often develop variances and
mood changes that previously did not exist in the presence
of strangers. This stranger reaction is to be differentiated
from stranger anxiety, which is a more intense discomfort.
Although stranger reaction is physically seen in normal
development, stranger anxiety often heralds later
problems related to separation.
The prevalence of this disorder has been estimated to
be between 3.5 and 4.1 percent. Sex ratio figures seem to
show female predominance of 3 to 1.
Etiology
Mothers of children with separation anxiety disorder very
commonly have a history of psychiatric illness, especially
an anxiety or a depressive disorder. It is suspected that
separation anxiety disorder is an early form or a prodromal
indicator of depression.
Clinical Features
Children with separation anxiety disorder show intense
anxiety, to the point of panic, when they are separated
from their primary caretaker. They can have difficulties
playing outside of home, staying with babysitters, going
to school, or even being alone in a part of their home.
Physical symptoms (e.g. headache, pain abdomen, etc)
can occur when separation is about to occur (e.g. when
going to school) or does occur. Indeed, school refusal may
1221
be a presenting symptom. Sleep disruption can occur with

the child requiring someone to stay with them till they fall
asleep. They may also refuse to sleep alone. Children can
worry about getting lost and never being reunited with
parents. Fears about harm to the family may become
exaggerated (e.g. fears of kidnappers/monsters coming
into house).
Treatment
The role of pharmacotherapy in the treatment of separation
anxiety disorder is not clear. Even the non-pharmacological treatments are only in their infancy. Both
individual therapies like cognitive behavioural therapy
and family therapy are being tried.
No prospective studies to answer the question of what
happens to patients with separation anxiety disorder have
been conducted. However, retrospective research on adults
has indicated that separation anxiety disorder was
frequent in childhood of adults with panic disorder,
agoraphobia and depression.
Overanxious Disorder
Children who suffer from this disorder have unrealistic
worries about future events, the appropriateness of past
behaviour, and concerns about competence. They
frequently present with somatic complaints (e.g. sweating,
palpitation, chest pain, difficulty in breathing, nausea,
etc) are markedly self-conscious, need large amounts of
reassurance, and have trouble relaxing. These children
may be managed with self-control measures like relaxation
techniques and biofeedback.
Phobias
Children with phobias are anxious only under specific
conditions. They try to avoid specific objects or situations
that automatically lead to anxiety (e.g. animals, closed or
open spaces, heights, etc.). School phobias are commonly
seen in children; in this the child develops irrational fear
to some aspects of school situations. The child is not able
to attend school in spite of deep interest in studies. Though
anxiety is prominent some children also have depressive
feelings. Other complaints may be abdominal pain,
vomiting, anorexia, headache and giddiness. The
symptoms are usually intense or present during the school-
1222
going hours. Generally the cause of school phobia is

disturbed family relationships.
The first step in treatment is to help the child to attend
school. Behavioural techniques (like graded exposure) are
very effective in the management of school phobias. Parents
should be given insight into the mechanism involved.
Drugs may be considered when anxiety and depression
are severe.
Somatoform Disorder
Somatoform disorder or conversion disorder is the most
common disorder seen in our child psychiatric clinics. It
is the disturbance of voluntary motor or sensory system.
Often the symptoms are means to get primary and
secondary gains. These patients commonly seek first
consultation with the pediatrician as the symptoms are
primarily physical, viz, seizures, aches and pains,
hyperventilation, vomiting and paralysis. The symptoms
are variable, fluctuating and usually do not follow any
organic pathway. It occurs in both males and females,
generally above the age of eight years.
A variety of methods have been recommended for
symptom removal. They include such interventions as
reassurance, suggestions, behavioural modification
(operant conditioning and aversive therapy), hypnosis,
use of placebo, and use of sedatives. Parent counseling is
very important to decrease parents anxiety and to modify
their reinforcing behaviour. A simple ABC (antecedent,
behaviour, consequence) chart may be maintained by the
parents to understand the cause of the symptoms.
Obsessive-compulsive Disorder
Many children present with repetitive thoughts
(obsessions) that invade consciousness or repetitive rituals
or movements (compulsions) that do not obviously
contribute to a high level of adaptation in any given
situation. Obsessions have been defined as intrusive
thoughts, fears or images which become imposed on the
conscious mind repeatedly and which cause anxiety.
Typically, the thoughts or fears are perceived as senseless
and the individual tries to resist them but is unsuccessful.
Obsessions are concerned with fears of contamination with
bodily secretions and wastes or fear that something
calamitous might happen. The most common compulsions
are hand-washing, continuous checking of locks and
repeated touching. This condition is treated with
specialized behavioural techniques (e.g. thought stopping,
systemic desensitization or exposure with response

prevention). The role of drug treatment with serotonin
specific reuptake inhibitors (e.g. fluoxetine) remains to be
established for children with OCD.
Post-traumatic Stress Disorder (PTSD)
PTSD characterized by recurrent and intrusive
recollections and dreams of noxious events in addition to
intermittently intense psychological and physiological
distress in situations that symbolize the original trauma.
The noxious event is usually a near death experience in
relation to self or another in their close proximity. A variety
of treatments including pharmacotherapy (clonidine,
imipramine, propranolol, etc) and psychotherapy
(individual or group) have been found to be useful.
MOOD DISORDERS
Mood disorders have been traditionally considered to be
conditions of adulthood. This view has undergone a
change recently.
Major Depression
The concept of the existence of depression in children has
been controversial. Many have argued that because
depression has a component replete with feelings of
hopelessness and helplessness about future, an
individual can become depressed only after achieving the
ability to string together hypothetical thoughts about
future. But research has clearly shown the presence of
mood disturbance, anhedonia, and vegetative symptoms
in prepubertal children.
The prevalence of depressive disorders in childhood
has been estimated to be 0.15 to 2.0 percent. This is less
than the prevalence in childhood. Girls report significantly
more depressive symptoms than boys.
Clinical Features
Depressive symptoms vary according to the age and
developmental level. Spitz described the anaclitic
depression of infancy. Separation from a primary caregiver
after 6 to 7 months of age leads to a sequence of behaviours.
The first phase of this sequence is labeled as protest
(crying, searching, hypermotility of arms and legs, etc).
This is followed by the infants close strutiny of each
approaching adult, looking for the caregiver. The final
phase involves apathy in which infant becomes apathetic
Child Psychiatry
and hypotonic, exhibiting and obviously sad facial
expression.
Depressed school aged children present with sad
facial expressions, easy tears, irritability, social withdrawal, vegetative symptoms, anxiety and behavioural
disturbances. Delusions are uncommon in depressed
prepubertal children.
Treatment
Pharmacological approaches include antidepressants of
various classes, the tricyclic antidepressants, (e.g.
imipramine, amitriptyline etc) or serotonin reuptake
inhibitors (e.g. fluoxetine, sertraline etc.) Nonpharmacological treatment includes individual psychotherapy
and cognitive behavior therapies.
About 40 percent of children who have a depressive
episode will have another episode within 2 years of the
first. As many as 20 percent develop into a bipolar disorder
over the course of 3 to 4 years following the initial
depressive episode.
Bipolar Disorder
Bipolar illness is defined as either alternating depression
and mania or as mania alone. Manic episodes are
characterized by excessive activity, euphoria and elation
of mood, increased attempts to socialize with peers,
excessive speech which is full of boastful or grandiose
content, excessive spending and sexually inappropriate
behaviour like masturbating in front of others. The illness
typically presents in the second and the third decade of
life. However, there are descriptions of cases beginning
before puberty.
Though essentially the features of bipolar disorder of
childhood resembles that of adults, manic episodes in
childhood are found to have the following distinct features.
Associated medical or neurological problems were
common.
Dysphasia (an unpleasant mood) was found as
frequently as elevated mood in mania.
Convincing entrenched delusions were rarely seen in
prepubertal children.
The earlier the onset of bipolar symptoms, the more
susceptible the patient is to suicide later, increases in
frequency of episodes, and rapid cycling. Treatment is
mainly pharmacological, with good response reported to
1223
lithium for both acute mania and also prophylactic

treatment of bipolar disorder. Experience with other mood
stabilizing drugs like carbamazepine has just started
building up.
CHILDHOOD ONSET SCHIZOPHRENIA
Schizophrenia with childhood onset refers to the
development of mood-incongruent delusions,
hallucinations, disorganized speech plus a deterioration
in functioning (in academic performance, peer
relationships etc) under 15 years of age. It is an uncommon
disorder and prepubertal onset is particularly rare.
Epidemiological data regarding childhood onset
schizophrenia is lacking.
The current concepts followed in both the major
classifications, i.e. ICD-10 and DSM IV, prescribe the same
diagnostic criteria for schizophrenia regardless of the age
of onset-childhood, adolescence or adulthood. Management guidelines too are as for schizophrenia of adult onset.
This involves long-term treatment with antifluoperazine
or clozapine. However, therapy not only involves
medication but also individual, family, and educational
approaches.
The meager outcome data suggests that roughly onethird of the subjects with childhood onset schizophrenia
received a diagnosis of affective disorder over a follow-up
period of 4 to 5 years. This suggests that affective disorder
of childhood is often initially misdiagnosed as
schizophrenia.
DEVELOPMENTAL DISORDERS
Rumination Disorder
The hallmark of this disorder is a weight loss or failure to
gain at the expected level because of repeated regurgitation
of food without nausea or associated gastrointestinal
illness. This rare condition occurs more commonly in
males and usually appears between 3 and 14 months of
age. It is potentially fatal in up to one fourth of affected
children. Behavioural treatment is directed towards
positively reinforcing correct eating behaviour and
negatively reinforcing rumination. Parent counseling and
family therapy are often necessary .
Pica
This disorder involves repeated or chronic ingestion of
non-nutrient substances, which may include plaster,
1224
charcoal, day, wool, ashes, paint, and earth. The age of

onset is usually 1 to 2 years. Although tasting or mouthing
of objects is normal in infants and toddlers, pica after the
second year of life needs investigation. Psychological
theories of pica have found evidence for mental
retardation, high frequency of maternal and paternal
deprivation, family disorganization, poor supervision and
low socioeconomic status.
Nutritional theories of commonly postulate that the
deficiencies of such substances as iron and zinc produce
craving for substances like ice or dirt. These theories do
not have much support.
Children with pica are at increased risk for lead
poisoning and parasitic infestations. Pica can be treated
with a combination of education and guidance, family
counseling, and behaviour modification.
Enuresis
The word enuresis is derived from the Greek enourein
which means to void urine. In medical terminology, the
term has evolved into a clinical diagnosis that is usually
taken to mean the inadvertent voiding of urine during
sleep.
The prevalence at age 5 years is 7 percent for males
and 3 percent for females. At age 10 years it is 3 percent for
males and 2 percent for females, and at age 18 years it is
1 percent for males and extremely rare for females. General
population studies carried out in India show that 2.5
percent in the age group of 0 to 10 years have enuresis (Lal
and Sethi, 1977).
Etiology
Enuresis has been classified into persistent (primary) type
and regressive (secondary type). In primary enuresis, the
child has never been dry at night. About 75 percent belong
to this category and is probably the result of inadequate or
inappropriate toilet training (e.g. excessively primitive
parents).
The regressive type is often precipitated by stressful
environmental events, such as a move to a new home,
marital conflict in parent, birth of a sibling, or death of a
family member. Bed wetting in this case is transitory and
prognosis is better.
Clinical Features
Enuresis is the in voluntary voiding of urine not
occasioned by a physical condition. The severity is
determined by frequency of urination, quantity is not a
diagnostic consideration. The child should have a mental

age of at least 4 (ICD-IO) or 5 years (DSM-IV).
While a majority of patients have nocturnal bed
wetting, a diurnal (but during sleep) variety and a
combined variety have also been described.
Treatment
Management depends on understanding of possible
specific causative factors and appropriate measures to
tackle any stressors. Often, in addition, the following
general instructions are helpful:
Reward the child for dry night.
Once bed wetting occurs, older children should be
asked to wash their own clothes and soiled bed sheets.
Children should not be given any fluids after dinner.
Waking the child 1 to 2 hours after sleep to void urine
again may help.
Punishment and humiliation by parents or siblings
should be discouraged.
Behavioural techniques may also be used. Often a bell
and pad instrument, based on principles of classical
(Pavlovian) conditioning, is used with up to 75 percent
success rate.
Pharmacological agents tried in the condition include
imipramine, or amitriptyline orally. Desmopressin acetate
(DDAVP) nasal spray is used in some centers. The effect
of medication is, however, temporary only.
Encopresis
Encopresis refers to passage of feces into inappropriate
places at any age when bowl control should have been
established. Encopresis indicates a more serious emotional
disturbance than enuresis and is less common (around
1% of school age children). Management is primarily with
behavioural techniques.
Sleep Disorders
A substantial portion of children have struggle around
bed time (insomnia). Many use a special toy or a night
help them fall asleep. Infants who show difficulty in
establishing regular night time sleep patterns may also
show general fussiness and irritability as a temperamental
characteristic. Sleep difficulty may be a reflection of
parental strife or underlying anxiety disorder such as
separation anxiety disorder.
Child Psychiatry
Different types of parasomnias have also been described.
Narcolepsy is characterized by frequent daytime naps,
cataplexy, sleep paralysis, and/or hypnagogic
hallucinations. Polysomnographic studies, showing
early onset of REM sleep following sleep onset, are
required for definite diagnosis. Stimulants have been
used for daytime naps and antidepressants for
cataplexy.
Nightmares are common phenomena occurring in the
REM (rapid eye movement) phase of sleep. These occur
more often in girls with affective or anxiety disorders.
Night terrors occur in the stage 4' of non REM sleep.
The child usually wakes with a scream, is confused,
shows signs of intense autonomic activity (labored
breathing, dilated pupils, sweating, tachypnea or
tachycardia) and appears frightened. The patient often
does not recall the incident on waking up the next
morning. They may be related to a specific developmental conflict or to a precipitating event.
Sleep walking or somnambulism occurs in stages 3 or
4 non REM sleep. There may be an associated history
of enuresis or family history of sleep walking. It is
usually benign but temporal lobe epilepsy should be
ruled out.
HABIT DISORDERS
Habit disorders include tension-discharging phenomena
such as head banging, body rocking, thumb sucking, nail
biting, teeth grinding (bruxism) and tics.
Rhythmic head banging or rocking in early life can persist
without parental reinforcement, occurring when the child
is alone. These movements seem to provide a kind of
sensory solace for the child who is otherwise uncared for
or understimulated by human touch or interaction. Such
patterns are often seen in mentally retarded or child
suffering from maternal or emotional deprivation.
Teeth grinding or bruxism results from tension
originating in unexpressed anger or resentment. It may
crate problems in dental occlusion. Helping the child to
find ways to express resentment may relieve the problem.
Thumbsucking is normal in early infancy. It makes the
older child appear immature and may interfere with
normal alignment of teeth. Like any other rhythmic
patterns, it can be seen as a way of securing extra selfnurturance. Parents should ignore the symptom if possible,
while giving attention to more positive aspects of the
childs behaviour. The child who actively tries to restrain
1225
thumbsucking should be given praise and encouragement.

Tics involve repetitive movement of muscle groups that
have no apparent useful function and represent
discharges of tension originating in emotional and
physical states. Parts of the body most frequently involved
are muscles of face, neck, shoulders, trunk and hands.
Examples of tics include lip smacking and grimacing,
tongue thrusting, eye blinking, throat clearing, and so on.
They are not accompanied by any loss of consciousness.
They are not seen during sleep and can be controlled
voluntarily for short periods of time. This differentiates it
from involuntary movements, e.g. dyskinesia.
Gilles de la Tourette syndrome is a special type of tic
disorder characterized by multiple motor tics, compulsive
barking, grunting or shouting obscene words. Children
with Gilles de la Tourete syndrome often suffer from
secondary behavioural, emotional and academic
problems. Many environmental precipitants have been
noted to serve as emotional stesors, which also precipitate
or worsen tics and Gilles de la Tourettes syndrome.
Mainstay of pharmacotherapy of this condition is
dopamine antagonists, e.g. haloperidol or pimozide.
Clonidine, carbamazepine and clonazepam have also been
tried. The disorder usually persists throughout life, but
studies have shown a diminution in symptoms in half to
two-third of cases 10-15 years after the initial evaluation.
GENERAL PRINCIPLES IN THE TREATMENT OF CHILD
Pharmacotherapy
Certain elements of standard pharmacological treatment
as development in adults require modification when
treating disorders in the context of the developing body
and brain. The potential for long term adverse effects of
psychotropic drugs on the development of the brain and
the body is of critical concern. Indeed, there are at least
two instances of age-related effects of drugs on biological
development-the slowing of body growth by psychostimulants (like methylphenidate) and the hepato-toxicity
induced by valproate.
Because of these fears, the clinician will need to
carefully consider if pharmacological treatments are
required at all.
Compared to adults there are some pharmacokinetc
differences as well. Specifically, the rate of hepatic
metabolism and the glomerular filtration rate are both
higher than that seen in adults. A combination of these
1226
two factors leads to shorter drug half-life than in adults.

This in turn means that clinical duration of most drug
effects would be briefer in children requiring the
administration of doses at more frequent intervals than in
an adult. Faster clearance would also imply that blood
levels drawn for therapeutic drug monitoring should be
sampled earlier than in adults, e.g. lithium samples may
need be taken earlier than in adults. Also due to the faster
rate of hepatic metabolism, the children actually need a
greater dose of drug per kg per day. A partial list of the
commonly used pharmacological agents and their adverse
effects is given in Table 25.1.1.
Psychological Interventions
Psychological interventions for childhood psychiatric
disorders have become more efficacious than pharmacological agents for several disorders with the possible
exception of psychoses. Psychological intervention takes
place through the relationship between the therapist and
patient and/or his or her family, occurring both at verbal
and nonverbal level. The kind of therapy to be used in a
particular case is determined not only by the diagnosis
but also by the age and the competencies of the child.
Parental Counselling
Individual or group counseling sessions can tackle several
issues. The first of these is to inform the parents about the
nature of the problem. The misconceptions, common in
the rural regions of India and the attitudes and
expectations, which parents tend to have about the
capacity of medicines in providing a miraculous cure for
the child, slow down the pace of acceptance of the problem.
At this stage, parents need accurate information about the
nature of the childs problem, its casual factors, and the
management issues. They also require reassurance and
support in accepting the problem realistically. The
counselor must pace the information and help at the rate
at which the parents are able to receive it.
The parent must be led to an understanding of the
importance and the benefits of the treatment, and may
need to be persuaded to participate in it actively. Engaging
the parents motivation is a problem often encountered
even in the West. Low motivation, non-acceptance of the
problem, low priority given to the problem, etc. are factors
that lead to a high drop-out rate. Parental counseling in
dealing with problems that interfere in the parents
handling of a psychologically disturbed child, are thus
the cornerstone of successful therapy.
Play Therapy
Play is very essential for the process of development of a
child. Through play, children develop their intellectual,
emotional, perceptual, motor and social skills. The
therapeutic usefulness of play lies in the fact that it is a
natural mode of childs self-expression. It also helps in
the establishment of rapport since it is interesting,
enjoyable and provides for a natural relationship. The
therapist observes the content of childs playas well as
the manner in which the child plays. Simultaneously,
active attempts are made to elicit accompanying fantasies
and emotions. Among the typical themes to look for are
the childs perception of self and others (e.g. the parents).
The therapist may then use the derived material for making
some suggestions to the child through play and thereby
alleviate the distress or ameliorate the symptoms.
Psychoanalysis and Psychodynamically
Oriented Therapies
Initiated by Freud, the techniques of psychoanalysis (e.g.
free association) have been used extensively in the
management of neurotic conditions in the adults. The same
techniques have been applied on children. The two
necessary preconditions for therapy are (i) the child must
have a minimum capacity for comprehension of language,
and (ii) the child should be capable of verbalization. This
is usually possible for children who are older than two
and half years old.
Psychodynamically oriented therapies use the
principles of psychodynamics but do not employ the
psychoanalytic techniques. These therapies unlike
psychoanalysis are of shorter duration and as such are
much more suitable for the Indian settings, where
economic constraints preclude repeated and prolonged
contact with the therapist.
Behaviour Therapy
In behavioural therapy, it is assumed that childrens
problem behaviours are largely learned according to
systematic laws of learning in the course of the childs
experiences within his or her environment. The two
commonly invoked laws of learning are:
Classical condition of Pavlov (who showed that a dog
can be made to salivate when a sound/light appeared,
if it was regularly paired with food stimulus in the
past).
Child Psychiatry
1227
TABLE 25.1.1: Psychopharmacology

Medication class
Indications
Dosage
Side effects/ Toxicity/cautions
Antipsychosis
Low potency
Thioridazine
Chlorphromazine
Mid potency
Mesoridazine
All classes
Severe agitation
Childhood and Adolescent
schizophrenia
Mania, stereotypic symptoms of pervasive developmental disorder and autism;
self-abuse, extreme aggressiveness
Low potency
30-150 mg/24 hr individed doses;
available in concentrated form
All classes
Sedation, weight gam, anticholinergic effects (dry mouth, blurred
vision, constipation) hypersensitive
reaction (hepatic, skin); blood
dyscrasias, parkinsonism
High-potency
Trifluoperazine
Thiothixene
Haloperidol
High-potency class
High-potency
Gilles de la Tourette syndrome; other tic 1-6 mg/24 hr in
disorders (haloperidol)
dovoded doses
Mid-potency
10-75 mg/24 hr in
divided doses
Long-term effects
Risk of tardive
dyskinesia
Stimulants (6 yr and older)

Methylphenidate
Attention deficit disorder
Dextroamphetamine Attention deficit disorder
Pemoline
Attention deficit disorder
0.3-1.0 mg/kg/24 hr
0.2-0.5 mg/kg/24 hr
37.5-112.5 mg/kg/24 hr
Insomnia, decreased appetite,

possible weight loss; irritability and
tearfulness; abdominal pain,
headache, elevated systolic blood
pressure; development and
worsening of tics. A long-term
effect may be height and weight
reduction. Pemoline is associated
with hypersensitivity reactions,
especially hepatic
Antidepressants
Desipramine
Major depressive disorder.
Separation anxiety, attention deficit
disorder unresponsive to stimulants
(12 yrs and above)
Fluoxetine
Mild depression anxiety
For major depressive disorder and

separation anxiety, 2-3 mg/kg/24 hr in
divided doses (blood levels;
therapeutic, 100-250 mg/ml) and
10-30 mg/24 hr
ECG and blood pressure should be

monitored for hypertension,
orthostatic hypotension, cardiac
arrhythmia, or lengthening of PR or
QRS interval. Monitor plasma levels
for therapeutic range. Agitation,
headaches, anxiety, insomnia,
weight loss, binds tenaciously to
proteins and has a long half-life.
Mania, some cases of unipolar illness,

extreme aggression
600-1200 mg/24 hr (blood levels,

therapeutic 0.6-1.2 mEq/I)
Mania, aggression, self-injurious

behaviour in organically impaired
patients
400-1000 mg/24 hr blood levels;

therapeutic 8-12 ug/ml)
Gastrointestinal disturbance,
tremor, ataxia, confusion, coma,
death; hypothyroidism
Fever, sore throat, hematological
problems, dizziness, drowsiness,
neuromuscular distrurbance
Mood stabilizers
Lithium carbonate
Carbamazepine
Antihypertensives
Clonidine
ADHD not responding to stimulants
ADHD with aggression
0.1-0.25 mg/24hr
Operant/instrumental conditioning which assumes

that behaviours are enhanced or occur at greater
frequency due to reinforcements (e.g .praise, reward
or fear of criticism if a desired behaviour is not
performed) and that behaviours can be reduced in
intensity or frequency by using punishment (e.g. being
reprimanded for being naughty).
Bradycardia, hypotension
It is argued that if behaviors are learned, they can be

unlearned or otherwise modified, according to the same
laws of learning. Treatment involves the child and family
actively. This includes direct practice of new behaviour,
home-based learning programmes for child and parents,
active programmes of rewards for improvements, record
keeping by child and family and so on.
1228
Cognitive Behavioural Therapy (CBT)

Cognitive behavioural therapy deals with cognitive
(thought) function and cognitive distortions (errors) in
the child that interferes with optimal functioning. The
patients deficits and distortions are addressed with
several cognitive problem-solving processes such as
generalizing alternative solutions. The basic principles
underlying CBT are that (i) most human learning is
cognitively mediated, and (ii) thoughts, feelings, and
behaviours are casually interrelated. The emphasis of CBT
is on how children may utilize a variety of thinking
processes to mediate their behaviour. Therapists usually
play an active role and model the cognitive processes by
making verbal self-statements first to teach those principles
to the child.
Cognitive behavioural interventions have proved
useful in children who have attention deficit/hyper
activity disorder (ADHD) and have been used for
behaviour-disordered children provided that parents and

children are able to cooperate with the treatment. Selfmanagement training programmes for autistic and
retarded children have been reported to benefit school
refusal, phobias, encopresis, and enuresis. Long-term
effects remain to be assessed.
Family Therapy
In the 1950s, John Bowlby noted that problems presented
by the child often reflected the tension between the
members of the family. Family therapy is based on the
assumption that problem behaviour in a child is merely
an expression of a more deep-rooted pathology involving
the entire family.
Family therapy is a process of understanding why the
child has a symptom in a particular family context, what
triggers off and maintains the symptoms in that system, and
how to change it by engaging the whole family (Table 25.1.2).
TABLE 25.1.2: Management strategies for selected childhood psychiatric problems

S.No. Clinical conditions
Pharmacoloical agents
Psycholoical intervention
Haloperidol
Phenothiazines
Bensodiazepines
Special education
Behavior modification using operant conditioning
Social skills training
Family education and therapy
Self control training
Behaviour modification using
Operant conditioning
Remedial education
1.
Autism
2.
Attention deficit disorders Methyl phenidate

Pemoline
Amphetamines
Imipramine/Fluoxetine
Haloperidol
Buspirone
Conduct disorders
Antipsychotics
Carbamazepine
Lithium carbonate
Anxiety disorder
Propranolol
Imipramine
Biofeedback
Depression
Tricyclic
Antidepressants
Serotonin specific reuptake inhibitors
Monoamine oxidase inhibitors
Schizophrenia
Antipsychotics
Haloperidol
Phenothiazines
Enuresis
Imipramine
Gille De La Tourette
Haloperidol
Syndrome
Clonidine
3.
4.
5.
6.
7.
8.
Behaviour therapy using operant conditioning
Benzodiazepines
Relaxation techniques
Cognitive therapy
Education of the family

Special education under individualized conditions
Behaviour modification using classical conditioning (Bell and Pad)
Supportive psychotherapy to enhance self image
Social skills training
Modified from Naik US. Treatment of childhood psychiatric disorder. In Malhotra S. Malhotra A, Varma VK (Eds) : Child Mental Health in India.
MacMillan: New Delhi, 1992.
Child Psychiatry
4.
Group Therapy
This is a treatment in which carefully selected emotionally
ill persons are placed into a group guided by a trained
therapist to help one another effect personality change.
Two of the main strengths of group therapy, when
compared with individual therapies are:
The opportunity for immediate feedback from the
patients peers, and
The opportunity for both the patient and the therapist
to observe the patients psychological, emotional and
behavioural responses to a variety of persons.
In summary, several pharmacologic agents and
psychotherapeutic techniques are employed currently in
the management of the various child psychiatric disorders.
These have been instrumental in improving the living
conditions of the unfortunate children and their families.
Table 25.1.2. shows the pharmacologic and psychological
interventions employed in selected psychiatric disorders
of childhood.
BIBLIOGRAPHY
1. Alsaker FD, Annotation - the impact of puberty: Journal
of Child Psychology and Psychiatry, 1996; 37; 249-58.
2. Bailey, A., Philips W, Rutter M. Autism. Towards an
integration of clinical, genetic, neuropsychological and
neurobiological perspectives. Journal of Child Psychology
and Psychiatry 1996; 37; 89-126.
3. Cantwell DP. Classification of Child Psychology and
Psychiatry 1996; 37. 3-12.
1229
Fagerstrom KO. Measuring degree of physical

dependence to tobacco smoking with reference to
individualization of treatment. Addict Behav. 1978; (3-4):
235-241.
5. Indian Council of Medical Research. Report of the task

force project Multicentre study child and adolescent
disorders. ICMR, New Delhi, 2001.
6. Kapur M. Mental Health of Indian Children. Sage
Publications: New Delhi 1995.
7.
Kelly D, Aylward G. Attention deficits in school aged

children and adolescents - current issues and practice.
Pediatric Clin. North Am. 1992: 39:487-511.
8. Levine MD. Neurodevelopmental dysfunction in the

school-aged child. In Behrman RE, Kliegman RM. Arvin
AM (Eds). Textbook of Pediatrics. Prism Publications:
Bangalore 1996: 100-107.
9. Mehta M. Child Mental Disorders in Rural Sch Children.
Project sponsored by ICMR, 1990.
10. Mehta M, Pandav CS, Pande P. Mental Health Problems
in rural primary children. Indian 1. Social Psychiatry 1991:
7; 32-39.
11. Peterson BS. Neuroimaging a child and adolescent
neuropsychiatric disorders. Journal of American
Academy of Child and Adolescent Psychiatry 1995: 34:
1560-75.
12. RAS in substance use disorder manual for physicians.
Edited Lal Rakesh. 2004.
13. Verma VK Child psychiatry as an academic super
specialty in India: Relevance and feasibility: In Malhotra
S., Malhotra A., Verma V (Eds): Child Mental Health in
India, MacMillan: Delhi 1992: 15-26.
25.2 Child Guidance Clinic (CGC)

T Ravikumar
The American Academy of Pediatrics (AAP) defines the
domain of the Pediatrician as including both physical
and psychosocial aspects of growth, development and
health of the individual. This commitment begins prior to
birth when conception is apparent and continues
throughout infancy, childhood and early adulthood by
which time growth and developmental processes are
generally completed.
Concept and Definition
For a child to be balanced physically, mentally and
intellectually, we need to address ourselves to the childs
physical and psychological development and to the

environment to which he is exposed at home, at school
and in the neighborhood. All this is possible only through
repeated interactions and counseling of the child and
family by a team of specialists, which should include
the pediatrician, a neuropsychologist, a behavioral
therapist, a speech therapist and special tutors trained
towards dealing with children who have mental
retardation, learning disabilities and behavioral
problems. This is the basic philosophy of the Child
Guidance Clinic.
1230
Objectives
Faculty
The objectives the Child Guidance Clinic are:

1. Providing help for children with behavioral problems
(like pica perverted appetite/taste for non-edible
things), bed wetting (nocturnal enuresis), sleep
walking (somnambulism), breath holding spells,
temper tantrums, habits (thumb sucking, nail biting,
head banging, etc.), teeth grinding (bruxism),
stammering, tics (habit spasms or mannerisms),
autism, drug abuse and school phobia (school refusal,
school withdrawal or school absenteeism) including:
i. Interviewing and interacting with child and
parents.
ii. Give appropriate advice and counseling to both
child and parents.
iii. Behavior modification therapy (wherever
appropriate).
2. Providing care and guidance for children with mental
retardation, including:
i. Offering counseling to the parents about the exact
nature of mental subnormality in their wards.
ii. Providing supportive medical and physical
rehabilitation services.
iii. Advise regarding placement in appropriate
schools/vocational training centers.
iv. Forming peer support groups.
3. Providing care for children with learning difficulties,
which includes:
i. Early identification of cause and type of learning
difficulty in the child.
ii. Complete physical (including vision and hearing
evaluation wherever needed), developmental and
neuropsychological assessment.
iii. Personal interview of the concerned family
members to identify any environmental/family
factor affecting the child and advise regarding
modification of the same.
iv. Individual remedial training to correct the specific learning disability.
v. Counseling the parents and referring the children
to special schools for training/education (when
needed).
4. Providing counseling, guidance and information to
parents regarding care and bringing up of their
children (including normal children).
1.
2.
3.
4.
5.
6.
7.
8.
9.
Pediatrician
Pediatric Psychiatrist
Clinical Neuropsychologist
Pediatric Neurologist
Speech Pathologist and Audiologist
Pediatric Ophthalmologist
Clinical Geneticist
Occupational and Physical Therapist
Special Educators
Activities
A team approach specific to the problems delineated in
the objectives will define the appropriate activities of a
Child Guidance Clinic. Good follow-up, continuous
monitoring and counseling and need based assistance
are the basic approaches in a CGC. Active co-operation of
the involved parents and other care-givers of the child
(such as teachers, etc.) and the constant guidance and
help from the CGC team members are mandatory for the
successful functioning of the Child Guidance Clinic.
ACKNOWLEDGEMENT
The help rendered by Dr A Andal (Consultant Pediatrician, Chennai) in the preparation of this manuscript is
gratefully acknowledged.
BIBLIOGRAPHY
1. Blumsack J, Lewandowski L, Waterman B. Neurodevelopmental precursors to learning disabilities: A preliminary report from a parent survey. Journal of Learning
Disabilities 1997;30(2):22837.
2.
Dyson LL. The experiences of families of children with

learning disabilities; parental stress, family functioning
and sibling self-concept. Journal of Learning Disabilities
1996;29(3):28086.
3. Lyon GR. Learning disabilities. The future of children

special education for students with disabilities.
1996;6(1):5476.
4. Philips EL, Kollins S, Edgerly D. Behavioural assessment
of children and adolescents. Indian Journal of Pediatrics
1999;66:38999.
5. Pratt HD, ODonnell D, Orfuss MF. Disorders of cognition, attention and learning. Indian Journal of Pediatrics
1999;66:40114.
6.
Spreen O. Prognosis of learning disability. Journal of

Consulting and Clinical Psychology 1998;56(6):6673.
26.1 Common Pediatric Surgical Problems: Subhash J Dalal, Ketan Praveen Parikh, Amrish Vaidya ............................................... 1232
1232
26.1 Common Pediatric

Surgical Problems
Subhash J Dalal, Ketan Praveen Parikh, Amrish Vaidya
SURGERY IN THE NEWBORN
INTESTINAL OBSTRUCTION IN NEWBORNS
Intestinal obstruction is the failure of aboral progression
of intestinal contents. In case the progression is due to
absence of peristalsis in a segment or whole of bowel the
obstruction is of an adynamic nature and in case it is due
to a physical occlusion of a portion of bowel it is invariably
a dynamic form of obstruction. Pathologically, the cause
of a dynamic obstruction of the bowel may be either from
outside the wall of the bowel as in compression due to
bands etc; from within the wall e.g. atresia etc or even
from within the lumen like inspissated meconium etc.
Clinically, the presentation and the urgency of the
obstruction is dependent on the level of obstruction, the
severity of obstruction, the acuteness of the obstruction
and associated vascular compromise if any.
Obstructions higher in the intestinal tract will have an
early onset of vomiting and failure to tolerate feeds. The
vomitus may be bilous or nonbilous, depending on the
level of block in relation to the ampulla of Vater. Abdominal
distension may not be significant in these cases since most
of the intestine (distal to the obstruction) is empty. Even if
distension is present, it is confined to the upper abdomen,
usually due to a large stomach. Some normal coloured
meconium may be passed if the obstruction is of recent
onset or if the block in the intestines is proximal to the
ampulla of Vater (from where bile is secreted) in which
case the vomitus may be non-bilious. However, in case
the intestinal obstruction is distal to the ampulla the child
may still pass pale coloured meconium. Since the fetus
with a high intestinal obstruction is not able to retain the
swallowed amniotic fluid, antenatally these cases are
characterized by an excessive accumulation of amniotic
fluid (hydramnios).
Distally placed intestinal obstructions are characterized by abdominal distension. There is usually a failure
to pass meconium, and vomiting may be seen a little later,
and is invariably bilous. Bilous vomiting or a bilous
aspirate in a nasogastric tube in the newborn can be said
to be pathognomonic of intestinal obstruction. The
common causes of neonatal intestinal obstruction are as

follows:
Upper intestinal obstruction:
Duodenal atresia
Malrotation with midgut volvulus
Small intestinal obstruction:
Jejunal or ileal atresia
Meconium ileus
Large intestinal obstruction
Anorectal malformations
Meconium plug syndrome
Colonic atresias.
Intestinal Atresia
Introduction
Atresias are congenital blocks in the intestine due to a
complete or partial occlusion of the lumen.
The cause of atresia is either a failure of canalization
of the tubular intestine as it begins to develop a lumen
during the first trimester or later, after the intestine has
already formed possibly after an episode of vascular
insufficiency causes a part of the intestine to become
ischemic and be resorbed. The ends of the proximal and
distal loop then become sealed off to block the lumen.
Incidence
The incidence of duodenal atresia is more than ileal and
jejunal atresias. Colonic atresias are the least common.
Duodenal atresia is especially common in babies with
Downs syndrome, and there is a high association with
heart anomalies.
Clinical Features and Diagnosis
These are as already discussed dependant on the site of
atresia, i.e. whether the intestinal obstruction caused is
high, mid or low form.
With the increasing use of routine antenatal ultrasound, the atresia may be suspected antenatally, and the
baby may be investigated postnatally before the classical
symptoms and signs are seen.
Pediatric Surgery
1233
abdomen is entered, the atresia is identified, and a resection

of the atretic part of the intestine followed by anastomosis
of the proximal and distal ends is carried out. High atresias
lead to a significant loss of body fluids through vomiting
and a basic metabolic correction may be required preoperatively.
Prognosis
This should be fairly good in uncomplicated bowel
atresias which present early. If the presentation is late, the
birth weight and gestational age low, if sepsis has set in,
or if other anomalies are also present, then the prognosis
becomes poor. Occasionally, the atresia affects multiple
sections of the bowel or there is a large section of the bowel
which does not have a proper vascular supply (apple peel
atresia). This may necessitate removal of a large portion of
intestine and this or multiple anastomoses, may
compromise the overall prognosis.
Intestinal Malrotation
Introduction
Between the fourth and tenth weeks of intrauterine life,
the intestines protrude from the abdominal cavity into the
umbilical cord. When the intestines return into the
abdominal cavity, they arrange themselves through a
process of rotation through 270 degrees, into the normal
orientation. The salient features of the end result of rotation
are that the duodenum passes from right to left under the
superior mesenteric vessels; the transverse colon overlaps
the duodenum as it passes to the splenic flexure. The root
of the mesentery runs diagonally from left to right, from
above downwards.
Figures 26.1.1A and B: (A) Double bubble sign in duodenal
atresia, (B) Upper abdominal fluid levels in jejunal atresia
A plain X-ray of the abdomen is usually diagnostic. In

the case of duodenal atresia, the stomach and first part of
the duodenum are the only parts of the intestine filled
with gas, thus exhibiting the Double Bubble sign
(Fig. 26.1.1A). More distal atresias show bowel loops filled
with gas, with the appearance of air fluid levels, and a
gasless lower abdomen, representing the distal unfilled
intestine (Fig. 26.1.1B).
Treatment
Surgery should be done as soon as possible to restore the
intestinal lumen and allow early feeding. After the
If this process of rotation is incomplete, i.e. only 180

degrees of rotation take place, then malrotation is said to
have taken place. The clinical outcomes of the intestinal
malrotation are a result of the following anomalies
(Fig. 26.1.2).
1. The cecum lies just below the pylorus and adjacent to
the d.j.flexure thus significantly narrowing the root of
the mesentery; the ascending and transverse colon are
mobile and liable to be twisted in a clockwise direction
and this is called volvulus neo-natorum.
2. Abnormal peritoneal bands run from the rt. lateral
peritoneal wall to the cecum, over the third part of the
duodenum known as Ladds Bands. This can cause
external compression on the duodenum.
1234

bands are released and the root of the mesentery is
widened to prevent further episodes of volvulus.
Prognosis
When the operation can be done before gangrene sets in
the prognosis is excellent. When gangrene sets in, it can
involve a variable extent of bowel. In most cases, the whole
midgut is almost completely involved, with a poor
outcome.
Meconium Ileus
Introduction
Figure 26.1.2: Diagram showing pathological anatomy in

intestinal malrotation
In case of twisting of the intestine or volvulus, the blood

supply of the entire midgut can get compromised, and
can lead to gangrene of the midgut if not derotated early.
Clinical Features
An apparently normal child, who may have passed
normal meconium earlier, suddenly develops:
1. Bilous vomiting.
2. May have bleeding per rectum
3. Other signs of upper intestinal obstruction.
If volvulus neonatorum sets in with gangrene of the
midgut, there is a progressive deterioration in the
general condition with dehydration and later
septicemia.
This is the neonatal manifestation of mucoviscidosis. This

is a condition affecting the mucus secreting glands of the
body, causing excessive viscidity of the mucus secretion.
Glands that secrete mucus all over the body are affected.
Pathology
In meconium ileus, the mucus secreted in the intestine is
extremely sticky, like plasticine, and this leads to
adherence of this meconium to the intestinal mucosa. The
viscid mucus collects in the distal intestine and chokes
up the lumen of the intestine, not allowing any contents to
pass through.
Etiology
There is possibly a genetic basis for the disease, the mode
of inheritance being autosomal recessive. The disease is
rare in our country, but common in Western countries. In
recent years, the incidence is increasing in India also.
Diagnosis
Clinical Features
A plain X-ray of the abdomen shows a large stomach

bubble with few distal gas shadows. A barium meal will
show that the duodenum is oriented abnormally and lies
to the right of the midline, i.e. does not cross over to the left
side. Alternatively a Ba enema would show the entire colon
to the left of midline.
In recent years, USG with Doppler can identify the
superior mesenteric vascularity and ischemia if any.
The symptoms and signs are those of distal intestinal

obstruction. The baby may pass some white chalky
meconium. The viscid meconium is sometimes palpable
as a doughy, rubbery substance in the right lower
abdomen.
Treatment
After resuscitation as required, exploratory laparotomy is
done and Ladds procedure is performed. The Ladds
Diagnosis
A plain X-ray of the abdomen shows dilated bowel but no
fluid levels. A conray or gastrograffin enema shows
microcolon, which is basically a thin narrow segment of
distal bowel which is relatively unused due to the
congenital obstruction.
Pediatric Surgery
1235
Treatment
The conray or gastrograffin enema may itself be curative,
since the very high osmolarity of the dye causes dissolution
of the inspissated mucus. In cases that do not open up
after the use of conray, surgery will be required to relieve
the obstruction.
Hirschsprungs Disease
This is a common condition characterized by congenital
aganglionosis of a variable length of the colon extending
proximally from the anorectal junction.
Physiology
Normal peristaltic activity involves a wave of relaxation
preceding a wave of contraction, allowing a smooth
passage of the bowel contents downward. A normal
parasympathetic innervation is essential for the relaxation
wave to be propagated.
Pathological Anatomy
In Hirschsprungs disease, the parasympathetic ganglia
are absent from the Meissners plexus and the Auerbachs
plexus of the affected bowel. The propagation of normal
peristalsis is thus not possible. The aganglionic bowel is
normal in caliber but because of the absence of the
peristaltic activity, the wave of relaxation which precedes
the wave of contraction is absent thus leading to a
functional obstruction. The normally ganglionic proximal
bowel undergoes dilatation and hypertrophy.
Etiology
This is not exactly known. The disease runs in some
families thus a genetic basis for inheritance exists. Males
are four times more commonly affected than females.
Clinical Features
The presentation may be at birth or later. The main
symptom is constipation dating back to early infancy or a
delay in passage of the first meconium beyond 24 hours of
life. Rarely, attacks of foul smelling diarrhea interspersed
with constipation may confuse the picture. There may be
absolute constipation causing intestinal; obstruction,
which may be relieved by enemas. The abdominal
distension is usually marked and is due to the collection
of feces and flatus within the dilated and hypertrophied
proximal intestine. In chronic cases the child fails to thrive
and is malnourished.
Figure 26.1.3: Ba enema showing cone in

On abdominal examination, the transverse colon is

often visible. The findings on rectal examination may be
pathognomonic. The rectum is felt to be empty, and on
withdrawal of the examining finger, there is an explosive
passage of flatus and feces.
Diagnosis
A plain X-ray of the abdomen shows features of intestinal
obstruction.
Large dilated colon loops are seen. In newborns, the
pelvic region is frequently gasless due to the lower colon
being empty.
A barium enema will show a cone shaped colon at the
junction of the ganglionic and aganglionic segments
(Fig. 26.1.3).
Anorectal manometry is a test that measures the
contraction and relaxation of the internal sphincter in
response to rectal distension. This test can confirm the
diagnosis of Hirschsprungs disease, since in this
condition the internal sphincter does not relax in response
to rectal distension.
A full thickness biopsy of the rectal wall shows an
absence of ganglion cells in the rectal muscle wall, and is
the final confirmation of the diagnosis.
Treatment
Once proved, the treatment is surgical. The principle of
the surgery is the removal of the aganglionic segment of
colon and ensuring that normal ganglionic bowel is
1236
brought down to the anus. This is usually done in stages.

A preliminary colostomy is done. Subsequently the main
operation is performed. Various commonly performed
surgeries include the modified Duhamels procedure,
Swensons procedure and Soaves procedure. The
procedures may be performed laparoscopically. Once
healing is complete, the colostomy can be closed.
Meconium Plug Syndrome
In this form of intestinal obstruction, a thick plug of
meconium blocks the lower colon and causes signs and
symptoms of intestinal obstruction. The affected babies
are otherwise normal. On giving a rectal wash or a glycerin
syringe, the baby passes a white plug of variable length,
followed by a small length of light colored meconium.
Another wash may need to be given, following which a
normal pattern of defecation is seen. In most of these cases
the babies are asymptomatic subsequently.
Anorectal Anomalies
Introduction
The anorectal malformations are a group of anomalies
that affect the perineum in either the male or the female.
The incidence of these malformations is roughly 1 in 5000
live births. A common defect in all the anomalies is that
the anus does not open normally at the usual site. The
opening may be severely stenotic or may be entirely absent
(Fig. 26.1.4), in which case the rectum or anus ends as a
blind pouch. A blind ending rectum frequently has a
fistulous communication to the urinary tract which lies
Figure 26.1.4: Hypertrophied midline raphe in

imperforate anus
just anterior to the rectum. A further variant of the

malformation is the anal opening being present anterior
to the normal site, especially in the female, where it may
open in the vestibule or in the vagina.
The usual muscles of continence are present in the
normal positions in the pelvis and perineum. If the
abnormal rectum and anus do not pass through these
muscles, there may be problems related to continence either
before or after operation for the correction of these defects.
Classification
The basic classification centers around the main muscle
of continence, namely the levator ani, through which the
rectum passes.
The shape of the levator sling (muscle) is somewhat
like that of a funnel. If the rectum is blind ending above
the levator funnel, it is termed a HIGH variety of malformation. Here, if a fistula is present, it opens in the urinary
bladder or the vagina. The muscles of continence are
relatively poorly developed and the prognosis for
continence is not so good in these patients, in spite of very
accurate surgery.
If the rectum passes through the levator funnel entirely,
this is termed a LOW variety of malformation. Fistula
through the anorectal pouch opens out on the skin either
at the site of the anus or anteriorly on the perineal or scrotal
raphe in the male or in the vestibule or at the vulva in the
female. The continence muscles are well-developed and
the prognosis for continence is excellent.
In the intermediate variety, the rectum enters the levator
funnel but does not pass through it entirely. There is
frequently a fistula to the posterior urethra in the male, or
the vestibule in the female. The continence muscles are
fairly well-developed and the prognosis for continence
should be fairly good.
Clinically, once anorectal malformations are detected,
an Invertogram (Fig. 26.1.5) is performed. This is a lateral
X-ray of the babys abdomen taken when the baby is held
upside down, suspended by the legs. The air which passes
down to the blind rectum will rise up in this position and
show the level of the rectal pouch.
Once the level of the pouch is determined, further
treatment can be planned. If the anomaly is a low anomaly,
a primary surgical exploration of the perineum is
performed. Since the rectum has already descended
through the levator muscles, it is possible to locate the
same and mobilize it without a danger of damaging these
muscles, and the new anus is created by suturing the
pouch to the skin after opening it.
Pediatric Surgery
Figure 26.1.5: Invertogram in a low variety of

imperforate anus
If the anomaly is intermediate or high, a colostomy

must be made to relieve the intestinal obstruction. At a
later stage, a formal operation can be performed. The
commonest definitive surgery for anorectal malformation
is the PSARP (posterior sagittal Ano-rectoplasty) or one of
its variants. An incision is made between the sacrum and
the perineum. The levator muscles are carefully identified,
divided and the blind rectum is found. This rectum is
then brought down and the levator muscles are carefully
repaired to try and preserve as much of the continence
mechanism as possible. the colostomy can be closed as
the third stage of surgery.
Special mention must be made of the associated
anomalies with this group. Genitourinary anomalies,
especially vesicoureteric reflux, are probably the most
frequently observed. The term VACTERL denotes a group
of commonly associated anomalies, namely, Vertebral,
Anorectal, Cardiac, Tracheoesophageal, Renal and the
Limb.
Infantile Hypertrophic Pyloric Stenosis (IHPS)
In this condition the muscle of the pyloric sphincter
hypertrophies, causing the pylorus to become thick and
long. The hypertrophied muscle impinges on the lumen
of the pyloric canal, causing a partial gastric outlet
obstruction (Figs 26.1.6 and 26.1.7). The partial obstruction leads to a retention of curdled milk in the stomach.
This rancid curdled milk causes an edema of the gastric
mucosa and precipitates a complete obstruction within a
few weeks.
1237
Figure 26.1.6: Laparoscopic view of hypertrophied

pyloric tumor
Figure 26.1.7: Diagram showing pathological

anatomy in IHPS
Clinical Features
The condition is more common in boys than girls,
especially in first born children. Symptoms typically, occur
around the third week of life although some newborns too
may be symptomatic and an occasional patient may
present late.
Vomiting is usually projectile (due to a reverse
peristalsis from a hypertrophied stomach) and occurs
some time after a feed. The contents of the vomitus is milk
which may be curdled. Bile is never present, but altered
blood may be present on account of gastritis. The baby is
typically hungry after vomiting and demands another
feed, only to bring it out as before. This eventually causes
1238
constipation since the food and fluid intake is decreased.

Later in the course of the disease, there is dehydration
and weight loss.
On examination the baby is noted to have an alert and
hungry look. There may be evidence of dehydration in the
form of dry and wrinkled skin and weight loss manifested
as loss of subcutaneous fat. Unlike a toxic or septicemic
baby, these patients have a slow and shallow breathing
due to alkalosis. Jaundice is often seen in these babies. On
abdominal examination, epigastric fullness may be seen.
On offering a test feed of either glucose water or of breast
milk, the distended stomach is easily visible on inspection.
Peristaltic waves are seen passing from left to right. The
abdomen is next palpated for the pyloric tumor. This is a
firm grape sized mass, felt just under the lateral margin of
the right rectus muscle, and is best felt from the left side
with the left hand while the abdomen is completely relaxed
(e.g. during the act of feeding). This triad of visible
peristalsis, palpable pyloric tumor and projectile vomiting
is diagnostic of IHPS and rarely warrants further
investigations.
Diagnosis
A plain X-ray shows a large stomach bubble with a paucity
of gas in the rest of the abdomen. An USG is often diagnostic
when the thick pyloric muscle is seen along with a long
pyloric canal.
In doubtful cases a barium study will show a narrow
pyloric channel and retention of barium in the stomachstring sign (Fig. 26.1.8). Serum electrolytes should be done.
The typical electrolyte picture is that of hyponatremic,
hypochloremic alkalosis, due to loss of acid from gastric
juice along with chloride ions.
Figure 26.1.8: STRING SIGN on Ba meal

examination in IHPS
Management
Preoperative treatment includes insertion of a nasogastric
tube and cleaning the stomach with warm saline washes.
This also serves to decrease the mucosal edema at the
inflamed pyloric canal and will facilitate early feeding
after surgery. Intravenous fluids will need to be given to
correct the dehydration and electrolyte abnormalities. A
suitable concentration of normal saline is given. Once a
good urine output is achieved, potassium can be added to
the fluids.
Surgery should be performed only after this brief period
of stabilization. The standard operation is the Ramstedts
operation. Here, through a small incision on the abdomen,
the pylorus is identified and brought out through the
wound. An incision is made longitudinally over the entire
length of the pylorus. The pyloric musculature is split
along its entire length to expose the intact mucosal layer
a Pyloromyotomy is thus, performed. Postoperatively
feeding is begun gradually and the recovery is usually
excellent. In recent years this procedure is also being
performed laparoscopically to offer the benefits of minimal
invasive surgery to these patients.
Congenital Diaphragmatic Hernia (CDH)
Embryology, Pathology and Pathophysiology
The diaphragm is formed from different embryonal
components viz:
1. The septum transversum,
2. The pleuroperitoneal membranes
3. The dorsal esophageal mesentery, and
4. The body wall. Failure of formation or fusion of anyone
of these components can result in a defect in the
diaphragm which allows the abdominal viscera to
herniate into the chest cavity. This causes pressure on
the lung and a shift of the mediastinum to the opposite
side of the chest. This may, in turn, compress the lung
on the opposite side (Fig. 26.1.9).
The result is that both lungs, the ipsilateral more than
the contralateral, may not develop adequately, causing
pulmonary hypoplasia. This hypoplasia affects the
bronchial, alveolar and the vascular component of the
lung. Due to involvement of the vasculature of the lung,
there is an increase in the resistance offered by the
pulmonary circulation, and thus pulmonary hypertension. This eventually may prevent closure of the ductus
arteriosus.
Pediatric Surgery
1239
2. Morgagnis hernia: The anterior parasternal hernias take

place through a defect between the costal and sternal
attachments of the diaphragm. These are more common
on the right side.
A bochdalek hernia may or may not have a sac, and
the herniated viscera may include stomach, spleen, left
liver lobe, varying lengths of the intestine and the left kidney
in left sided hernias, and the liver in hernias on the right
side.
Clinical Features
Figure 26.1.9: Congenital diaphragmatic hernia showing marked

shift of mediastinum and pressure on contralateral lung also
Respiratory distress in CDH is caused by a number of

pathophysiological events:
The physical pressure effect of the abdominal contents
that does not allow the lung to expand fully, this
compounds with gaseous distension of the bowel in a
breathless or crying baby,
The pulmonary hypoplasia, which affects the gaseous
exchange in the available lung tissue.
The hypoplastic lung may not be able to handle normal
inspiratory pressures and the resultant alveolar
rupture may result in pneumothorax on the affected
side or even on the other side.
The failure of the PDA to close may further affect the
hemodynamics and lead to a persistent fetal circulation.
The severity of symptoms and signs depends mainly
on the status of lung development. A severely hypoplastic
lung may not be compatible with life, whereas at the other
extreme, some cases of congenital diaphragmatic hernia
may be relatively asymptomatic for years and may present
much later in childhood due to repeated chest infections
in a poorly expanding lung.
Two common varieties of congenital diaphragmatic
hernias exist:
1. Bochdaleks hernia: This is the most common type of
CDH. It involves the posterolateral part of the
diaphragm, and is caused by failure of formation of
the pleuroperitoneal component of the diaphragm.
These hernias are more common on the left as
compared to the right.
In the severely affected baby, there is respiratory distress

and cyanosis. The chest appears prominent on the affected
side and there is evidence of mediastinal shift. Breath
sounds on the involved side are absent, occasional
peristaltic sounds can be heard. The heart sounds are displaced. The abdomen is scaphoid due to displacement of
viscera to the chest and this clinical sign is highly
suggestive of a CDH.
Investigations
A chest X-ray is diagnostic. It shows loops of bowel in the
chest cavity. There maybe a significant mediastinal shift
and an associated pneumothorax. In right sided
Bochdalek hernia, the liver is the main constituent of the
chest cavity. In doubtful cases, an abdominal USG or a CT
scan of the chest is useful. A blood sample should be sent
for arterial blood gas sampling to find out the extent of
hypoxia and acidosis.
Treatment
A nasogastric tube should immediately be passed to deflate
the stomach and reduce aerophagia to relieve some
pressure from the lung. Oxygen should not be given by a
bag and mask for fear of inflating the stomach along with
the lungs. It maybe administered by an oxygen hood. If
the oxygen hood is insufficient, an endotracheal tube may
need to be passed, and mechanical ventilation may be
necessary.
Acidosis should be corrected. After attempting to
stabilize the babys condition as much as possible, surgery
should be performed to repair the defect. Through a
laparotomy, the defect in the diaphragm is identified, the
herniated viscera are reposited in the abdomen, and the
defect is repaired. In case of severe pulmonary hyper-
1240
tension, which may complicate the metabolic status of the

baby, drugs to cause pulmonary vasodilatation may be
required.
Tracheoesophageal Fistula
Embryology
The trachea and esophagus are formed from the primitive
foregut around the fourth week of intrauterine life. The
foregut tube at this stage develops lateral indentations
forming ridges, which deepen and fuse, to form two separate
tubes. An abnormality in this process causes this anomaly.
The exact etiology is unknown. Associated anomalies
occur as a part of the VATER syndrome, i.e. Vertebral,
Anal, Tracheoesophageal, Radial and Renal. This has now
been extended to VACTERL, the C denoting Cardiac
anomalies and L for Limb defects.
Incidence ranges from 1:3000 to 1:4500 live births. Thirty
percent of the affected infants are born prematurely.
Five types of anomalies are recognisable (Fig. 26.1.10A):
Esophageal atresia without tracheoesophageal fistula
Esophageal atresia with an upper pouch fistula
Esophageal atresia with lower end fistula
Esophageal atresia with fistula at both ends of the
esophagus
H fistula (Fig. 26.1.10B)
Esophageal stenosisa variant of esophageal atresia.
The most common of these is the variety with
esophageal atresia and a fistula from the lower pouch of
the esophagus to the trachea. The upper end of the
esophagus ends in a blind pouch and the lower end
connects to the trachea close to its bifurcation
(Fig. 26.1.10C). Saliva thus collects in the upper pouch
and may spill over in the trachea leading to aspiration
pneumonia. Air which is inspired is partly shunted into
the stomach through the fistula causing gaseous distension of the stomach. The gastric distension leads to reflux
of the acidic contents of the stomach through the trachea
into the lungs causing chemical pneumonia.
Clinical Features
There is pooling of saliva in the pharynx and the
expiration of air through this pool of saliva, manifests as
frothing at the mouth. Attempts to feed the baby cause
choking, dyspnea and cyanosis. There is respiratory
distress due to splinting of the diaphragm due to the
distended stomach and due to the pneumonia which may
coexist. In several nurseries it is routine to pass a tube into
a newborn babies esophagus to rule out this anomaly. In
this case there is obstruction to the passage of the tube.
Atresia of the G.I. tract should be suspected in any

case of maternal polyhydramnios.
Diagnosis
A plain X-ray of the baby with a radiopaque tube held in
the esophagus advanced as far as possible is diagnostic.
Catheter usually stops 10 to 11 cm from upper gum
line.
Contrast medium if used for roentgenography should
be water soluble, less than 1 ml given under fluoroscopy control is sufficient to outline the blind upper
pouch and to diagnose an associated upper pouch
fistula if present. The contrast should be with-drawn
immediately to prevent overflow into the lungs.
Treatment
Early correction of the anomaly is essential. The surgical
priorities are disconnection of fistula to achieve normal
respiration and prevent further acid reflux into the lungs,
prevention of salivary pooling and establish esophageal
continuity to enable effective deglutition and ensure
nutrition. This is done after stabilizing the baby with chest
physiotherapy, good oral suction and after assessing the
cardiac status to rule out any serious anomalies. Surgery
is performed through a right sided thoracotomy. The fistula
is located, dissected and disconnected. The upper and
lower ends of the esophagus are identified and are
anastomosed to restore the tube in select cases a staged
approach is adopted.
Prognosis
Depends on the weight, associated anomalies especially
cardiac and the amount of time elapsed before treat-ment
can be started. Sometimes the anomaly is missed for a few
days, by which time severe pneumonia sets in, which is a
significant cause of post-operative death. Very small and
preterm babies do not do as well as normal sized term
babies. If all factors are favorable, survival rates of over 80
percent can be achieved.
Sacrococcygeal Teratoma
Teratomas are tumors which are composed of multiple
tissue types representing cells from all the three germ layers
of the embryo. All these tissues have varying degrees of
differentiation. Commonly seen tissues seen in teratomas
are bones, muscles, neural tissues, teeth and epithelial
structures. Sacrococcygeal teratomas present at birth as a
large bosselated soft tissue mass in the region of the lower
Pediatric Surgery
1241
Figures 26.1.10A to D: (A) Diagrammatic representation of different types of tracheo-oesophageal anomalies, (B) Ba swallow showing
an h-type of tracheo-oesophageal fistula, (C) Diagrammatic representation of the commonest variety of TO anomaly (D) Sacro-coccygeal
teratoma-anus pushed anteriorly
sacrum. The tumor will usually push the anus forwards

(Fig. 26.1.10D) and occasionally may extend into the
abdomen through the pelvis. Most tumors at birth are
benign, but the incidence of malignant change increases
rapidly with age. The treatment thus consists of total
excision of the tumor by the second week of life. A strict
follow up should be kept to detect malignant change in
residual tumor cells. The prognosis is very good in tumors
that are completely excised at birth.
Choanal Atresia
This condition is characterized by an obstruction in the
passage between the nostril and the nasopharynx. This
may be complete or partial [choanal stenosis]. It may be
unilateral or bilateral. The nature of the obstruction may
either be bony or cartilaginous. Since newborn babies are
nose breathers at least for the first few weeks of life, this
condition may cause severe respiratory distress if it is
bilateral and complete. The typical history is that of a baby

who has difficulty in breathing causing discomfort and
sometimes cyanosis. As soon as the baby cries, the
respiratory distress is temporarily relieved due to the
mouth breathing which accompanies crying.
Diagnosis is achieved by passing a feeding tube
through the nose or by attempting a study with contrast
medium. A CT scan of the nasopharynx may outline the
anomaly in more details. Treatment consists of creating a
passage through what is most often a bony obstruction,
and subsequently stenting the newly created passage to
avoid restenosis.
There may be significant bleeding during this
procedure, but the prognosis is fairly good. There may be
other anomalies associated with choanal atresia which
may need attention. A known syndrome is the CHARGE
group of anomalies, namely Coloboma of the iris, Heart
anomalies, Atresia of the choanae, Retardation. Genital
anomalies and Ear defects.
1242
Anomalies of the Umbilicus: Exomphalos and

Gastroschisis
Introduction
In both exomphalos and gastroschisis, there is herniation
of the contents of the abdominal cavity through a defect in
the anterior abdominal wall (Fig. 26.1.11A). In
exomphalos, the umbilicus itself is widely open allowing
herniation of the abdominal viscera, whereas in gastroschisis there is a full thickness defect in the anterior
abdominal wall next to a normally formed umbilicus.
In exomphalos, the herniation may be of a variable
size. In some cases only a few loops of small bowel are
present within a sac in the umbilical cord (Exomphalos
minor). In more severe cases, there may be a large gaping
defect in the umbilical region, with almost the entire intraabdominal viscera including most of the intestine,
stomach, and liver present in the sac. (Exomphalos major)
The sac itself is formed by a layer of Whartons jelly lined
by peritoneum inside and amniotic membrane outside,

and appears at birth to be a thick translucent membrane
[Fig. 26.1.11B], which after some hours becomes white and
opaque. The umbilical cord inserts onto the apex of the
sac in smaller sacs, but in the larger ones it is usually
pushed inferiorly. At the junction of the abdominal wall
and the exomphalos sac, the skin merges with the
translucent membrane of the sac.
In gastroschisis the umbilicus is well-formed. There is
a defect of variable size, usually to the left of the umbilicus,
through which loops of intestine and some-times the
stomach are herniated. There is no sac, and the herniated
intestines are thick, edematous and appear leathery, being
matted together and covered by a gelatinous, slimy peel.
Associated Malformations
Cases of exomphalos major are often part of syndromes
with multiple system involvement. The most well known
association is the Beckwith-Wiedemann syndrome, also
called the EMG syndrome, i.e. Exomphalos, Macroglossia
and Gigantism. Major cardiac defects may occur and are
partly responsible for the poor prognosis of this condition.
With gastroschisis the most common associated
anomalies are intestinal atresias.
Diagnosis
The diagnosis of both conditions does not require any
special investigations as they are obvious clinically.
Antenatal ultrasound should be able to diagnose both
conditions in utero. If exomphalos major is diagnosed,
further tests like amniocentesis are indicated to rule out
major chromosomal anomalies. After birth, cardiac
anomalies should be ruled out by echocardiography.
Management
Figures 26.1.11A and B: (A) Gastroschisis, (B) Whartons

jelly in exomphalos minor
The aim in both conditions is to secure closure of the

abdominal wall after reduction of the contents within the
abdominal cavity. This is usually simple in exomphalos
minor, but in exomphalos major, there may be difficulty in
reducing the contents of the sac in the abdominal cavity,
since the abdominal cavity may not have the capacity to
include the herniated contents. In this situation, conservative therapy may have to be used. The skin from the
abdominal wall eventually grows over the sac forming a
large ventral hernia which will need to be closed at a later
stage. There is however, a high incidence of infection in
this case, causing morbidity and mortality.
Pediatric Surgery
The overall prognosis for exomphalos minor is good
but exomphalos major and gastroschisis have a guarded
prognosis and should be referred to centers where
facilities for long-term parenteral nutrition and neonatal
ventilation are available to ensure the best chances for
survival.
Surgical Causes of Jaundice in the Newborn
Jaundice in the newborn is a common feature, and is most
often physiological jaundice of the indirect type with
unconjugated hyperbilirubinemia. This type of jaundice
settles spontaneously and does not usually need special
investigations. However, when jaundice does not resolve
by two weeks of life, or when the serum conjugated
bilirubin rises more than 2 mg percent, further investigations are indicated.
A rise in conjugated bilirubin implies that the jaundice
is of the cholestatic type. This type of jaundice may be of
the intrahepatic type or the extrahepatic type. Intrahepatic
cholestasis may be a result of infective, metabolic,
endocrine and genetic causes, and are not treatable by
surgery.
Extrahepatic cholestasis, also called surgical
jaundice, is due to biliary atresia or choledochal cyst.
Biliary Atresia
This condition is characterized by atresia of the
extra-hepatic biliary apparatus. The hepatic ducts and
the common bile duct along with the gallbladder are atretic.
The exact cause is not clear but it is thought to be a result
of an inflammatory process in fetal life.
The clinical picture is one of jaundice that persists
beyond two weeks of life. The urine is dark colored, and
most significantly, the stools will be chalky white.
Investigations include the tests for liver function and other
serological tests to rule out the causes of intrahepatic
cholestasis. Ultrasonography may exclude a choledochal
cyst but is unreliable to diagnose a biliary atresia. A HIDA
scan may show that the radiotracer is taken up by the
hepatocytes but is not excreted into the intestine. Finally a
percutaneous liver biopsy will show the changes of biliary
atresia. The only reliable investigation to confirm biliary
atresia is an operative cholangiography.
Treatment is by surgery. It is imperative that surgery
should be performed by 2 to 3 months of life; otherwise the
liver suffers irreversible damage as cirrhosis sets in. At
operation, a loop of intestine is anastomosed to the porta
1243
to replace the absent hepatic and bile ducts. This operation

is known as Kasais portoenterostomy.
The prognosis is fair if operation can be performed
early. Later the chances of the liver being able to secrete
bile diminishes and the child will suffer chronic liver cell
failure, portal hypertension as a result of biliary cirrhosis.
The only answer in this situation is liver transplant.
Choledochal Cyst
Choledochal cyst refers to a congenital dilatation of the
biliary system. The dilatation may affect the extra or
intrahepatic bile ducts. The etiology is believed to be due
to a congenital abnormality of the junction of the biliary
and pancreatic ducts which may allow reflux of pancreatic
juice into the biliary tree causing weakening of the wall of
the bile ducts with subsequent dilatation.
The cysts may vary in size and position. Some cysts
may reach enormous sizes and cause a clinically evident
or even visible lump in the abdomen. In the newborn the
presentation is similar to biliary atresia. More often, the
disease presents in infancy or in later life. In older patients,
the triad of pain in the right hypochondrium, jaundice and
a palpable lump is considered diagnostic of a choledochal
cyst. More often the diagnosis is made on sonography for
the investigation of jaundice or of abdominal pain. A HIDA
scan may be useful to see the pattern of excretion of the bile
and as a confirmation that the cyst visible on sonography
is in continuation with the biliary tree.
The cyst, once diagnosed, must be excised completely.
Complications of untreated cases are infection causing
cholangitis, stone formation and eventually malignancy
(Fig. 26.1.12).
Figure 26.1.12: Cholangiogram in a case of

choledochal cyst
1244
SURGERY IN INFANTS AND CHILDREN
4. Esophageal pathologies like achalasia cardia or

gastroesophageal reflux.
THE GASTROINTESTINAL TRACT

Surgical Causes of Vomiting in Children
Roundworm Obstruction
Vomiting is one of the most common symptoms in

childhood. When persistent, important surgical causes
should be ruled out before these children develop major
complications.
The most important questions to be asked in the case
of a child who is vomiting are:
1. Frequency and quantity of vomitus. This gives an idea
of the severity of the problem. Profuse and recurrent
vomits are likely to cause dehydration.
2. Nature of the vomitus, i.e. the color and content. A bile
stained or feculent vomit is indicative of intestinal
obstruction unless proved otherwise.
3. Relationship to intake of feeds. In case of persistent
vomiting if the child looks healthy, one may suspect
forced feeding.
4. Whether projectile or not. Projectile vomits are seen in
Pyloric Stenosis and in severe gastroesophageal reflux.
5. Loss of weight or failure to gain weight in chronic
vomiting is an indication of the severity of the problem.
6. Associated problems like abdominal pain, etc. This
may indicate colic due to hollow viscus obstruction.
Introduction
Vomiting in Newborns
In most cases, vomiting in newborns is due to faulty
feeding practices and is nonbilous in nature. Gastroesophageal reflux is an important cause but may be
considered physiological up to the age of six months due
to incompetence of the esophagogastric junction. Pyloric
stenosis is another important cause of non-bilous vomiting
where the vomiting is projectile in nature and there may
be visible peristalsis in upper abdomen.
Bilous vomiting almost always indicates intestinal
obstruction.
Vomiting in Older Children
Surgical causes of vomiting may be:
1. Due to intraperitoneal inflammation, as in acute
appendicitis or acute cholecystitis
2. Due to intestinal obstruction. Roundworm obstruction,
acute intussusception and complicated Meckels
diverticulum.
3. Pathologies in other intra-abdominal organs, e.g. due
to pelviureteric junction obstruction or due to urinary
stones.
In areas where roundworm infestation is endemic, a mass

of roundworms may get entangled with each other to form
a bolus which gets inspissated in the ileum causing
obstruction to the lumen. In some cases there may be a
history of consuming an anthelminthic the previous day,
causing roundworms which are dispersed through the
intestine to collect together and become entangled.
Clinical Features
The age group is 5 to 10 years. The symptoms and signs
are those of lower intestinal obstruction, with abdominal
pain, vomiting, constipation and abdominal distension.
On examination, a bolus of roundworms may be felt as a
variegated mass, usually in the right lower abdomen. The
mass may be tender, but marked tenderness or guarding
may indicate the possibility of an impending perforation.
The differential diagnosis is an intussusception in an
older child where a similar mass may be felt, though this
is an unusual condition.
Diagnosis
A vertical X-ray of the abdomen may show distended
bowel loops. Fluid levels are often absent in the subacute
stage. Sometimes the streak like shadows of the worms
can be seen on plain X-ray. In later cases, fluid levels are
seen as in typical intestinal obstruction.
An ultrasound will show the nature of the mass since
an experienced sonologist will identify the bolus of worms
in the ileum as the cause of obstruction.
Treatment
In the earlier stages, this is conservative. By starving the
child, introducing a nasogastric tube to prevent vomiting,
and giving intravenous fluids, the mass often dissipates
and the problem is resolved.
The newer paralysing anthelminthics like piperazine
which cause neuromuscular paralysis can be used in dose
of 50 to 75 mg/kg for 2 days after the vomiting has settled.
Once the roundworm bolus has passed into the colon,
the use of enemas can hasten its dissipation and passage.
Hypertonic saline enemas are often used for this purpose.
Pediatric Surgery
If the conservative treatment shows no response or if
there is a deterioration in the general or local findings,
then surgery should not be delayed. At surgery, every effort
should be made to avoid opening the intestine, since the
incidence of leaks at intestinal suture lines is higher in the
presence of roundworms. The bolus of roundworms,
usually in the distal small intestine is kneaded to break it
and is milked into the colon, where roundworms will not
reside and will be passed out. In case the bowel is showing
signs of discoloration and signs of early necrosis, it should
be resected along with the entire bolus of worms. Suturing
for anastomosis should be done with non-absorbable
suture material to minimize breakdown.
1245
The ileum, being the most commonly involved,

invaginates into the cecum and through it into the colon
carrying with it the lead point at the apex. The part of the
intestine which lies within is called the intussusceptum
while the part that lies externally, which receives the
proximal intestine within it is called the intussuscipiens.
As the mass advances, there is venous congestion
within the innermost layer, causing the secretion of bloody
mucus, which is characteristically passed as currant jelly
stool. Finally there is further vascular compromise
espe-cially at the apex, and in cases which are not reduced
early enough, gangrene may set in.
Clinical Features
Intussusception
Introduction
Intussusception refers to the telescoping of one part of the
intestine into another (Fig. 26.1.13). It is a well-recognized
event in pediatric patients especially around 8 to 10
months of age.
Figure 26.1.13: Diagram showing pathological anatomy in

intussusception
Pathology
The most common site of intussusception is the ileo-colic
region, just proximal to the ileocaecal valve. In a few cases
there is a definite lesion in the intestine which is recognized as the cause of the lead point of the intussusception,
such as a polyp, or a Meckels diverticulum. In more than
95 percent of cases, it is thought that the lead point is a
hypertrophied Peyers patch which may cause a loop of
intestine to invaginate within the distal loop during the
propagation of a peristaltic wave. The hypertrophy in the
Peyers patch is thought to be due to a change in the
bacterial flora that accompanies weaning from breast feeds
and introduction of other feeds, which is a feature in
babies of this age group. In other instances, it is postulated
that an upper respi-ratory tract infection may cause a
generalized lymphoid hyperplasia, leading to Peyers
patch hypertrophy.
Intussusception classically affects a healthy, wellnourished child less than one year of age. Males are
affected oftener than females. There may be a history of an
upper respiratory tract infection just prior to the attack.
The main complaints are recurrent abdominal colics,
vomiting and passage of currant jelly stools.
The pain is colicky, and occurs in short bursts of severe
pain causing an otherwise well child to shriek with pain
and draw the legs up towards the abdomen. As soon as
the colic settles, the baby quietens down. The relief is
temporary, since the attack repeats itself.
After a few episodes of such attacks the child vomits
and passes a blood stained mucoid stool per rectum,
traditionally known as the red currant jelly stool.
Significantly, there is no fecal matter mixed with this stool,
a differentiating factor from dysentery.
On examination, the child may have fever. On
palpation of the abdomen, a typical banana-shaped mass
representing the intussusception can be felt in the
abdomen, the concavity of the mass being oriented
towards the umbilicus. Occasionally the tip of the mass
can be felt per rectally.
In cases which are diagnosed late, there are general
signs of septicemia. The abdomen may be distended and
may show evidence of peritonitis.
Investigations
An ultrasound of the abdomen can diagnose an
intussusception. A plain X-ray is nonspecific, but in cases
where the diagnosis has been delayed, there will be signs
of intestinal obstruction.
A barium enema is diagnostic and can be therapeutic
in the early stages of an intussusception (Fig. 26.1.14).
1246

Meckels Diverticulum
Introduction
This is the persistence of the proximal (intra-abdominal)
part of the vitello-intestinal duct. The diverticulum is
present on the antimesenteric border of the terminal ileum
(Fig. 26.1.15). It has an independent blood supply coming
from the superior mesenteric artery, (in utero) known as
the vitelline artery. This artery may terminate on the
diverticulum or may be attached to the anterior abdominal
wall at the umbilicus through a fibrous cord. In 40 percent
of cases there is heterotopic gastric tissue present at the
base of the diverticulum.
Figure 26.1.14: Ba enema showing coiled spring sign in

intussusception
Treatment
When an intussusception is diagnosed early, i.e. within
24 hours of the onset of the attack, and when frank signs
of intestinal obstruction have not set in, hydrostatic
reduction of the intussusception using barium or saline
or air instilled through the rectum may be successful. It
must be stressed that this procedure should be considered
as significant as surgery is, and should only be done by a
surgeon with facilities for operation being kept ready in
case of failure.
On instilling the barium the intussusception is seen
as the barium outlines the rounded head of the leading
end known as the coiled spring sign or the claw sign. The
pressure of the column of barium may be able to push
back the invaginated mass of intestine till it completely
reduces. If barium is ultimately seen freely filling the coils
of small intestine, the reduction has been complete and
successful. There is usually passage of flatus and stools
soon after, the mass felt earlier disappears and there are
no more episodes of colic. To further prove the completeness of reduction, some charcoal powder is usually given
to the child through the stomach tube. Recovery of the
charcoal in the stool the next day is proof that the patency
of the intestine has been restored.
If reduction of the intussusception is not successful by
barium, then operative reduction should be performed. At
surgery, if there is no evidence of bowel gangrene, manual
reduction is done. If there is gangrene, then resection of
the entire intussuscepted mass, with anastomosis of the
proximal and distal intestine must be performed.
Figure 26.1.15: Laparoscopic view of Meckels diverticulum

arising from anti-mesenteric border of ileum
The Rule of Two

Meckels diverticulum is present in 2 percent of the
population. It is situated 2 feet from the ileocecal junction,
and is 2" long and is usually symptomatic before the age
of 2 years.
Complications due to Meckels Diverticulum
The diverticulum is symptomatic only if complications
arise. In most cases the diverticulum remains symptomless
through life.
1. Bleeding: This is usually painless, profuse bleeding,
usually before five years of life. The bleeding is due to
the heterotopic gastric mucosa which produces acid.
The surrounding ileal mucosa is susceptible to this
acid and ulcerates, similar to a peptic ulcer. Bleeding
develops from this ulcer. It may be massive bleeding
leading to shock.
Pediatric Surgery
2. Intestinal obstruction: A Meckels diverticulum can be
the lead point of an intussusception. If associated with
a band leading upto the umbilicus, there may be
volvulus around the band; there may be internal
herniation around the band or kinking around the
band.
3. Diverticulitis: Inflammation of the diverticulum produces symptoms and signs identical to appendicitis.
The prognosis is however worse than appendicitis
since the thinner wall of the diverticulum makes it
more prone to perforation and since it lies at the center
of the peritoneal cavity, the peritoneal contamination
can spread more easily.
Diagnosis
In most cases the diagnosis is either a clinical suspicion
or at exploration.
In cases of bleeding, a 99m-Technetium labeled
radionuclide scan may show up the diverticulum as a hot
spot, since the ectopic gastric mucosa in the diverticulum
picks up the radiotracer.
A barium study is helpful only in a rare cases.
Treatment
When complications have taken place, diverticulectomy
should be done.
1247
4. Umbilical polyp: Causes a discharge and should be

excised.
5. Fibrous cord from the ileum to the umbilicus: May exist
with or without a Meckels diverticulum. There is a
possibility of intestinal obstruction and the diagnosis
will be made only at laparotomy.
The Umbilicus: Other Common
Surgical Conditions
Umbilical Discharge
The causes are:
1. Umbilical sepsis
2. Infection of the vestigial umbilical artery
3. Urachal sinus or fistula
4. VI duct anomalies, including umbilical polyp
5. Umbilical granuloma
6. Crohns disease
7. Tuberculous sinus.
Umbilical Hernia
Introduction
An umbilical hernia is caused by weakness in the
umbilical fascia and subsequent protrusion of the intraabdominal contents through the umbilicus into a skin
lined sac of variable size.
Etiology
Other Manifestations of Vitello

Intestinal Duct Remnants
1. Persistent VI duct or Vitello intestinal fistula: When
the entire VI duct is persistent, the result is an intestinal
fistula at the umbilicus. The child is brought with a
wet umbilicus. There is an umbilical discharge and
there may be a history of passing bubbles (gas)
alongwith the discharge. On probing, there is a tract
that leads down from the umbilicus. Insertion of a tube
down the tract brings out greenish intestinal juice. A
sinogram may be done to demonstrate continuity with
the intestine. The treatment is surgery since intestinal
obstruction by internal herniation and kinking is a
possibility.
2. Umbilical sinus: This manifests as a wet umbilicus.
On probing, there is no deep tract. Treatment is by
excision to stop the continuous discharge.
3. Umbilical cyst: This presents as a mass below the
umbilicus which should be excised.
The exact cause for herniation is not known. In some cases,

the hernias are associated with specific medical diseases
and syndromes, like hypothyroidism, trisomy 13, 18 and
the Beckwith syndrome.
Clinical Features and Course
The sac may attain a fairly large size, especially when the
child cries or strains. This fact may lead the parents to
believe that the hernia is responsible for the crying rather
than the converse.
The defect through which the hernia occurs can be felt
easily when the baby is quiet and the hernia reduced. It is
a firm fibrous ring whose dimensions may vary from that
which allows just the tip of the examining finger to be
introduced to one which will allow the entire finger to be
invaginated into the defect.
Most hernias close spontaneously by the age of three
years, especially those with an orifice size of less than 1.5
cm. However, complications are most likely in those
1248
hernias with very small defects. These are irreducibility,

incarceration and strangulation of either the intestine or
of a tag of omentum. The above complications are, however,
unusual.
Treatment
Observation is recommended at least till the age of three
years. If by the school going age the hernia has not
spontaneously closed then surgery may be advised.
If there is a complication like irreducibility, the child
should be sedated and reduction attempted when the child
is quiet and not straining or struggling. In the majority of
cases this is successful. Surgery should be performed in
such a case after a few days.
Clinical Features
There is a history of passing a hard stool with a streak of
blood on it.
The child cries during the passage of this stool.
Occasionally there may be frank bleeding per rectum.
The fissure is usually evident on local examination.
Treatment
Management of constipation using dietary modification and stool softeners.
Application of local anesthetic jellies to reduce pain
Warm hip baths after every motion.
Bleeding per Rectum in Children
Intestinal Polyps
Bleeding per rectum is a common symptom encountered

in children. In our country it is commonly associated with
infective diarrheas, but various surgical causes should be
ruled out.
Various familial hereditary polypoidal conditions of the

small and large intestine have been described, but are
unusual in clinical practice. The child presents with
bloody and mucoid diarrhea that is prolonged and severe
enough to cause anemia and hypoproteinemia. Diagnosis
is on clinical suspicion and demonstration of multiple
polyps on proctosigmoidoscopy and by barium enema.
The polyps must be biopsied and in most cases are found
to be adenomatous polyps. Extensive surgery is required
in most cases.
Juvenile polyps of the rectum are common in children
(Fig. 26.1.16). The history is of passing a few drops of
blood after the passage of a stool. Unlike a fissure, the
blood is distinct from the stool and not smeared on it. The
polyp is readily felt of rectal examination, and should be
removed per rectum using routine instruments if it can be
Surgical causes of rectal bleeding

In newborns
1. Anal fissure
2. Neonatal necrotizing enterocolitis
3. Volvulus neonatorum
In infancy
1. Anal fissure
2. Intussusception
3. Meckels diverticulum
4. Polyps in the intestine
In older children
1. Rectal polyps
2. Miscellaneous conditions like vascular malformations
involving the intestine or tumors involving the Gl tract.
Fissure-in-Ano in Neonates and Infants
This is the most common cause for rectal bleeding. The
cause is constipation and passage of a hard stool which
tears the sensitive anal mucosa during passage. This
causes pain during the next evacuation which leads to
stool retention and further constipation, starting a vicious
cycle.
Common causes of constipation are inappropriate
feeds especially using milk powder formulas and refined
processed foods.
Figure 26.1.16: Juvenile rectal polyp prolapsing out
Pediatric Surgery
approached from below. For polyps that are slightly higher
up, endoscopic removal using wire snares and electrocautery is as effective.
THE GENITOURINARY SYSTEM
Urinary Tract Infection in Childhood
Urinary tract infection is an important differential
diagnosis in the infant or child with pyrexia, since undiagnosed and untreated infection can cause pyelonephritis
and renal damage, which may be irreversible and may
compromise renal function for life.
The clinical presentation of urinary tract infection may
be misleading and urinary symptoms, may, in fact, be
absent, especially in the very young. Presenting symptoms
may include fever, irritability and failure to thrive in the
neonate and infant. At times, diarrhea, vomiting and
unexplained anemia may be the pointers to UTI in very
young children. In the older child, there may be the above
symptoms, with abdominal pain, frequency of micturition,
wetting or dysuria.
Early diagnosis and prompt treatment are important.
A good clinical rule is that UTI should be considered in
any child with unexplained fever for more than three days,
and a urine examination should be asked for.
The method of collecting urine for examination is
important as is its storage before sending it for examination. In adults, the collection of a clean void, mid stream
sample may be easy to achieve, but in a child this requires
special efforts.
In the male child, the foreskin is often adherent to the
glans penis. Ideally, the foreskin should be separated
completely to expose the meatus. The entire glans is
cleaned well before collecting the midstream sample. In
the female child, during the normal act of micturition, when
the labia are adherent, the urine may actually reflux into
the vagina before being voided. There is thus the potential
for contamination of the sample, giving misleading results.
Thus, in girls, the labia should be separated completely to
visualize the urethral meatus, the area cleaned well, and
then the sample should be collected as a midstream sample.
Both these above methods will be difficult to carry out in
very young and uncooperative children. Either catheterization or suprapubic aspiration are the answer in these
children. An additional alternative in newborns is the
use of adhesive bags which can be fixed to the perineum
to collect any voided urine. This is not accurate when
bacteria are grown from this sample, but a sterile sample
collected in this manner can be used to disprove a UTI.
1249
Since urine is a good culture medium, there is a good

possibility of organisms growing in a sample which cannot
be processed immediately. If the collected sample cannot
be examined within half an hour from the time of collection, it should be refrigerated till the time of examination.
The diagnosis of UTI rests on counting the colony
forming units or CFUs in the given sample. Generally, a
count of 100,000 CFU/ml of the same organism is sure
evidence of UTI. A count of less than 10,000 CFU/ml is
indicative of absence of infection, while counts between
10,000 and 100,000 CFU/ml is usually indicative of
contamination of the specimen, especially if multiple
organisms are grown. While the above statements are true
for the clean catch, midstream sample of urine, for a
sample collected by suprapubic aspiration, a count of
2000-3000 CFU/ml of a single organism may be significant, since the chance of contamination of this sample is
low. Similarly, for a catheter collected specimen, 50,000
CFU/ml may be significant, in fact, sometimes infection
may be diagnosed with counts as low as 10,000 to 50,000
CFU/ml if a single organism is grown from a catheter
collected specimen.
Once urinary tract infection is proved, it is important
to find out if there is an underlying cause for the infection.
In female children, due to the short and straight course of
the urethra, simple cystitis is well known, and no other
cause will be identified. However, roughly two-thirds of
all boys and one third of all girls having proven urinary
tract infection will have some underlying abnormality.
The three main categories of abnormalities detected are
obstructive problems, vesicoureteric reflux and neurogenic
bladder.
The Obstructive Uropathies
Obstruction to the flow of urine promotes urinary stasis
which leads to infection. Common sites where obstruction to the urinary flow is encountered are:
1. The pelviureteric junction: This causes dilatation of the
pelvis and calyces of the kidney causing hydronephrosis.
2. The vesicoureteric junction: This causes ureteric dilatation which, if severe, can also affect the kidneys and
result in hydroureter and hydronephrosis.
3. The posterior urethra: Posterior urethral valves are
curtain like membranes in the posterior urethra in
males, which cause obstruction to the flow of urine
from the bladder.
1250
Pelviureteric Junction Obstruction
Investigations
Pathology
1. Blood Investigations: A hemogram and tests for renal

function are necessary.
2. Urine examination: A urine routine test and urine
culture, if infection is suspected.
3. Imaging: The test of first choice is an ultrasonogram,
which will confirm the diagnosis. An Intravenous
urogram, which was previously considered mandatory, is no longer so, with more information available
from sonography and radio isotope renal scans.
Sometimes, it may still be indicated if clear anatomical
information is desired this purpose is however better
served with a CT Urogram. An IVU will show
dilatation of the calyces and the pelvis, and nonvisualization of the ureter on the affected side. In more
severe cases, where the renal parenchyma is compressed towards the periphery of the hydronephrosis,
the contrast is seen as thin crescents around a nonopacifying central mass. This is called the crescent
sign. There may be delayed uptake of the contrast, and
in severe cases, there may be no uptake seen on the
affected side. An equally important observation is to
note the appearance of the contralateral kidney.
A micturating cystourethrogram is useful to see if
concomitant vesicoureteric reflux is present.
4. Radionuclide scanning: A scan using DTPA with
furosemide is considered mandatory to quantify the
function of the affected kidney, and hence gauge the
severity of obstruction. This test, though expensive,
and not readily available, is perhaps the most useful
noninvasive test for decision making on the course of
management.
The obstruction is a result of a congenital stenosis at the

PU junction, or due to external compression of the PUJ
most commonly due to an abnormal artery to the lower
pole of the kidney that causes a kink in the ureter at its
origin.
The urine formed in the kidney thus cannot be
transported into the ureter and collects in the pelvis. The
pelvis dilates to accommodate the increasing amount of
urine being formed. The pressure in the pelvis rises and
is transmitted to the calyces which also distend. The
increasing size of the pelvis and calyces causes pressure
upon the kidney parenchyma, which is compressed and
is eventually thinned out. The function of the kidney
begins to get affected as the parenchyma becomes thinner.
In severe cases, the kidney may be represented by a thin
membranous sac containing urine. If this urine gets
infected, pyonephrosis (the collection of pus or infected
urine in a dilated pelvi-calyceal system) results.
Clinical Features
Common presenting symptoms are UTI, pain in the
abdomen, and less commonly, hematuria. Sometimes, a
lump in the abdomen is noted by the parents or the
examining physician.
The abdominal pain may be of variable nature or may
be classic flank pain suggesting a kidney pathology.
Gastrointestinal symptoms like nausea, vomiting and
anorexia may be present, and at other times the symptoms
are nonspecific such as failure to thrive, weakness and
lethargy.
Since antenatal screening by ultrasound is now
common, frequently, the pathology is picked up in utero.
Dietels crisis is the term used to describe a typical
feature of hydronephrosis. There is an abdominal lump
with pain which may be severe, and which is suddenly
relieved and accompanied by diuresis. This happens when
the pressure in the renal pelvis builds up to a great degree
and is able to overcome a stenosis at the PUJ. The collected
urine is passed down with symptomatic relief. A lump in
the abdomen due to hydronephrosis is noted to have
disappeared.
Management
On the basis of the renal scan, we now know that some
cases of PUJ Obstruction still have excellent kidney
function, and will continue to retain this excellent function
in spite of the hydronephrosis. Some cases of hydronephrosis resolve spontaneously over a few years.
Thus, if kidney function on the affected side is more
than 40 percent, and if there is no complication, or
symptoms, the child can be observed. In case of function
less than 40 percent, or if there are complications, like
recurrent infections, or symptoms, like pain, or if the renal
function is seen to be deteriorating on observation, then
surgery, is performed.
Pediatric Surgery
1251
This entails restructuring the pelviureteric junction, to

eliminate the obstruction and allow easy passage of urine
through it. The most common operation done is the
Anderson Hynes Pyeloplasty.
due to infection or voiding difficulty. Here the kidney

function is relatively better preserved and the long-term
prognosis should be better.
Posterior Urethral Valves
Introduction
Posterior urethral valves are thin curtain like membranes

that are seen in the posterior urethra. These valves cause a
partial obstruction to the flow of urine, resulting in high
pressures being generated in the urinary bladder, as it
attempts to overcome the obstruction. Refer to Chapter
13.10.
The diagnosis is usually at birth due to antenatal
ultrasound which shows bilateral hydroureteronephrosis.
The distended bladder may be seen. Since amniotic fluid
is formed by excretion of urine by the fetus, in PU valves,
there may be oligohydramnios on account of both kidneys
being affected. After birth, confirmation of the diagnosis
is done by repeating an ultrasound and performing a
micturating cystourethrogram (MCU) (Fig. 26.1.17). If PU
Valves are present, they need to be burnt (fulgurated) to
restore the caliber of the bladder outflow. However,
frequently, the kidneys have already suffered significant
damage and the prognosis for renal function is not good.
These children in spite of having had a good urine flow
do not grow well and may suffer renal failure in childhood
or adolescence. Kidney transplant is the only alternative
in this group. Other children who are fortunate to have a
lesser degree of obstruction may present in later childhood
Normally, urine is transported down the ureter and enters

the bladder through the vesicoureteric junction. This
junction functions as a one way valve and does not allow
urine to reflux up the ureter. This is partly due to the
anatomic arrangement at the junction and partly due to
the capacity and compliance of the bladder which allows
it to distend as it fills and maintains a low pressure
through the processes of filling and emptying.
At times the valvular action at the vesicoureteric
junction is not functional due to the faulty insertion of the
ureter into the bladder. This allows urine to reflux into the
ureter and sometimes even into the kidney.
Vesicoureteric Reflux
Pathology
The vesicoureteric junction is normally seen as an oblique
slit like opening. In VUR it sometimes remains widely
open and is called a golf hole orifice, and may be situated
more laterally than normal.
The ureter may show varying degrees of dilatation due
to increasing quantities of urine that enter it from above as
well as below. The kidneys may also show varying degrees
of hydronephrosis.
The kidneys are prone to damage by the refluxed urine
in case the urine is infected, and when subjected to high
pressures as are generated with neurogenic bladders.
Thus, infection should be avoided at all costs in a patient
with VUR. Infection causes pyelonephritis, which causes
areas of fibrosis and scarring in the kidney and affects
renal function. The result is reflux nephropathy which
may ultimately result in renal failure.
Clinical Features
Most children are detected during the investigation of UTI.
Antenatal diagnosis through routine screening, which
may show unilateral or bilateral hydroureteronephrosis,
is also common.
Investigations
Figure 26.1.17: MCU in a case of post urethral valves, showing

dilated posterior urethra, trabeculated bladder and grade 5
vesico-ureteric reflux on lt side
A hemogram and renal chemistry are routine tests which

must be done.
A routine urine examination is performed. Repeated
culture examinations are required to detect the presence
of infection if any.
1252
Imaging studies include ultrasonography to see the

dilated ureters and kidneys and to check the kidney size
and parenchymal thickness.
Definite proof is obtained by performing a micturating
cystourethrogram which will show dye entering the ureter
and even the kidney during the act of micturition.
Once reflux is proved it is important to find out whether
kidney damage has occurred. This is possible by
performing a radionuclide scan using a substance called
DMSA which can show kidney scars.
Management
Minor degrees of reflux, especially when seen in neonates
and infants have a very good chance of spontaneous
resolution and these children should be followed
conservatively. It is very important to treat any urinary
tract infection promptly and completely and give low doses
of antibiotics continuously till reflux persists to prevent
renal damage.
Severe degrees of reflux usually require surgery in the
form of ureteric reimplantation, where the faulty
vesicoureteric junction is dissected out and a new
functionally competent junction is created.
Recently, an endoscopic treatment for reflux has been
introduced, where through a cystoscope a substance called
dextranomer hyaluronic acid [deflux] is injected near
the ureteric orifice. This creates an additional support at
the orifice and prevents reflux.
Neurogenic Bladder
The act of micturition is a very finely coordinated process
which involves several mechanisms of relaxation and
contraction of the bladder, to achieve the two main
functions of the bladder, namely to STORE the urine till it
is time to empty the bladder, and to EVACUATE the
bladder when the circumstances are appropriate.
During the act of filling the bladder must keep relaxing
to allow it to fill and expand its capacity. When full
capacity is reached, appropriate signals are sent to the
brain which commands the bladder to either retain the
urine if the circumstances are inappropriate for voiding.
If suitable, the act of voiding is initiated by causing a
contraction of the bladder detrusor muscle and
simultaneously causing the ure-thral sphincter to relax.
If this fine balance is disturbed, a variety of disorders
may result which can broadly be classified into two main
categories.
Disorders of Voiding and Disorders of Storage

Both categories result in either incontinence of urine (when,
for instance voiding is hyperactive and inappropriate or
when the capacity to store urine is diminished) or urinary
retention (when voiding cannot be initiated).
These disorders are seen in a variety of clinical
conditions that affect the entire sequence of neural control
of the bladder from the brain through the spinal cord
through the peripheral nerves to the bladder muscle itself.
An important test in this condition is a urodynamic
study which measures the activity of the detrusor muscle
and the urethral sphincter, as also the pressures generated by the bladder, and allows a rough diagnosis to be
made of where the fault lies.
The treatment of these conditions may involve drug
therapy to control inappropriate contractions or to
strengthen weak contractions. One of the most important
components of therapy is to ensure regular bladder
emptying by performing a Clean Self Intermittent
Catheterisation (CSIC). Surgery can be offered in select
cases to increase the bladder capacity or to tighten the
sphincter mechanism. The subject is complex and details
of the above are beyond the scope of this book.
Other Anomalies of the Kidney
Embryology
The definitive fetal kidney arises from the metanephric
bud with which the ureteric bud makes contact. Elongation of the ureteric bud and growth of the metanephros,
along with straightening of the curvature of the body results
in the ascent of the kidney from the original pelvic position
to the lumbar regions. Failure of the kidney to ascend to its
adult position can result in abnormal positions of the
kidney.
In early fetal life while the kidney is still in the pelvis,
the metanephric tissue on either side is close to the midline,
being confined in this position by the umbilical arteries
on either side. In this situation, the two metanephric buds
on either side can get fused, causing the various anomalies
of fusion.
Ultimately the ureteric bud and the metanephric tissue
which forms the collecting system in the mature kidney
must connect with each other to form a unified single
system. Failure to connect can result in polycystic or
dysplastic kidneys.
Pediatric Surgery
Anomalies of Position and Fusion
Ectopic kidneys can occur on the same side or can be
crossed ectopic kidneys. On the same side the kidney may
be in the pelvis, draining into a short ureter and deriving
its blood supply from the lower aorta and the common
iliac arteries. The other abnormal position is in the thorax
due to excessive ascent.
Simple ectopic kidneys may not be symptomatic and
may be detected on screening for other diseases.
Crossed ectopia (Fig. 26.1.18) refers to the situation
where the ureter ascends from the bladder, crosses the
midline to reach the kidney on the opposite side. This
kidney generally lies below the normally situated kidney
and may be malrotated. Ectopic kidneys may exhibit fusion.
A fused pelvic kidney may not be normally shaped and is
called the disk kidney, since it is a large discoid structure.
1253
kidneys, and may actually contain renal parenchyma or

may contain fibrous tissue.
The incidence of horseshoe kidney varies from 1 in
400 to 1 in 1800 and is more common in boys. Associated
anomalies include Trisomy 18, Turners syndrome,
neural tube defects and cardiovascular and other renal
anomalies.
Clinically, about one-third of all horseshoe kidneys
are asymptomatic. Symptoms are due to complications,
namely hydronephrosis, UTI and renal stones. Lower
abdominal pain and nausea are the common symptoms.
Diagnosis is by imaging studies, usually sonography. The
findings on IVU are also diagnostic. The calyces of both
kidneys are lower and more medially placed than normal.
The calyces are malrotated. There may be associated
hydronephrosis. A renal scan will show whether
functioning tissue is present at the isthmus. A CT scan or
an MRI will also diagnose the fusion of the kidneys.
Treatment is aimed at relieving the complications. The
usual cause of symptoms is hydronephrosis, with the
ureters being obstructed by a renal vessel or due to a high
insertion of the ureter. Division of the isthmus is not
usually required, except in unusual situations like a tumor
in one of the moieties of the kidney.
Polycystic Kidney
Figure 26.1.18: IVP showing crossed renal ectopia
Crossed kidneys may also be fused, the lower pole of

the normally sited kidney being fused with the upper pole
of the crossed kidney.
Any kidney with anomalies is more prone to developing diseases like obstruction or reflux causing hydronephrosis and/or infection, with the usual symptoms.
Appropriate imaging studies in the form of sonograms,
IVU, MCU and if available, a CT urogram will determine
the exact nature of the abnormality to prepare the surgeon
for unusual situations that may be encountered during
surgery.
Horseshoe Kidney
Horseshoe kidney is the most common fusion anomaly of
the kidney. Here, the two kidneys are fused at the lower
pole and lie in the lower abdomen, on either side of the
midline. The isthmus is formed by the fused portion of the
Polycystic kidneys occur in two forms, the infantile form

and the adult form. The infantile form is characterized by
varying degrees of cyst formation in the kidneys. The
function of the kidneys is compromised to the extent of
involvement, and renal failure will occur in more severely
affected kidneys. In general, the more a kidney is affected,
the earlier the presentation. When most of the renal tubules
are involved, the child may be stillborn or may die in the
neonatal period. In others with less severe involvement,
survival for several years is seen. A noteworthy feature is
the association with hepatic fibrosis and cyst formation,
causing hepatomegaly and portal hypertension.
Diagnosis is by imaging studies, namely sonography
and IVU, where the characteristic findings are bilaterally
enlarged kidneys with multiple elongated cysts throughout the renal parenchyma. There is retention of contrast
material in the kidneys for a considerable period of time.
Diagnosis should be suspected if there is a family history,
especially if hepatomegaly is also noted on examination.
Treatment is for renal failure as and when it presents.
Renal transplantation is the ultimate answer to the
problem. Genetic counseling should be offered to
1254
parents of an affected child who may plan to have more

children.
Multicystic Dysplasia
In this condition, there is replacement of the normal kidney
tissue by cysts of varying sizes. The ureter is almost always
abnormal in that it may be completely atretic or it may
have a very small lumen that does not allow significant
drainage. The histological picture is that of primitive renal
tubules surrounded by a cartilaginous stroma. The
collecting ducts are poorly formed and dilated, forming
cysts.
The dysplastic kidney does not function significantly.
Usually this kidney is asymptomatic and does not require
any treatment. Most kidneys do not grow with age, rather
they shrink into insignificant masses. Some believe that
these kidneys may cause hypertension. If there is
hypertension in a child that cannot be ascribed to any
other cause, then a nephrectomy may be performed. In
some instances, the kidney may present as a mass in the
newborn child. This is best tackled surgically after
investigation.
Anomalies of the Pelvis and Ureters
Duplicated Systems
Duplicated systems imply that the pelvis and/or ureters
of a single kidney are duplicated. In the simplest form,
there may be a bifid renal pelvis. A further affection is an
incompletely duplicated ureter, i.e. a duplicated renal
pelvis drains into separate ureters which however, fuse
into a single channel before entering the bladder. The above
examples are those of incomplete duplications. Complete
duplications imply that the entire ureter is duplicated, i.e.
two ureters drain through two separate ureteric orifices in
the bladder. Of the two orifices that lie inferomedial and
superolateral to one another, the lower orifice always
drains the superior part of the kidney. This is known as
the Weigert-Meyer rule. Duplicated systems may have a
number of problems. Significant complaints in incompletely duplicated systems are infection or stone formation.
Complete duplications exhibit obstruction at the ureterovesical junction or vesicoureteric reflux. The ureter
draining the lower moiety of the kidney, and opening
superolaterally, is the one most affected by reflux, while
the upper moiety ureter is likely to be the obstructed one.
The treatment of complications is surgical. It must be

mentioned that several cases of duplication may exist
without causing any symptoms and these should be left
alone.
Exstrophy of the Bladder
Exstrophy of the bladder is a rare anomaly that is
characterized by failure of fusion of the two lateral
processes that form the body wall below the umbilicus.
The basic embryological defect appears to be the failure of
the mesoderm to invade the infraumbilical membrane.
This results in the infraumbilical body wall to be composed of a thin layer of ectoderm and endoderm which
are in close contact without the support of the mesoderm
in between. This thin membrane soon disintegrates, with
the result that the pelvic viscera, notably the bladder pout
out on the body wall.
The usual anatomy is that the abdominal wall is
deficient below the umbilicus. The bladder bulges out in
the lower abdominal midline. The ureteric orifices are
visible on the exposed bladder mucosa, through which
urine continuously dribbles out. The exposed bladder neck
and urethra are widely splayed out. The penis is
epispadiac, and is present some distance from the scrotum.
The distance between the scrotum and anus is thus
diminished. There may be inguinal hernias on either side.
Due to the viscera which protrude out, the pubic bones on
either side are not fused and are widely separated.
Ideally this condition should be operated at birth. The
bladder and urethra are reconstructed, and the pubic
bones brought together. At later stage, the epispadias is
corrected. Finally, an additional procedure may be required
for making the child continent.
In the female child the anatomy is slightly different, in
that the urethra is splayed out but the vagina is normally
situated behind the urethra. The clitoris is bifid and the
labia are widely separated on either side of the midline.
The principles of reconstruction in the female remain the
same, with the exception of epispadias repair.
INGUINOSCROTAL PROBLEMS IN CHILDREN
Hernia and Hydrocele
Introduction
Hernia and hydrocele result from a patent processus
vaginalis, which is a tongue like extension of the
peritoneum which develops along the inguinal canal
in utero.
Pediatric Surgery
In most children, the processus closes down or fuses
and there is no connection between the peritoneum and
the inguinoscrotal region. However, in some children, the
processus remains patent and can allow contents from
the abdominal cavity to enter the scrotum.
If the opening of the processus is large, the abdominal
viscera like intestines can herniate into the scrotum
forming a hernia. If the opening is very small, only
peritoneal fluid can enter, forming a hydrocele.
Clinical Features
The main complaint is a swelling in the groin or the
scrotum. In the case of a hernia, there is a history of an
increase in the size of the swelling on crying or after
activity. In a hydrocele, there is an increase in the size of
the swelling in the evening after an active day, and a slight
decrease on waking up in the morning.
On examination, the hernial swelling is reducible,
whereas the hydrocele is irreducible. This is because a
hydrocele, though in communication with the peritoneum,
has a very small orifice, and on application of pressure on
it, the inverted ink bottle effect is produced, causing
irreducibility. After a nights rest, however, there is a
decrease in size due to slow spontaneous reduction.
1255
surgery should be performed. The chances of complication

in emergency hernia surgery are much more than during
routine surgery, hence, as far as possible, hernias should
be treated on an elective basis as soon as diagnosed.
Undescended Testes
Introduction
The testes develop within the abdomen from the indifferent gonad in the first trimester of pregnancy. By the
third month, they lie adjacent to the internal inguinal ring.
During the third trimester, they begin to descend through
the inguinal canal to reach the scrotum, by birth. After the
testes descend, the patent processus vaginalis usually
closes.
Descent of the testes is essential for adequate germ cell
development, since the scrotum maintains the testes at a
temperature a few degrees lower than the body core
temperature.
Etiology
The causes of nondescent of the testes have been postulated
to be due to genetic, hormonal or mechanical causes. The
exact cause is not always known.
Course and Complications
Clinical Features
A hydrocele has a very high chance of resolution by the

age of 18 months since the patent processus will often
close spontaneously. Since a hydrocoele is not prone to
complications, surgery is not performed till the age of 18
months. After this age, there is a very small chance of
spontaneous cure, hence an operation should be done.
At surgery, the communication with the peritoneum is
exposed and ligated. This operation is essentially the same
as that done for a hernia and is called a herniotomy.
For an inguinal hernia, surgery should be advised as
soon as the hernia is diagnosed. This is because a hernia
has a good chance of complication in the form of irreducibility, obstruction and strangulation of its contents. In
fact, premature babies and infants have a higher chance
of complication, hence one should not wait till the baby
has grown to advise surgery.
If the hernia does become irreducible, the child is kept
under observation and sedated. Reduction is tried under
sedation and after keeping the child in the head low
position for a few hours. In most cases, the hernia can be
reduced, in which case surgery should be planned within
a few days. If the reduction is not successful, an emergency
The scrotum on the side of nondescent will be seen to be

empty and not as well-developed as the contralateral
normal side. The testis may be palpable in the inguinal
region. It may sometimes be necessary to milk the testis
down the inguinal canal to be able to palpate it on the
abdominal wall. The testis, in spite of manipulation and
milking cannot be brought down into the scrotum and
maintained there. The differential diagnosis of an empty
scrotum includes undescended testis, retractile testis,
ectopic testis and testicular atrophy.
A true undescended testis lies in the abdomen along
the line of testicular descent (Fig. 26.1.19) or in the inguinal
region or in the groin outside the external ring. These
varieties are called, respectively, the abdominal testis, the
inguinal testis, and the emergent testis. Clinically they
may also be broadly be classified into the palpable and
the impalpable testes. A true undescended testis is often
associated with inherent defects in the testis itself as also
in the epididymis and the vas. The chances of fertility of
such a testis will be lower than that of a normally
descended one. In these cases, the higher the testis, the
more are the chances of abnormal structure and function.
1256

3. Prone to torsion: The undescended testis is prone to
torsion and can present as an acute abdomen or as an
enlarged tender mass in the groin. The scrotum should
always be examined. If empty on the side of symptoms,
a valuable clinical clue is obtained.
4. Prone to tumor: Undescended testes are prone to
malignant change. This propensity may be decreased
by bringing the testis down to the scrotum by the age
of one year.
Treatment
Figure 26.1.19: Lap view of intra-abdominal testis
An ectopic testis is one which has successfully

descended, but has not found its way into the scrotum
after emerging from the external inguinal ring. Such a testis
may be in the superficial inguinal pouch, a space between
the fascial layers of the abdominal wall in the region of
the groin, or the pubic, perineal, femoral or contralateral
scrotal positions.
A retractile testis is one where the normal cremasteric
reflex is hyperactive. The testis gets pulled up due to the
action of the cremaster and lies above the scrotum. In such
a case, the scrotum is well-formed. On examining the child
in the cross legged squatting position the testis can be
seen to descend in the scrotum. During sleep, the testis is
usually in the scrotum, and following manipulation the
testis can be brought down into the scrotum and be
maintained in that position.
Testicular atrophy can occur in a testis that has
descended normally but has undergone a vascular
accident such as torsion in utero.
Course and Complications
An undescended testis can undergo complications:
1. Fertility problems. Poor germ cell maturation if the
testis is not brought down by the age of one year. This
affects fertility. However, many undescended testis
have inherent defects and defects in the epididymis
and vas deferens. This will affect fertility even if the
testis is brought down at the right time.
2. Prone to trauma: In the inguinal region the testis can
get damaged due to blunt trauma by getting crushed
against the rigid body wall and its musculoskeletal
structure. In the scrotum, it is well-protected between
the thighs.
An undescended testis at birth may spontaneously

descend into the scrotum by three months of age.. The
chances of spontaneous descent after this are not high.
Electron microscope studies have demonstrated that if a
testis remains undescended beyond the age of six months,
irreversible changes develop in its structure, that are
damaging to the ability of the testis to form mature germ
cells. For this reason, surgery should be performed anytime
after six months, but definitely before the age of a year, the
earlier the better.
In some cases giving hormones like HCG or GnRH
has proved successful in bringing down an undescended
testis, since it has been felt that a poor secretion of hormones
is responsible for nondescent. However, the use of these
hormones is controversial and not everybody is convinced
that they are really useful.
Acute Scrotum
Introduction
An acute scrotum implies the sudden onset of scrotal pain
with signs of acute inflammation in the scrotum. An acute
scrotum occurs in two age groups in pediatric patients:
neonatal and adolescent.
The causes of an acute scrotum can be testicular torsion
and epididymoorchitis. Less common causes are testicular
trauma. It is a dictum that an acute scrotum should be
considered to be testicular torsion unless it is proved
otherwise. This is because a torted testis will rapidly undergo
necrosis, if the torsion is not relieved within a few hours.
Factors responsible for torsion of the testis include:
1. A long mesorchium, the layer of connective tissue that
attaches the testis to the epididymis.
2. High attachment of the tunica vaginalis. This allows
the testis to be suspended in a loose sac of tunica and
predisposes it top torsion. This attachment and
subsequent testicular lie is likened to the clapper of a
bell.
Pediatric Surgery
Clinical Features
The history is that of pain in the scrotum of sudden onset.
There is redness and swelling on that side and the testis
appears to be pulled up towards the scrotum. On palpation the testis will be tender and the cremasteric reflex is
lost.
In the case of neonatal torsion, there may not be very
clear symptoms. The baby may in fact be quite comfortable and the torsion is detected on chance examination of
the scrotum.
Investigations
Possible investigations are a scrotal ultrasound, a
radionuclide scan to see the blood flow to the scrotum.
However, time should not be wasted since testicular
necrosis will set in rapidly.
Treatment
An acute scrotum is one of the most urgent situations in
pediatric surgery. Without wasting any time, the scrotum
should be explored and torsion corrected if possible. The
testis should then be fixed to the scrotum to prevent further
episodes of torsion. If the testis has already undergone
necrosis, it should be removed since there is evidence that
such a testis will cause an immune mediated damage to
the opposite testis.
The normal testis on the opposite side should also be
exposed and fixed to the scrotum to prevent torsion on
that side.
GENITAL CONDITIONS IN CHILDREN
Phimosis
Introduction
Phimosis is the inability to retract the prepuce fully and
freely to expose the glans penis. It is one of the most
common problems referred to the pediatric surgeon.
Phimosis is physiological in infancy and early childhood since there are adhesions between the glans and the
foreskin that separate spontaneously by the age of two to
three years, sometimes taking upto five to eight years.
Phimosis is pathological when it causes symptoms
such as straining at micturition, burning micturition or
recurrent attacks of balanoposthitis.
Paraphimosis implies that the foreskin that has been
retracted back to expose the glans and the coronal sulcus
1257
cannot be repositioned to cover the glans. The foreskin

gets entrapped behind the coronal sulcus due to a small
preputial opening.
Treatment
Physiological phimosis should be left alone. Unless there
are clearly symptoms associated with phimosis, no
specific treatment is required in early childhood. If symptoms occur, gentle retraction of the prepuce followed by
the application of a mild steroid topically has been
successful in relieving the phimosis. If unsuccessful,
surgery may be needed in the form of a circumcision , or a
preputioplasty, which is a procedure that can enlarge the
preputial orifice, while retaining the foreskin. It was the
practice in some Western countries to routinely circumcise
all newborn boys. This has now been found to be
unnecessary since there is no clear medical benefit to
performing this operation. In certain communities,
neonatal circumcision may be performed for religious
reasons.
Hypospadias and Epispadias
Hypospadias indicates that the external urethral orifice
is abnormally placed on the ventral aspect of the penis
(Fig. 26.1.20). In most of these cases, there is an additional
ventral curvature of the shaft of the penis called ventral
chordee (Fig. 26.1.21A). The prepuce is also deficient
ventrally, forming a hood like covering to the dorsal glans
(Fig. 26.1.21B).
These cases need evaluation and eventual surgery for
psychological reasons and since future sexual function
will be compromised due to the deformity.
Epispadias is a more uncommon anomaly that is
caused by the urethral meatus opening abnormally on the
dorsal aspect of the penis. Some cases of epispadias may
have urinary incontinence additionally and will need
corrective surgery after evaluation.
NEUROSURGERY IN CHILDHOOD
Hydrocephalus
Hydrocephalus denotes an increase in the amount of
cerebrospinal fluid (CSF) in the brain, usually under raised
pressure, with an increase in the size of the ventricles.
Under normal circumstances, CSF is formed by the
choroid plexus which is present on the medial wall of the
lateral ventricle and the roof of the third ventricle. The
1258
Figure 26.1.20: Hypospadias: 1glanular, 2coronal, 3

penile, 4peno-scrotal, 5perineal types
Figure 26.1.21A: Chordee in a case of hypospadias
Figure 26.1.21B: Dorsal hood in a case of

peno-scrotal hypospadias
fluid which is formed in the lateral ventricles flows

through the foramen of Monro to the third ventricles. From
here through the aqueduct of sylvius to the fourth
ventricles and thence to the subarachnoid space through
the foramina of Magendie and Lushka. After bathing the
subarachnoid space of the brain and spinal cord the fluid
is absorbed through the arachnoid villi to enter the dural
sinuses.
The usual cause for accumulation of excessive CSF is
a block in the pathway of CSF circulation that impedes
absorption of the fluid. This block may be either proximal
to the outlet of the fourth ventricle, i.e. within the brain, in
which case it is termed a noncommunicating
hydrocephalus since there is a block in the communication
between all the ventricles. If all the ventricles communicate
freely, but there is a block distal to the ventricles in the CSF
circulation pathway, i.e. there is a block in the
subarachnoid space that prevents the CSF from reaching
the arachnoid villi, this is termed a communicating type
of hydrocephalus.
When CSF collects in the ventricles it causes the
ventricles to distend. In the infant while the fontanelles
are open and the sutures are not fused, the increase in
ventricular volume can be compensated by increase in the
dimension of the vault of the skull. Thus, there is no
increase in the intracranial pressure at first, but there will
be an increase in the skull circumference at a rate more
than normally expected.
As the ability of the pliable cranium to accommodate
the increase in the CSF volume is exhausted, general and
local signs of raised intracranial pressure are evident.
Acute episodes of raised ICT can occur in some patients,
and these may have a fatal outcome.
Clinical Features
The earliest presentation of congenital hydrocephalus is
at birth when a large head can cause cephalopelvic
disproportion and dystocia. Routine antenatal sonography may pick up some cases before birth.
In infancy there will be an increased rate of growth of
the skull circumference. In more advanced hydrocephalus,
the head appears disproportionately large as compared
to the body. The dome of the skull appears large and the
eyes and ears seem low set. The skin on the scalp is shiny
and thin and shows prominent scalp veins. The fontanelle
is bulging and tensed. And the sutures may show diastasis.
Local signs of raised ICT manifest as signs of
compression of specific areas or nerves. The abducent
nerve is affected early manifesting as loss of lateral gaze
and unilateral or bilateral medial squint. The setting sun
Pediatric Surgery
sign denotes that the upper limbus of the eye is visible in
the resting state.
Other signs include Macewens sign, where percussion on the head produces a cracked-pot sound.
General signs of raised ICT and of chronic compression of the brain substance are general irritability,
delayed milestones, altered sensorium, and an exaggeration of the deep tendon reflexes.
Confirmation of the diagnosis is mainly by MRT, CT
scan and sonography. In infants, before they have closed
the open fontanelles provide a window to scan the interior
of the skull. Plain X-rays can be done to show thinning of
the calvarium or the beaten silver appearance, but are less
useful compared to the previous investigations.
Treatment is by surgery. A shunt operation is
performed, in which a tube is placed in the ventricle to
drain away the excessive fluid into either the right atrium
(Ventriculoatrial shunt) or into the peritoneal cavity
(Ventriculoperitoneal shunt).
If the shunt can be done relatively early, the prognosis
can be good in terms of development and achievement of
milestones. If done late there may already be thinning of
the brain parenchyma, in which case the outlook may not
be so good, but at least further damage will be prevented.
A point to be noted is that all shunts are prone to
complications like infection and blocks in the tubes. These
are responsible for the significant complication rate of
hydrocephalus.
Recently, in indicated cases of aqueductal stenosis, an
endoscopic third ventriculostomy can be performed. An
important advantage of this procedure is the absence of
the shunt tube, which is largely responsible for complications and morbidity in these cases.
from either side to form the coverings of the spinal cord.

An abnormality in the formation of these coverings results
in the vertebral bodies being split or bifid posteriorly with
the meninges herniating out through the defect so formed.
When this herniation consists of meninges only,
forming a CSF filled sac, the condition is called a
meningocele (Fig. 26.1.22). In more severely affected cases,
the spinal cord forms part of the herniation and is seen as
an exposed nerve plaque at the apex of the herniated
meninges. This condition is called a meningomyelocele
(Fig. 26.1.23).
Clinical Features
Meningoceles and meningomyeloceles can occur in any
part of the spine, namely the cervical, thoracic or lumbosacral regions.
Meningomyeloceles can be dangerous since the
exposed spinal cord may have lost or may rapidly lose
capacity to function normally, thus causing an upper
motor neuron type of paralysis affecting the segments
below the lesion. In practical terms, in the commonly seen
lumbosacral meningomyelocele, there may be paralysis
of both the lower limbs with loss of control of the bladder
and bowel functions. Once lost, this function never returns
and the child must learn to live with the disability for life.
There are other associated malformations that cause
hardship:
1. Hydrocephalus may be present in a majority of children
with meningomyelocele.
2. Vertebral deformities like kyphosis or scoliosis may be
present.
3. Limb deformities like clubfoot may be associated.
4. The spinal problem may be part of a generalized
syndrome.
Spina Bifida
Introduction
Spina Bifida is one of the most common congenital
anomalies, occurring in 1-2/1000 live births. Since the
defect involves the spinal cord, meninges vertebral column
and the brain, the consequences of the problem can affect
several functions.
Embryology
The primitive spinal cord is formed by the neural plate
which tubularizes to form the neural tube. The neural tube
is covered by folds of ectoderm and mesoderm which join
1259
Figure 26.1.22: Meningocoele-skin covered
1260

instruments similarly introduced through puncture
incisions. The entire procedure is visualized on a monitor
for magnification and ease of working (Fig. 26.1.24) and
may also be recorded for future reference.
Figure 26.1.23: Meningomyelocoeleexposed central

neural plaque and meninges

Treatment can be offered in the form of surgical repair of
the herniated meninges with or without the spinal cord,
however, function that has been lost cannot be regained.
Children with meningomyelocele who are operated
early, before loss of function have to be followed carefully
for bladder and bowel function, assessment of motor
function and evaluation for hydrocephalus. The management is best done by a team of pediatricians, pediatric
surgeons, with a special interest in neurosurgery and
urology, and with physiotherapists.
Those unfortunate children who have lost nerve function of the distal cord and who have hydrocephalus
additionally, form the subject of a continuing ethical debate
regarding the appropriate course of action to be taken.
There are several who believe that the future quality of life
in these children and for the entire family, does not warrant
intervention in the newborn period, and that these children
are best left alone without any therapy.
LAPAROSCOPY IN PEDIATRIC SURGERY
Laparoscopic surgery has introduced a new modality of
treatment in the surgical disorders of children.
Laparoscopy involves visualization of the various
structures of the abdominal or thoracic cavity under high
illumination by a telescope introduced through the
respective parietes (abdominal or thoracic wall). Simultaneous surgical procedure is done through micro-
Figure 26.1.24: Diagram showing the concept in

laparoscopic surgery
The procedure offers all the benefits of minimal access

surgery to children.
Advantages
Almost blood less and painless access.
Decreased chances of wound infection/dehiscence/
weakness of abdominal wall
Smaller incisions of MAS lead to better aesthetic
healing and provide a cosmetic scar
Minimal chances of postoperative adhesions or
intestinal obstruction
Reduced exposure of organs to atmosphere facilitates
early return of peristalsis and thus early feeding.
Early convalescence decreases loss of schooling or
sports time.
Panoramic and magnified surgical view.
Reduced metabolic response to surgery and better
preservation of immune response.
Reduced postoperative pulmonary complications like
atelectasis and pneumonia.
Various indications for this modality of treatment
include:
Diagnostic
In the evaluation of children with:
Chronic and unexplained abdominal pain
Unexplained lower GI bleeding
Intersex evaluation
Abdominal tuberculosis
Pediatric Surgery
Therapeutic
Appendectomy
Non-palpable testis
In the evaluation of contralateral processus vaginalis
in a case of congenital inguinal hernia.
Cholecystectomy
Adheseolysis and division of bands
Fundoplication for GER
Pyloromyotomy for pyloric stenosis
Appendicostomy for fecal incontinence
Splenectomy
Meckels diverticulum diagnosis and excision
Nephrectomy
Adrenalectomy
Figure 26.1.25: Lap viewmesenteric cyst causing

recurrent vomits in a 6 month old
1261
Pull through surgery for Hirschsprungs disease or

imperforate anus (high variety)
Evaluation and if possible surgical treatment of intraabdominal cysts (Fig. 26.1.25).
INDICATIONS FOR THORACOSCOPY (VATS)
27.1 Congenital Anomalies: PP Kotwal, Bhavuk Garg ............................................................................................................................ 1264

27.2 Infections of Bones and Joints: PP Kotwal, Bhavuk Garg ............................................................................................................ 1268
27.3 Neuromuscular Disorders: Mayilvahanan Natarajan ....................................................................................................................... 1278
27.4 Osteochondritis: Mayilvahanan Natarajan ........................................................................................................................................ 1282
27.5 Inequality of Limb Length: Mayilvahanan Natarajan, PP Kotwal, MK Varshney ........................................................................... 1285
27.6 Pediatric Bone Tumors: Mayilvahanan Natarajan, PP Kotwal, MK Varshney ................................................................................ 1288
27.7 Miscellaneous Orthopedic Conditions: PP Kotwal, MK Varshney ............................................................................................... 1296
1264
27.1 Congenital Anomalies

Only commonly seen congenital anomalies in the pediatric patients are discussed in this chapter. The deformities, where early diagnosis or differential diagnosis is
considered important have been included in this chapter.
It is outside the scope of this book to discuss all the
congenital anomalies seen in the musculoskeletal system.
CONGENITAL TALIPES EQUINO VARUS (CTEV)
Clubfoot or CTEV is a deformity of the foot in which the
foot is turned inwards (Fig. 27.1.1). The characteristic
elements of the deformity complex are: Equinus (plantar
flexion) of the ankle, inversion of the foot, adduction of
the forefoot and medial rotation (torsion) of the tibia. The
incidence of this deformity is 1 in 1000 live births. It may
be associated with spina bifida and/or congenital
dislocation of the hip.
Pathological Anatomy
The clubfoot, typically is at first a deformity of the soft
tissue only. The bony changes develop secondarily.
Muscles and Tendons
The muscles of the calf are poorly developed. The tendoAchilles is contracted and inserted more medially on the
calcaneum, which contributes to the inversion of the heel.
The plantar muscles on the medial side are contracted
while those on the dorsum of the foot are elongated and
occasionally poorly developed.
Ligaments
The ligaments and joint capsules on the posteromedial
side of the foot are contracted.
Etiology
Bones
Clubfoot may result from an osseous, muscular or

neuropathic error; or may be idiopathic. Various theories
of etiology have been put forward, however, in general,
two types of CTEV may be seen at birth:
i. Primaryidiopathic.
ii. Secondarythe clubfoot is a part of the systemic
disease such as arthrogryposis multiplex congenita
(AMC), muscular dystrophy or meningocele, etc.
The bones of the foot are smaller than normal. The talus
is tilted plantar ward and subsequently the position of
the navicular, calcaneum and cuboid is also altered.
In neglected cases, the foot may be turned inward
completely with the result that the child may walk on
the lateral border of the foot or even on the dorsum of
the foot.
Clinical Features
Figure 27.1.1: Congenital talipes equino varusCTEV

(clinical photograph)
Ideally, a routine screening of the newborn children for

detection of congenital malformations should also
include the following, apart from other anomalies:
i. Clubfoot
ii. Congenital dislocation of hip
iii. Spina bifida
It may be an unilateral or bilateral deformity. In unilateral cases the deformity may not be very severe. The
foot is smaller and less developed than on the normal
side. Normally the foot can be dorsiflexed till the dorsum
touches the anterior part of the leg. However, in clubfoot,
especially in mild unilateral cases, this maneuver is not
possible due to the contracture of tendo-Achilles.
The calf is smaller in size and underdeveloped; so also
the heel. Deep skin crease is seen on the medial side of the
Pediatric Orthopedics
foot. The foot is deformed and the outer border of the foot
is convex. Passive correction of the deformity may be
possible in mild cases. However, the equinus deformity
may not be corrected fully due to the tight tendo-Achilles.
In rigid clubfoot the deformity is not correctable passively.
In neglected clubfoot where the child presents late,
callosities are seen over the lateral border of the foot or the
dorsum of the foot, depending upon the severity of the
deformity.
A thorough systemic examination should also be
undertaken to detect any underlying disease such as
poliomyelitis, AMC, etc.
Diagnosis
The diagnosis of clubfoot is generally obvious on clinical
examination alone. However, it should be differentiated
from paralytic conditions causing it or from AMC.
Radiographs of the foot may be done to measure the
talocalcaneal angle which quantifies the deformity, forms
a baseline documentation and a method to assess the
correction of the deformity after treatment.
Treatment
The principles of treatment are as follows.
The goal of treatment is to correct the foot deformity
fully, and to maintain the correction achieved up to the
skeletal maturity so that the deformity does not recur.
The treatment should start as early as possible.
Correction of the Deformity
Nonsurgical Methods
Passive manipulation: In the newborn, the mother is taught
to manipulate the childs foot passively in an attempt to
correct the deformity. The foot is held in the corrected
position, by applying firm pressure, for 5 to 10 seconds.
This maneuver is repeated several times during the day.
The method of passive manipulation is continued till the
child is about 6 weeks old when other methods such as
strapping or Plaster of Paris (POP) cast may be applied.
Strapping: After the age of six weeks, the foot is corrected
by passive manipulation, and the correction is maintained
by strapping the foot using adhesive plaster.
Plaster of Paris cast: Like in the method of strapping, in this
method also, the deformity is corrected by passive
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manipulation and the correction is maintained by a POP

cast. This method is also employed after 6 weeks of age.
The plaster is maintained for a period of two weeks after
which the plaster is removed, the status of the foot
deformity is assessed and the plaster cast is reapplied.
The cast is changed every two weeks till the deformity is
fully corrected or if the deformity is rigid, some surgical
intervention is resorted to.
The passive manipulation by any of the above
mentioned methods is carried out in the following
specified mannerthe adduction of the forefoot is
corrected first, then the inversion of the foot is corrected
and the equinus deformity at the ankle is the last
deformity to be corrected. If this sequence is not followed,
a rocker-bottom foot may result which may be difficult
to treat.
The correction of the deformity is maintained with
the help of splint or special shoes.
Ponseti Treatment
This treatment was developed by Dr. Ignacio Ponseti from
USA. This treatment of clubfoot is based on the biology of
the deformity and the functional anatomy of the foot.
The cavus, or high arch, is a characteristic deformity
of the clubfoot which is corrected first followed by
simultaneous correction of the other deformities of the
foot, i.e., the varus, inversion, and adduction. Most of
the cases of clubfoot, by this technique, require only five
to six cast changes; occasionally an additional procedure
of Tendo-Achilles tenotomy may be required. This method
has gained wide popularity in the recent past since it
results in feet that are strong, flexible and plantigrade with
a shorter duration of treatment.
Surgical Methods
In rigid clubfoot or in cases where some residual deformity
is left after conservative treatment, surgical treatment is
resorted to. The commonly performed surgical procedures
are as follows:
Tendo-Achilles lengthening: The tendo-Achilles tendon is
lengthened to correct the equinus deformity.
Posteromedial soft tissue release: As the name suggests, the
tight/contracted soft tissue structures (ligaments,
tendons and joint capsules) on the medial and posterior
aspects of the foot and ankle are lengthened or released
to correct the deformity.
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Bony operations: These are done after 4 years of age to correct

the deformity. These operations can be: Osteotomy of a
tarsal bone (usually calcaneum) or fusion of the tarsal
joints.
CONGENITAL DISLOCATION OF HIP (CDH)
Congenital dislocation of hip (CDH) is a spontaneous
dislocation of the hip which occurs before, during or
shortly after birth. It is relatively uncommon in India. Its
significance lies in its early diagnosis because neglect or
delay in treatment can make the patient crippled.
Etiology
The exact etiology is not well-understood, however,
various theories have been suggested.
Joint laxity: Generalized joint laxity may predispose
dislocation of the hip.
Hormonal joint laxity: CDH is more common in girls. In
females, the fetal uterus secretes a ligament relaxing
hormone (called relaxin) in response to the maternal
estrone and progesterone. The ligament laxity at the hip
may cause dislocation.
Breech malposition: The dislocation of hip is more common
after breech delivery. Ligamentous laxity again, during
breech delivery, may cause dislocation of the hip.
Pathology
The following changes are seen in the hip joint:
The epiphysis of the femoral head is small and it
appears late. The femoral head is dislocated upwards
and laterally in relation to the acetabulum (Fig. 27.1.2).
The angle of anteversion of the femoral neck (normal 510) is about 25. The acetabulum is shallow and its roof
is sloping upwards. The fibrocartilaginous labrum of the
acetabulum (also called limbus) is folded into the
acetabular cavity and may come in the way of reduction
of the dislocation. The capsule of the hip joint is
elongated.
Clinical Features
The girls are affected 5-6 times more in comparison to
boys. One or both hips may be affected. The diagnosis is
difficult in the early cases and therefore, the condition
has to be looked for. It must form a part of the general
screening program in the newborn for detection of
congenital anomalies.
In the Newborn
There may be asymmetrical skin folds on the inner aspect
of thigh. Abduction of the hip joint may be limited. The
following clinical tests may help in the diagnosis:
Figure 27.1.2: Pre- and post-operative radiograph of congenital dislocation of hip treated by open reduction,
varus derotation osteotomy and shelf procedure
Barlows test: The clinician grasps the upper part of both
thighs with his or her thumb on the hip anteriorly and the
fingers on the buttocks. The hip joints are now adducted
while pressure is exerted on the thumb trying to push the
head of the femur out of the acetabulum. The hip may
dislocate with an audible clunk.
Ortolanis test: The child is held in a similar manner as
described in the Barlows test. The hips are steadily
abducted and the middle finger of the examiner applies
forward pressure behind the greater trochanter. A click
is heard as the dislocated femoral head slips into the
acetabulum.
In Older Children
The diagnosis may not be difficult in older children. There
is widening of the perineum, marked lumbar lordosis and
a characteristic waddling gait.
Investigations
A radiograph will confirm the diagnosis. Arthrography
helps to show the outline of the cartilaginous parts of the
joint. An MRI may be equally useful.
Treatment
The treatment varies with the age of the patient. The
prognosis is better when the treatment is started as early
as possible, preferably in the first week of life.
The goal of treatment is to reduce the dislocation of the
hip and to maintain it till a stable and full round
acetabulum develops.
The reduction of the dislocation can be achieved by
the following methods:
i. Closed manipulation under general anesthesia and
POP cast application.
ii. Traction with the hip in abduction.
iii. Open reduction of the hip joint by surgical operation.
The reduction can be maintained by POP cast or special
type of splints, etc.
If the acetabulum is too shallow, the acetabular roof
can be reconstructed by doing an osteotomy of the ilium
bone or a shelf operation (Fig. 27.1.2). A varus derotation
osteotomy is required to correct excessive anteversion of
the neck of femur (Fig. 27.1.2).
OTHER ANOMALIES
Scoliosis
Scoliosis is defined as lateral curvature of the spine.
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Growth of only one-half of a vertebra (called as

hemivertebra) can result into congenital scoliosis.
Patients with congenital scoliosis should be screened
for cardiac, renal and other musculoskeletal anomalies.
Scoliosis can also develop without any known
pathology and is known as Idiopathic Scoliosis. This is
the commonest type. Scoliosis can also develop in patients
with paralytic disorders like polio because of muscle
imbalance and is known as Neuromuscular scoliosis.
Torticollis
Torticollis results from contracture of the sternomastoid
muscle on one side. There occurs thickening of the muscle
(sternomastoid tumor) in infancy, replaced by fibrous
tissue. The tight sternomastoid muscle exerts a pull on the
head tilting it on the same side (Fig. 27.1.3). If not treated
early, it results in asymmetrical development of the face.
Treatment is surgical release of the tight muscle followed
by physiotherapeutic exercises.
Radial Club Hand
In this condition, the radius is either absent or rudimentary
(Fig. 27.1.4). The hand is deviated laterally due to the lack
of normal support by radius (Fig. 27.1.5). The thumb is
often absent. There may be associated anomalies of the
heart and a bleeding diathesis. The treatment is surgical
correction of the deformity by centralizing the ulna in
Figure 27.1.3: Congenital torticollis. The tight sternomastoid

muscle on the right side is tilting the head to right side. There
is also an asymmetrical development of the face (Clinical
photograph)
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Fig 27.1.4: Radiograph of spine of a patient with congenital

scoliosis showing hemi vertebrae
relation to the hand. In cases where thumb is absent, the

thumb is reconstructed by pollicization of the index finger.
Trigger Thumb
Trigger thumb occurs in infants and young children where
free gliding movement of the long flexor tendon of the
thumb (flexor pollicis longus) is affected due to a nodular
Figure 27.1.5: Radial club hand. (A) Preoperative clinical photograph showing deviation of hand to the radial side and absence
of thumb. (B) X-ray of same patient showing absence of radius.
(C) Post-operative clinical photograph after centralization of
ulna
swelling of the tendon, proximal to constriction at the

mouth of the flexor sheath. The infants thumb cannot be
straightened since it is locked in flexion. On examination,
a nodular swelling is palpable at the base of the thumb on
the volar aspect. Passive stretching may or may not extend
the thumb fully. Treatment is surgically incising the
constricted mouth of the tendon sheath.
27.2 Infections of Bones and Joints

OSTEOMYELITIS
Osteomyelitis is defined as infection of the bone. It can be
acute, subacute or chronic osteomyelitis. Osteomyelitis can
either be hematogenous or exogenous in its origin.
Bloodstream infection is the most common, however, with

the increasing incidence of accidents and compound
fractures, the exogenous osteomyelitis is also becoming
common.
ACUTE OSTEOMYELITIS
The common organism responsible for osteomyelitis is
Staphylococcus aureus. Sometimes Streptomyces albus may
be found but in that case the symptoms are less acute.
Occasionally, Streptococcus may be responsible for the
infection. Escherichia coli and Clostridium welchii are found
in cases where the original injury was a compound
fracture.
Salmonella is a rarely isolated organism but is
frequently seen in patients with sickle cell disease.
Pathogenesis
Hematogenous osteomyelitis starts in the region of
metaphysis of the long bones. A mild bacteremia usually
precedes the actual onset of the disease in the metaphysis.
A history of recent trauma is an important localizing
factor for the infection in the metaphysis. The trauma
usually causes hemorrhage and cell destruction in that
region, thereby, reducing tissue resistance. The microorganisms multiply in the metaphyseal region, an
inflammatory edema is setup and virtually results into
an abscess. The abscess then rapidly spreads to the
medullary canal filling up the whole interior of the shaft
with pus. The infection then spreads, through the
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haversian canals, to the periosteum. The pus gets under

the periosteum, lifting the latter from the bone, resulting
in a subperiosteal abscess (Fig. 27.2.1).
As the subperiosteal abscess lifts the periosteum from
the bone, it cuts off the periosteal vessels to the cortex of
the bone and thereby the blood supply. The bone
underneath becomes dead and develops into a sequestrum. In children the periosteum can get lifted off easily
resulting in a large diaphyseal sequestrum (Fig. 27.2.2),
whereas in adults the periosteum cannot get lifted off easily
and therefore, the abscess bursts open outside resulting
in multiple discharging sinuses.
In certain situations where the metaphysis is intracapsular, e.g. upper end of the femur, the abscess may
burst open from the metaphysis directly into the joint
(hip joint) and cause septic arthritis (Figs 27.2.3 and
27.2.4).
Figure 27.2.2: Chronic osteomyelitis. Large diaphyseal

sequestrum involving radius (radiograph)
Figure 27.2.1: Hematogenous (acute) osteomyelitis. Spread

of pus from metaphysis to: (1) the medullary canal,
(2) subperiosteal abscess. The pus has come out through the
cortex and lifted the periosteum. The cortex underneath will
loose its blood supply and become sequestrated, (3) directly
into the joint (rarely), (4) the joint, since the metaphysis is intracapsular (note the attachment of the joint capsule), and (5) the
muscular plane or outside through a sinus
Figure 27.2.3: The metaphysis is extra-articular and the

abscess from metaphysis will not open into the joint
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(diagnostic for osteomyelitis) appears as late as 7-12 days,
and (iv) a technetium-99m bone scan may show an
increased uptake by the affected bone earlier than the
changes on the plain radiographs.
Acute osteomyelitis has to be differentiated from the
following conditions.
Acute Pyogenic (Septic) Arthritis
Figure 27.2.4: Here the metaphysis is intracapsular and

hence the pus will directly open into the hip joint
The symptoms and signs are pertaining more to the joint

than to the bone (metaphysis). Swelling and tenderness
are localized to the joint. The joint effusion sets earlier
than in acute osteomyelitis. The muscle spasm and
restriction of joint motion are more marked. Aspiration
of the joint under aseptic conditions will strike pus.
Acute Rheumatism
Diagnosis
The diagnosis of acute osteomyelitis is based usually on a
thorough clinical examination since radiograph may look
normal in the initial period. There may be a history of
trauma to the affected part preceding the onset of
symptoms. One may also find a primary focus of infection
somewhere in the body, e.g. skin, throat, etc.
In the acute stage the child presents with high fever,
headache, restlessness and dehydration. In rare neglected
cases, there may be signs of toxemia. The affected limb is
held in a position of flexion of the adjacent joints, the
position which relaxes the capsule to accommodate
effusion which is usually sympathetic in nature. In the
affected limb, maximum tenderness is present over the
site of original focus, i.e. metaphysis. Swelling may become
evident in the leg when pus comes into the muscular/
subcutaneous plane. Handling the affected limb elicits
extreme pain and therefore, the child resists any examination of the limb or even changing clothes/bedsheet, etc.
In the acute stage investigations may support the
clinical diagnosis, they are not specific to clinch the
diagnosis: (i) a raised local leukocyte count (up to 20000
cells) and a raised ESR are always present, (ii) blood
culture may isolate the causative organism, (iii) radiograph of the local part should always be taken to rule out
any other condition/injury, although the earliest sign of a
periosteal reaction in the region of the metaphysis
The onset is gradual with pain in the joints which is

flitting in nature. More than one joint are affected at
the same time. There may be raised antistreptolysin-O
(ASLO) titer and C-reactive protein values.
Acute Poliomyelitis
Fever with tenderness more in the affected group of
muscles than in bones.
Hemophilia
A bleed into muscle or joint may produce pain, swelling
and marked tenderness locally. However, a history of a
bleeding diathesis should be inquired into.
Treatment
The most important factor in the successful treatment of
this condition is early diagnosis. At the first suspicion of
acute osteomyelitis, the child should be admitted and
investigated. A blood culture is sent and empirically
intravenous chemotherapy using ampicillin and cloxacillin should be started. One may also add gentamicin to
broaden the spectrum. The antibiotic is subsequently
changed according to the culture and sensitivity report.
The limb should be immobilized in a plaster of Paris
(POP) cast, and a window may be made to observe the
local condition. Immobilization helps to stop or decrease
the spread of infection by reducing the muscle action and
blood flow.
The local site should be inspected every six hours for
any palpable abscess or increased swelling. And if there
is failure to this treatment within 24 hours of starting the
treatment, surgery should be carried out. The surgery
consists of draining the abscess or drilling multiple holes
in the medullary cavity of the bone to drain the pus.
Immobilization and antibiotics are continued for a period
of 3 weeks and 6 weeks respectively.
CHRONIC OSTEOMYELITIS
Acute osteomyelitis, when treated inadequately, may
pass on to chronic osteomyelitis. Sometimes, the host
defense mechanism may be weak as compared to the
high virulence of the organisms and thus, the disease
may become chronic. Occasionally, the disease may
present in subacute form and is called as:
i. Sclerosing osteomyelitis of Garre.
ii. Brodies abscess.
Diagnosis
The chronic osteomyelitis is characterized by persistence
of discharging sinuses (Fig. 27.2.5). The sinus is fixed to
the underlying bone. The cause for the discharging sinus
is an underlying sequestrum or an unobliterated cavity
Figure 27.2.5: Discharging sinus in the upper

arm due to osteomyelitis of the underlying
bone [(humerus), (clinical photograph)]
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in the bone. Pain may occasionally be present during an

acute exacerbation. The adjacent joint may be stiff due
to secondary arthritis.
A radiographic examination is usually diagnostic for
chronic osteomyelitis. The following features may be seen
on a radiograph (Fig. 27.2.6):
Thickening or irregularity of the cortex (bone).
A cavity may be seen in the bone.
One or more sequestra may be seen inside the cavity
Sequestra may be seen involving large areas of the
bone, e.g. diaphyseal sequestrum (Fig. 27.2.2).
New bone formation is seen outside the sequestrum
This is called as involucrum.
The radiograph may show a pathological fracture
occurring through the weakened part of the bone
(Fig. 27.2.7).
Sequestrum is defined as a piece of dead bone surrounded by infected granulation tissue. The sequestrum
has a smooth surface which is bathed in pus and a
ragged edge which is surrounded by granulation tissue.
The size of a sequestrum may vary from a flake of bone
to a large diaphyseal segment of a long bone.
Involucrum: It is the new reparative bone formed
underneath the elevated periosteum. This is situated
Figure 27.2.6: Radiograph of

chronic osteomyelitis
Figure 27.2.7: Pathological fracture

of humerus in chronic osteomyelitis
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outside the sequestrum. The pus makes its way through

the involucrum by way of holes which are called as
cloacae.
Chronic osteomyelitis should be differentiated from:
i. Ewings sarcoma, and
ii. Tuberculous osteomyelitis.
Treatment
Antibiotics are given according to the pus culture and
sensitivity reports.
Surgical operations are performed to remove the
sequestrum (sequestrectomy), to remove the infected
granulation tissue (curettage), make the cavity in the bone
shallow (called as saucerization) which prevents
accumulation of pus inside them.
The sinus tract is excised.
The cavities in the bone are sometimes obliterated by
filling them up with bone grafts or a viable muscle from
the neighborhood.
Amputation may be indicated very rarely, especially
when the sinus undergoes a malignant change or the
patient develops amyloidosis.
Figure 27.2.8: Septic arthritis of ankle

(secondary to osteomyelitis of lower tibia)
Complications
Acute-on-chronic osteomyelitis.
Stiffness of the adjacent joints may occur either due
to scarring of the soft tissues, or ankylosis (fusion) of
the joint due to secondary infection of the joint
(Fig. 27.2.8).
Pathological fracture may occur through the weakened part of the bone.
Deformity of the limb may occur due to malunion of
a pathological fracture.
Discrepancy in the limb lengthshortening may occur
when the growth plate is damaged due to infection
(Fig. 27.2.9).
Lengthening may occur occasionally because of the
increased vascularity in the region of the growth plate
(which is close to the site of infection, i.e. metaphysis).
A long-standing discharging sinus may rarely transform into squamous cell carcinoma.
Amyloidosis may develop in a long-standing disease.
Osteomyelitis in HIV disease: The destruction of the bone
is much more extensive with little or no reparative new
Figure 27.2.9: Limb length discrepancy due to destruction of

growth plate by infection
bone formation. The bones usually involved are upper
tibia and lower femur. The disease is often bilateral and
septic arthritis is common.
ACUTE SEPTIC ARTHRITIS OF INFANCY
(TOM SMITH ARTHRITIS)
This type of septic arthritis of the hip joint is seen in
children under one year of age, and is generally
secondary to a neighboring bone lesion. In infants the
head of femur is cartilaginous and therefore, may be
completely destroyed by the infection, thereby, affecting
the future function of the limb. The most common
causative organism is Staphylococcus aureus or hemolytic
Streptococcus. The infection produced by the former is
more virulent and more destructive. This type of infection
is being seen more commonly in neonatal intensive care
unit.
The child presents with fever, occasionally signs of
toxemia, and swelling of the hip joint, of rather abrupt
onset. On examination, there is muscle spasm, fluid
within the joint and pain on slightest movement. The
hip is held in a position of flexion. Radiograph may show
complete absence of the head and neck of femur.
The treatment is early drainage under proper
antibiotic cover.
PYOGENIC (SEPTIC) ARTHRITIS
Pyogenic (septic) arthritis is caused by pyogenic
organisms, mainly Staphylococcus aureus. However,
streptococci, pneumococci, gonococci, meningococci and E.coli
may infect the joint occasionally. In young children
Hemophilus influenzae has also been reported to be a
common organism.
Acute pyogenic arthritis may also occur in children
in acute infectious diseases such as enteric fever,
influenza, pneumonia, etc.
Routes of Infection
The organisms gain entry through:
i. Hematogenous route from a primary focus in the
respiratory tract, genitourinary tract, intestinal tract,
teeth, tonsils, etc. or umbilical cord sepsis in children.
ii. An infection in the bone, particularly when the
metaphysis is intra-articular as in hip or shoulder.
iii. A puncture wound.
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Diagnosis
Knee is the commonly affected joint. However, hip, elbow
and shoulder joints may also be affected. The child
presents with pain in the joint, high-grade fever, signs of
toxemia in severe cases and is unable to move the affected
limb. Locally, there is swelling and restricted motion of
the affected joint. The limb is held in a position of flexion
of the affected joint.
In the early stages of the disease, the radiograph may
either be normal or may show an increase in the joint
space (due to collection of fluid). A soft tissue swelling
may also be appreciated on a better quality radiograph.
A radiograph of the unaffected joint of the other limb
should be taken for comparison. In the later stages of the
disease, the radiograph will show diminution in the joint
space, destruction of the articular cartilage, new bone
formation and eventually total bony ankylosis.
The blood examination may not be very helpful since
a rise in the total leukocyte count and ESR will be present
in most of the inflammatory conditions likely to be
confused with pyogenic arthritis.
Aspiration of the joint and examination of the fluid
may show features of pyogenic arthritis.
Tuberculous arthritis
Acute rheumatism
Acute pyogenic osteomyelitis.
Treatment
Early diagnosis and joint drainage can save the joint from
complete destruction and disorganization. Antibiotics are
started as per the culture and sensitivity report of blood
and/or pus. Joint aspiration is carried out and if pus
strikes, an open drainage of the joint (arthrotomy) should
be performed.
Immobilization of the limb by traction or POP slab
helps to reduce pain, muscle spasm and spread of the
disease. Mobilization of the joint is started after the
patient becomes afebrile, the pain subsides, and the joint
is quiescent clinically.
OSTEOARTICULAR TUBERCULOSIS
Tuberculosis of the bones and joints is still fairly common
in India. It is almost always secondary to a primary focus
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elsewhere in the body. However, the primary focus may

be detected only in 40 percent cases, half of which may
be in the lungs. The organisms reach the site of affliction
through bloodstream. It is doubtful whether a history of
trauma is a causative factor. If at all, trauma precipitates
the onset of the disease, trauma causes damage to the
capillaries in the bone and thereby causes vascular
stagnation resulting in stasis of bacteria and their
subsequent multiplication.
TUBERCULOUS OSTEOMYELITIS
The bones commonly affected by tuberculous infection
are short long bones, e.g. metacarpals, metatarsals and
phalanges, and short bones such as calcaneum, carpals,
etc. Tuberculosis of the phalanges is called as spina
ventosa (Fig. 27.2.10). The long bones are rarely affected.
Tuberculous osteomyelitis is a subacute infection and
therefore, presents as pain and swelling of the affected
part. There is irregular thickening of the bone and
occasionally a discharging sinus too. The radiographs
show a lytic lesion in the bone associated with little sclerosis or new bone formation. The treatment consists of:
i. Antituberculous drugsa three or four drug regime
is started initially and then maintained on two drugs
for a total period of about 12 to 18 months.
ii. The affected part may be immobilized in a plaster

cast/slab for about 4 to 6 weeks to give rest to the
part.
iii. Surgery may be undertaken occasionally in the form
of curettage of the lesion with or without bone
grafting. Bone grafting is essential in cases of big
cavities.
TUBERCULOUS INFECTION OF THE JOINT
Tuberculosis may affect any joint, however, the
commonly affected joints are hip, knee and elbow. The
shoulder, wrist and ankle joints are rarely affected. The
tuberculous infection of the joint may be:
i. Synovial, or
ii. Osseous.
The Course of the Disease
A synovial infection may resolve with adequate
treatment and the joint may return to normalcy, or the
disease may progress to involve the bone and the
articular cartilage (osseous) and result in destruction of
the joint and subsequent fibrous ankylosis. Or it may start
as an osseous disease from the very beginning.
Clinical Features
The patient usually presents with pain and swelling of
the affected joint with restriction of all movements of that
particular joint. In advanced cases, there may be a
discharging sinus and deformity of the joint.
Synovial disease: There is synovial thickening and effusion
in the joint. The local temperature may be raised and the
movements at that joint are painful and restricted.
A radiograph may show generalized haziness due to
synovial edema/hypertrophy. The bones and the
articular cartilages are normal. The joint space may
appear increased due to the presence of fluid in the joint.
Figure 27.2.10: Tuberculosis of phalanges
Osseous disease: In addition to the synovial thickening,

there is effusion in the joint and raised local temperature.
There may also be a discharging sinus and a deformity
at the joint.
A radiograph may show diffuse osteoporosis or
rarefaction of bone and diminution of joint space in the
early stages of the disease. In the later stages of the
disease, the articular cartilages are destroyed. The
subchondral bone may be destroyed and a sequestrum
may be seen.
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Treatment
Antituberculous drugs: The drug regime is same as discussed
earlier for tuberculous osteomyelitis.
Immobilization: The joint is immobilized temporarily for a
period of 3 to 4 weeks for relief of pain and to overcome the
muscle spasm or deformity. This may be done by traction
or plaster cast/slab.
Aim of treatment: Based on the clinical and radiological
assessment of a case, one must decide whether the
outcome of the treatment should be a fixed joint or a
mobile joint.
Mobile joint: One can achieve a mobile joint when (i) the
disease is entirely synovial and the articular cartilage is
not involved, and (ii) the subchondral bone may be
involved but the articular surfaces are intact.
Figure 27.2.11: Sites of tuberculous infection in the hip joint
In tuberculosis of the hip, the infection may start in

the: (i) acetabular roof, (ii) head of the femur, (iii) neck of
the femur, (iv) greater trochanter (Fig. 27.2.11). In the
course of the disease, the hip joint may have a deformity
of flexion-adduction. Occasionally, destruction of the
acetabular roof permits an upward displacement of the
femoral head. This is called the traveling or
wandering acetabulum.
In tuberculosis of the knee joint, a triple deformity
develops. This deformity consists of flexion, posterior
subluxation of the tibia and lateral rotation of the tibia.
Figure 27.2.12 shows an advanced case of tuberculosis
of the knee joint. There is destruction of the articular
cartilages of the tibia and femur, diminution of the joint
space and posterior subluxation of the tibia.
Fixed joint: A fixed or an ankylosed joint is usually the

outcome when the articular cartilages are destroyed due
to the disease process. Any attempted movements in such
a case can be painful and at times impossible.
Treatment directed to achieve a mobile joint: The limb is
immobilized by traction so as to keep the articular
surfaces of the bones of the affected joint apart. The joint
is mobilized as early as possible. Occasionally, a partial
synovectomy, i.e. excision of the synovium, may be done
along with removal of the infected tissues from the joint.
Treatment directed to achieve a fixed joint: The aim here is
to achieve fusion (ankylosis) of the affected joint in a
functionally optimum position of the joint.
Conservative Method
The deformity of the joint, if any, is corrected either by
traction or by manipulation under general anesthesia and
the limb is immobilized in a plaster cast in an optimum
position. The plaster immobilization is maintained for 3
to 4 months or till we achieve ankylosis (fibrous or bony)
of the joint.
Operative Method
Figure 27.2.12: Tuberculosis of the knee joint. Thereis destruction of the bones and posterior subluxation of the knee joint
Arthrodesis (fusion) of the joint may be achieved by

surgical intervention. The affected joint is excised and
the raw surfaces of the bones of the joint, thus created,
are opposed to each other and compressed by an internal
or external fixation. It is maintained for a period of 3 to 6
months till bony ankylosis is achieved.
1276
TUBERCULOSIS OF THE SPINE (POTTS SPINE)
Course of the Disease
Tuberculosis of the spine commonly affects the thoracolumbar spine, however, it is also seen in the other regions
of the spinal column. The thoracolumbar spine is
commonly affected because of the excessive stresses and
strains it is subjected to, due to excessive mobility in this
region. The proximity of the cisterna chyli may cause
lymphatic spread of the infection from foci in the
mesenteric lymph nodes.
The tuberculous infection in the vertebra starts at any
of the following sites (Fig. 27.2.13):
Tuberculous infection causes destruction, cassation and

necrosis of the vertebra. Pus forms and may come out of
the vertebra and present as an abscess. The abscess may
remain close to the vertebra and present, on the
radiograph, as prevertebral or paravertebral abscess, or
may move distantly along tissue planes, or along vessels/
nerves to present clinically as a cold abscess. The
common sites of cold abscess, depending upon the
region of the spine involved, are on the side of the chest
wall, in the lumbar triangle, along the course of the psoas
muscle as psoas abscess in iliac fossa or as an abscess on
the medial side of the upper thigh (simulating as femoral
hernia). The pus may go posteriorly into the spinal canal
and cause compression on the spinal cord resulting in
paralysis. The affected vertebra becomes weak due to
the destruction by the disease process and collapses
under the forces of the body weight. This results in
deformity (kyphosis) of the spine (Fig. 27.2.14). In an
advanced disease the destruction may lead to displacement/dislocation of the vertebra resulting again into
paralysis due to cord compression.
Central: In this variety the central part of the body of the

vertebra undergoes destruction and later on may collapse
under the body weight resulting into a wedge-shaped
vertebra.
Metaphysial: This is the most common variety in which
the disease starts under the endplate of the vertebra (close
to the intervertebral disk) either at its superior or inferior
end. In this type, the intervertebral disk is also affected
resulting into narrowing of the intervertebral disk space
as seen on radiography. In fact, a radiographic finding
of destruction of a vertebra along with diminution of the
intervertebral disk space is considered to be pathognomonic of a tuberculous lesion of the spine.
Clinical Features
Pain: A few patients may present with constitutional
symptoms such as fever, cough, loss of appetite and
Anterior: This is a rare type where the disease starts in

the vertebra under the anterior longitudinal ligament. A
lesion under the posterior longitudinal ligament is
extremely rare, and is called as spinal tumor syndrome.
Appendiceal: Occasionally the disease may affect the
posterior elements of the vertebra such as lamina, spinous
process, etc.
Figure 27.2.13: Sites of tuberculous infection in the vertebra.

1central, 2metaphysial, 3anterior, and 4appendiceal
Figure 27.2.14: Kyphosis due to tuberculosis of spine
1277
weight, but generally pain in the back is the predominant

symptom. It is usually the first indication of the disease
and is localized over the affected area of the spine.
Occasionally, the patient may feel referred pain in areas
other than spine, e.g. girdle pains along the intercostal
nerves, in tuberculosis of the dorsal spine.
Deformity
Deformity of the spine results from destruction and
collapse of the affected vertebra, as discussed earlier. It
is usually kyphosis, which may be of the following types:
i. knuckle kyphus (gibbus) results from destruction
and collapse of a single vertebra.
ii. angular kyphus occurs due to collapse of 2 to 3
vertebral bodies.
iii. rounded kyphus results from collapse of multiple
vertebrae, which is rare in tuberculosis.
Figure 27.2.15: Course of disease in tuberculosis of spine
of the intervertebral disk space. Later on one may see

destruction and collapse of the vertebra (Fig. 27.2.15). A
paravertebral shadow will be cast by an abscess in that
area.
Treatment
Abscess
Antituberculous Drugs
It is called as cold abscess because it presents away

from the site of activity of the disease and, therefore, does
not present with the usual signs of inflammation over it.
The abscess which may be detectable on clinical exami
nation can be: (i) psoas abscess, (ii) abscess in the lumbar
triangle, (iii) abscess over the side of the chest wall, and
occasionally (iv) an abscess in the gluteal region.
The drug regime is same as discussed earlier in this chapter. Drug therapy is given for a total period of 18 months.
Paralysis
An incomplete or complete paraplegia is quite often the
presenting symptom in patients with tuberculosis of
spine. This results from compression of the spinal cord
due to abscess, granulation tissues, bony sequestrum or
due to mechanical pressure caused by angulation of the
vertebral column. The paralysis is usually spastic in the
early stages of the disease and later may become flaccid.
Quadriplegia will result from a lesion with cord compression in the cervical spine.
Radiographic picture: The earliest features on radiological
examination are localized decalcification and diminution
Rest to the Part

Rest to the spine may be given by means of a POP jacket
or a corset. This immobilization may be continued for a
period of 6 to 12 weeks. However, in a child, a plaster
jacket must be applied for about 3 months. A plaster
jacket in the initial stages of treatment may restrict the
degree of kyphotic deformity.
Drainage of the Abscess
A cold abscess may require aspiration or drainage.
Aspiration may remove the pus temporarily only,
because generally the abscess cavity fills up again.
Surgical drainage of the abscess is, therefore, advisable.
The various procedures include costotransversectomy,
anterolateral decompression, radical operation or
laminectomy.
1278
27.3 Neuromuscular Disorders

ORTHOPAEDIC ASPECTS OF CEREBRAL PALSY
Clinical Features
Cerebral palsy ( Littles Disease ) is defined as a disorder

of movement and posture caused by a non-progressive
defect or lesion in a developing brain. In the neurological
literature, cerebral palsy is referred to as a static
encephalopathy.
The common patterns of movement disorders that

characterize cerebral palsy may not manifest until a child
is 12 to 18 months of age. Sometimes the only physical
sign of cerebral palsy during the first year of life may be
persistent infantile reflexes. Usually the orthopedician gets
to see the child between the ages 2 to 4, when the child is
brought with the complaint of inability to walk. There is a
definite history of delay in developmental milestones.
On examination, there is poverty of movement of the
limbs. The main signs are adductor spasm at the hips and
resistance to passive dorsiflexion of the feet.
If the child is brought around the age of 10 years, the
characteristic lower limb position is adduction at the hips,
flexion at the knees and equinus deformity of the ankle.
The knee and ankle jerks are exaggerated and there may
be patellar or ankle clonus. The plantar response is
extensor. The child walks with a scissoring gait, if the
child is helped to walk.
When the upper limbs are affected, the shoulder is
held in adduction and internal rotation, the elbows are in
flexion with the forearms pronated. Further, the wrist is
flexed and the thumb drawn into the palm with the fingers
being flexed at the metacarpophalangeal joint.
In general, the orthopedic deformities in a cerebral
palsy child can be summed up as below :
Classification
Based on Motor Involvement
Spastic
Athetoid
Ataxic
Hypotonic
Rigid
Mixed
Spastic cerebral palsy is the most common type,
occurring in about 70% to 80% of patients with cerebral
palsy.
Based on Topography
Monoplegia
Diplegia
Hemiplegia
Quadriplegia
Causes
Prenatal Causes
TORCH infections.
Infants born to mothers with mental retardation or
epilepsy.
Anoxia in the prenatal period due to various causes
such as a ruptured placenta, placental infarction,
maternal pneumonia, or cardiorespiratory disease.
Upper limb
Pronation contracture of the forearm

Flexion deformities of the wrist and fingers
Thumb in palm deformity
Swan neck deformity
Shoulder adduction and internal rotation deformity
Hip
Natal Causes
Prematurity and low birth weight is the most common
natal cause of cerebral palsy.
Other causes for cerebral palsy are trauma or asphyxia
occurring during labor.
Adduction deformity ( most common )

Flexion and internal rotation deformity
Dysplastic and subluxated hip
Dislocated hip
Pelvic obliquity
Spine
Scoliosis
Kyphosis
Knee
Knee flexion contracture

Genu valgum
Genu recurvatum
Patella alta
Subluxation or dislocation of patella
1279
In moderate cases the aim is to correct the deformities

with physiotherapy and orthotics, to make the children
walk and be independent. These children should be
educated in special schools. In case the children are not
educable but trainable, the aim is to train them in
activities that require only repetitive skills, so that they
could be employed in simple occupations.
In children who are afflicted very severely and are
bedridden, the goal is to train them to do their own self
care activities like feeding and attending to their toilet
and dressing. These children need special custodial care.
Foot
Varus or valgus
Equinus deformity
Calcaneus deformity
Talipes cavus
Hallux valgus
Claw toes
Associated Disturbances
40% of all children with cerebral palsy have some
abnormality of vision or oculomotor control. Hearing loss
has been reported to occur in 10% to 25% of cerebral palsy
patients.
Seizures occur in about 30%. Bulbar involvement can
occur with drooling, difficulty in swallowing, and speech
impairment.
Management
The treatment and rehabilitation of the spastic child needs
the willing co-operation of the parents without which
nothing can be achieved. Further, it requires the coordinated efforts of the orthopedic surgeon, neurologist,
psychiatrist and the physiotherapist. Their efforts should
be supplemented and guided by the psychologist, speech
therapist, a medical social worker and a teacher.
The role of the orthopedic surgeon in the treatment of
children with cerebral palsy is to improve function and
prevent the development of deformities by prescribing
braces and by re-establishing the balance of muscle forces
through soft tissue releases, transfers, or bony reconstructions.
Guidelines of Treatment
As there is no cure available for cerebral palsy, the aim of
treatment is to achieve the maximum functional ability
and skill that the child can acquire. Each child requires a
regime that is appropriate to its developmental age,
intelligence and severity of disability. The thing to keep in
mind is that realistic goals have to be set.
Physiotherapy
It is the mainstay of treatment of all cases of cerebral palsy.
The general regime consists of passive movoments of all
joints to correct contractures and stretch out the muscles.
The children are also taught exercises to relax the spastic
muscles. Active exercises are given to establish movement
patterns and to teach rhythmic contractions and relaxation
of the muscles. Walking calipers or below knee orthoses
are prescribed to steady their standing postures and to
train children in walking. Night splints are used to
maintain the correct position of knee, foot and hand.
Occupational Therapy
It is very useful in older children. Certain activities
involving repetitive movements of the legs, hands and
fingers are utiltised to relax the spastic muscles and to
establish rhythmic and coordinated movements. This
helps to fit into certain occupations so that the children
can be economically independent and socially productive.
Surgical Treatment
The chief role of surgery is to help correct local physical
defects that interfere with the childs rehabilitation, but
it can also help to correct defects that interfere with nursing
care. Surgery that is properly timed for specific indications
may decrease the need for physical therapy and orthotic
treatment.
Surgery may be useful in cerebral palsy to (1) correct
deformity; (2) balance muscle power; or (3) stabilize
uncontrollable joints.
Some of the commonly done surgeries in children with
cerebral palsy are psoas tendon lengthening, adductor
tenotomy, hamstring release, achilles tendon release, flexor
release in the hand and wrist arthrodesis.
Surgery has only an adjuvant role in the management
of these children.
1280
Rehabilitation
Children with cerebral palsy require patient, prolonged
treatment. Special institutions where physiotherapy,
occupational therapy and special education form part of
the core curriculum have a big role to play in nurturing
these children and training them in suitable occupations.
ORTHOPEDIC ASPECTS OF POLIOMYELITIS
Anterior poliomyelitis is a viral infection of the anterior
horn cells of the spinal cord or the nerve cells of the
brainstem that results in temporary or permanent
paralysis. It is the major cause of crippling disabilities in
Indian children. It is caused by the Picorna group of
viruses. Though the incidence of polio in India has come
down, it is still a cause to worry because of the morbidity
it causes to the affected individual as well as the strain it
places on the economic and social system at large.
In neglected cases, gross fixed deformities of the hip,

knee and foot occur with severe wasting of the muscles.
Children with extensive paralysis and gross deformities
may even be reduced to crawling around (Fig. 27.3.1).
Common Orthopedic Deformities seen in Poliomyelitis
Foot and ankle
Claw foot, Claw toes
Talipes equinus
Flail foot
Flat foot
Talipes equino varus/valgus
Knee
Flexion contracture of the knee
Quadriceps paralysis
Genu recurvatum
Flail knee
Etiopathogenesis
Three serotypes of the polio virus cause the disease, of
which Type I is the most common in man. The mode of
entry is oropharyngeal and once infected the virus has
affinity for the anterior horn cells of the spinal cord and
motor nuclei in the brainstem. There may be reversible or
irreversible damage to the motor neurons.
Gross changes include atrophy and fatty degeneration
of muscles and tendons. Bones are small and osteoporotic.
There is reduced blood flow to the affected limb resulting
in shortening. Joints are stretched and unduly mobile
leading to dislocations. Skin changes such as cyanosis
and chilblains may be seen.
Clinical Features
Acute stage
Recovery stage
Residual paralysis stage
Hip
Flexion, abduction and external rotation contractures
of the hip
Paralysis of gluteus medius and maximus
Paralytic dislocations of the hip
Ilio-tibial band contractures
Spine
Kyphosis
Scoliosis
Upper Limb
Paralysis of the shoulder
Paralysis of the elbow, forearm and hand muscles.
Acute Stage
The diagnosis is mainly clinical during this stage. The
subjective symptoms predominate. Importantly, Nuchal
and spinal rigidity are present. At times the child may
support himself on three limbs giving rise to the classic
tripod sign. Deep tendon reflexes are absent.
Residual Paralysis Stage
The period after 2 years of onset of the disease is the
residual paralysis stage where no recovery of muscle power
occurs. Deformities result due to imbalance of muscle
power and bad posture. Disuse atrophy of muscles and
shortening of the leg also occur due to interference with
growth.
Figure 27.3.1: Deformity of foot in polio
Treatment
Orthopedic Care in the Acute Stage
The paralysed legs are supported by splints, pillows or
sandbags to keep the hip joint in 5 flexion and in neutral
rotation. The knee is held at 5 of flexion and the foot is
supported in a 90 position. The splinting relieves pain,
spasm and prevents development of deformities. In this
stage recording of muscle power is not required and an
approximate estimation of paralysis is adequate.
Recovery Stage
The treatment at this stage is mainly physiotherapy and
splinting. The aims of treatment are:
1. To assist the recovery of paralysed muscles by remedial
exercises.
2. To prevent deformities by the use of orthotics.
An assessment is first made of the extent of muscle
paralysis by charting the power of various groups of
muscles and grading them according to the international
nomenclature (Medical Research Council Grading) as
follows:
0Complete paralysis
1Slight flicker of contraction present
2Muscle can move a joint only when gravity is
eliminated
3Muscle can move a joint against gravity
4Muscle can move a joint against gravity and resistance
5Full normal power
Total functional assessment of the limb is made before
planning the treatment. This will include:
1. Charting muscle power grades
2. Method of ambulation
3. Amount of limb shortening
Efficient physiotherapy is the mainstay of management on this stage of poilo. A good physiotherapy
department with facilities for exercise therapy, hydrotherapy and electrical stimulation of the muscles is very
essential to treat paralytic polio cases.
Role of Surgery
Correction of Established Deformities
The common deformities seen are the flexion-abduction
contracture at the hip, flexion contracture at the knee and
equinus contracture at the ankle. These contractures are
corrected by surgical release of the contracted soft tissues
or the lengthening of the tendons, e.g.
Soutters release: Structures arising from anterior
superior iliac spine are released for hip contractures.
1281
Obwer-Younts procedure: Consists of sectioning the

ilio-tibial band contractures.
Tendo-Achilles lengthening for equinus deformity of
the foot.
Improvement of Muscle Balance
This can be achieved by surgical redistribution of the
available muscle power, by tendon transfer operations,
e.g. In case of marked weakness of knee extension, the
quadriceps power is improved by transferring one of the
hamstring muscles into it.
Stabilisation of Joints
Some joints are unstable due to the loss of power in one of
the muscle groups. This is corrected by arthrodesis of such
joints. The best example is triple arthrodesis of the foot in
paralysis of evertors or dorsiflexors of the foot.
Commonly used Splints/Braces
Abduction shoulder splint

Cock up wrist splint
Weight bearing caliper
Spinal braces
Knee-Ankle-Foot (KAF) orthoses
Rehabilitation
Medical rehabilitation of these affected children by
physiotherapy, orthopedic surgery and orthotic aids is
only the first stage in their total rehabilitation. This must
be followed by social assistance for their education,
vocational training, productive employment and social
integration to make them useful members of the
community.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
6.
7.
Barr JS. The management of poliomyelitis: The late stage,

In Poliomyelitis, First International Poliomyelitis
Congress, Philadelphia: Lippincott, 1949.
Bodian D. In Poliomyelitis, First International Poliomyelitis Congress, Philadelphia: Lippincott, 1949.
Goldner JL. Cerebral palsy, I: general principles, Instr
Course Lect 1971;20:20.
Graham HK. Classifying cerebral palsy, J Pediatr Orthop
2005;25:127.
Huckstep RL. Poliomyelitis. Churchill Livingstone
Edinburgh, London and New York 1975;64.
Kerr Graham H, Selber P. Musculoskeletal aspects of
cerebral palsy. J Bone Joint Surg 2003;85B:157.
Schwartz MH, Viehweger E, Stout J, et al. Comprehensive
treatment of ambulatory children with cerebral palsy:
an outcome assessment. J Pediatr Orthop 2004;24:25.
1282
27.4 Osteochondritis
The term Osteochondritis has been applied by convention to a group of conditions in which there is
compression, fragmentation or separation of a small
segment articular cartilage and bone. These are noninfective and non-inflammatory lesions where the exact
etiology is unclear. They affect children and young
adolescents, often during phases of increased physical
activity and may be initiated by trauma. The radiological
changes seen in these conditions are suggestive of
vascular disturbances in the epiphysis or the ossifying
centre.
Usually, the broad term Osteochondritis is considered
in the following groups:
1. Osteochondritis affecting the hip, knee and foot.
2. Osteochondritis dessicans affecting the knee, talus
and metatarsal heads
3. Traction apophysitis affecting the tibial tuberosity
and calcaneal apophysis
Osteochondritis in various regions bear the names of
those who described the condition first. The following
are some synonyms of the diseases and the sites involved:
1. Perthes disease Upper femoral epiphysis
2. Osgood-Schaltter disease Tibial tuberosity
3. Johansson-Larsen disease Patella
4. Severs disease Calcaneum
5. Kohlers disease Navicular
6. Friebergs disease Metatarsal head
7. Scheuermanns disease Vertebral head
8. Kienbocks disease Lunate
Given below are the features of a few important
Osteochondroses:
PERTHES DISEASE
(LEGG-CALVE-PERTHES DISEASE)
Perthes disease is one of the most common Osteochondroses. Also known as Coxa Plana, it is a condition
that affects the capital epiphysis of the upper end of the
femur. It occurs between the ages of 3 and 10 years, with
80% male preponderance. Usually unilateral, bilateral
cases are relatively rare (10%).
The exact etiology of this disease is still not known.
The pathology is an avascular necrosis (AVN) of the head
Figure 27.4.1: Perthes disease of the right hip
of the femur resulting from interference with the blood

supply, followed by the healing process of revascularization. There is simultaneous osteoclastic and osteoblastic
activity in the head and neck of the femur with trabecular
fragmentation. The deformity in the head and neck of
the femur is due to uneven revascularization and is
worsened if the head is subluxated.
Clinical Features
Though the classical presentation is that of a child with a
painless limp, the child may present with a history of
periodic attacks of limping with pain. The child may have
pain in the hip or referred pain in the knee. There are
signs of local inflammation. In early stages there will be
limitation of movement with muscle spasm. Flexion will
be full but the axis of movement may be altered so that
on full flexion of hip and knee, the thigh will rest on the
outer border of the abdomen. There will be a fixed flexion
deformity of around 15 degrees. Abduction, internal and
external rotations are limited. On palpation, the greater
trochanter may be thickened and elevated. The average
duration of symptoms is six weeks.
MRI of the hip is the gold standard investigation.
Bone scans and plain X-rays are also helpful in
establishing diagnosis.
Radiological Features
The radiological changes are seen in the head and
metaphysis of the femur and the acetabulum.
Elizabeth Town staged the disease features into four
stages based on the evolution of the disease and the
changes in the head of the femur are characteristic of the
stage of the disease.
Stage I: Stage of AVN
Stage II: Stage of fragmentation
Stage III: Stage of regeneration
Stage IV: Stage of healing
In the early stage, the joint space is widened medially
(Waldenstrom Sign). In the stage of revascularization, the
head is flattened and fragmented. Finally, there is a
deformity of the head with mushrooming.
The radiological changes are as follows:
HeadWidening, shortenening of the head
MetaphysisDiffuse osteoporosis, cyst formation and
widening of the neck
AcetabulumDeepening, loss of contour and osteoporosis
A list of head at risk changes are present radiologically. The importances of these changes are that they
are pointers towards a more aggressive line of treatment.
These changes are:
Lateral subluxation of the femoral head
Horizontal alignment of the growth plate
Metaphyseal cysts
Calcification lateral to the capital epiphysis
Positive Gage sign
Classification
Some of the systems of classification of Perthes disease
are:
1. Caterall classification is radiological and based on
the amount of involvement of the capital femoral
epiphysis.
2. Salter-Thompsons classification based on the
presence of fracture line at the dome.
3. Herring classification based on the lateral pillar
height.
Unilateral cases have to be differentiated from tuberculosis
and transient synovitis. Bilateral cases have to be
1283
differentiated from cretinism, multiple epiphyseal

dysplasia, mucopolosacchariodosis and sickle cell
anemia.
Prognosis
The factors associated with poor prognosis are:
Age of onset more than 6 years, girl children, when
the pathology is associated with fragmentation of the
head, duration of symptoms more than 6 weeks, when
more than half of the femoral head is avascular and when
there is loss in containment of the head within the
acetabulum.
Treatment
Pathologically, the condition is self-limiting. The aim of
treatment should be prevention of deformity of the
femoral head and promotion of containment of the head
within the acetabulum by surgical or non-surgical
methods.
In the early stage of pain and muscle spasm the child
is put to bed rest with skin traction. When the muscle
spasm is relieved, the child is allowed to walk with a
weight relieving caliper. Avoiding weight bearing
stresses prevents femoral epiphyseal deformation. This
caliper is continued till the head of femur shows
revascularization.
Cases which show lateral subluxation of the head or
evidence of head at risk will need restoration of normal
containment of the head. This is done by a special orthotic
appliance which keeps the leg in abduction and internal
rotation. Surgical treatment like femoral varus osteotomy
and innominate osteotomy aims to promote better
containment of the head in the acetabulum and may be
considered in head at risk cases.
OSGOOD-SCHLATTER DISEASE
It is an osteochondritis of the apophysis of the tibial
tubercle. A form of traction apophysitis, it occurs
commonly in boys between the ages of 10-15 years. They
present with insidious onset of pain in the front of the
knees. There could be a history of physical stress. There
is tenderness and localized swelling over the tibial
tubercle. There are no signs of inflammation and the
range of motion is complete. Radiologically, there is
increased density, fragmentation and separation of the
tibial tunercle with haziness in the adjacent tibial
metaphysis. It has to be differentiated clinically from
1284

The condition should be differentiated from calcaneal
bursitis, infection of calcaneum and teno-synovitis of the
tendo-calcaneum.
Treatment consists of analgesics and plaster cast for 3
weeks from toe to just above the knee to hold the foot in a
10-15 deg equinus position and relax the pull on the tendoAchilles.
SCHEUERMANNS DISEASE
Figure 27.4.2: Osgood Schlatters disease
Figure 27.4.3: Osgood-Schlatter disease
osteomyelitis, sarcoma of the proximal tibia, bone cysts

and infrapatellar bursitis. The condition is self-limiting
and responds to rest, immobilization and physiotherapy.
Recurrence is common until the time of fusion of the
epiphysis. Some complications are development of patellofemoral arthritis and genu recurvatum.
OSTEOCHONDRITIS OF THE CALCANEUM
(SEVERS DISEASE)
Osteochondritis of the calcaneum is a syndrome of heel
pain seen particularly in boys 9 to 15 years of age. The
condition appears to be related to repeated stress of trauma
to the tendo-Achilles at its insertion. On examination, there
is tenderness over the tendo-Achilles and the calcaneum.
A radiograph may show increased density of the
apophysis of the os calcis.
The etiology of Scheuermanns Disease remains unknown,

although Scheuermann in 1921 had suggested that
wedging of the vertebral bodies was due to avascular
necrosis of the vertebrae. Presently, traumatic, metabolic
and genetic causes have been proposed as etiological
factors.
The child presents between the ages of 10 and 15 years
with a round back deformity. There are generally no
symptoms. Occasionally there may be a history of poor
posture and back pain. This condition is commoner in
boys. There are two types of Scheuermanns Diseasethe
thoracic type and the thoracolumbar type, the former being
commoner.
Clinical examination shows a rounded kyphosis in
the thoracic or thoracolumbar spine. There is classically
tightening of the hamstring muscles. Radiographs show
wedging of the vertebrae, end plate irregularity and
Schmorl node formation.
As the deformity in Scheuermanns Disease is
uniplanar, it is amenable to conservative treatment. The
treatment is body awareness to correct the poor posture
and spinal extension exercises for strengthening the trunk
muscles. Extension plaster cast immobilization is used to
improve posture. Surgical correction is indicated very
rarely.
OSTEOCHONDRITIS DISSECANS
Osteochondritis dissecans is a condition affecting the
articular surface of certain joints like knee, ankle and
elbow. There is separation of an area of articular cartilage
along with the subchondral bone. Over a period of time,
this gradually separates and forms a loose body. It occurs
in the age group of 15-20 years. The most common sites
are the inferolateral aspect of the medial femoral condyle
in the knee, the supero-medial aspect of the talus in the
ankle and the capitulum in the elbow. The exact cause is
not clear. One school of thought supports trauma as the
etiological factor while another attributes it to ischemia.
1285
Clinical Features
Arthroscopy
In the knee, which is by far the most common joint to be

affected, the patient presents with recurrent attacks of pain,
swelling and the knee giving way. There may be
tenderness in the medial femoral condyle with the knee
partially flexed.
When the disease has progressed to the loosened
fragment stage, the patient presents with recurrent attacks
of pain and locking of the knee. The locking episode is
followed by an effusion into the joint and the history
resembles that of a patient with torn semi-lunar cartilage.
There is no definite joint line tenderness. Very often, the
patients state that they feel something moving inside the
joint and sometimes they are able to demonstrate the
palpable loose body. Since the loose body changes its
position inside the joint, it is called a joint mouse. There
is quadriceps wasting in the affected side.
Arthroscopy of the knee is useful to locate the site of lesion

and also to note the degree of separation of the fragment.
Investigation Modalities
Radiological Imaging
The early changes that occur before demarcation are best
seen in an MRI. There is decreased signal intensity in the
area around the affected osteochondral segment.
Radionuclide scanning with technetium HDP shows
markedly decreased activity in the same area.
Treatment
The treatment is largely based on the time of appearance
of the condition. In juvenille type of osteochondritis
dissecans the fragment rarely separates into the joint and
healing frequently occurs. The treatment is symptomatic
and the problem subsides with reduction of activities and
use of a tube cast for 3 weeks.
In the adult type of osteochondritis dissecans, surgical
treatment must be considered because if left untreated it
will lead to secondary osteoarthritis. The fragment must
be repositioned and this is done by using pins. Loose
fragments which cannot be reattached are best removed.
Arthroscopic surgery is currently the treatment of choice
in these cases.
BIBLIOGRAPHY
1.
2.
3.
Roentgenographic Features
In the early stages, a saucer shaped defect with a fragment
of denser bone over the defect is seen in the medial femoral
condyle. This is best seen in the intercondylar tunnel view.
In the late stage radiographs may show the loose body
lying free and a crater defect in the articular surface of the
femoral condyle.
4.
5.
6.
Agus H, Kalenderer O, Eryanilmaz G, et al. Intraobserver

and interobserver reliability of Caterall, Herring, SalterThompson classification system in Perthes disease. J
Pediatr Orthop 2004;13B:166.
Cahill BR. Current concepts review: Osteochondritis
dissecans. J Bone Joint Surg 1997;79A:471.
Caterall A. The natural history of Perthes disease. J Bone
Joint Surg 1971;53B:37.
Herring JA. Management of Perthes disease. J Pediatr
Orthop 1996;16:1.
Joseph B, Nair S, Rao N, et al. Optimal timing for
containment surgery for Perthes disease. J Pediatr
Orthop 2003;23:601.
Nowinski RJ, Mehlman CT. Hyphenated history: Osgood
Schlatter disease. Am J Orthop 1988;27:584.
27.5 Inequality of Limb Length

Gross limb length inequality is a functional and cosmetic
disabling problem. Patients usually seek cosmetic
improvement but for the orthopedician the challenge in
correcting limb length goes beyond just cosmetic improvement, it is essential to prevent osteoarthritis of the hip and
knee of the longer leg, fixed scoliosis and backache in later
life.
Leg length inequality most commonly results from limb

shortening. Only occasionally does one encounter
inequality arising out of lengthening due to growth
stimulation resulting from hypervascularity in various
A-V malformations or chronic osteomyelitis. Paralytic
poliomyelitis is the commonest cause of limb length
inequality in Indian subcontinent.
1286
Wasting almost always accompanies limb shortening

barring a few conditions like DDH, scoliosis and fixed
pelvic obliquity which should be borne in mind when
presented with such a patient.
CAUSES OF LIMB LENGTH DISCREPANCY
Congenital
Include a whole spectrum of dysplasias for, e.g.
phocomelia, congenital short femur, congenital short
tibia. Also includes conditions such as congenital
pseudoarthrosis of tibia, neurofibromatosis, etc.
Trauma
Can cause limb length discrepancy due to the following
effects:
1. Premature epiphyseal closure following injury.
2. Malunited fractures with shortening, angulation and
malrotation in femur or tibia.
3. Segmental bone loss in open fractures.
Infection
Infection usually results in inequality of limb length
because of:
A. Destruction of the epiphysis, e.g. Septic epiphysitis.
B. Segmental loss due to diaphyseal sequestration.
It is also very vital to assess if there are any disturbances of the lumbar spine and to work out its effect on
the overall limb length discrepancy if any.
MANAGEMENT PRINCIPLES
The goal of treatment and the choice of the treatment
method are two different steps in the management of these
patients. Equal limb lengths are aimed in isolated limb
length inequality (viz., hemiatrophy) whereas deliberately
leaving the limb short by 1-2 cm is preferred in paralytic
conditions to provide ground clearance. In general,
treatment planning for short limbs could be decided as
follows:
a. Shortening less than 2 cms can be ignored due to
effective body compensatory mechanisms like pelvic
tilt.
b. Shortening 2-6 cm can be treated with shoe raise,
epiphysiodesis or shortening.
c. 6-20 cm shortening is better dealt with simple limb
lengthening procedures or some complex surgeries like
rotation-plasty.
d. Shortening more than 20 cm are better dealt with
extension prosthesis or for a rudimentary limb by
amputation and functional prosthetic fitting.
SURGICAL TREATMENT
Neurological Disorders
They include a host of disorders like poliomyelitis, spina
bifida, cerebral palsy, spinal dysraphism, etc.
Surgical methods of equalization of limb-length discrepancy follow broadly the principles of either:
1. Limb shortening, or
2. Limb lengthening
Miscellaneous
Some factors such as genetic, nutritional, endocrine,
vascular and physical are well-recognized as affecting
the epiphyseal growth.
WORK-UP OF THE PATIENT
It is very important to assess the precise cause of the
discrepancy. Then assessment of predicted growth in leg
length is done according to the charts of Anderson and
Green (1948) or Greulich and Pyle (1950), which were
prepared after statistical survey of limb length in a large
number of children in England over a period of time.
In addition to clinical measurements of inequality,
radiological methods of evaluation like scanograms,
orthoroentgenography are used to determine the discrepancy.
Limb Shortening
During the growth period:
By Stapling
Limb shortening during the growth period can be carried
out by arresting the growth of the bone at the epiphysis of
the longer leg, temporarily, by stapling the epiphyseal
plate. The staples are subsequently removed when the
length discrepancy gets corrected.
Epiphysiodesis
Surgical fusion of the epiphysis or epiphysiodesis will
arrest the growth of the bone permanently. It is carried out
if there is sufficient growth left to effect a correction and
only if the discrepancy is 6 cm or less.
1287
After completion of growth: After epiphyseal fusion and

completion of growth, the bone is shortened by bone
resection and internal fixation.
Limb Lengthening
Various methods have been tried on an experimental basis
to lengthen the shorter limb. For example,
1. Local stimulation by periosteal stripping to promote
growth.
2. Lumbar sympathectomy to increase limb blood flow.
3. Creation of an AV fistula.
But none of the above methods are predictable and
their effects are transitory.
SURGICAL RECONSTRUCTION
More commonly, limb lengthening uses the principle of
osteotomy and distraction. This can be done at any age
and both in the tibia and the femur.
The Andersons method of lengthening involves
osteotomy of the above bones fixed on an external fixator
and gradual distraction to achieve lengthening. New bone
gradually grows into the periosteal tube and gets
consolidated in a few months time. The process of bone
formation and consolidation can be hastened by opening
up the periosteal tube and putting in bone grafts.
Gavril Ilizarov, the eminent Russian Orthopedician,
is one of the most important contributors towards our
understanding of the biology of limb length. His technique
revolves around his discovery of a new biological
principle, i.e. the principle of distraction osteogenesis
which simply put means that slow distraction induces
regeneration of bone. He demonstrated the method using
a circular model of external fixator using rings and
tensioned wires called compression-distraction apparatus
(Fig. 27.5.1).
Figure 27.5.1A: Ilizarov ring fixator for lengthening in

tibial hemimelia
Principles Involved in Distraction Osteogenesis

1. Corticotomy: Division of cortex of the bone without
dividing the intramedullary vasculature and maximally preserving the periosteum.
2. Rate of distraction: After the apparatus is fixed to the
bone and corticotomy done, controlled distraction is
started after 5-7 days at the rate of 1 mm a day till the
required length is obtained.
3. Function and weight bearing: The patient is encouraged
and made to bear weight with the frame on. This gives
psychological impetus to the patient and also allows
faster bone growth.
4. In children: Involves distraction at the epiphyseal plate
to produce lengthening in the bone.
Figure 27.5.1B: Ilizarov ring fixator (lat. view) for

lengthening in tibial hemimelia
1288

4. Jackson AM. Treatment of leg length inequality. In:
Bentley G, Greer RB (Eds): Rob and Smiths Operative
surgery: Orthopaedics 1991;1152-68.
BIBLIOGRAPHY
1. Anderson WV. Lengthening of the lower limb: Its place in
the problem of length discrepancy. In: Modern Trends in
Orthopedics, 1967.
2. Barr JS, Stinchfield AJ, Reidy JA. J Bone Joint Surg
1950;32A,793.
3. Hostrup H, Pilgaard S. Epiphysiodesis and epiphyseal
stapling on lower limbs. Acta Orthopaedica Scandinavica
1969;40:130-36.
5. Moseley CG. A straight line graph for leg length

discrepancies. J Bone Joint Surg 1977; 59A:174-79.
6.
Moseley CF. Leg lengthening: A historical perspective

In: Orthopaedics Clinics of North America 1991;22:56.
27.6 Pediatric Bone Tumors

Though the incidence of bone tumors is very low (1-15%
of the total malignancies of the body), the skeletal system
like the other systems also develop tumors, either as a
primary from the system itself or as a secondary from a
distant primary location.
In clinical practice, true neoplasms of bone will have
to be differentiated from hamartomas and reactive bone
lesions. The group of lesions which show abnormal
proliferation of cells which soon mature and stop
proliferation are called hamartomas. They are really
benign growth disorders and examples are ostechondroma, osteoma and enchondroma.
Bone also reacts to many types of injury by new bone
formation and this reactive reparative tissue can also
simulate neoplasia histologically.
CLASSIFICATION
True bone tumors can be benign or malignant. A malignant
bone tumor is a progressive, invading, metastasizing and
non-maturing proliferation of the cells of the bone tissue.
Tumor-like Lesions of Bone
Reactive bone lesions simulating tumors:
1. Osteoid osteoma
2. Benign osteoblastoma
3. Nonosteogenic fibroma
Hamartomas of bone
1. Osteoma
2. Osteochondroma
3. Enchondroma
Cystic lesions in bone

1. Solitary bone cyst
2. Aneurysmal bone cyst
True Bone Tumors
Primary bone tumors:
1. Osteogenic
Osteosarcoma
2 Chondrogenic
Chondroblastoma
Chondromyxoid fibroma
Chondrosarcoma
3. Fibrohistiocytic (connective tissues)
Fibrosarcoma
Malignant fibrous histiocytoma
4. Myelogenic
Plasma cell myeloma
Ewings tumor
Lymphoma of bone
5. Osteoclastoma (giant cell tumor)
Secondary Malignant Deposits in
Bone from Primary in
Thyroid
Breast
Bronchus
Kidney
Prostate
Lymphoma
Diagnosis
It is vital to first confirm the diagnosis of the tumor so as to
plan for the treatment modality to be adopted.
Diagnosis is based on:
1. Clinical examination eliciting the history and
physical signs.
2. Imaging from plain radiography to the modern
imaging techniques.
3. Laboratory investigations.
4. Biopsy.
Imaging
Plain radiography still has a big role to play in arriving at
an accurate diagnosis, on the basis of five parameters.
1. The anatomical location of the tumor, e.g.
DiaphysealEwings tumor
Diaphyseo-metaphysealOsteosarcoma
MetaphysealOsteosarcoma
Metaphyseo-epiphysealGiant cell tumor
2. The borders of the tumors
3. Bone destruction
4. Matrix formation
5. Periosteal reaction.
CT, MRI and the newer nuclide scans have their own
role in early diagnosis and planning the treatment
protocol.
Angiogram is done before surgery for operation
planning, treatment and embolization.
1289
Closed biopsy: It implies that no incision is required and

that the tissue specimen is obtained through a skin
puncture by a needle or a trephine. It minimizes tissue
contamination.
Surgical Procedures
Surgical procedures are divided into those done to save
limb (reconstructive) and those by limb ablation. These
are subdivided on the margins achieved.
Limb Sparing Surgery
Historically the treatment of malignant bone tumors had
been mostly by amputation. Current concepts in the
biological behavior of tumors, clinical staging, tumor
surgery, adjuvant chemotherapy and radiotherapy have
made local tumor clearance possible without ablation of
the limb. Limb sparing treatment schedules are currently
feasible options in the management of bone sarcomas and
limb salvage as a treatment modality is steadily gaining
ground even in our country.
More recently custom prosthesis made of titanium or
ceramics have been used as replacement for the excised
bone and the adjacent joint in the knee, hip and shoulder.
REACTIVE BONE LESIONS
Blood Investigations
RBC count, hemoglobin, ESR, VDRL, calcium, inorganic
phosphates and alkaline phosphatase must be done.
Serum albumin globulin electrophoretic pattern and urine
examination for Bence-Jones protein are other investigations helpful to arrive at a diagnosis.
Biopsy
Types of biopsy:
1. Open biopsy and
2. Closed biopsy
Open biopsy: The periphery of any malignant tumor is the
most viable and diagnostic portion of the tumor, whereas
the central region is often necrotic, hence care must be
taken to take biopsy from the periphery. A correctly placed
biopsy incision must be capable of being excised en bloc
with a malignant tumor when a definitive surgical
procedure is contemplated.
Osteoid Osteoma
It is a reactive bone lesion simulating a tumor. The exact
pathogenesis of this lesion is still not clear.
Clinical Features
It occurs in children and young adults in the age group of
10 to 30 years. It is common in males mostly in the cortical
areas of femur, tibia and vertebrae. It presents as localized
pain in the bone, which progressively increases in the
course of time. The pain is worse at night and typically
responds to salicylates.
Radiograph shows a small osteolytic lesion in the cortex
or subperiosteal region surrounded by a dense sclerotic
area (Fig. 27.6.1). There is a small dense spot in the center
of the area called nidus. This may be better demonstrated
on a CT scan.
1290

Radiograph reveals an eccentrically placed osteolytic
defect which is clearly demarcated by a sclerotic margin.
Microscopically, the lesion is composed of a cellular
whorled connective tissue with spindle shaped cells
interspersed with multinucleated giant cells.
Asymptomatic small lesions need no treatment. Large
lesions need curettage and bone grafting for mechanical
reasons since this is a self limiting disease.
HAMARTOMAS
Osteochondroma (Solitary Exostosis)
Figure 27.6.1: Osteoid osteoma
Osteochondroma is a bony swelling arising from the

metaphyseal ends of long bones. This is the most
common among the tumor like lesions of bone. It is
noticed first during the age of 5 to 15 years. Its common
sites are the distal end of femur, proximal end of tibia and
upper end of humerus.
Treatment
Conservative line consists of rest to the part and analgesics.
If the tumor is larger, total excision of the lesion is
mandated. Recent advances in treatment of osteoid
osteoma includes the use of Radiofrequency Ablation of
the lesion.
Osteotoma (Giant Osteoid Osteoma)
Benign osteoblastoma is a lesion similar to osteoid
osteoma, but of a size larger than 2 cm. It occurs in children
and young adults in the second and third decades.
Pain is the usual presenting feature. It occurs in the spine
and the epiphysis of the long bones. It can present as
swelling in the end of the femur. In the vertebra, it can present
neurological signs of cord or root compression.
Radiologically, there is an expanding osteolytic lesion
with a thin cortex of sclerosis. It may resemble an
aneurysmal bone cyst. Microscopically there is vascular
connective tissue stroma with numerous osteoblasts. These
osteoblasts do not show abnormal mitotic activity.
Treatment consists of curettage or excision of the lesion.
Nonosteogenic Fibroma (Histiocytic Fibroma)
Nonosteogenic fibroma is an eccentric fibrous lesion
occurring in the metaphysis of long bones in children.
The lesion is found in children between 10 to 15 years of
age in the distal femur or proximal or distal tibia. It appears
first in the metaphysis and expands slowly into the
cancellous tissue.
Pathogenesis
Osteochondroma is a growth disorder (hamartoma).
During growth, a small mass of cartilage cells from the
periphery of the epiphyseal plate migrates and continues
to grow in a transverse direction. It matures into bone
but continues to have a cartilaginous cap which
contributes to its further growth till the completion of
epiphyseal fusion.
Clinical Features
The adolescent child presents with the complaint of a hard
swelling usually near the knee. Examination shows a bony
hard swelling arising from the bone near the metaphysis
and then projects away from the joint.
The patient may also present with complications:
1. Pain due to inflammation in an adventitious bursa
overlying the swelling.
2. Difficulty in movement of the neighbouring joint
due to mechanical obstruction.
3. Pressure effects on nerves, e.g. exostosis of upper
end of fibula compressing the lateral popliteal
nerve (Fig. 27.6.2)
4. Pressure effect on vessels causing compression
5. Fracture of the exostosis itself, and
6. Rarely malignant change of the exostosis
Outgrowth of the bone at metaphyseal attachment is seen.
It could be sessile or pedunculated. The characteristic
1291
filled cyst lined by epithelial-like cells. It occurs in the

ends of long bones in children and adolescents. The
common sites of occurrence are the proximal ends of
humerus (80%) and femur (20%). There is a male: female
preponderance of 2:1. Fifty percent of the tumors occur in
less than 10 years of age and 40 percent between 10 and
20 years of age.
Clinical Features
Clinically, the cyst is asymptomatic till the child sustains
a pathological fracture. Occasionally the patient presents
with pain in that region.
Figure 27.6.2: GCT of fibula
radiological feature of exostosis is that the cortex and

medulla of the stem of the exostosis are continuous with
the cortex and medulla of the main bone. The distal end is
bulbous.
The cyst is seen usually as a radiolucent area in the

metaphyseal region near the epiphyseal plate. The cyst
may occupy the whole width of the bone and cause
thinning of the cortex. A fracture may be seen across the
cyst. As the child grows, the cyst is seen to shift away from
the metaphysis towards the middle of the shaft.
Pathological Features
A small asymptomatic osteochondroma needs no

treatment. Larger ones are treated by excision.
The cyst usually contains serous or serosanguinous fluid

and the inner wall shows bony ridges and is lined by a
thin membrane. Microscopically, the lining membrane
shows connective tissue with scattered giant cells. The
exact pathogenesis is not clear. It is believed to be a
hemorrhagic cyst due to mild trauma and intraosseous
bleeding.
Enchondroma
Treatment
Enchondroma is a benign cartilaginous growth disorder.

The lesion occurs in the short long bones like metacarpals
and phalanges. The age group ranges from 10 to 50 years.
It is usually asymptomatic. Mild trauma may result in a
pathological fracture. The lesion should be curetted and
bone grafted.
The generalized manifestation of such enchondroma
is called Olliers disease (enchondromatosis) and is a
developmental disorder.
The conventional treatment is surgical curettage and

packing with bone grafts. Small cysts sometimes heal
after fracture. Injection of methylprednisolone acetate
into the cyst has been found to produce healing and is
being frequently used.
Treatment
CYSTIC LESIONS IN THE BONE

Unicameral Bone Cyst
Solitary bone cyst otherwise known as unicameral bone
cyst is a true cystic lesion of bone where there is a fluid-
Aneurysmal Bone Cyst

Aneurysmal bone cyst is a solitary rapidly progressive
expansile lesion occurring in the metaphyseoepiphyseal
area of long bones and the pedicle and lamina of the
vertebrae. It commonly occurs in the second and third
decades. The exact pathogenesis is not known. It may be
an arteriovenous malformation in the bone resulting from
trauma. It may also be induced on a pre-existing
neoplastic pathology.
1292
Clinical Features
Clinically the patient presents with pain and swelling in
the affected bone which is tender. Pathological fracture
through the cyst causes increased pain and local
tenderness. A lesion in the spine can present with
neurological signs (Fig. 27.6.3).
The lesion presents as an osteolytic area in the metaphyseal region of a long bone or in the vertebra. There is
a thin shell of cortical bone covering the eccentrically
expanded lesion (Fig. 27.6.4).
Pathology
Microscopically it appears as a honeycomb of blood-filled
cavities lined by fibro-osseous cystic tissue. Micro-
scopically there are fibrous tissue septa with some osteoid

in it. There are variable number of giant cells, xanthoid
cells and altered blood pigment.
Treatment
Extraperiosteal excision or curettage with local adjuvant
therapy (liquid nitrogen) and bone grafting can be curative.
There is a high incidence of local recurrence. Large or
inaccessible cysts can be treated by radiation therapy.
OSTEOGENIC TUMORS
Osteosarcoma
It is a highly malignant primary bone tumor, arising from
the multipotent mesenchymal tissue of bone.
Incidence
It is the most common malignant tumor of bone constituting nearly 20 percent of the malignant tumors of the
bone. It occurs in the young between the ages of 10 to 20
years. It is more common in males. The common sites of
occurrence are the distal end of femur, the proximal end of
tibia, and the proximal end of humerus in the metaphysis.
Clinical Features
Figure 27.6.3: Aneurysmal bone cyst
Pain is the initial and dominating symptom. After some

weeks, a bone swelling appears and progressively
increases in size.
On examination, the swelling is fusiform, the skin is
stretched, shiny and vascular with prominent veins. The
swelling is warm to touch and may also show pulsation
if the tumor is very vascular. It is firm to hard in consistency
with areas of softening where the tumor has invaded the
soft tissues. In the late stages, the tumor fungates. The
patients general health deteriorates with anemia, loss of
weight and cachexia. The patient develops pulmonary
symptoms due to secondaries.
Figure 27.6.4: Aneurysmal bone cyst
The tumor arises at the metaphyseal region of the bone,

either centrally or over the cortex (Fig. 27.6.5). There are
mottled areas of rarefaction with areas of osteosclerosis.
When it extends beyond the cortex, the periosteum is raised
and there is new bone formation in lines at right angles to
the cortex. This causes the sun-ray appearance on the
radiograph (Fig. 27.6.5). There is also reactive new bone
formation subperiosteally to the junction of the lifted
periosteum and the normal bone. This is called Codmans
1293
Microscopic appearance: The most characteristic features are

the anaplastic sarcomatous stroma with newly formed
woven bone and the presence of malignant osteoid. It may
also show areas of malignant cartilage and fibrous tissue.
The stromal cells are spindle-shaped osteoblasts showing
excessive mitosis, pleomorphism and hyperchromatism.
There may be areas of hemorrhage and necrosis.
Classification
Figure 27.6.5: Osteosarcoma distal femur
triangle. The radiographs may also show a pathological

fracture. Radiograph of the chest must be taken. It may
show round shadows caused by secondary deposits
(Canon-ball appearance).
Laboratory Findings
Investigations should include blood count of RBC which
may show anemia. Serum alkaline phosphatase levels
may be significantly elevated.
Biopsy
In all cases the diagnosis should be established by a
biopsy. This should be done at the growing periphery of
the tumor, which gives the typical microscopic appearance.
Pathology
Macroscopic appearance: The tumor is located in the
metaphyseal region and reaches the subperiosteal area
through the cortex. It is grayish white, the consistency
may be hard and fleshy with streaks of tumor bone or it
may be soft and vascular with areas of hemorrhage. The
tumor edge stops at the epiphyseal cartilage and does
not break through it. The tumor also extends into the
medullary canal. In advanced cases the tumor breaks
through the periosteum invades the soft tissues and even
fungates through the skin.
Osteosarcomas are broadly classified as:

1. Central (intramedullary) type:
a. Primary
Conventional
Telangiectatic
Small cell
Multicentric
b. Secondary:
Pagets disease
Radiation induced
Arising from other benign conditions like
fibrous dysplasia and osteochondroma
2. Juxtacortical (surface) type:
a. Parosteal
b. Periosteal
c. Differentiated
Treatment
After the histopathological examination has confirmed
the diagnosis of osteosarcoma, an evaluation is done
regarding the spread of the disease locally and also the
metastasis. A radiograph and CT scan of the chest may be
done to detect metastasis.
An MRI scan of the local area may help to know the
extent of the tumor so as to plan whether limb salvage is
possible or not.
Broadly speaking the treatment of osteosarcoma is
usually a combination of the following:
Surgery: A limb saving surgery may be possible if the case
is diagnosed early and the lesion is small. In such a
situation, after neoadjuvant chemotherapy, the lesion is
excised, including a margin of normal tissue all around,
and the gap thus created may be bridged by bone grafts or
artificial prosthesis whichever is feasible (Figs 27.6.6 to
27.6.8).
Amputation remains the only option if limb salvage is
not feasible. The amputation can be a palliative amputation
1294

if the disease is advanced. In this situation, the goal of
operation is either pain relief or to prevent complications
in a fungating tumor. A definitive amputation removes
the tumor completely. The level of amputation and the
length of the remaining stump of the limb, etc. can be better
planned.
Radiotherapy: It is indicated for local control of the disease
after incomplete surgical removal of the tumor and also
for tumors situated at surgically inaccessible sites.
Figure 27.6.6: Excision of small lesion in osteosarcoma
Chemotherapy: It consists of three drugsifosfamide/

cyclophosphamide, adriamycin and cisplatin given as 6
cycles, pre and/or post-operatively to control the micrometastasis.
A regular follow-up every 3 months is mandatory to
detect any recurrence or spread of the tumor.
Chondroblastoma
It is a rare benign tumor of cartilaginous origin. It is more
common in males and occurs in the age group of 10 to 20
years. It arises from the epiphysis of long bones of femur,
humerus and tibia. Pain is the presenting feature.
Radiograph shows a radiolucent area in the epiphysis
with a sclerotic margin and areas of calcification which
appear hazy. Microscopically the characteristic cell is the
chondroblast. There is chondroid production. There are
several scattered giant cells. Treatment is by curettage and
bone grafting.
Figure 27.6.7: Bone graft in osteosarcoma
Chondromyxoid Fibroma
It is a rare benign tumor and is one of the giant cell
variants. It occurs in the metaphysis of long bones in the
lower limbs. Pain and later swelling are the presenting
features. Radiograph shows an eccentric osteolytic lesion
with a thin sclerotic margin. Microscopy shows areas of
lobulated cartilaginous cells with myxomatous zones.
Scattered giant cells are also present. Treatment is mainly
by removal of the tumor including the wall, and bone
grafting.
Ewings Tumor
Figure 27.6.8: Custom mega prosthesis for osteosarcoma
It is an uncommon type of highly malignant bone tumor

occurring in children. Ewings tumor forms about 10
percent of all malignant bone tumors. It occurs in the age
group of 10 to 20 years and is more common in males. It
arises from the primitive mesenchymal cells of the
medullary cavity. The sites affected are the diaphyseal
regions of long bones like femur, tibia and humerus. It
also occurs in flat bones like pelvic bones.
Clinical Features
The patient presents with pain which gradually increases
and is followed by a swelling. The swelling is firm to soft
in consistency with indefinite margins. There is usually
fever, anemia and leukocytosis so that the condition often
simulates subacute osteomyelitis. The swelling rapidly
increases in size with involvement of soft tissues and the
general condition deteriorates.
The peculiar feature of Ewings tumor is that metastasis occurs in other bones like skull, vertebrae and ribs,
in addition to the lungs by spread through bloodstream.
Radiograph shows areas of mottled rarefaction in the
affected bone (Fig. 27.6.9). There will be marked destruction
of the bone cortex and involvement of the soft tissues. There
is also reactive new bone formation in layers under the
raised periosteum producing the characteristic onionpeel appearance.
Pathology
Microscopically the tumor is a pale soft mass with minimal
bone tissue. There are areas of degeneration and
1295
hemorrhage. There is further simulation of osteomyelitis

by the presence of milky pus-like fluid in the tumor tissue
due to degeneration.
Microscopically, the tumor is very cellular with
minimal stromal tissue. The characteristic cell is the small
polyhedral cell with pale cytoplasm and large nucleus.
The appearance is monotonously uniform with cells
arranged in compact sheets with loose and vacuolated
stroma. In some areas there is a pseudorosette formation
by the tumor cells, this simulates the rosette formation of
neuroblastoma. The tumor must be differentiated from
lymphoma (reticulum cell sarcoma).
Treatment
Radiation therapy is the traditional treatment of Ewings
tumor. This tumor is radiosensitive and regression
following therapy is remarkable. Multidrug chemotherapy
with vincristine, adriamycin and cyclophosphamide given
at the same time has remarkably increased the survival
rate.
However with this type of treatment, the local
recurrence rate is high. Hence, currently after preoperative
chemotherapy, surgical resection of the tumor bearing bone
is done with skeletal reconstruction followed by postoperative chemotherapy. This regimen has increased the
survival rate from 5 to 50 percent.
Surgical ablation (amputation) is indicated in locally
advanced cases.
Rhabdomyosarcoma
It is a malignancy of the striated muscle cells. Occurring
commonly in the infants and young adults around head,
neck and limbs. It presents as a fleshy tumor within the
muscle, grows rapidly and may even fungate. Metastasis
to regional lymph nodes and bone are common. It is poorly
radiosensitive.
Orthopedic Aspects of
Lymphoma/Hodgkins Disease
Figure 27.6.9: Ewings sarcoma
Lymphomata may involve the bone either as a part of the

multisystem spread of the disease or as a primary lesion.
Bone changes can occur in both sexes at any age. The
prognosis is better in primary lesions of the bone. The
bone shows destruction with loss of trabecular pattern
and subperiosteal new bone formation. Pathological
fracture of a long bone or collapse of a vertebrae are
1296
common. Pain otherwise is the first indication of the

osseous spread of the disease.
The bones commonly involved are vertebrae, pelvis,
ribs and proximal femur.
Treatment
The bone changes generally respond to radiotherapy.
BIBLIOGRAPHY
1.
Alazraki NP, Davis MA, Jones AG, et al. Skeletal system

malignant tumours. In: Nuclear Medicine Review
Syllabus 1980;284-97.
2. Bacci G, Toni A, Avella M, et al. Long-term results in 144

localized Ewings sarcoma patients treated with combined
therapy. Cancer 1989;6:1477-86.
3. Bloodgood JC. How to diagnose and treat a bone lesion:
I. Central lesions. J Bone Joint Surg 1926b;8:471-78.
4. Campanacci M, Bacci G, Bertoni F, Picci P, Minutillo A,
Franceschi C. The treatment of osteosarcoma of the
extremities: Twenty years experience at the Istituto
Ortopedico Rizzoli. Cancer 1981;48:1569-81.
5. Coley WB. The differential diagnosis of sarcoma of the
long bones. J Bone Joint Surg 1928;10:420-73.
6. Kolodony A. Diagnosis and prognosis of bone sarcoma.
J Bone Joint Surg 1925;7:911-48.
7. Simon MA, Enneking WF. The management of soft-tissue
sarcomas of the extremities. J Bone Joint Surg 1976;58A:
317-28.
27.7 Miscellaneous Orthopedic Conditions

PP Kotwal, MK Varshney
TRANSIENT SYNOVITIS OF THE HIP
Treatment
It is also called as observation hip. It is a sterile inflammation and effusion of the hip joint affecting children
between 4 and 8 years of age. Not much is known about the
etiology of this condition. The importance of this condition
lies in the fact that it may be preceding other conditions
such as septic arthritis of the hip or Perthes disease. The
child, therefore, is to be kept under observation.
The child suspected to be having transient synovitis of

hip should be admitted for observation. Immobilization
by skin traction to the limb may relieve the muscle spasm
and improve the pain. The condition resolves spontaneously within a weeks time.
Clinical Features
Definitions
The main complaints are pain in the groin and refusal to

move the limb or walk. There is usually no fever. The
movements of the hip are restricted, especially the internal
rotation. However, the child is otherwise comfortable
when resting in bed with a pillow under the knee.
Genu varum denotes a malalignment in the frontal

(coronal) plane, in which the part distal to the site of
deformity deviates toward the midline.
Diagnosis
The condition should be differentiated from septic arthritis
of the hip joint, the latter may have a florid course with
high fever, toxemia, raised WBC count and ESR.
An ultrasonography examination may be positive in
both these conditions. Rarely, aspiration of the joint may
be required.
BOW LEGS (GENU VARUM) AND

KNOCK KNEES (GENU VALGUM)
Genu valgum denotes a malalignment in the frontal

(coronal) plane, in which the part distal to the site of
deformity deviates away from the midline (Fig. 27.7.1).
The Normal Development
Many children have bow legs when they start walking.
Then they develop knock-knees between the age of 3 and
6 years. These deformities are physiological and will get
corrected spontaneously in the majority. A community
study conducted by Salenius and Vankka (1975) showed
1297
goes down to 5-6 (normal) by the age of

6-7 years.
Genu Valgum
The child is examined in standing position. He or she
should be standing on an even surface with his or her
knees approximated to each other. Now the distance
between the medial malleolus of both sides is measured. It
is called as intermalleolar distance. In case the intermalleolar distance exceeds 10 cm, the child should be
examined radiologically to exclude any underlying
pathology as the causative factor. Unilateral genu valgum
may be caused by disturbance in the epiphyseal growth
at the lower femur or upper tibia due to trauma or
osteomyelitis. Bilateral genu valgum can be caused by
endocrine or metabolic disorders, rickets, epiphyseal
dysplasia or can be idiopathic.
Figure 27.7.1: Clinical photograph of genu varum of
both knee joints
Treatment
The genu valgum deformity can be ignored in the toddlers
since the deformity at that age is generally within normal
limits and will get corrected spontaneously. However, if
the deformity is severe and the distance between the two
medial malleoli (intermalleolar distance) is more than 10
cm at the age of 10 years, it will need surgical correction.
The deformity is corrected by osteotomy of the femur or
tibia, depending upon the site of the deformity.
Genu Varum
In genu varum or bow legs, there is lateral curvature of
the leg involving either the tibia or femur or both.
Causes
Physiological bowingmild genu varum in a child
up to 3 years of age.
Idiopathic.
Post-traumatic or infectivedue to defective growth
of the medial side of femur or tibia.
Blounts diseasegenu varum develops due to failure
of growth of the posteromedial part of the proximal
tibial epiphysis between 2 and 6 years of age.
Rickets.
Figure 27.7.2: Genu valgum
that the children have marked genu varum before the age
of one year, which changes to valgum between the ages of
18 months and 3 years. The valgum may be extreme, but
Clinical Features
Bowing of the leg is the main complaint. The severity of
bowing is measured by bringing the medial malleoli of
1298
both sides together and measuring the distance between

both knee joints. If this distance exceeds 6 to 8 cm, the
underlying cause must be investigated.
Treatment
Mild degrees of genu varum can be treated by modifications
in the sole of the shoes3/16" raise is given on the outer
side of the shoes. Moderate to severe degrees of genu varum
deformity need surgical correction.
FLAT FOOT
Normally the foot has longitudinal and transverse arches.
The normal longitudinal arch is visible on the medial side
of the foot. When this arch is less developed, it is called as
flat foot. The arch of the foot is maintained by the tarsal
and metatarsal bones, the plantar ligaments and the
posterior tibial group of muscles.
Causes and Types of Flat Foot
of movements at the knee joint. There is always a flexion

deformity at the knee and limitation of movements. The
most common associated pathology is myofibrosis of the
quadriceps muscle (Quadriceps contracture) and
hypoplastic patella. The other type in this category is
Habitual dislocation of patella. Here the patella dislocates
every time knee is flexed. The patients present early in
their life or not at all (it becomes a habit for them). This is
a classical example of a disorder in which compensatory
pathology develops to pursue a physiological function.
The movements are often full at the knee joint.
Recurrent Dislocation of Patella
This is usually post-traumatic and patellar dislocation
occurs at intervals. There may be associated ligament laxity
on the medial side of joint or small (hypoplastic) lateral
femoral condyle.
Treatment of both these types of dislocation is surgical
but with a guarded prognosis for chronic dislocation.
Congenital
OSTEOGENESIS IMPERFECTA
Congenital vertical talus The talus bone is placed vertically
in the foot, instead of being horizontal which is normal. A
radiograph will confirm the diagnosis. The treatment is
difficult. Manipulation and serial plaster casts may be
indicated in mild cases, whereas severe cases need surgery.
The patella dislocates laterally either due to injury or

congenital deformity. The dislocation of patella can be
broadly grouped into:
It is a connective tissue disorder in which the maturation

of woven bone suffers, leading ultimately to less bone per
unit area than normal. The presentation is variable but
clinically bone fragility identified in the form of
pathological fractures is the hallmark of the disease. Other
features variably present include dentinogenesis imperfecta (deformities of teeth), hyperlaxity, blue sclera, excessive
sweating, easy skin bruising, short stature, etc.
Classically two basic forms are recognized congenital
and tarda. Congenital form is characterized by numerous
fractures ensuing from birth and bears a poor prognosis
and high mortality. While in the latter, fractures may be
delayed until first decade. Irrespective of the type the
fractures heal with considerable deformity. Bluing of sclera
has ironically inverse relationship to prognosis of disease.
Puberty seems to have a stabilising influence against
fractures.
Diagnosis is established by clinical stigmata and
radiographic features. Early in life the features must be
differentiated from battered baby syndrome. Orthopedic
management is primarily based to maintain present
function and prevent deformities by skillfully protecting
bones. Disabling deformities may be later corrected by
osteotomies. The encouraging results with bisphosphonate therapy are still under evaluation.
Chronic Dislocation
BIBLIOGRAPHY
Physiological or Infantile flat foot This is the most common

type in which the child has flat feet when he or she starts
walking. But gradually the arch develops within the next
2 to 3 years. In such a case, no specific treatment is required.
However, an arch support inside the shoe and slight
modification in the sole of the foot may be prescribed. In
an older child, intrinsic foot exercises may be taught.
Acquired flat foot It may be: (i) osseousdue to injury or
disease of bones, and (ii) ligamentousinjury to plantar
ligaments, and (iii) muscularparalytic or spastic type
which results due to muscular imbalance.
The treatment is directed to the underlying cause of
the problem. In severe cases triple arthrodesis, i.e. fusion
of the selected tarsal joints is indicated after skeletal
maturity.
DISLOCATION OF PATELLA
This category includes permanent dislocation of patella where

the patella remains congenitally dislocated irrespective
1.
Salenius P, Vankka E. The development of the tibio-femoral angle in children. J Bone Joint Surg 1975;57A:259-61.
28.1 Pediatric Radiology: Arun Kumar Gupta, Chandan J Das ............................................................................................................... 1300
1300
28.1 Pediatric Radiology

Arun Kumar Gupta, Chandan J Das
Over the last several decades, pediatric radiology has not
only emerged in the forefront but has established itself as
a definite subspecialty. A pediatric radiologist should not
only have knowledge of general radiology, embryology
and basic pediatrics, but should also be acutely aware of
the indications, technicalities of various procedures and
should be radiation conscious. Although problemoriented approach is ideal, in this chapter, an organ
approach is used to present the essentials.
Imaging Techniques
Conventional radiology, i.e. plain radiography and
contrast studies (e.g. barium studies, excretory urography
and contrast studies for the lower genitourinary tract) still
remain the mainstay of pediatric radiology. However, with
the introduction of ultrasound, computed tomography
(CT) and magnetic resonance imaging (MRI), the diagnostic
algorithm in a number of diseases has changed
dramatically. Role of important imaging modalities will
be discussed under each organ system.
CHEST
Imaging Techniques
Conventional radiographs are still the most frequently
carried out procedure. Proper immobilization is essential.
Radiograph is taken in supine AP for children less than
3 years of age and in erect PA for older children. Computed
tomography, nowadays spiral CT, is the next best costeffective imaging technique for complete chest evaluation.
MRI and MR angiography are now increasingly used for
assessing relationship of mediastinal vessels to
mediastinal masses or for primary vascular diseases like
aortoarteritis, coarctation, etc. Sonography has limited role
in chest diseases due to reflection of ultrasound beam by
air. However, for pleural diseases, mediastinal or
pulmonary lesions abutting the chest wall and for cardiac
and major vessel evaluation, sonography is a quick and
easy technique which can be carried out even at bedside.
Normal Chest X-Ray
Usually only a frontal chest radiograph (AP or PA) is taken.
If any abnormality is detected or in patients with high
index of suspicion, appropriate lateral radiograph is also

taken.
Interpretation
Patient rotation and quality of exposure are first checked
because improper patient position or exposure can be
disastrous. Next, the film is read either from out-to-in or
vice versa. Carefully examine, in a sequence, always
comparing with the opposite side for soft tissues, bones
under review (ribs, clavicles, scapulae, humeri, etc.);
aeration of each lung in the upper, mid and lower-thirds
as well as medial-mid-and outer-thirds; vascularity in each
of these zones; tracheal position, diaphragm position and
shape; costophrenic angles; mediastinal silhouette on each
side; cardiac size and shape; retrocardiac space; position,
size and density of each hilum; and last but not the least
look under the diaphgrams for free air and dilated loops.
Lateral radiograph is usually taken to localize a lesion
already detected on the frontal films, for evaluation of the
hilar nodes and for assessing the position of diaphragm.
In a case with suspected free pleural effusion, a lateral
decubitus view film is required with the affected side lower
and closer to the film cassette.
Normal thymus An anterior mediastinal soft tissue mass
is a common finding on conventional chest radiograph
(Fig. 28.1.1) in normal children up to the age of 3 years
and is due to normal thymus. A number of radiographic
signs are helpful to identify it as normal thymus, e.g. wave
sign; sail sign; change in shape during respiration
and shrinking under the stress of steroid therapy (which
reverts to the original size on stoppage of steroid).
Pathological Conditions
Discussion on important neonatal chest conditions like
hyaline membrane disease, transient tachypnea of the
newborn and meconium aspiration, are beyond the scope
of this chapter.
Developmental anomalies Agenesis of a lung is an extremely
uncommon clinical entity. Completely opaque hemithorax
on a frontal chest radiograph and absent pulmonary artery
or main bronchus on the pulmonary angiogram or
bronchogram, respectively, confirms the diagnosis.
Pediatric Radiology
1301
Figure 28.1.1: Normal frontal and lateral chest radiograph: Note a large right anterior mediastinal mass due to
normal thymus (Sail sign). Correlation with clinical information is mandatory before assigning a pathological label
Persistence of pleuroperitoneal canal results in

herniation of intestinal loops into the chest cavity
(Fig. 28.1.2). Clinically the baby presents with respiratory
distress.
Foreign body inhalation One of the most important,
noninfective cause of acute respiratory distress in children
is inhalation of foreign body, which could be either
radiolucent (in about 90%) or radiopaque (in 10%)
(Figs 28.1.3A and B). Radiographic findings depend upon
a number of factors. Collapse (Fig. 28.1.3C), hyperlucent
enlarged lobe (or lung) due to ball valve type of block or
consolidation may be seen. In a suspected case of
radiolucent foreign body inhalation and with equivocal
chest radiographic findings, deep expiratory film may be
very useful for the correct diagnosis.
Figure 28.1.2: Congenital diaphragmatic hernia on the right

side: Note the bubbly bowel loops in the right hemithorax,
mediastinal shift to the left and paucity of bowel loops in the
abdomen. Important D/D of bubbly chest includes congenital
cystic adenomatoid malformation, pneumatoceles and
multiple lung cysts
Figures 28.1.3A to C: Foreign body inhalation: Radiograph showing collapse right lower lobe (A). CT mediastinal window is
showing intraluminal foreign body in right lower lobe bronchus (B) and collapse right lower lobe (C)
1302
Bacterial pneumonia It is most commonly caused by

H.influenzae (between 612 months age), Pneumococcus
(13 years of age) and Staphylococcus aureus (early infancy).
About 50 percent of staphylococcal pneumonia cases are
complicated by pneumatoceles (Fig. 28.1.4). Staphylococcal or pneumococcal pneumonia may produce a
round-shaped pneumonia termed round pneumonia
which may mimic hydatid cyst or metastatic lesion.
Abscess (Figs 28.1.5A to C) is not an uncommon
complication. Empyema is another important complication necessitating imaging and many a times surgical
intervention.
Viral infection Unlike bacterial infections which result in
air space disease, viral infections tend to affect
predominantly the airways. The resultant radiologic
picture is bilateral hyperinflation with perihilar striations
(Fig. 28.1.6), the latter due to peribronchial thickening
(cuffing). Radiograph may even appear normal. Pathologic-cum-clinical term used to describe this condition is
bronchiolitis or bronchitis. Thus, in a child presenting
with acute respiratory distress but with very subtle
radiologic changes, one should suspect this clinical entity.
Pulmonary tuberculosis is one of the most commonly
seen chest condition in India. A wide spectrum of
radiologic findings are observed in these children. Primary
complex (Fig. 28.1.7) consists of the pulmonary
parenchymal focus, draining lymphatics (rarely seen on
chest radiograph) and mediastinal nodal enlargement.
Once the child develops resistance then radiological
Figures 28.1.5A to C: Lung abscess in evolution: Initially (A)

consolidation which progressed to a huge lung abscess with
a large air-fluid level (B) The finding is confirmed on CT (C)
Figure 28.1.4: Staphylococcal pneumonia with

pneumatocele
changes of post primary tuberculosis are seen. Findings

may include only nodal enlargement, pleural effusion (Fig.
28.1.8), lobar or segmental consolidation; pneumonic
consolidation with air bronchogram (Figs 28.1.9A to C)
and pulmonary cavitations. Lymphatic or venous seeding
Pediatric Radiology
Figure 28.1.6: Viral pneumonia, bronchiolitis. Bilateral, generalized hyperinflation

with minimal flattening of both domes. Note
minimal perihilar striations, better appreciated on the left side due to peribronchial
soft tissue thickening
1303
Figure 28.1.7: Primary pulmonary complex: Consolidation just above the

minor fissure
in lungs produces miliary tuberculosis. Following healing,

by chemotherapy or by development of body immunity
chest radiograph may become either completely normal
or residual changes like calcified nodes, pulmonary scar,
pleural thickening or loss of volume may be seen.
Figure 28.1.8: Free pleural effusion on the right side,

running along the lateral chest wall
Bronchiectasis is another common clinical problem

which usually follows infection by tuberculosis and viral
or bacterial pneumonias. After the chest radiographs, thin
section, high-resolution CT is the imaging modality of
choice to detect subtle bronchiectasis. Bronchograms are
rarely, if ever, used nowadays.
On a chest radiograph; round, soft tissue density, either
single or multiple is most commonly due to hydatid cyst
in our country. CT would readily show its content to be
Figures 28.1.9A to C: Primary progressive type of pulmonary tuberculosisan uncommon presentation
1304
fluid. If the lesion is abutting the chest wall or diaphragm,

then ultrasound can also be used for characterizing the
soft tissue mass.
Primary lung tumors are rare in children. Metastatic
lung disease is much more common and is usually from a
Wilms tumor.
Mediastinum is divided into three compartments, viz.,
anterior, middle and posterior. It is important to remember
that the radiological division of the mediastinum is
different from the anatomical division. Masses can arise
from any one of the structures normally present in these
compartments. Germ cell tumor is an anterior mediastinal
malignant tumor. Lymph nodes, bronchogenic cyst,
pericardial tumors and hiatus hernia are important
masses of middle mediastinum while neurogenic tumors
predominate in the posterior mediastinum.
Radiological finding in diseases of heart and great
vessels is beyond the scope of this chapter.
SKELETAL SYSTEM
Imaging Techniques
Conventional radiographs still remain the mainstay for
the evaluation of musculoskeletal diseases. CT and MRI
provide detailed soft tissue, articular and bony imaging
and are thus helpful, especially for examination of masses
regarding their content, extent and degree of vascular and
marrow involvement. MRI is superior to CT due to its
better soft tissue resolution and multiplanar capability.
Sonography has a role in the evaluation of congenital
dislocation of hip, hip effusion and soft tissue masses.
Scintigraphy is the primary modality in the detection of

metastatic disease and osteomyelitis.
Before interpreting abnormality one must have knowledge
about the normal development of bone, parts of different
areas of skeletal system and a number of normal variants
which may mimic abnormalities.
Rickets is still a relatively common clinical problem in
India. Vitamin D deficiency results in failure of normal
mineralization of the growing cartilage into bone. Classic
radiographic findings are found in the most rapidly
growing ends of bone and includes generalized osteopenia,
disappearance of zone of provisional calcification,
cupping with fraying and irregularity of the metaphyseal
ends and perpendicular striations extending from the
metaphyseal end towards epiphysis (Figs 28.1.10A and B).
Enlargement of anterior ends of ribs (rachitic rosary) and
lower ends of radius and ulna may also be noted.
Thalassemia major (homozygous form). Radiographic
changes are at times dramatic (Figs 28.1.11A to C) and are
the result of marrow hyperplasia.
Congenital syphilis is caused by transplacental spread.
Bone lesions may appear even up to 2 months later.
Hallmark of this condition is metaphysitis (Figs 28.1.12A
to C), i.e. a metaphyseal lucent band located directly
beneath a dense band in the subphyseal region. Focal
destructive bony lesions in diaphysis, periosteitis and
pathological fracture may also occur.
Skeletal tuberculosis is still prevalent in India.
Tuberculosis may affect any part of the skeletal system. In
Figures 28.1.10A and B: Rickets: Primarily a metaphyseal disease. Note cupping of metaphyseal ends of both radius and
ulna, widened physis, perpendicular striations extending from metaphysis into physis towards the epiphysis. Generalized
osteopenia is seen in the background (A). Post treatment radiographs (B) show healing
Pediatric Radiology
1305
Figures 28.1.12A to C: Congenital syphilis, both lower limbs

AP view: Characteristic metaphyseal changes (metaphysitis)
and periostitis seen in all the long bones (A). Epiphysis are
normal. Important differential diagnosis is scurvy which is
characterized by osteopenia with subperiosteal hemorrhage
lifting up the periosteum and metaphyseal changes (B and
C)
Figures 28.1.11A to C: Thalassemia major: CXR showing

marked expansion of the ribs (A). Striking hair-on-end
appearance in the skull (B) and osteoporosis, widening of
medullary spaces of all the bones of hands with coarse
trabecular pattern, loss of lateral concavity of small bones of
hand and moulding abnormality of distal ends of long bones
(C). Radiographic changes reflect marked degree of marrow
proliferation
the spine, it typically affects the vertebral body. Partial

collapse produces para (and/or pre) vertebral abscess and
short angle gibbus. Long bone tuberculosis may be isolated
or affect an adjacent joint. A high index of suspicion, chest
radiograph, biochemical and hematological findings,
family history, positive tuberculin test and nowadays
enzyme-linked immunosorbent assay (ELISA)all help
in establishing the diagnosis in an equivocal case.
Developmental dysplasia of hip (congenital dislocation
of hip) is a common clinical problem. Following a thorough
clinical examination, ultrasound is usually the first
screening modality to confirm the diagnosis. On plain
radiographs a number of lines have been described to
identify cases with subtle dislocation. Nowadays, 3dimentional-CT and 3-dimentional-MRI have shown
promising results for indepth evaluation of this entity.
Osteogenic sarcoma is the most common primary
malignant bone tumor between 10 to 25 years of age and
is usually located in the metaphysis of a long bone,
especially around the knee. Typically the tumor matrix is
ossified and its metastases to lungs may also be ossified.
Metastatic disease affecting the skeletal system is
common in the pediatric age group. Commonly it is due to
a round cell tumoracute lymphoblastic leukemia,
neuroblastoma, lymphoma, rhabdomyosarcoma or
1306
Ewings sarcoma. Skeletal survey shows generalized

demineralization, moth-eaten osteolytic lesions
diffusely involving all the bones, metaphyseal lucent
bands, periosteal new bone formation with loss of focal
areas of cortical line due to tumor invasion.
Radiology of skeletal system would be incomplete
without a few words on the methodology for skeletal
maturity assessment or bone age assessment. Earlier method
of observing the appearance and fusion of ossification
centers, is an obsolete technique even though in India it is
still the only method used in most hospitals. More accurate
methods are by using an atlas either by Greulich and Pyle
or Tanner and White house (TW3 method). The latter is, at
present, the most accurate method for assessment of
skeletal maturity in a child.
GASTROINTESTINAL TRACT (GIT)
Imaging Techniques
Once again, plain radiograph coupled with contrast
examination (barium studies) play a major role in a large
number of GIT disorders. Sonography, CT and MRI
provide valuable information especially in cases of
masses, mesenteric vascular and nodal status, retroperitoneal anatomy, trauma, and abscess or other fluid
collections.
Erect plain abdominal radiographs are usually adequate
in intestinal obstruction (Fig. 28.1.13), perforation with
free air (Fig. 28.1.14) or necrotizing enterocolitis with

classical intramural air (Fig. 28.1.15), calcified mesenteric
or retroperitoneal nodes, diseases of the spine (e.g.
tuberculosis) and a host of other conditions are also readily
diagnosed on plain radiographs.
However, contrast examination with barium is
required for the diagnosis of mucosal diseases, e.g. polyps
or ulcer; intestinal muscular wall diseases, e.g. congenital
hypertrophic pyloric stenosis (Fig. 28.1.16) and stricture,
obstruction, Hirschsprungs disease, etc. GIT related
masses require a cross-sectional imaging modality, i.e.
sonography, CT or MRI, with or without intravenous
contrast. Esophageal atresia is diagnosed on day 1 of life,
usually with negative contrast, i.e. air only, but positive
contrast (i.e. barium or nonionic isotonic contrast) may
also be used (Fig. 28.1.17). Thus, for GIT-related conditions,
a radiologist can choose a specific imaging modality in a
particular case to derive maximum information with
minimum cost and harm (radiation, invasive technique)
to the patient.
HEPATOBILIARY SYSTEM
Imaging Technique
Nowadays ultrasound is usually the first imaging
modality for evaluating diseases of the hepatobiliary
system. In the presence of a tumor, contrast-enhanced CT
(CECT) tailored for the suspected pathology is usually
adequate. However, MRI with its multiplanar capability
may add new information regarding involvement of
Figure 28.1.13A and B: Abdomen, AP erect view in a newborn with vomiting and abdominal distention: Multiple, small, air-fluid
levels predominantly in the central abdomen (A). Absent gas in the colon and rectum. A case of Ileal atresia. Number, type and
distribution of bowel loops and air-fluid levels help in localizing the level of obstruction. Barium enema (B) revealed microcolon
Pediatric Radiology
Figure 28.1.14: Perforation of GIT with free

peritoneal air seen between the right
diaphragm and liver. Both sides of the
intestinal walls are visible, another sign
of presence of free peritoneal air
Figure 28.1.15: Necrotizing entero

colitis (NEC) in a newborn: Classical linear gas shadows due to
intramural gas (pneumatosis
intestinalis) and bubbly appearance
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Figure 28.1.16: Congenital hypertrophic

pyloric stenosis, upper gastrointestinal
barium study. Pyloric canal is markedly
narrowed, elongated with indentation at
the base of duodenal cap. Currently,
sonography is the first and many a times
the only investigation of choice since it
can diagnose the condition in a large
number of patients
adjacent structures. Angiography is rarely required either

for preoperative arterial road map in cases of tumor or for
diagnosing primary vascular diseases, e.g. aneurysm,
arteritis, etc. Plain radiographs have very limited role, if
any.
Figure 28.1.17: H-(or N) type of tracheoesophageal fistula:

Tube esophagogram showing communication between
esophagus and trachea
Most common clinical problem is to differentiate medical

from surgical type of jaundice. This differentiation is made
by observing presence or absence of dilatation of biliary
channels. Sonography can readily identify dilatation of
intra and/or extrahepatic biliary channels, level of
obstruction and many a times even the cause, e.g. calculus,
pancreatic head tumor or choledochal cyst.
Choledochal cysts are congenital ectatic dilatation of
biliary channels either totally extra, intrahepatic or a
combination of the two. Sonography is usually adequate
for its diagnosis (Fig. 28.1.18A) but endoscopic retrograde
cholangiopancreatography (ERCP, Fig. 28.1.18B) or
magnetic resonance cholangiopancreatography (MRCP)
may also be done to demonstrate it preoperatively
(Fig. 28.1.18C).
Biliary atresia, an important differential diagnosis of
neonatal jaundice requires US coupled with nuclear scan
1308

for diagnosis. Nowadays, MRCP is the first and usually
the only imaging modality required to differentiate it from
neonatal hepatitis. However, intraoperative cholangiogram is the most definitive investigation for its diagnosis.
Liver tumors are common and of these malignant
neoplasms (hepatoblastoma or hepatocellular carcinoma)
are the most common. Any of the cross-sectional imaging
modality can diagnose and stage it. A cystic liver spaceoccupying lesion (SOL) is usually due to hydatid cyst or
liver abscess in India.
Splenic enlargement is another common clinical
problem. Malaria and kala-azar are two important medical
causes while portal hypertension, usually secondary to
extrahepatic block in the splenoportal axis, is the most
important surgical cause. Initial evaluation of portal
hypertension and portal biliopathy is with ultrasound
which can be confirmed by splenoportovenography,
arterial portography and nowadays with 3D-CT arterial
portography (Fig. 28.1.18D).
URINARY SYSTEM
Imaging Techniques
For evaluation of the upper renal tracts, sonography,
especially color duplex sonography coupled with plain
abdominal radiographs is usually adequate for anatomical assessment. However, it needs to be supplemented by
a functional study. Nowadays renal scintigraphy is
preferred due to its low radiation dose, higher sensitivity
and more objective assessment of renal function. Excretory urography is required when complex anatomical
details need to be clarified or in patients with ureteric
disease. CT or MRI is added in the work-up of a case of
tumor or trauma. For examination of the lower urinary
tract, sonography for bladder and contrast examination
for urethral evaluation, are usually adequate.
Figures 28.1.18A to C: Huge, extrahepatic, cystic choledochal

cyst onultrasound (A) and on endoscopic retrograde
cholangiopancreatography (B), Note the slightly dilated right
main bile duct entering the cyst on ultrasound. Gallbladder
should be documented separate from the cyst. MRCP image
(C) elegantly documenting the choledochal cyst
Hydronephrosis is one of the most important and common

problems encountered in pediatric practice. Sonography
and contrast study not only diagnose it reliably, but also
provide a clue to its possible cause, e.g. pelviureteric
junction (PUJ) obstruction (Fig. 28.1.19), calculus, etc. and
it can also delineate an associated hydroureter, if present.
A number of congenital anomalies can be seen, e.g.
horseshoe kidney, crossed ectopia, low lying kidney, etc.
Of the solid renal masses, Wilms tumor is the most
Pediatric Radiology
1309
Figures 28.1.18D: Portal biliopathy: MRI axial (1) and coronal (2), CT axial (3) and coronal (4) images showing portal
cavernoma causing biliary dilatation. 3D CT (5) showing
exquisite detail of the porto splenic axis and the collaters
developed
1310
Figure 28.1.19: Nephrostogram of left kidney shows dilated,

rounded renal pelvis with caliectasis, a case of PUJ obstruction. Ureter is not opacified even on delayed images
common. On cross-sectional imaging, it is seen as a solid

tumor with variegated enhancement due to areas of
necrosis. In 10 percent it may be bilateral. For staging purposes, CT or MRI may be done in addition to sonography.
Bladder tumors are relatively rare in children and of
these a malignant tumor, rhabdomyosarcoma, is the most
common. On the cystogram phase of a contrast study,
characteristic lobulated filling defects are seen from the
bladder base. This appearance gives it the name of
sarcoma botryoides.
Vesicoureteric reflex (VUR) is one of the most important
causes for urinary tract infection. Voiding cystourethrography (VCUG), either using contrast or an isotope
is required to diagnose it (Fig. 28.1.20). The latter is
reported to be more accurate. Nowadays even
sonocystography is used in certain clinical situations to
diagnose VUR with the added advantage of lack of ionizing
radiation.
The most common cause for urinary outflow obstruction
in a male child is posterior urethral valve (PUV).
Micturating cystourethrography (MCU) is mandatory for
its diagnosis (Fig. 28.1.21). Back-pressure changes in the
bladder and associated VUR is common. MR urography
has been tried to be useful for demonstrating VUR.
Moreover it is free of radiation.
Figures 28.1.20A and B: Micturating cystourethrography (MCU)

(A): Vesicoureteric reflux on both sides. Urinary bladder shows
trabeculation and sacculations due to neurogenic dysfunction (neurogenic bladder). Same information could be seen
on MR urography (B)
Figure 28.1.21: MCU shows marked dilatation of posterior

urethra, thin urinary stream and narrowing at the junction of
posterior and anterior urethra due to posterior urethral valves.
Also note gross VUR on the right side.
CRANIAL AND SPINAL IMAGING

Imaging Techniques
Conventional radiographs of the skull should include at
least frontal and lateral view. Depending upon the
suspected clinical disease, more views can be taken, e.g.
for sinuses, atlantoaxial junction, pituitary fossa, etc. Plain
X-rays of the spine are routinely done in all cases of spinal
dysraphism, scoliosis, back pain, etc.
Pediatric Radiology
1311
Transfontanel cranial ultrasonography (US) has a role

to play only if the anterior fontanel is open. Diagnosis of
hydrocephalus, intracranial bleed, congenital malformations and tumors of the brain can be made. However, US
has its own limitations. CT is the most cost-effective
technique for cranial imaging. For posterior fossa,
brainstem and white matter diseases, however, MRI is far
superior to CT.
For the evaluation of spine and its contents, MRI is the
modality of choice. But if it is not available then myelogram
with nonionic media followed by postmyelo-CT should
be routinely done.
The term craniosynostosis denotes premature fusion of

cranial sutures. Depending upon the pattern of sutural
closure, the shape of the head varies and different names
are used to describe them, e.g. brachycephaly (fused
coronal sutures,) and scaphocephaly (sagittal sutures
fusion). Besides the plain radiographs, CT, and nowadays
3D-CT, is the investigation of choice to assess the sutural
status. Growing fracture at times may mimick a widened
suture (Fig. 28.1.22).
Intracranial calcification (Fig. 28.1.23) could be seen in
post-infectious states, e.g. cytomegalovirus, toxoplasma
infection, tuberculous meningitis; in brain tumors,
B
Figure 28.1.22: Growing Fracture: Frontal Radiograph of face

and skull showing a linear oriented lytic lesion with beveled
margins in left frontal bone
Figure 28.1.23A to C: Intracranial calcification: NCCT axial

sections showing periventricular calcification in congenital
CMV infection (A). Axial NCCT images (B and C) showing
intracranial calcifications in the bilateral basal ganglias and
cerebellar hemispherestypical presentation of calcification
in hypoparathyroidism
1312
hypoparathyroidism and or in dysplastic brain tissue. CMV

produces periventricular calcifications (a calcified mould
of the ventricles) whereas, toxoplasmosis produces diffuse
cerebral calcification. Bilateral basal ganglia calcifications
have been reported in AIDS encephalopathy also. CT is
essential for anatomical localization.
Skull vault may be affected in a number of diseases,
e.g. histiocytosis (Fig. 28.1.24); neuroblastoma metastases
(Fig. 28.1.25), hematological and metabolic diseases and
various skeletal dysplasias.
Infectious conditions like brain abscess (Fig. 28.1.26),
tuberculomas (Fig. 28.1.27), neurocysticercosis (Fig. 28.1.28)
are readily diagnosed with CT and MRI.
Hydrocephalus, one of the most common causes of a
large head in children, is readily diagnosed on any one of
the cross-sectional imaging modalities (Figs 28.1.29).

Similarly, other intracranial pathologic lesions can be
imaged.
Spinal dysraphism (Figs 28.1.30) is the most common
congenital abnormality affecting the spine. It is a complex
disorder. Information required by the surgeon regarding
level of spinal involvement, contents of the sac, presence
or absence of diastematomyelia (transfixion of the spinal
cord by a bony spur congenitally) demyelinating changes
in the cord and associated hydrocephalus and ArnoldChiari malformationscan all be, nowadays, reliably,
noninvasively delineated by MRI. If MRI is not available,
then myelogram with nonionic contrast followed by CT is
mandatory.
Figure 28.1.24: Skull X-rays: Multiple, large geographic type bone destruction, characteristic of
histiocytosis. These type of bone lesions indicate relatively slow growing pathology
Figure 28.1.25: Skulllateral view: Multiple

lytic lesions with sunray type of periosteal
reaction in a case of neuroblastoma with
skull metastases
Figure 28.1.26: Brain abscess: Axial

CT showing multiple ring enhancing
lesions in bilateral frontal and right
occipital lobes with perilesional
edema
Pediatric Radiology
Figure 28.1.27: Tuberculomas; CECT

axial sections showing multiple ring enhancing lesions with hypodense centers
and perilesional edema in bilateral high
parietal lobes
1313
Figures 28.1.28A and B: Neurocysticercosis(NCC): Multiple hyperdense lesions

in brain suggestive of NCCS. Note the eccentrc scolex in figure (B)
Figures 28.1.29: Hydrocephalus with

ventriculitis: Axial CT showing dilated
ventricles with enhancing ventricular
margin and periventricular ooze
Figures 28.1.30A to C: Diastematomyelia: Radiograph showing bony septum in the spinal canal at L 2 level with spina bifida
from L3 onwards (A) T2W axial MRI images (B) showing splitting of the cord into two (C) Chiari III malformation- Sagittal T2W
MRI showing herniation of tonsil and brain stem (chiari II) with occipital meningoencephalocele
1314
SUMMARY
3.
To conclude pediatric radiology is a very large subject

covering all the organ systems. Knowledge of the
pathological appearance, awareness of the advantages
and limitations of an imaging modality, availability and
expertise in performing and interpreting the results of an
investigationall are crucial for an overall management
of pediatric patients.
4.
BIBLIOGRAPHY
8.
1.
Barkovich AJ (Ed). Pediatric Neuroimaging: Contemporary Neuro-imaging. Raven Press: Philadelphia, 1990;1.
2. Berry M, Mukhopadhyay S, Chowdhury V, Suri S, Gupta
AK (Eds). Paediatric Imaging (AIIMS-MAMC-PGI
Imaging Diagnostic Series), (2nd edn). Jaypee Brothers
Medical Publishers (P) LTD: New Delhi, 2004.
5.
6.
7.
9.
10.
Blickman JG (Ed). Pediatric Radiology: The Requisites.

Mosby: St Louis, 1994.
Carty H, Shaw D, Brunelle F et al (Eds). Imaging Children.
Churchill Livingstone: Edinburgh, 1994;I and II.
Castillo M, Mukherji SK (Eds). Imaging of the Pediatric
Head, Neck and Spine Lippincott Raven: Philadelphia,
1996.
Hilton SW, Edwards DK (Eds). Practical Pediatric
Radiology (2nd edn). WB Saunders Company:
Philadelphia, 1994.
Kirks DR (Ed). Practical Pediatric Imaging (1st edn). LittleBrown and Co: Boston, 1984.
Kuhn JP, Slovis TL, Haller JO (Eds). Caffeys Pediatric
Diagnostic Imaging. Mosby (10th edn), 2004.
Mukhopadhyay S, Gupta AK. Imaging in childhood
tuberculosis. In Seth V (Ed): Essentials of Tuberculosis in
Children. Jaypee Brothers Medical Publishers (P) LTD:
New Delhi, 1997.
Swischuk LE (Ed). Imaging of the Newborn, Infant and
Young Child. (4th edn), 1996.
29.1 Common Eye Problems in Children: Supriyo Ghose ..................................................................................................................... 1316
1316
29.1 Common Eye Problems in Children

Supriyo Ghose
To effectively handle common ocular problems, the
pediatrician must have some basic ophthalmic equipment (good torch with focal illumination, cotton swabsticks, eyepads and dressings, and preferrably a
magnifying device such as a loupe, and an ophthalmoscope). Common drugs must be available, as topical
anesthetic agents (2 and 4% xylocaine), antibiotic drops
and ointments, mydriatics (phenylephrine drops 2.5 and
5%), and fluorescein paper strips (fluorescein solutions
are often contaminated by Pseudomonas). Cycloplegics are
not necessary normally to dilate the pupils for a good
fundus examination, and drugs like topical atropine,
which viciate the pupillary findings, should preferrably
be avoided, unless the ocular condition demands it.
Tropicamide 0.5 and 1 percent may be useful.
Clinical Approach to Diagnosis and Management
There are certain milestones in ocular development during
neonatal life, infancy, and at least up to 5 years of age,
which are important to appreciate, even though visual
acuity assessment may be fraught with difficulties.
Generally speaking, most ocular disorders would
present to the pediatrician with one or more of the
following: History of injury, pain, red eye, watering,
swelling, a squint or diminution of vision.
Before actually seeing the eye, it is important to have
a proper history (such as the exact nature of the injury),
as accurate an assessment of the vision as possible (careful
observation for both eyes separately, with a proper
Snellens chart in the older and cooperative child), and a
quick examination of the adnexal structures.
On ocular examination, the details of the ocular
structure should be noted and looked for. The textbook
points are well known. In practice, it is the abnormal
features which should strike us: ocular movements, any
squint, and size of the globes; lidsedema, margins,
lashes, swellings, injuries, ptosis, puncta and canaliculi;
conjunctivacongestion, discharge (watery or mucopurulent), xerosis, Bitots spots, foreign body, subconjunctival hemorrhage, and tears in the conjunctiva;
scleracolor, nodules, ectasia, staphyloma, and scleral
tear; cornealustre, haze (localized or generalized),
opacities, ulcer, foreign body, lacerations, and incarceration or prolapse of iris tissue; anterior chambernormal
black optically transparent appearance, depth (shallow
or deep, regular or irregular), clarity of contents, blood
(hyphema), pus (hypopyon), pseudohypopyon (as in
leukemia and retinoblastoma), and lens matter or foreign
body in the anterior chamber (as after injury); lens
opacities (cataract), subluxation, and dislocation;
intraocular tensiona digital assessment may be possible;
irismuddiness, loss of normal luster, color and pattern,
synechiae, nodules, new blood vessels, hole in the iris,
detached root of the iris, smearing of blood on the iris
face, foreign body lodged in the iris, and the pupillary
margins; pupilshape and size, record of pupillary
reactions (direct and consensual) and the swinging light
test (before any medication topically), and change of
normal black lustrous reflex in the pupillary area; and
fundusglow by distant direct ophthalmoscopy, direct
ophthalmoscopy (may be under dilated pupils), any signs
of inflammation, and mass or tumor in the fundus.
Noting such details would be of great help in the
initial diagnosis and treatment, and their first hand
recording would afford a lot of useful and reliable
information to the ophthalmologist, if the patient has to
be referred later.
Examination of an eye after injury should be undertaken with great caution, especially after a suspected
perforating injury. Forcible examination is dangerous, as
the eye may suffer further damage, and the intraocular
contents may be lost. The lids may be gently retracted and
held against the bony orbital marginssedation or a
general anesthetic may be required.
PHYSICAL AND CHEMICAL TRAUMA
Foreign Body
A conjunctival foreign body should be located and easily
removed. It is not quite so easy when the foreign body is
lodged in the upper tarsal conjunctiva in the subtarsal
sulcus, as this requires the eversion of the upper lid, a
procedure easily mastered with a little practice.
A corneal foreign body should be gently removed with
wet swab or spudif difficult, apply antibiotic ointment
and refer promptly.
Pediatric Ophthalmology
A suspected intraocular foreign body should be
immediately referred for investigations and urgent
management.
Chemical Injuries
Chemical injuries to eyes are common in laboratories and
industrial areas. They require immediate, prolonged (for
several hours) and copious irrigation with saline or tap
water. They often lead to limbal ischemia and
symblepharon. Alkalies such as ammonia or lime are far
more dangerous than acid burns. Plant juices can be
extremely irritant.
Thermal Burns
Thermal burns should be treated on conservative lines
and efforts made to protect the cornea. Explosive injuries
by fireworks, crackers and bombs may cause serious
damage to the eyes. Ocular fireworks injuries are much
more severe and dangerous in children than adults.
Blunt Injury
These can be caused by a ball, stone, fist, stick, slingshot,
gulli-danda, fireworks, etc. Blunt injuries are potentially
very dangerous. If the child has significant hyphema, he
or she should be administered hypotensive agents as
glycerol, diamox (acetazolamide) or intravenous
mannitol to reduce the chances of rise of intraocular
pressure and corneal blood-stainingbed- rest may help.
The visual prognosis is guarded, as many more
complications may or will take place. Referral without delay
is advocated after primary treatment. Atropine topically
may be contraindicated.
Perforating Injury
A perforating injury (with or without intraocular foreign
body) is the most important surgical ocular emergency in
children and demands urgent treatment, bandage and
immediate referral for proper examination and repair
under general anesthesia, preferrably with the operating
microscope. An extensive injury may necessitate
enucleation of the globe. The possibility and dangers of
sympathetic ophthalmia should always be borne in mind.
Lid lacerations also require prompt repair, and canalicular injuries have to be adequately managed.
Corneal Abrasion
Corneal abrasion can be very painful with marked
photophobiathe corneal epithelium may get abraded
1317
by trivial injuries as with edges of paper, leaves, twigs,

toys, and fingernail scratches, etc. and the area of
epithelial denudation can be easily demonstrated by
fluorescein staining. The treatment is almost the same as
for an ulcer, (i.e. topical antibiotics, cycloplegic agents
and lubricants) except that atropine is not routinely
indicated, and a 24-hour firm pad and bandage is very
beneficial in promoting epithelial healing. Analgesics are
useful, but topical anesthetics should be used minimally
or not at all.
Subconjunctival Hemorrhage
Subconjunctival hemorrhage is another common alarming
sign for the patient and the parents. The cause should be
elicited, as severe coughing (whooping cough), straining,
minor local trauma, hemorrhagic conjunctivitis and rarely
vitamin C deficiency. More serious entities such as head
injury, fractures, and deeper trauma must be kept in mind,
may be only to rule them outin such cases, the posterior
limit of the hemorrhage cannot be seen, the color of the
blood is darker, there is a significant time lag of hours to
days from the time of injury to be appearance of the
hemorrhage, which classically starts with the medial
corner of the lower lid being ecchymosed. Rarely, a small
subconjunctival hemorrhage may be overlying a small
scleral intraocular perforation, which may be due to an
intraocular foreign body. Small tears of the conjunctiva
may result from injury.
RED EYE
A red eye is by and large the most common ocular problem
to be seen, and a differential diagnosis has to be made between
the not so serious conjunctivitis, and the more grave
conditions of corneal ulcer, iridocyclitis, and glaucoma.
Acute glaucoma as typically described in adults is not
usually seen in children.
Corneal Ulcer
Corneal ulcer presents with a typical corneal picture, ciliary
congestion, and may be iridocyclitis. It demands immediate
attentionswab for culture and sensitivity (preferably from
ulcer edge scrapings), local hygiene, topical antibiotics
fortified drops and may be systemic coverage also, topical
atropine, application of heat for associated lid edema,
systemic supportive therapy, and, if necessary, ocular
hypotensive agents as acetazolamide to prevent
impending perforation. Steroids should be avoided.
Children should be discouraged from touching the eye or
bandageif necessary, mechanical restraint, as by a
1318
hollow cardboard cylinder over the elbows, may have to

be resorted to.
A history of trauma or a corneal foreign body may be
evident. Injury with vegetable matter may lead to a fungal
corneal ulcer, more recalcitrant to therapy and requiring
specific antifungal measures.
A herpetic ulcer may exhibit a typical dendritic figure
on fluorescein staining, and may be associated with
herpes simplex lesions elsewhere as on the lips, nose and
genitalia, recurrences may be associated with lowering
of body resistance. Antiviral therapy topically with atropine
are indicated to start with. The corneal sensations
diminish in this condition, as they also do in early
keratomalacia.
If the Bowman's membrane is damaged in a corneal
ulcer, a corneal opacity will result on healingearly
institution of therapy would restrict the opacity to a
minimum, and reduce the chances of corneal blindness.
Nonhealing or progression of the ulcer, or the appearance of a
hypopyon merits urgent referral. Early xerophthalmia
should be tackled most energetically before full-blown
keratomalacia develops with irreparable loss of vision.
Iridocyclitis has a rather typical picture of a muddy
inflamed iris, with miosis, ciliary congestion and pain
with tenderness. The etiology may be difficult to establish even after thorough investigations, but early treatment is essential. Topical atropine and steroid-antibiotic
combinations are the sheet anchors of treatment. One
should remember that steroids are, as a rule, contraindicated in corneal ulcer, and atropine is undesirable
even in congenital or juvenile glaucoma.
If the other conditions are ruled out and a diagnosis
of conjunctivitis (or ophthalmia neonatorum) is made, the
ideal would be to start topical antibiotics (after
conjunctival swab and a smear) and frequent washes.
As a rule, steroids should be avoided.
Chlamydial ophthalmia neonatorum (ON) may be acquired
from the maternal birth passages, with a longer incubation
period than the earlier more common gonococcal
ophthalmia. Proper diagnosis and aggressive with
systemic antibiotics therapy are necessary. Trachoma is
still widely prevalent in our country, and manifests
mostly in the upper palpebral conjunctiva with follicles
and scarring later with cicatrization. An early diagnosis
and treatment prevents serious complication of blinding
trachoma.
Membranous Conjunctivitis
Diphtheritic conjunctivitis is associated with true
membrane formation. Pseudomembranes may form in
other bacterial infections and Stevens-Johnson syndrome.

It may be dangerous to peel off the membrane, as toxins
may be released with grave consequences.
A pinkish white elevation appearing at the limbus in
the bulbar conjunctiva, could be a phlycten with engorged
conjunctival vessels clustering around its base.
Phlyctenular keratoconjunctivitis is believed to be an allergic
response to tubercular or other bacterial proteins, often
associated with undernutrition and poor health. Treatment
consists of topical steroid/NSAID therapy. A systemic
tubercular focus should be ruled out and respiratory
infections looked for.
The presence of congested nodules on the sclera are
suggestive of episcleritis, or the more severe condition of
scleritis (usually with associated underlying uveitis).
Episcleritis and scleritis should be differentiated from acute
conjunctivitis by their more localized nature and presence
of pain and tenderness.
Vernal keratoconjunctivitis usually affects boys and is
associated with intense ocular itching, foreign body
sensation, lacrimation and photophobia. Superior
palpebral conjunctiva demonstrates giant flat topped
papillae. Corneal involvement can occur in severe cases.
Treatment includes topical mast cell stabilizers like
nedocromil sodium 0.1 percent and topical steroids in
acute stage. Of recently Olopatadine 0.1 percent eyedrops
have been found to be very effective and safe for
treatment of this condition.
Uveitis
Uveitis may be exogenous or endogenous in origin, and
tuberculosis is an important cause in our country. Still's
disease is well known for its association with band-shaped
keratopathy. Choroiditis or chorioretinitis is known to be
associated with many conditions, such as tuberculosis,
syphilis, toxoplasmosis, toxocariasis, rubella, etc.
Endophthalmitis (as with measles) or panophthalmitis is a
serious condition which demands an early blood culture,
urgent institution of systemic antibiotics, and prompt
referral.
In the adnexae, the lacrimal sac on pressure may show
regurgitation and child may present with a swelling
(mucocele), or may develop the more acute condition of a
lacrimal abscess (with or without fistula). For the latter,
conservative therapy with warm compresses, analgesics,
and topic and systemic antibiotics are recommended. The
definitive surgical treatment should be undertaken by
an ophthalmologist.
Table 29.1.1 depicts differentiating features of
conjunctivitis, corneal ulcer and iridocyclitis.
WATERING
Watering may be because of inflammation, infections,
foreign bodies, ENT problems, uveitis, glaucoma, and
nasolacrimal obstruction. Persistent watering from one
or both the eyes in infants should lead to the suspicion of
blockage of the nasolacrimal duct with congenital dacryocystitis.
The regurgitation of mucopus from the puncta on pressure
over the lacrimal sac clinches the diagnosis ofdacryocystitis.
The discharge should be sent for culture and antibiotic
sensitivity. The mother should be advised to massage the
sac firmly twice a day, clean the discharge, and instil an
appropriate antibiotic as drops. The associated rhinitis
should be controlled and the nose kept dry so as to facilitate
the opening up of the blocked nasolacrimal duct. The
child may be referred for further management to an
ophthalmologist. The probing and syringing of the
nasolacrimal duct should preferably not be delayed beyond six
months of age, though many infants do undergo spontaneous
resolution by one year of age with proper conservative
treatment.
LID EDEMA
Lid edema is not uncommon, and it is an alarming sign. It
may be due to allergy (topical medications), or due to an
insect bite. The loose areolar tissues of the lids allow
considerable swelling to occur. Conservative treatment is
quite satisfactory. Systemic causes of lid edema should be
excluded. Stye (hordeolum externum), a painful tender
erythematous infection of the hair follicle of eyelashes,
and furuncles may also produce lid edema. The temptation
to express the pus should be avoided, as it may lead to
development of lid abscess. A chalazion is a painless
1319
granulomatous nodule of the meibomian tarsal glands in

the eyelidit may start as an acute hordeolum internum,
at which stage it may be aborted with timely fomentation,
antibiotic drops and massage. Once established, a
chalazion may require incision and curettage as an elective
procedure. Causes of eye strains as refractive errors and
orthoptic problems need to be ruled out in styes, chalazia
and blepharitis, especially if recurrent. Squamous, and
especially ulcerative blepharitis require energetic treatment.
The associated dandruff should also be managed.
Vaccinial and herpetic blepharitis are known to occur. A
swelling in the lid may be neoplastic in nature. Injury
around the lids and a black eye may be associated with
lid edema.
PROPTOSIS
Proptosis of the eye may be due to orbital cellulitis, orbital
tumor (hemangioma, rhabdomyosarcoma, glioma,
leukemic infiltration, extraocular extension of retinoblastoma, neuroblastoma, etc.), orbital hemorrhage,
vascular malformations, and other rarer causes.
The exposure of the eye should be prevented by viscous
drops and lubricating ointments, and, if necessary, by a
tarsorrhaphy, to prevent the avoidable and tragic
complication of exposure keratitis and severe corneal
ulceration with resulting blindness.
The above principle of corneal protection is extremely
important, but often forgotten, in the management of a
semicomatose or unconscious child. The cornea should
always be protected by an oily film, especially if a pad
and bandage has to be applied, though a pad is better
avoided unless there is actual keratitis.
Orbital cellulitis is a potential life and vision threatening
condition which can also occur following preseptal
cellulitis. Most commonly it occurs as a complication of
TABLE 29.1.1: Differentiating features between conjunctivitis, corneal ulcer and iridocyclitis
Features
Conjunctivitis
Corneal ulcer
Iridocyclitis
Cornea
Pupil
Anterior chamber
Congestion
Intraocular tension
clear
normal
normal
conjunctival
normal
ulcer, hazy
often miosed
usually normal
ciliary
may be high
Vision
normal
reduced
may be hazy
miosed
may be deep
ciliary
low, may be
normal or high
reduced
1320
ethmoidal sinusitis, dacryocystitis or dental infections.

Parenteral antibiotic therapy should be started without
delay. Surgical intervention may be needed to drain
associated abscesses.
Rhabdomyosarcoma is the commonest primary orbital
malignancy in childhood, average age at onset being 6 to
7 years. Child will present with rapidly progressive
proptosis. Radiation and chemotherapy are the mainstay
of treatment after biopsy confirms the diagnosis.
CONGENITAL ANOMALIES
As for congenital abnormalities anywhere in the body,
several teratogenic factors have been implicated for
congenital anomalies of the eye, operating prenatally or
perinatally. These teratogens include physical, chemical,
mechanical, drugs and poisons (including vasoconstrictors), inflammations and fevers and the (noxious)
treatments thereof, malnutrition, and of course irradiation. Any such factor operating very early in intrauterine
life in the first 6 to 8 weeks may produce organogenetic
deformities as anophthalmos, microphthalmos, congenital
cystic eye, and even cyclopia. These deformities often present
with other ocular and systemic associations. Several lesser
anomalies of differentiation may be the result of noxious
influences later on in intrauterine development.
Congenital Cataract
Congenital cataract is associated with intrauterine infections
(rubella, toxoplasmosis), antenatal malnutrition (zonular
cataract), metabolic diseases (galactosemia, hypocalcemia), chromosomal anomalies (Down syndrome),
ocular malformations (microcornea, nystagmus, megalocornea, keratoconus, pigmentary retinitis), mental
retardation and various cutaneous, neurological,
musculoskeletal and endocrine disorders (diabetes
mellitus, hyperparathyroidism). Cataract may develop
secondary to eye disease such as trauma, retrolental
fibroplasia, uveitis and glaucoma. Marfan syndrome and
homocystinuria may be typically associated with ectopia
lentis. Cataracts in children may be hereditary and familial,
and require early referral for proper management and
visual rehabilitation.
Acute Glaucoma
Acute glaucoma as typically described in adults, is usually
not seen in children. Up to 3 years of age, congenital (or
secondary) glaucoma manifests by progressive enlargement
of the globe (buphthalmos), hazy cornea, watering,
photophobia, and poor vision. After 3 years of age, the eye
loses its stretchability, and glaucoma does not manifest
with buphthalmos. A suspicion of glaucoma definitely
warrants an immediate referral. Intraocular inflammation,
metabolic disorders like homocystinuria and tumors like
retinoblastoma, may manifest as secondary glaucoma.
RETINOBLASTOMA
A typical cat's eye reflex or leukocoria is a well known
feature of retinoblastoma. However, many other congenital
and acquired conditions may produce an identical
pupillary reflex such as retinal dysplasia, retinal vascular
folds, persistent hyperplastic primary vitreous (PHPV),
retinal detachment, retained intraocular foreign body,
endophthalmitis, cataract, uveitis, Coats' disease, and
retrolental fibroplasia (RLF) or retinopathy of prematurity
(ROP). Retinoblastoma (Rb) is usually associated with
neovascularization, high intraocular tension, features of
bilateral involvement, optic nerve extension with distant
metastases, and hereditary predisposition. Besides the
pathognomonic yellowish white reflex, retinoblastoma as
may present with a squint, red eye, pain and secondary glaucoma.
These children should be immediately referred for further
investigations and management, because delay may
adversely affect survival. In spite of various imaging
modalities, the differential diagnosis during the early
stages may be difficult, and the exact diagnosis may be
possible only after histopathological examination of the
enucleated eye. Earlier radical treatment modalities, as
enucleation are giving way to eye salvaging procedures as cryotherapy, chemoreduction and lens-sparing techniques of
modern radiotherapy (See Chapter 16.8 Retinoblastoma
for a detailed discussion).
RETINOPATHY OF PREMATURITY (ROP)
The development of retrolental fibroplasia (or retinopathy
of prematurity) is probably related to exposure of preterm
low birth weight (LBW) infants to high concentrations of
oxygen above 40 percent, because of the immaturity of the
retinal vasculature in these premature eyes. Initially, there
is vasoconstriction of retinal vessels. Later the vessels
dilate and become tortuous. Hemorrhages occur along the
blood vessels. Retinal detachment may occur.
Neovascularization and vitreous opacities may be seen at
the junction of the detached retina with the normal retina.
Organization of vitreous and formation of retrolental
membranes follow (retrolental fibroplasia). The eye
becomes small with marked visual loss. The anterior
chamber becomes shallow. Myopia and strabismus are
common. The progression of disease may be arrested at
any stage.
Eyes of all infants born at or earlier than 32 weeks
gestational age or weighing 1.5 kg or less, who have
received supplemental oxygen should be screened for
ROP, using indirect ophthalmoscopy. Cryotherapy or
laser photocoagulation if carried out timely can prevent
progression of disease in these infants.
REFRACTIVE ERRORS
Hyperopia (Hypermetropia, Far-sightedness)
Moderately severe hyperopia may cause headache, reading
difficulty and even squinting. Hyperopia with symptoms
may require correctional glasses after cycloplegic refraction.
Myopia (Near-sightedness)
In congenital myopia, children are born with high myopia
and one or both parents are often myopic. Usually myopia
develops between the age of 5 and 15 years because of
rapid growth of the eyes. They have few early symptoms
and the detection is often made at school or on routine
visual testing. Associated astigmatism may lead to eye
fatigue, headache and blepharitis. Corrective glasses (or
contact lenses) after cycloplegic refraction should be
prescribed for constant use, and the child is encouraged to
wear them all the time for distance as well as for near.
Astigmatism (Inability for Point Focus)
Mild degrees of astigmation are common. Red eyes,
recurring blepharoconjunctivitis, stye and chalazia often
indicate the presence of astigmatism. Eye strain
(asthenopia), pain in and around the eyeballs, headache,
and nausea may occur. Astigmatism may be associated
with hyperopia or myopia. If the vision is not subnormal
and there are no symptoms, glasses may not be required,
but in case of either, correction should be ordered for constant
use after cycloplegic refraction.
1321
Strabismus (Squint)
Early detection and treatment of squint is very important
since significant improvement in the vision of the deviated
eye and good binocular vision cannot be achieved if
proper therapy is not undertaken as early as possible and
not later than 5 years of age. Some degree of occasional
squint may be normal in the first few months of infancy,
since binocular vision is not well-developed. If squint
persists beyond 2 to 3 months of age, an ophthalmologist
should be consulted. A false impression of convergent
squint (pseudostrabismus) may be given by epicanthal
folds with a wide bridge of nose.
Concomitant squint accounts for most cases. There is no
muscle paralysis but the muscles fail to act in coordination.
The degree of deviation is the same irrespective of the
direction of gaze. In noncomitant (paralytic) squint resulting
from ocular muscle paralysis, the eyes deviate most on
turning in the direction of the paralyzed muscle. Diplopia
may develop and to avoid it, the child learns to suppress
the vision in the affected eye. Abnormal head posture may
develop.
The treatment of concomitant squint consists of
cycloplegic refraction and corrective lenses, drugs such
as cycloplegics or miotics, patching of the normal eye for
determined periods to prevent image suppression and
amblyopia in the deviating eye, orthoptic exercises and
surgery, singly or in combination. Timely referral is vital
children do not grow out of squint. Involuntary ocular
rhythmic movements (nystagmus) should also be referred
early for complete investigations.
Amblyopia occurs during critical period of visual
development in the first decade of life when the visual
nervous system is plastic. After eradiating amblyogenic
factors, the mainstay of treatment is patching the sound
eye. Other treatment modalities include fogging of the
sound eye with cycloplegic drops. The earlier treatment is
begun, the better the chance of improving visual acuity.
Treatment is usually discontinued after the age of 9 years.
MISCELLANEOUS DISORDERS
Conjunctival xerosis and Bitot spots are not emergencies
per se, but they may be the forerunners of keratomalacia.
Most pediatricians in developing countries are familiar
with the grim picture and hopeless visual prognosis of
keratomalacia. The treatment consists of administration of
systemic vitamin A, topical and systemic antibiotics,
atropine ophthalmic ointment and warm compresses.
1322
Vitamin A 100,000 to 200,000 IU is given orally daily for 2

successive days if the child does not have any diarrhea,
otherwise a water dispersible preparation of vitamin A is
administered by intramuscular route. This dose should
be repeated 2 to 4 weeks later. The nutritional status (and
education) of these children should be improved. The
condition must be identified early before irreversible
damage to the eyes has taken place. The alarming
magnitude of nutritional blindness in the country can
be reduced by vitamin A prophylaxis with suitable shortterm, medium- and long-term measures. Besides
xerophthamia, diffuse or focal corneal haze can occur due to
several causes; congenital, traumatic, inflammatory (intrauterine or postnatal), neoplastic, degenerative, allergic
and metabolic (mucopolysaccharidoses) disorders.
Night blindness most commonly occurs due to vitamin
A deficiency. Pigmentary retinal degeneration (retinitis
pigmentosa) as in Laurence-Moon-Bardet-Biedl (LMBB)
syndrome and other uncommon hereditary conditions
may also produce night blindness.
Some congenital lid conditions require early surgical
intervention such as congenital coloboma with corneal
exposure (Goldenhar's syndrome), and severe ptosis.
Entropion (congenital or trachomatous) and distichiasis
may require correction if the cornea is endangered.
Congenital ectropion is rare, but the more common
cicatricial type necessitates repair by skin grafting.
Congenital craniofacial and CNS disorders such as
hydrocephalus, microcephaly, mental retardation, cerebral
palsy (to maximize head control) encephalocele,
meningomyelocele, and craniosynostosis often produce
significant ocular features. These conditions should be
reviewed in detail by a pediatric ophthalmologist.
Corneal exposure and early papilledema constitute virtually
emergency situations for the pediatrician and the pediatric
surgeon.
Some inborn errors of metabolism such as homocystinuria (subluxated lens) and galactosemia (cataract),
albinism, lipidoses, chromosomal aberrations, Marfan's
syndrome (ectopia lentis), Weill-Marchesani syndrome
with spherophakia and inverse glaucoma (responding
to dilation of pupils), and phakomatoses can also produce
urgent ocular situations. Color vision defects, often
hereditary, are not yet amenable to any treatment, except
eugenics.
Sudden diminution of vision in children may be
associated with serious neurological disease, like
meningitis and encephalitis and may occur due to optic
neuritis, or brain damage (cortical blindness). The
importance of careful evaluation of pupillary reflexes

cannot be overemphasized. Prompt empirical treatment
with systemic corticosteroids and antibiotics along with
specific therapy, may save the vision. Parenteral administration of vitamins B1 B6 and B12 as injection (TriredisolH) may be of some help. In a child with poor vision,
common conditions like refractive errors (high myopia)
and amblyopia (blunting of vision following sensory
visual deprivation due to squint, anisometropia, corneal
opacities, cataract, etc.) should be ruled out. Other causes
of sudden visual deterioration in children include
demyelinating and convulsive disorders, vascular
lesions, migraine and iatrogenic reasons due to the toxic
effects of drugs. Functional blindness may occur in adolescent children and simple tests for visual malingering
may help the clinician.
PREVENTION
Of all the ocular problems in childhood, injuries,
infections and malnutrition form the major group, and all
are largely preventable. It is hoped that programs for
better nutrition, sanitation, dietary education, and control
of infectious diseases especially diarrheal disorders will
reduce the incidence of blinding malnutrition. Prophylactic administration of vitamin A to preschool children can
eradicate blindness due to vitamin A deficiency. The
current recommendations by the Government of India
are to administer first dose of prophylactic vitamin A
100,000 IU at 9 months (along with measles vaccination)
followed by second dose of 200,000 IU around the age of
15 to 18 months (along with first booster of DPT/OPV)
and three more doses at an interval of every 6 months.
Children should be discouraged from playing with
pointed objects and sharp toys. The hazards of arrows,
airguns, catapults and fireworks should be highlighted
through the mass media. Eyes are precious and must be
protected both at work and play. The teachers should be
well-informed to teach preventive and promotive aspects
of eye health care of the students.
Gonococcal ophthalmia neonatorum can be prevented
by prophylactic topical instillation of either silver nitrate
1 percent or tetracycline/erythromycin 0.5 percent
Emphasis
Amblyopia
Rb (Retinoblastoma)
Orbital (and preseptal) cellulitis
Cavernous sinus thrombosis
ROP (Retinopathy of
prematurity)
ophthalmic ointment to newborn babies at risk. The
erythromycin prophylaxis provides additional protection
against eye infections due to chlamydiae. However, if the
eye damage has occurred, the earlier it is effectively
managed, the better are the chances for salvaging useful
vision. Injuries and inflammation of other parts of the body
may heal with minimal or no side effects, but the delicate
ocular tissues are greatly compromised by the reparative
process leading to serious cosmetic and visual handicaps.
BIBLIOGRAPHY
1.
2.
3.
4.
5.
Dhir SP, Shishko MN, Krewi A, et al. Ocular fireworks

injuries in children. J Pediatr Ophthalmol 1991;28:
354-55.
Duke-Elder S, MacFaul PA. Injuries. System of Ophthalmology. Henry Kimpton: London 1972;14.
Ghose S, Kalra BR: Red eyea common problem in
children. Indian J Pediatr 1982;49:75159.
Ghose S, Seth V, Singhal V, et al. Diagnostic problems in
leucocoria. Indian J Ophthalmol 1983;31:233-37.
Ghose S, Mahajan VM. Microbiology of congenital
dacrocystitisits clinical significance. J Ocul Ther Surg
1985;4:54-57.
6.
1323
Ghose S. Ocular emergencies. In Singh M (Ed): Medical

Emergencies in Children (2nd edn). Sagar Publication:
New Delhi 1993;31:418-25.
7. Gordon DM. The management of pediatric ocular

emergencies. In Holt LB (Ed): Pediatric Ophthalmology.
Lea and Febiger: Philadelphia 1964;100-17.
8. Harley RD. Pediatric Ophthalmology. WB Saunders:
Philadelphia 1975.
9. Helveston EM. Eye trauma in childhood. Pediatr Clin N
Am 1975;22:501-11.
10. Hughes WF: What the pediatrician should know about
the management of ocular injuries. Pediatr Clin N Am
1958;5:203-24.
11. Judge J. Overview of the red eye. J Ophthal Nurs Technol
1992;11:197-202.
12. Kalra BR, Ghose S, Sood NN. Homocystinuria with
bilateral absolute glaucoma. Indian J Ophthalmol
1985;33:195-97.
13. Miller SJH. Parson's Diseases of the Eye (17th edn),
Churchill Livingstone: Edinburgh 1984.
14. Verma N, Ghose S, Sekhar GC. Ultrasonic evaluation of
retinoblastoma. Jap J Ophthalmol 1984;28:222-29.
30.1 Common Problems of Ear, Nose and Throat in Children: Divya Prabhat .................................................................................. 1326
1326
30.1 Common Problems of Ear, Nose

and Throat in Children
Divya Prabhat
HEARING TESTS
As development of natural speech is all but over by the
age of 3 years, the earlier an auditory disease is diagnosed,
the better are the chances of helping a child to overcome
the handicap.
Reflex Tests
At birthMoro or startle reflex

3 monthsBlinking on response to sound
5 monthsEyes turn towards sound
6 monthsHead turns towards sound.
Behavioral Tests
7 to 18 monthsDistraction tests are performed. The
child may be distracted from behind by various
sounds.
18 to 30 monthsChilds cooperation is sought. The
child is given simple tasks to perform in response to
certain sounds.
Performance Tests
These are done between the age of 2 to 5 years, where the
child is asked verbally to perform tasks.
Subjective Tests
Peep-show audiometryHere a young child is conditioned to press a button when a sound is heard.
Conditioned audiometryThe child is taught to build a
tower of bricks each time he or she hears the (test)
sound.
Objective Tests
Impedance audiometryWhere a low frequency sound
is introduced into a sealed external canal. The
impedance to sound would be much greater if the
tympanic membrane is stiff (e.g. middle ear fluid) than
when compliant. Various graphs obtained help us to
diagnose eustachian tube block, serous otitis media,

ossicular discontinuity, otosclerosis, etc.
Brainstem auditory evoked responses (BERA)Electrical
signals are picked up by surface electrodes resulting
from acoustic signs passing from the cochlear nerve to
the brainstem.
DEAFNESS
Depending upon the site of diseases, the hearing loss or
deafness is classified as:
1. Conductive deafnessWhere the disease affects the
external or middle ear, i.e., involving the sound conducting mechanism of the ear.
2. Sensorineural deafnessWhere the disease affects the
perceiving apparatus, i.e., cochlea or VIII nerve or any
area up to the brainstem.
Causes
Prenatal
1. Genetic
a. Waardenburg syndrome
b. Klippel-Feil syndrome
c. Pendred syndrome
2. Nongenetic
a. Diseases during pregnancy
i. Toxemia
ii. Diabetes
iii. Nephritis
iv. Measles and other viral infections
b. Drugs taken during pregnancy
i. Streptomycin
ii. Quinine
iii. Salicylates
Perinatal
1. Birth traumaanoxia
2. Hemolytic diseasekernicterus
3. Prematurity
Pediatric Otorhinolaryngology 1327

Postnatal
ACUTE SUPPURATIVE OTITIS MEDIA (ASOM)
1. Genetic
a. Otosclerosis
b. Familial perceptive deafness
2. Nongenetic
a. Infectious diseases, e.g. measles, mumps, etc.
b. Trauma
c. Otitis media
d. Ototoxic drugs
It is nearly always a sequel to an upper respiratory tract

infection which is seen commonly during childhood. In
infants the eustachian tube is relatively short, wide and
horizontal, thus, allowing easy access of milk and vomitus
in the middle ear. Thus feeding while lying down,
vomiting or forcible nose blowing in older children may
lead to acute otitis media.
Etiology
Management
Conductive deafness is completely corrected by either
medical or surgical treatment. Sensorineural deafness is
managed by using a hearing-aid which amplifies the basic
sound. Children with sensorineural loss not benefitting
with a hearing aid (glatiol profound loss) are candidates
for a cochlear implant, which now can be done as early as
10 months of age.
FOREIGN BODY IN THE EAR
The types of foreign bodies that are found in the external
canal may be living (e.g. maggots or insects) or nonliving,
(e.g. stones, beads or hygroscopic foreign bodies like pea,
bean, etc.).
Symptoms include pain, irritation, noise and cough.
Organisms reach the middle ear:

i. Via the eustachian tube following nasopharyngitis,
rhinitis, sinusitis, tonsillitis, pharyngitis, etc.
ii. Through a perforated tympanic membrane due to a
previous disease, trauma or tympanotomy.
iii. Rarely by blood-borne infections.
Stages of ASOM
1.
2.
3.
4.
5.
6.
Hyperemia
Exudation
Suppuration
Coalescent mastoiditis
Complications
Resolution.
Investigations
Management
1. Living foreign bodies are killed by borospirit drops
and then syringed out.
2. Nonliving foreign bodies are removed with wax hook.
Forceps should never be used for removal as they push
the foreign body dangerously further in. Impacted
hygroscopic foreign bodies may be removed after using
glycerin drops, which would shrink the foreign body.
3. General anesthesia may be required for the above
procedure in an uncooperative child for impacted
foreign bodies.
Complications
Otitis externa.
Damage to the tympanic membrane or ossicles by
instrumentation.
The foreign body might get lodged into the middle ear,
which then has to be removed via a postaural incision.
1. Ear discharge for culture and antibiotic sensitivity.

2. X-ray mastoid to detect the destruction of air cell
partitions.
3. Hearing test to detect conductive hearing loss.
Treatment
Local
1. Aural toilet is maintained by sucking out the ear
discharge.
2. Borospirit eardrops are used only after a perforation
occurs. Eardrops are not recommended before a
perforation as they are unable to disinfect the middle
ear, and they may obscure the otoscopic picture.
Systemic
1. Antibiotic therapy is the most important form of
treatment and must be used in all stages of the disease.
1328
2. Nasal decongestant drops are used to improve

drainage of the exudate via the eustachian tube.
3. Antihistaminics are given to decongest the middle ear,
eustachian tube and paranasal sinus mucosa.
4. Analgesics to relieve pain.
Surgical
Myringotomy may be done only in cases of severe earache
with a bulging drum or when impending intracranial
complications present with an inadequate drainage.
Figure 30.1.1: Different types of perforation (shaded)
CHRONIC OTITIS MEDIA

Types
1. Tubotympanic disease (safe type) occurs as a residual
effect of an acute suppurative otitis media.
2. Atticoantral disease (unsafe type) is associated with a
cholesteatoma which is a three-dimensional epidermal and connective tissue structure in the form of a
sac, that has the capacity for progressive and
independent growth at the expense of the underlying
bone (Fig. 30.1.1).
The characteristic of each type is given in Table 30.1.1.
TABLE 30.1.1: Clinical features of chronic otitis media
1.
2.
3.
4.
Clinical features
Safe ear
Unsafe ear
Type of disease
Perforation site
Granulations
Discharge
Tubotympanic
Central
Absent
Copious, mucoid, and
non-foul smelling
Never
Increase in the
amount of discharge
Conductive
hearing loss
Sclerotic
Atticoantral
Attic
Common
Scanty, purulent
and foul smelling
Sometimes
Not affected
5. Bleeding
6. Respiratory
tract infection
7. Audiogram
8. X-ray mastoid
9. Complications (Fatal) Nil

10. Treatment
Tympanoplasty
Mixed hearing
loss
Sclerotic with
destruction
Common
Mastoidectomy
1.
2.
3.
4.
5.
6.
7.
8.
Upper respiratory tract infection

Adenoid and tonsillar hypertrophy
Tumors of nasopharynx
Otitic barotrauma
Radiation therapy
Antibiotic-suppressed otitis media
Cleft palate
Systemic diseases like hypothyroidism.
Clinical Features
1. Deafnesswhich is of mild conductive type.
2. Fullnesswith sensation of fluid moving in the ear.
3. Air-bubbles or fluid may be seen on otoscopic
examination.
Treatment
1. Valsalvas inflation to improve eustachian tube
function.
2. Local decongestant nose drops as well as antihistaminics for the same.
3. Myringotomy may be required, if no response to
medical line of treatment.
4. Grommet insertion when recurrence seen after a
myringotomy.
Grommet
SEROUS OTITIS MEDIA

Serous otitis media is characterized by the presence of
nonpurulent fluid in the middle ear, also known as glue
ear.
Grommet is a hollow tube of inert material which

is placed as a ventilating tube for the middle ear
spaces.
Rationale of Grommet Insertion
Etiology
Malfunction of the eustachian tube is the underlying cause.
The predisposing factors are:
1. Drainage of the fluid of middle ear leads to immediate

improvement of hearing. Useful in children, as helps
in natural speech development.

2. To accelerate the return of normal eustachian tube
function by aeration of the mucosa. This helps to
reverse the pathology of the middle ear mucosa which
was caused by prolonged negative middle ear
pressure.
3. To tide over the problems of adenoid hypertrophy and
underdeveloped tensor palati muscles seen in
childhood.
NASAL OBSTRUCTION
TABLE 30.1.2: Clinical features of nasal polyps
1.
2.
3.
4.
5.
6.
Number
Side
Etiology
Source
Age
Type
7. Direction
Causes
Unilateral
1.
2.
3.
4.
5.
6.
7.
8.
Sinusitis
Foreign body
Antrochoanal polyp
Deviated nasal septum
Rhinolith
Unilateral choanal atresia
Meningocele/encephalocele
Rhinosporidiosis
Bilateral
1.
2.
3.
4.
5.
6.
7.
8.
Allergic rhinitis
Ethmoidal polypi
Adenoids
Sinusitis
Angiofibroma
Diphtheria
Septal abscess
Atrophic rhinitis
NASAL POLYPS
Nasal polyp is prolapsed edematous respiratory mucosa.
Types
1. Antrochoanal polyp arises from the maxillary sinus,
enters the nasal cavity through the natural ostia of the
sinus and also passes backwards into the posterior
choanae.
2. Ethmoidal polyp arises from the mucosa of the
ethmoidal sinuses and by the effect of gravity occupies
the anterior choanae.
Clinical features of nasal polyps are given in Table
30.1.2.
8. Recurrence
9. Operation
Antrochoanal
Polyp
Ethmoidal
Polyp
Single
Unilateral
Infective
Maxillary sinus
Small children
Triradiate polyp
Multiple
Bilateral
Allergic
Ethmoid sinus
Young adults
Single
attachment
Towards anterior
choanae
Common
Polypectomy
(LASER)
Grow towards
posterior choanae
Rare
Nasal sinus
endoscopy
EPISTAXIS
Epistaxis is bleeding from the nose.
Causes
Local
1. Congenital
a. Osler-Weber-Rendu disease (hereditary hemorrhagic telangiectasia)
2. Traumatic
a. Breach in mucosal continuity
i. Fractures of nose
ii. Operations, e.g. submucosal resection (SMR),
polypectomy, etc.
iii. Nose picking.
b. Barotrauma
i. Nose blowing
ii. High altitudes
3. Inflammatory
a. Acute
i. Nonspecific rhinitis, e.g. coryza
ii. Specific rhinitis, e.g. diphtheria, adenoiditis,
sinusitis, etc.
b. Chronic
i. Nonspecific, e.g. atrophic rhinitis
ii. Specific, e.g. scleroma, rhinosporidiosis, chronic
sinusitis, etc.
iii. Midline nasal granuloma
4. Neoplastic
a. Benign
i. Angiomatous polyp
ii. Papilloma
iii. Nasopharyngeal angiofibroma
1330
b. Malignant
i. Carcinoma
ii. Sarcoma of the sinuses/nasopharynx
5. Miscellaneous
a. Foreign body
b. Rhinolith
c. Nasal parasites
Systemic
1. Cardiovascular system
a. Rheumatic heart disease
b. Pulmonary hypertension
c. Infective endocarditis
2. Blood disorders
a. Christmas disease
b. Hemophilia
c. Purpura
d. Aplastic anemia
3. Drugs
a. Salicylates
b. Quinine
4. Renal failure
5. Hepatic failure
6. Septicemia
Investigations
1.
2.
3.
4.
5.
Vital parametersfor evaluation of shock

Hemoglobinanemia
Coagulation testsbleeding disorders
Radiologysinusitis, fractures, tumors
Biopsymalignancy
Management
1. Immediate
a. Pressureby compression of the nose between the
thumb and first two fingers.
b. Ice cold packsapplied on the bridge of the nose,
which may stop the bleeding by reflex vasoconstriction.
c. Trotters methodthe patient is made to sit upright
and incline forwards with mouth open and
pinched (self) nostrils, then asked to breathe out
quietly spitting out all the blood from pharynx.
2. Assessment of blood loss and vital parameters checked.
Treatment of shock and hypovolemia.
3. Measures to control bleeding:
a. Cautery
i. Chemical
ii. Electrical
b. Cryosurgery
c. Packing
i. Anterior nasal packing
ii. Posterior nasal packing
d. Foleys catheter
e. Surgeryligation of
i. Anterior ethmoidal artery
ii. Maxillary artery
iii. External carotid artery
4. General measures
a. Sedation: This reduces restlessness of the patient
and allays anxiety.
b. Hematinics and multivitamins to improve the
hemoglobin.
c. Antibiotics are required along with packing to
prevent infections.
SINUSITIS
Etiology
1. Age: Affects children above 5 years of age, but infants
are liable to suffer from acute ethmoiditis.
2. Sex: Affects both equally.
3. Acute rhinitis causes spread of infection to the sinuses
by the way of their natural ostia from the nasal cavities.
4. Pharyngeal infections especially tonsillitis act as a
focus of infection.
5. Dental infections
a. Bacteria may spread from an apical granuloma or
a peridontal pocket or are carried to the antrum by
lymphatics.
b. Chronic dental infections cause localized areas of
granulations in the sinus mucosa.
c. Dentigerous cyst may get infected in relation to an
unerupted tooth.
d. Periodontal abscess.
e. Acute periapical abscess.
f. Tooth extraction, leading to a fractured root which
is left behind in the maxillary sinus.
g. Dental fillings may be driven into the maxillary
sinus.
6. Swimming and diving lead to water penetrating into
the sinus.
7. Trauma may be due to
a. Contusion of the sinuses
b. Compound fracture of one of the sinuses

c. Foreign bodies
d. Barotrauma
8. General health, if poor, precipitates sinusitis.
1. Prolonged exposure to cold or even excessive heat
2. Obstruction
a. Anatomical caused by a septal deviation on one
side with turbinate hypertrophy on the other side,
both causing blockage of the ostia of the paranasal
sinuses
b. Infection causes congestion, leading to obstruction
c. Allergy causing mucosal swelling
d. Tumors usually are malignant.
3. Chest conditions
a. Bronchiectasis
b. Bronchitis
c. Asthma.
Symptoms
1.
2.
3.
4.
5.
6.
7.
Headache, malaise and fever

Loss of normal vocal resonance
Pain around the various sinuses
Referred pain in the ear
Nasal discharge
Nose block
Epistaxis
i. mucosal thickening
ii. opacity of sinuses or
iii. an air-fluid level
3. Diagnostic antral puncture
4. Nasal sinus endoscopy.
Treatment
1. Prevention by improving general condition of the
patient. Lowering of resistance affects the mucosal
blanket integrity as well as the ciliary action.
2. Medical
a. Antibiotics: Appropriate for the infectious agent
b. Local decongestants are used, which do not
interfere with the ciliary function.
c. Analgesics and anti-inflammatory drugs
d. Antihistaminics
e. Steam inhalationfor clearing out the secretions
3. Surgical
After the acute phase is over:
a. Correction of a deviated septumseptoplasty
b. Antral puncture
c. Nasal sinus endoscopy to restore the normal
physiological mucociliary clearance of the sinuses
via its natural ostia.
ACUTE TONSILLITIS
It is a triad of sore throat, fever and malaise lasting for a
period of 5 days and usually responds to treatment rapidly.
Signs
1. Flushing of the cheek with swelling in case of maxillary
sinusitis and involving the upper eyelid in frontal
sinusitis.
2. Tenderness is elicited at the canine fossa in maxillary
sinusitis and above the medial canthus in frontal
sinusitis.
3. Anterior rhinoscopy reveals redness and mucosal
congestion. Pus may be seen trickling from the middle
meatus area.
4. Posterior rhinoscopy may also reveal pus from the
middle meatus area.
Investigations
1. Bacteriological examination is required if the sinusitis
does not respond to antibiotic treatment.
2. RadiologyWaters and Caldwells view of the
paranasal sinuses may show
Etiology
1. Agemore common between 2 and 5 years
2. Sexboth are equally affected.
3. OrganismsStreptococcus, Staphylococcus only and
viruses like adenovirus, rhinovirus and enterovirus.
4. Predisposing factors
a. Ingestion of cold foods
b. Contact with infected children
c. Polluted and ill ventilated environment
d. Pre-existing upper respiratory tract infection
e. Sinusitis
f. Lowered general resistance.
Symptoms
1. Throat pain
2. Fever
1332
3. Malaise and headache

4. Neck swelling
5. Earache (referred).
Signs
1.
2.
3.
4.
Tachycardia and fever

Tonsils are enlarged and congested
Pharynx is often inflamed
Tender and enlarged jugulodigastric lymph nodes.
Complications
Clinical Features
1. Due to nasal obstructionmouth breathing, nasal
discharge and voice becomes nasal (rhinolalia clausa).
2. Due to eustachian tube blockageearache, deafness,
secretory otitis media and later chronic suppurative
otitis media.
3. Due to mouth breathingdribbling of saliva, noisy
breathing at night, high arched palate and chronic
pharyngitis.
4. Generalmental backwardness and lethargy.
Local
Diagnosis
1.
2.
3.
4.
5.
1. Adenoid facies develop due to chronic infection of

the adenoids, i.e.
a. Open mouth
b. Pinched nostrils
c. Nasal discharge
d. Narrow maxillary arch
e. Crowded protruding teeth
f. Vacant facial expression.
2. X-ray lateral skull reveals the adenoids.
3. Nasal endoscopy to visualize the adenoids.
4. Examination under general anesthesia to visualize or
palpate adenoids.
Chronic tonsillitis
Quinsy (Peritonsillar abscess)
Parapharyngeal abscess
Suppurative cervical lymphadenitis
Acute otitis media.
Systemic
1.
2.
3.
4.
Rheumatic fever
Sydenhams chorea
Infective endocarditis.
Differential Diagnosis of Enlarged Tonsils

1.
2.
3.
4.
5.
6.
7.
8.
Acute tonsillitis
Infectious mononucleosis
Diphtheria
Leukemia
Vincents angina
Thrush
Scarlet fever
Keratosis of the tonsil.
1. Nasal obstruction due to antrochoanal polyp, sinusitis,
rhinitis, turbinate, hypertrophy, etc.
2. Dental abnormality giving an appearance of high
arched palate and crowded protruding teeth.
3. Thornwaldts cyst which is found in the midline of
the nasopharynx.
Management
Treatment
1.
2.
3.
4.
5.
6.
Bed rest
Plenty of fluids and soft solid foods
Analgesics to reduce fever and throat pain
Antibiotics
Gurgles
Tonsillectomy for chronic tonsillitis.
ADENOIDS
They are enlarged hypertrophied nasopharyngeal
tonsils.
Medical
1.
2.
3.
4.
Antibiotics
Antihistaminics
Local nasal decongestants
Improvement of general condition.
Surgical
1. Grommet insertion for treatment of deafness
2. Nasal sinus endoscopy for sinusitis
3. Adenoidectomy.

ACUTE RETROPHARYNGEAL ABSCESS
Symptoms
It is suppuration of the retropharyngeal lymph nodes in

the space of Gilette.
1.
2.
3.
4.
Etiology
1. Ageoccurs in children, mostly under 1 year of age.
2. Sexboys are more often affected.
3. Sourceoropharyngeal or nasopharyngeal infection,
usually tonsillar or dental infection is present.
4. Traumafollowing rupture if the pharyngeal wall by
a sharp foreign body.
5. Mastoid abscessvery rarely tracks down.
6. Causative organismsstreptococci and staphylococci.
Clinical Features
1.
2.
3.
4.
5.
6.
7.
Difficulty in breathing and suckling

Croupy cough
Nasal obstruction
Neck stiffness or torticollis
Neck swelling due to lymphadenitis
Pyrexia and toxemia
Posterior pharyngeal bulge on oral cavity examination.
Complications
1. Laryngeal edema
2. Spontaneous rupture of the abscess and aspiration
3. Dehydration due to decreased intake.
Treatment
1. Antibiotics and anti-inflammatory drugs.
2. Fluid intake is maintained.
3. Incision and drainage is done via transoral route. No
anesthesia is used. Infants are wrapped in a towel
and given head low position before the drainage.
Availability of suction is a must for fear of aspiration
of the pus. General anesthesia is avoided, as fear of
rupturing the abscess during intubation is present.
4. Tracheostomy may be required.
Cough
Fever
Breathlessness
Stridor.
Signs
1.
2.
3.
4.
Tachycardia
Tachypnea
Indrawing of the chest
Cyanosis.
Investigation
1. Radiograph of chest shows either an obstructive
emphysema or collapse or mediastinal shift or the
foreign body itself (metallic) or may even be normal
(Figs 30.1.2 and 30.1.3).
2. Virtual bronchoscopy scan may be required in some
cases.
Types
Foreign bodies are divided into various types according
to the air flow pattern.
1. Bypass of air: Foreign bodies like a button, ring or bead
which have an opening within itself allow passage of
air to either side. Therefore, the patient is never
breathless and the radiograph shows no abnormal
findings other than the foreign body.
2. One-way airway obstruction: Metallic and other
nonorganic foreign bodies lead to a unidirectional
TRACHEOBRONCHIAL FOREIGN BODIES

These foreign bodies may lead to a life-threatening
situation due to obstruction in the respiratory passage.
The absence of a definite history of foreign body
aspiration and the changing clinical signs as the disease
evolves, may mimic various other clinical conditions thus
making the diagnosis a difficult challenge in children.
Figure 30.1.2: Complete collapse of the (R) lung with mediastinal shift and emphysema of the (L) lung. Foreign body
(supari) was removed from the (R) main bronchus
1334

in airway pattern leads to obstructive emphysema and
therefore the radiographic findings and breathlessness.
3. Total airway obstruction: Vegetable foreign bodies like a
pea or groundnut swell up in the bronchus due to
their hygroscopic nature. This increase in size of the
foreign body causes impaction of the foreign body onto
the bronchial wall. The result being that air neither
can pass distal to the foreign body, nor can it escape
out. This leads to a collapse of the lung segment distal
to the foreign body and compensatory emphysema of
the other one. Changes occur accordingly which are
seen on the radiograph. The classical feature is
mediastinal shiftwhich is the change in position of
the mediastinum with each phase of respiration.
Management
1. Bronchoscopy for removal of the foreign body.
2. Tracheostomy as an absolute emergency only.
Figure 30.1.3: Radiopaque foreign body
seen in the (R) bronchus
obstruction in the airway. On inspiration the bronchial

diameter increases, and this leads to passage of air
distal to the foreign body. However, on expiration as
the bronchial diameter decreases, it leads to
entrapment of air distal to the foreign body. This change
BIBLIOGRAPHY
1.
2.
3.
4.
5.
6.
Ballengers Otolaryngology, Head and Neck Surgery,

2002.
Bluestones Paediatric Otolaryngology, (4th edition).
Cummings Otolaryngology: Head and Neck Surgery,
(4th edition).
Diseases of ENT: by Divya Prabhat (2nd Ed. 2007).
Practical ENT: by Divya Prabhat, (6th edition).
Scott Browns Otolaryngology, (6th edition).
31.1 Skin Diseases in Children: Jayakar Thomas ..................................................................................................................................... 1336
1336
31.1 Skin Diseases in Children

Jayakar Thomas
Dermatological problems are seen by pediatricians

everyday and comprise around one quarter of a busy
out-patient clinic. Most children present with skin
disorders that can be easily diagnosed and treated. This
chapter will present a brief account of some such skin
conditions.
STRUCTURE AND FUNCTIONS OF SKIN
The integument, or skin, covers the entire external surface
of the human body and is the principle site of interaction
with the surrounding world. It serves as a protective
barrier preventing internal tissues from exposure to
trauma, ultraviolet radiation, temperature extremes,
toxins, and bacteria. Other important functions include
sensory perception, immunologic surveillance, thermoregulation, and control of insensible fluid loss. The skin
consists of two mutually dependent layers, the epidermis
and dermis, which rest on a fatty subcutaneous layer,
the subcutis. The epidermis is derived primarily from
surface ectoderm but is colonized by pigment-containing
melanocytes of neural crest origin, antigen-processing
Langerhans cells of bone marrow origin, and pressuresensing Merkel cells also of neural crest origin. The
dermis is derived primarily from mesoderm and contains
collagen, elastic fibers, blood vessels, sensory structures,
and fibroblasts. During the fourth week of embryologic
development, the single cell thick ectoderm and underlying mesoderm begin to proliferate and differentiate.
The specialized structures formed by the skin, including
teeth, hair, hair follicles, fingernails, toenails, sebaceous
glands, sweat glands, and apocrine glands also begin to
appear at approximately this period in development.
Teeth, hair, and hair follicles are formed by the epidermis
and dermis, while the epidermis alone forms fingernails
and toenails. Hair follicles, sebaceous glands, sweat
glands, apocrine glands, and mammary glands are
considered epidermal glands or epidermal appendages,
because they develop as downgrowths or diverticula of
the epidermis into the dermis. The definitive multilayered skin is present at birth, but skin is a dynamic
organ that undergoes continual change throughout life

as outer layers are shed and replaced by inner layers.
Skin also varies in thickness among anatomic location,
sex, and age of the individual. This varying thickness
primarily represents a difference in dermal thickness, as
epidermal thickness is rather constant throughout life
and from one anatomic location to another. Skin is
thickest on the palms and soles of the feet (1.5 mm thick),
while it is thinnest on the eyelids and in the postauricular
region (0.05 mm thick). Children have relatively thin skin,
which progressively thickens until the fourth or fifth
decade of life after which it begins to thin. This thinning
is also primarily a dermal change, with loss of elastic
fibers, epithelial appendages, and ground substance. The
epidermis contains no blood vessels and is entirely
dependent on the underlying dermis for nutrient delivery
and waste disposal via diffusion through the dermoepidermal junction. The epidermis is a stratified
squamous epithelium consisting primarily of keratinocytes in progressive stages of differentiation from deeper
to more superficial layers. The named layers of the
epidermis include the stratum germinativum, stratum
spinosum, stratum granulosum, and stratum corneum.
The stratum germinativum or basal layer is immediately
superficial to the dermoepidermal junction. This single
cell layer of keratinocytes is attached to the basement
membrane via hemidesmosomes. As keratinocytes
divide and differentiate, they move from this deeper
layer to the more superficial layers. Once they reach the
stratum corneum, they are fully differentiated keratinocytes devoid of nuclei and are subsequently shed in the
process of epidermal turnover. Cells of the stratum
corneum are the largest and most abundant of the
epidermis. This layer ranges in thickness from 15 to100
or more cells depending on anatomic location and is the
primary protective barrier from the external environment. Melanocytes, derived from neural crest cells,
primarily function to produce a pigment, melanin, which
absorbs radiant energy from the sun and protects the skin
from the harmful effects of ultraviolet radiation. Melanin
accumulates in organelles termed melanosomes that are
Pediatric Dermatology 1337

incorporated into dendrites anchoring the melanosome
to the surrounding keratinocytes. Ultimately, the
melanosomes are transferred to the adjacent keratinocytes where they remain as granules. Melanocytes are
found in the basal layer of the epidermis as well as in
hair follicles, the retina, uveal tract, and leptomeninges.
These cells are the sites of origin of melanoma. In areas
exposed to the sun, the ratio of melanocytes to keratinocytes is approximately 1:4. In areas not exposed to solar
radiation, the ratio may be as small as 1:30. Absolute
numbers of melanosomes are the same among the sexes
and various races. Differing pigmentation among
individuals is related to the size of melanosomes and their
interspacing rather than cell number. Sun exposure,
melanocyte-stimulating hormone (MSH), adrenocorticotrophic hormone (ACTH), estrogens, and
progesterones stimulate melanin production. With aging,
a decline is observed in the number of melanocytes
populating the skin of an individual. Since these cells
are of neural crest origin, they have no ability to
reproduce. Langerhans cells originate from the bone
marrow and are found in the basal, spinous, and granular
layers of the epidermis. They serve as antigen-presenting
cells. They are capable of ingesting foreign antigens,
processing them into small peptide fragments, binding
them with major histocompatibility complexes, and
subsequently presenting them to lymphocytes for activation of the immune system. An example of activation
of this component of the immune system is contact
hypersensitivity. Merkel cells, also derived from neural
crest cells, are found on the volar aspect of digits, in
nailbeds, on the genitalia, and in other areas of the skin.
These cells are specialized in the perception of light touch.
The primary function of the dermis is to sustain and
support the epidermis. The dermis is a more complex
structure and is composed of two layers, the more superficial papillary dermis and the deeper reticular dermis.
The papillary dermis is thinner, consisting of loose
connective tissue containing capillaries, elastic fibers,
reticular fibers, and some collagen. The reticular dermis
consists of a thicker layer of dense connective tissue
containing larger blood vessels, closely interlaced elastic
fibers, and coarse bundles of collagen fibers arranged in
layers parallel to the surface.
The reticular layer also contains fibroblasts, mast cells,
nerve endings, lymphatics, and epidermal appendages.
Surrounding the components of the dermis is the gellike ground substance, composed of mucopolysaccha-
rides (primarily hyaluronic acid), chondroitin sulfates,

and glycoproteins. The deep surface of the dermis is
highly irregular and borders the subcutaneous layer, the
panniculus adiposus, which additionally cushions the
skin. The fibroblast is the major cell type of the dermis.
These cells produce and secrete procollagen and elastic
fibers. Procollagen is terminally cleaved by proteolytic
enzymes into collagen that aggregates and becomes
cross-linked. These tightly cross-linked collagen fibers
provide tensile strength and resistance to shear and other
mechanical forces. Elastic fibers constitute less than 1%
of the weight of the dermis, but they play an enormous
functional role by resisting deformational forces and
returning the skin to its resting shape.
The dermoepidermal junction is an undulating
basement membrane that adheres the epidermis to the
dermis. It is composed of two layers, the lamina lucida
and lamina densa. The lamina lucida is thinner and lies
directly beneath the basal layer of epidermal keratinocytes. The thicker lamina densa is in direct contact with
the underlying dermis. These structures are the target of
immunologic injury in diseases such as bullous
pemphigoid and epidermolysis bullosa.
Epidermal appendages are intradermal epithelial
structures lined with epithelial cells with the potential
for division and differentiation. These are important as
a source of epithelial cells, which accomplish re-epithelialization should the overlying epidermis be removed
or destroyed in situations such as partial thickness burns,
abrasions, or split-thickness skin graft harvesting.
Epidermal appendages include sebaceous glands, sweat
glands, apocrine glands and hair follicles. They often are
found deep within the dermis, and in the face may even
lie in the subcutaneous fat beneath the dermis. This
accounts for the remarkable ability of the face to reepithelialize even the deepest cutaneous wounds.
Sebaceous glands, or holocrine glands, are found over
the entire surface of the body except the palms, soles,
and dorsum of the feet. They are largest and most
concentrated in the face and scalp where they are the
sites of origin of acne. The normal function of sebaceous
glands is to produce and secrete sebum, a group of
complex oils including triglycerides and fatty acid
breakdown products, wax esters, squalene, cholesterol
esters, and cholesterol. Sebum lubricates the skin to
protect against friction and makes it more impervious to
moisture. It also has anti-microbial properties. Sweat
glands, or eccrine glands, are found over the entire
surface of the body except the lips, external ear canal,
1338
and labia minora. They are most concentrated in the

palms and soles of the feet. Each gland consists of a coiled
secretory intradermal portion that connects to the
epidermis via a relatively straight distal duct. The normal
function of the sweat gland is to produce sweat, which
cools the body by evaporation. The thermoregulatory
center in the hypothalamus controls sweat gland activity
through sympathetic nerve fibers that innervate the
sweat glands. Sweat excretion is triggered when core
body temperature reaches or exceeds a set point.
Apocrine glands are similar in structure but not identical
to eccrine glands. They are concentrated in the axillae
and anogenital regions. They probably serve a vestigial
sexual function, because they produce odor and do not
function prior to puberty. Hair follicles are complex
structures formed by the epidermis and dermis. They
are found over the entire surface of the body except the
soles, palms, glans penis, clitoris, labia minora,
mucocutaneous junction and portions of the fingers and
toes. Sebaceous glands often open into the hair follicle
rather than directly onto the skin surface, and the entire
complex is termed the pilosebaceous unit. The base of
the hair follicle, or hair bulb, lies deep within the dermis
and in the face may actually lie in the subcutaneous fat.
A band of smooth muscle, the arrector pili, connects the
deep portion of the follicle to the superficial dermis.
Contraction of this muscle, under control of the
sympathetic nervous system, causes the follicle to assume
a more vertical orientation. Hair growth exhibits a cyclical
pattern. The anagen phase is the growth phase, whereas
the telogen phase is the resting state. The transition
between anagen and telogen is termed the catagen phase.
Phases vary in length according to anatomic location,
and the length of the anagen phase is proportional to the
length of the hair produced. At any one time at an
anatomic location, follicles are found in all 3 phases of
hair growth.
Cutaneous vessels ultimately arise from underlying
named source vessels. Each source vessel supplies a
3-dimensional vascular territory from bone to skin
termed an angiosome. Adjacent angiosomes have
vascular connections via reduced caliber (choke) vessels
or similar caliber (true) anastomotic vessels. The
cutaneous vessels originate either directly from the
source arteries (septocutaneous or fasciocutaneous
perforators) or as terminal branches of muscular vessels
(musculocutaneous perforators). They emerge from the
deep fascia in the vicinity of the intermuscular or intra-
muscular septa or near tendons and travel toward the

skin, where they form extensive subdermal and dermal
plexuses. The dermis contains horizontally arranged
superficial and deep plexuses, which are interconnected
via communicating vessels oriented perpendicular to the
skin surface. Cutaneous vessels ultimately anastomose
with other cutaneous vessels to form a continuous vascular network within the skin. Clinically, this extensive
horizontal network of vessels allows for random skin flap
survival. In addition to the skins natural heat conductivity and loss of heat from the evaporation of sweat,
convection from cutaneous vessels is a vital component
of thermoregulation. Cutaneous blood flow is 10-20 times
that required for essential oxygenation and metabolism,
and large amounts of heat can be exchanged through
the regulation of cutaneous blood flow. The thermoregulatory center in the hypothalamus controls vasoconstriction and vasodilatation of cutaneous vessels through
the sympathetic nervous system. Skin lymphatics parallel
the blood supply and function to conserve plasma
proteins and scavenge foreign material, antigenic
substances, and bacteria. Blind-ended lymphatic
capillaries arise within the interstitial spaces of the dermal
papillae. They course through the deep dermal and
subdermal plexuses and numerous filtering lymph nodes
on their way to join the venous circulation near the
subclavian vein-internal jugular vein junction bilaterally.
Sensory perception is critically important in the avoidance of pressure, mechanical or traumatic forces, and
extremes of temperature. Numerous specialized structures are present in the skin to detect various stimuli.
Merkel cells of the epidermis detect light touch. Meissner
corpuscles also detect light touch. These are found in the
dermal papillae and are most concentrated in the
fingertips. Pacini corpuscles are found deep within the
dermis or even in the subcutaneous tissue. These
structures are specialized to detect pressure. Pain is
transmitted through naked nerve endings located in the
basal layer of the epidermis. Krause bulbs detect cold,
whereas Ruffini corpuscles detect heat. Heat, cold, and
proprioception also are located in the superficial dermis.
Cutaneous nerves follow the route of blood vessels to
the skin. The area supplied by a single spinal nerve, or
single segment of the spinal cord, is termed a dermatome.
Adjacent dermatomes may overlap considerably, of
importance to note when performing field blocks with
local anesthesia.
INFECTIONS AND INFESTATIONS

Parasitic infestations
Scabies
Definition/Description:
Scabies is a skin infestation by the mite, sarcoptes scabiei,
which is usually transmitted by skin-to-skin contact and
causes generalized intractable pruritus, with frequent
secondary bacterial infection.
Epidemiology/ Etiology
Scabies affects all ages but is most common in young
adults who often acquire it by sexual contact. In infants
and young children, scabies presents with different
clinical features. Epidemics of scabies occur in cycles
every 15 years. Nosocomial outbreaks have also occurred.
The causative agent is Sarcoptes scabiei var hominis. The
fertilized female parasite is responsible for the infestation;
it invades the stratum corneum and forms burrows
where it deposits its eggs. The eggs then hatch and continue the life cycle. The average number of adult female
mites on an individual suffering from the common form
of scabies is about 12. The incubation period is 14 days.
Clinical Evaluation
Nocturnal, severe pruritus is commonly present. In
children contracting the infection for the first time,
pruritus develops one month after infestation. In
subsequent infestations itching develops within a few
days (children already sensitized to the mite and its
products).
The eruption is usually polymorphic consisting of
small pointed papules, papulopustules, scratching marks
(excoriations), sometimes vesicles and urticarial lesions.
The characteristic burrows are usually present in small
numbers. The burrows are grayish brown, curved or Sshaped, slightly elevated ridges, about 5 mm in length.
The point of entry of the mite, the most superficial part
of the burrow, has a slightly scaly appearance, and at
the distal end there may be a tiny vesicle, adjacent to
which is the female mite.
Secondary pyogenic infection may complicate
neglected scabies. At times this may mask the original
disease, therefore, scabies should always be suspected
in cases presenting with extensive pyoderma. The lesions
of scabies show a characteristic distribution: Webs and
sides of the fingers, anterior and ulnar sides of the wrist,
anterior axillary fold, anterior abdominal wall and

around umbilicus, the waist, lower parts of the buttocks,
inner thighs, ankles, cubital and popliteal fossae. The face
and palms are never affected in adults. In infants,
however, they may be involved.
Investigations/Dermatopathology
Look with lens for typical burrows on finger webs, flexor
aspects of wrists, and penis.
Look for dark point at the end of the burrow this
is the mite.
Open this part of the burrow slowly and the mite will
stick to the needle and can be easily transferred to the
slide. If there is a nodule, biopsy may reveal portions of
the body of the mite in the corneal layer.
Treatment
All individuals in the house are preferably treated simultaneously. Clothes and bed sheets should be washed or
dry-cleaned. The antiscabetic preparation should be
applied from neck to toes. Any of the following may be
used:
Permethrin 2.5-5% dermal cream, single application
washed off after 8-12 hours. A second application may
be indicated a week later if symptoms do not improve.
Sulfur precipitate ointment 3-5% applied daily after
a hot bath for 3-4 successive nights.
Gamma benzene hexachloride applied after a hot
bath; the same clothing is retained for 48 hours and then
a further bath is taken and the clothing and bed sheets
are changed. Gamma benzene hexachloride must not be
prescribed to infants or pregnant women or children with
history of seizures.
Benzyl benzoate emulsion 25-33% applied to the
whole body except the head for three successive nights.
Crotamiton 10% has an antipruritic effect in addition
to its scabicidal action. The patient should take a hot bath
and dry himself/herself carefully on a towel. Crotamiton
should then be applied daily for 2 days followed by a
bath on the 3rd day.
An oral antihistamine may be prescribed for itching.
Children should also receive systemic antibiotics if
there is secondary bacterial infection (honey-colored
crusts or tender erythema surrounding the lesions).
Oral ivermectin 3 mg to 6 mg as a single dose is found
to be very effective as a scabicide and larvicide. It is best
suited for treament of groups of children, as in boarding
schools.
1340
Pediculosis capitis
Definition/ Description
Pediculosis capitis is an infestation of the scalp by the
head louse, which feeds on the scalp and neck and
deposits its eggs on the hair.
Epidemiology/Etiology
Pediculosis capitis is more common among school
children, especially girls, but all ages may be affected.
Pediculosis capitis does not respect any social class.
Etiology: Pediculus humanus var. capitis. Unlike
P. humanus corporis (the body louse), the head louse is
not a vector of infectious diseases. Transmission occurs
via shared hats, caps, brushes, combs, and also by direct
head-to-head contact. Epidemics may occur in schools.
Clinical Evaluation
Head lice may be identified with the naked eye or using
a hand lens. The majority of patients have a population
of less than 10 head lice. Nits, the parasites eggs, appear
as oval grayish-white egg capsules (1 mm long) firmly
cemented to the hairs. They vary in number from only a
few to thousands. Head lice deposit nits on the hair shaft
as it emerges from the hair follicle. So with recent
infestations, nits are seen near the scalp, but with longstanding infestations, nits may be 10 to 15 cm from scalp.
As scalp hair grows 0.5 mm daily, the presence of nits
15 cm from the scalp surface indicates that the infestation
is approximately 9 months old. New viable eggs have a
creamy-yellow color; empty eggshells are white.
Excoriations, crusts, and secondary impetiginized
lesions are commonly seen and may extend onto neck,
forehead, face and ears, and mask the presence of lice
and nits. In extreme cases, the scalp becomes a confluent,
purulent mass of matted hair, lice, nits, crusts, and
purulent discharge, so-called plica polonica.
Papular urticaria may be seen on the neck as a reaction
to louse bites.
Sites of predilection: Head lice are nearly always
confined to the scalp. The occipital and postauricular
regions are favorite sites. Head lice may rarely infest the
beard or other hairy sites.
a 12-hour period followed by shampooing with shampoo

containing the same pediculocide. Repeat after 10 days.
Carbaryl and malathion preparations are degraded by
heat, and a hot-air hair dryer should not be used. Unlike
carbaryl, malathion has been shown to possess a residual
protective effect against re-infection that lasts about six
weeks.
Pyrethroids, e.g., tetramethrin 0.3% combined with
piperonyl butoxide 3% applied for one hour and better
left overnight. Repeat on the second day.
Permethrin 1% rinse (a synthetic pyrethroid) applied
to scalp and washed off after 10 minutes. Permethrin is
a highly efficacious agent and is much better than gamma
benzene hexachloride.
Gamma benzene hexachloride is applied to the scalp
and left for 12 hours, followed by shampooing. Treatment
may need to be repeated. Gamma benzene hexachloride
should not be used on pregnant or nursing women.
Carbaryl and malathion, the acetylcholinesteraseinhibiting pediculocides, have replaced gamma benzene
hexachloride following evidence of the emergence of
resistance to organochlorines.
Remaining nits may be removed using a fine-tooth
comb. Patients should be re-evaluated 1 or 2 weeks after
the last pediculocide application; re-treatment may be
necessary if lice are found or eggs are observed at the
hair-skin junction. Affected family members and contacts
should be treated. Combs and brushes should be washed.
Secondary bacterial infection should be treated with
appropriate doses of systemic antibiotics, e.g., erythromycin or cloxacillin, before the application of any pediculocide.
Cutaneous Larva Migrans
Definition/Description
Cutaneous larva migrans is a cutaneous lesion produced
by percutaneous penetration and migration of larvae of
various nematode parasites. It is characterized by
erythematous, serpiginous, papular or vesicular linear
lesions corresponding to the movements of the larvae
beneath the skin.
Synonym: Creeping eruption, sandworm eruption,
plumbers itch, duckhunters itch.
Treatment
One of the following preparations may be used:
Carbaryl 0.5% (lotion - shampoo) or malathion 0.5%
(lotion - shampoo): The lotion is applied to the scalp for
The disease may be caused by the larva of Ancylostoma
braziliense, A. caninum, A. ceylonicum, uncinaria

stenocephala (hookworm of dogs), or Bunostomum
phlebotomum (hookworm of cattle), A. duodenale and
Necator americanus. Strongyloides stercoralis causes a
distinctive form of cutaneous larva migrans (larva
currens, which moves much faster).
The ova of hookworms are deposited in sand and soil
in warm, shady areas. They hatch into larvae that
penetrate human skin. The children at risk include those
indulging in sporting activities in open grounds and
seawater.
Clinical Evaluation
Local pruritus begins within hours after larval penetration.
Creeping larvae produce serpiginous, thin, linear,
raised, tunnel-like erythematous lesions 2 to 3 mm wide
containing serous fluid. Several or many lesions may be
present depending on the number of penetrating larvae.
Larvae move a few millimeters to many millimeters daily,
confined to an area several centimeters in diameter. The
lesions occur on exposed sites, most commonly the feet
and buttocks.
Larva currens is a variant caused by Strongyloides
stercoralis. Papules, urticaria and papulovesicles are seen
at the site of larval penetration, associated with intense
pruritus. Larva currens occurs on the skin around the
anus, buttocks, thighs, back, shoulders and abdomen. The
pruritus and eruption disappear when the larvae enter
blood vessels and migrate to intestinal mucosa.
Visceral larva migrans (toxocariasis) is characterized
by persistent hypereosinophilia, hepatomegaly, and
frequently pneumonitis. Generalized pruritus and
urticarial or papular eruptions of the trunk and legs are
the most frequently reported cutaneous manifestations.
Rarely, a migrating panniculitis may occur. Visceral larva
migrans is caused by Toxocara canis, T. cati and T.
leonensis, the common roundworms of dogs, cats and
wild carnivores.
Treatment
The treatment of choice is the topical application of
thiabendazole 10%. Oral thiabendazole 50 mg per kg
body weight per day in 2 doses (maximum 3 g/day) for
2 to 5 days is less effective and more toxic. Albendazole
400 mg daily by mouth for three days is safe and often
effective. Liquid nitrogen may be applied to the progressing end of larval burrow.
Papular Urticaria
Papular urticaria is a reaction pattern to insect bites most
commonly affecting children. Crops of very itchy red
bumps, 0.2 - 2 cm in diameter, appear every few days.
Sometimes each spot develops a fluid-filled blister. It is
sometimes called insect bite allergy. In infants it is
given the name strophulus infantum and in the more
chronic states, called lichen urticatus.
Papular urticaria is more common in winter. It may clear
up on holiday or on moving house. One or several
members of the family may be affected. Occasionally the
eruption can clear up for years and then recur unexpectedly. It is not associated with any internal complaint
and is never a serious disease. Papular urticaria is thought
to be an allergic reaction to insects in the environment.
Often after a few years the child becomes desensitized
to these insects and the reaction dies down. A bite isnt
usually noticed and it is thought that the reaction can
occur simply from skin contact with parts of the insect
such as its faeces and eggs - this accounts for spots in
unexpected places. The most common identified causes
are mosquitoes. It can be nearly impossible to work out
what a patient is reacting to. There have been reports of
allergy to bird mites, carpet beetles, caterpillars and
insects that live in masonry disturbed by renovation.
Quite often there exists an atopic background.
Clinical Evaluation
They are most often on the legs and other uncovered
areas such as forearms and face but sometimes they are
scattered in small groups all over the body. The lesions
are erythematous weals. It is difficult not to scratch the
spots, which become crusted and may get infected - they
are then purulent and sore. Sometimes one new spot
provokes all the old ones to come up again and itch
intensely. The spots seem to remain for a few days to a
few weeks and can leave persistent marks or scars,
especially if they have been scratched deeply. Recurrence
is the hallmark and itching is very disturbing.
Treatment
This is directed essentially towards prevention. All
measures possible, such as nets, covered clothing, and
1342
repellants, may prove futile. Treatment is then aimed at

topical antipruritics (crotamiton), oral antihistamines,
and antibiotics if needed. Counseling forms a major
portion of management with the parents be reassured of
the disorders self-limiting course.
BACTERIAL INFECTIONS
Impetigo Contagiosa
Impetigo is a contagious acute pyogenic infection which
is at first vesicular and later crusted. It is a superficial
infection of the upper layers of the epidermis and may
be caused by staphylococcus aureus, by group A betahemolytic streptococci, or by both.
Impetigo predominantly affects infants, preschool
children and young adults during hot humid seasons.
Predisposing factors include crowded living conditions,
poor hygiene, and neglected minor trauma. Impetiginization also occurs on lesions of eczema, scabies and
pediculosis capitis (itchy conditions). It is important to
obtain cultures of household and other close contacts,
and those who are positive should be treated.
Clinical Evaluation
The early lesions are thin-walled vesicles that rupture
quickly leaving red wet erosions, or dry up forming
gummy, golden-yellow/reddish-brown crusts. The
crusts eventually separate and leave erythema that fades
without scarring.
The lesions are scattered and discrete, 1 to 3 cm in
diameter, round or oval, and show central healing. There
may also be some large confluent lesions. Satellite lesions
may result from autoinoculation. The regional lymph
nodes may be enlarged and tender. The face is the
commonest site, but lesions also occur on the scalp, arms,
legs and buttocks.
Grams stain of early vesicle shows gram-positive
intracellular cocci, in chains or clusters. Use of a
moistened culture swab to dissolve crusts may be
necessary to isolate the pathogens. Biopsy is usually not
necessary, but if done, it will show an acantholytic cleft
in the stratum granulosum with leukocytes and cocci

(subcorneal pustule).
Treatment
Systemic antibiotics:
Erythromycin (30-50 mg/kg/day) in divided doses for
5-7 days or
Cloxacillin (25-50 mg/kg/day) in divided doses for 5-7
days.
Systemic treatment is required even when only a few
localized lesions are present. This helps combating
colonization of anterior nares or nearby apparently
healthy skin by staphylococci. Such colonization may
lead to relapses or treatment failure if topical antibiotics
are used alone. The use of systemic antibiotics is also
essential in cases caused by streptococci to prevent
possible renal complications.
Removal of the crusts:
This is done using warm olive oil or potassium
permanganate 1/8000 compresses. Removal of the crusts
permits delivery of a sufficient concentration of topically
applied antibiotics to the site of the lesion. Solutions such
as potassium permanganate are not suitable for hairy
areas like the scalp. Topically mupirocin 2% ointment/
sisomicin 1% cream/fusidic acid 2% cream/ gentamycin
0.1% cream or any other suitable topical antibiotic is
useful. A cream is preferred to an ointment. The antibiotic
should be applied 3-4 times daily.
When pediculosis or scabies is present it should be
treated as soon as there is a satisfactory response to
treatment of the impetigo.
Bullous Impetigo
Bullous impetigo (staphylococcal impetigo, impetigo
neonatorum) occurs as scattered thin-walled bullae
arising in normal skin and containing clear yellow or
slightly turbid fluid without surrounding erythema.
Bullous impetigo occurs mainly in the newborn and
in infants and young children, but may occasionally affect
adults. It may occur in epidemic form in infant nurseries.
Phage group II staphylococci, which produce an extracellular exotoxin is the causative agent. Phage group II
staphylococci also produce, besides bullous impetigo, a
rare exfoliative disease, the staphylococcal scalded-skin
syndrome.

Clinical Evaluation
Vesicles that rapidly progress to large, thin-roofed, flaccid
bullae with little or no surrounding erythema characterize the condition. The contents of the bullae are clear
at first; later on they may be turbid after rupture erosions
and brownish crusts form. Central healing and peripheral, extension may give rise to circinate lesions.
The lesions are scattered and discrete and occur on
the trunk, face, intertriginous sites and hands.
Grams stain of early vesicle shows gram-positive cocci,
extracellular and within polymorphonuclear leukocytes.
Culture reveals Staph. aureus.
Treatment
Sparkling cleanliness with local and general hygiene is
the hallmark of management. Mupirocin 2% ointment is
effective treatment for some cases of bullous impetigo
and should be applied to the lesions and to the nostrils.
Fusidic acid 2% cream can also be used. Standard
treatment, however, is the administration of systemic
antibiotic:
Cloxacillin (25-50 mg/kg/day in 4 divided doses for
10 days), or alternatively, and if Staph. aureus is sensitive,
erythromycin (30-50 mg/kg/day in 4 divided doses for
10 days).
Cellulitis
Cellulitis is an acute, spreading infection of dermal and
subcutaneous tissues, characterized by red, hot, tender
area of skin, often at the site of bacterial entry, caused
most frequently by group A beta-hemolytic streptococci
or Staphylococcus aureus.
Epidemiology
Cellulitis affects children less than 3 years old, and also
older individuals. The most common organisms are
group A Beta-Hemolytic Streptococcus pyogenes and
staphylococcus aureus. In children, the common
organisms include Hemophilus influenzae, group A
streptococci, and Staphylococcus aureus.
Risk factors include diabetes mellitus, hematologic
malignancies, IV drug use, chronic lymphedema, immu-
nocompromise, and pre-existing dermatosis (e.g. tinea

pedis).
Clinical Evaluation
The incubation period is few days. A prodrome occurs
less often than commonly thought. Patients may have
malaise and anorexia; fever and chills can develop
rapidly, before cellulitis is apparent clinically. Higher
fever (38.5 C) and chills are usually associated with
streptococci; lower fever (37.5 C) is usually associated
with staphylococci. Ask for history of previous treatment
of prior episode(s) of cellulitis in an area of lymphedema.
The patient may be an IV drug user, and the organism
may have entered through drug injection. Immunocompromised patients are susceptible to infection with
bacteria of low pathogenicity.
Skin findings: Entry sites: Breaks in skin, ulcers, and
chronic dermatosis. The typical lesion is a plaque: Red,
hot, edematous and very tender area of skin of varying
sizes; borders are usually sharply defined, irregular, and
slightly elevated; bluish-purple color is seen with
Hemophilus influenzae. Vesicles, bullae, erosions,
abscesses, hemorrhage, and necrosis may form in the
plaque. Lymphangitis may occur. Cellulitis may also
occur on the trunk at operative wound sites. In children,
the cheek, periorbital area, head, and neck are the most
common sites, and hemophilus influenzae is usually the
causative organism. On the extremities, cellulitis is
usually caused by Staphylococcus aureus and group A
streptococci.
The regional lymph nodes can be enlarged and
tender.
Laboratory examination of blood: White blood cell count
and ESR may be elevated.
Cultures: Material for culture is obtained from:
Primary lesion, aspirate or biopsy of leading edge of
inflammation, blood. Cultures are positive in only onequarter of cases. Fungal and mycobacterial cultures are
indicated in atypical cases.
Treatment
Supportive measures include rest, immobilization,
elevation, moist heat, and analgesics.
1344
Given that most cases are caused by group A betahemolytic streptococci and/or Staphylococcus aureus,
initial therapy is best directed at both organisms.
For mild early cellulitis: If staphylococci are
suspected, or if agent is not known, use oral cloxacillin
0.5 to 1 g every 6 hours. The alternative in penicillinallergic patients is oral erythromycin 0.5 g every 6 hours.
For more severe infections, use penicillin 10 million
units + cloxacillin 2 g t.i.d. IV. Ampicillin 1.0 to 1.5 g IV
every 4 hours may also be used. The alternative in
penicillin-allergic patients is vancomycin 1.0 to 1.5 g per
day IV. Subsequent antibiotic therapy is modified
according to response and cultured bacteria.
Erysipelas
mg 6th hourly). More extensive and severe cases require

hospitalization and intravenous antibiotics. Bed rest, limb
elevation, cold packs, and analgesics add to the childs
comfort and speed resolution of the illness. Long-term
administration of oral penicillin may be warranted to
prevent recurrences in selected cases.
Furuncles and Carbuncles
A furuncle, also called acute deep folliculitis and boil, is
an acute, deep-seated, red, hot, very tender, inflammatory nodule that evolves from a staphylococcal folliculitis.
A carbuncle is a conglomerate of multiple coalescing
furuncles.
A superficial cellulitis with marked lymphatic vessel involvement caused by group A (or rarely group C or G) -hemolytic
streptococci. An interdigital fungal infection of the foot
may provide a nidus for infection. The legs are the most
frequent anatomic location.
The disease occurs equally in both sexes in all parts of

the world. Release of toxins of streptococci periodically
into the system induces recurrent attacks as also minor
trauma or a pre-existing dermatosis such as tinea pedis
or fissured feet.
Furuncles occur in children, adolescents, and young

adults. They are more common in boys. Carbuncles occur
predominantly in men, and usually in middle or old age.
Predisposing factors include chronic staphylococcal
carrier state in nares or perineum, friction of collars or
belts, obesity, excessive sweating, bactericidal defects
(e.g. in chronic granulomatosis, defects in chemotaxis,
hyper-IgE syndrome), malnutrition and diabetes
mellitus. Furuncles and carbuncles may also complicate
scabies, pediculosis, or abrasions.
Clinical Evaluation
Clinical Evaluation
The lesion is well demarcated, shiny, red, edematous,

indurated, and tender; vesicles and bullae sometimes
develop. The face (often bilaterally), arms, and legs are
the most common sites, although not in that order. Patches of peripheral redness and regional lymphadenopathy occasionally occur. High fever, chills, and malaise
are common. Erysipelas may be recurrent and may result
in chronic lymphedema. The characteristic appearance
suggests the diagnosis. The causative organism is difficult
to culture from the lesion but may occasionally be cultured from blood. Staining bacteria by direct immunofluorescence may also identify the causative organism, but
the diagnosis is usually based on clinical morphology.
Erysipelas of the face must be differentiated from herpes
zoster, angioneurotic edema, and contact dermatitis.
Treatment
Mild or limited episodes of erysipelas usually respond
to oral penicillin, cephalosporins, or erythromycin (250
A furuncle appears as a bright-red, tender, indurated,

round, follicular nodule evolving into a fluctuant abscess,
with central suppuration and necrotic plug. The abscess
may rupture discharging purulent, necrotic debris, and
forming an ulcer with an erythematous halo. The ulcer
then heals leaving a scar. There may be an isolated single
lesion, or few, scattered, discrete lesions. The lesions
occur only where there are hair follicles and in areas
subject to friction and sweating, e.g. nose, neck, face,
axillae and buttocks.
A carbuncle is a conglomerate of multiple coalescing
furuncles, with separate heads. In the initial stage of
the infection, a carbuncle appears as a red, tender, hard,
dome-shaped nodule, rapidly increasing in size to reach
a diameter of 3 to 10 cm or more. Suppuration begins
after 5 to 7 days and pus is discharged from the multiple
follicular orifices. Necrosis of the intervening skin leaves

a yellow slough surmounting a crateriform nodule. In
some cases the necrosis develops more acutely without
a preliminary follicular discharge, and the entire central
core of the lesion is shed, to leave a deep ulcer with a
purulent floor.
Blood culture should be done in cases with fever and/or
constitutional symptoms before beginning treatment. If
blood culture is positive, then IV antibiotics are necessary.
Incision and drainage of abscess for Grams stain, culture,
and antibiotic sensitivity studies may be needed.
If the condition is recurrent diabetes mellitus must
be ruled out.
Treatment
Warm compresses and systemic antibiotics may arrest
early furuncles. Cloxacillin, erythromycin, or a cephalosporin should be given orally in a dose of 1 to 2 gm per
day according to the severity of the condition.
When the furuncle has become localized, showing
definite fluctuation, a free incision with drainage should
be done without delay and the cavity should be packed
with iodoform or vaseline gauze.
In furuncles of the external auditory canal, irrigations
and early incisions should not be attempted. An antibiotic
ointment (mupirocin) should be applied locally, and the
patient should also receive systemic antibiotics. Heat
should be applied to the auricle and the side of the face.
Nasal furuncles should be treated in the early stages by
the application of hot saline solution compresses inside
and outside the nostril, until softening occurs. They
should not be incised but steamed. Antibiotics should
be given internally and applied locally. On the upper lip
and nose, great care must be exercised and immediate
energetic treatment instituted because of the dangers of
sinus thrombosis, meningitis, and septicemia developing
from boils on these parts. Incision should not be made
and trauma must be prevented by the use of an adequate
dressing; local and systemic treatment should be
prescribed. Adequate doses of systemic antibiotics are
essential.
Recurrent furunculosis may be difficult to control.
This may be related to persistent staphylococci in the
nares, perineum, and body folds. Effective control can
sometimes be obtained with frequent showers (hot baths)
with povidone-iodine soap and antibacterial ointments
(mupirocin) applied daily to the inside of the nares.
Cutaneous Tuberculosis
Cutaneous tuberculosis is highly variable in its clinical
presentation, depending on the virulence and number
of mycobacteria causing the infection, the immunological
status of the host and the route of inoculation of the
mycobacteria into the skin. Cutaneous tuberculosis may
be classified as follows:
I. Inoculation tuberculosis (exogenous source):
1. Tuberculous chancre (primary tuberculosis of
skin, primary inoculation complex, occurs in a
non-immune host).
2. Warty tuberculosis (tuberculosis verrucosa cutis,
a form of secondary tuberculosis, i.e., occurs in
an immune person).
3. Some cases of lupus vulgaris (again a form of
secondary tuberculosis, i.e., occurs in an immune
person).
II. Secondary tuberculosis (endogenous source):
1. Contiguous spread (e.g. direct extension from
lymph node, bone or joint) may result in scrofuloderma.
2. Orificial tuberculosis (TB ulcer) from autoinoculation.
III. Hematogenous tuberculosis:
1. Acute miliary tuberculosis.
2. Some cases of lupus vulgaris.
3. Tuberculous gumma (metastatic tuberculosis
abscess).
IV. Eruptive tuberculosis (the tuberculides):
1. Micropapular variety: Lichen scrofulosorum.
2. Papular variety: Papular or papulonecrotic tuberculides.
3. Nodular varieties (there is no universal agreement
on nodular tuberculides):? erythema induratum
of Bazin,? nodular vasculitis (some cases),? erythema nodosum (some cases). Erythema induratum is sometimes considered one form of the
tuberculids, but the truth of its tuberculous etiological origin is still open to debate.
NB: Cutaneous tuberculosis may follow BCG
immunization.
Age: Acute miliary tuberculosis is more common in
infants and in adults with advanced immunodeficiency.
1346
Primary inoculation tuberculosis is more common in

infants. Scrofuloderma is more common in adolescents
and elderly. Lupus vulgaris affects all ages.
Sex: Lupus vulgaris is more common in females, while
tuberculosis verrucosa cutis is more common in males.
Etiology: Cutaneous tuberculosis is caused by the
obligate human pathogenic mycobacteria: Mycobacterium tuberculosis, Mycobacterium bovis, and
occasionally Bacillus Calmette-Guerin (BCG).
Incidence: Cutaneous tuberculosis has steadily
declined worldwide, paralleling the decline of pulmonary tuberculosis; lupus vulgaris and verrucous lesions
are more common in the tropics; tuberculosis verrucosa
cutis is a common type in Third World countries. Recently the incidence of cutaneous tuberculosis has been
increasing, often associated with AIDS.
Predisposing factors for tuberculosis include poverty,
crowding, and HIV infection. The type of clinical lesion
developing depends on the route of cutaneous inoculation and the immunologic status of the host.
Cutaneous inoculation results in a tuberculous chancre
in the non-immune host, and tuberculosis verrucosa cutis
in the immune host. The modes of endogenous spread
to the skin include:
1. Direct extension from an underlying tuberculous
infection, e.g., lymphadenitis or tuberculosis of bones
and joints (resulting in scrofuloderma);
2. Lymphatic spread to skin resulting in lupus vulgaris;
3. Hematogenous dissemination results in acute miliary
tuberculosis, lupus vulgaris, or tuberculous gumma
(metastatic tuberculosis abscess).
Route of cutaneous infection: may be exogenous, by
autoinoculation, or endogenous.
Clinical Evaluation
Primary inoculation tuberculosis: Initially, a papule occurs
at the inoculation site 2 to 4 weeks after the wound. The
lesion enlarges to a painless ulcer, i.e. a tuberculous
chancre (up to 5 cm), with shallow granular base and
multiple tiny abscesses, or alternatively may be covered
by thick crust. The ulcer margins are undermined and
reddish blue in color. Older ulcers become indurated
with thick crusts. Deeper inoculation results in subcutaneous abscess. Intraoral inoculation results in ulcers
on gingiva or palate. Regional lymphadenopathy occurs
within 3 to 8 weeks. Primary inoculation tuberculosis is
most common on exposed skin at sites of minor injuries.
Oral lesions occur following ingestion of bovine bacilli
in non-pasteurized milk; in the past, lesions in male

babies have occurred on the penis after ritual circumcision.
Tuberculosis verrucosa cutis:
Initially, there is a papule with a violaceous halo. It
evolves to a hyperkeratotic, warty, firm, brownish-red
to purplish plaque. Clefts and fissures occur from which
pus and keratinous material can be expressed. The border
is often irregular. Lesions are usually single but multiple
lesions occur. There is no lymphadenopathy. Tuberculosis verrucosa cutis occurs most commonly on the
dorsolateral hands and fingers. In children, the lower
extremities and knees may be involved.
Lupus vulgaris: The initial flat papule is ill defined and
soft. It evolves into a well-defined, irregular, reddish
brown plaque. The consistency is characteristically soft;
if the lesion is probed, the instrument breaks through
the overlying epidermis. Surface is initially smooth or
slightly scaly but may become hyperkeratotic. Hypertrophic forms result in soft tumorous nodules. Ulcerative
forms present as punched-out, often serpiginous ulcers
surrounded by soft, brownish infiltrate. Involvement of
underlying cartilage but not bone results in its destruction
(ears, nose). Scarring is prominent and, characteristically,
new brownish infiltrates occur within the atrophic scars.
Diascopy (i.e., the use of a glass slide pressed against the
skin) reveals an apple-jelly (i.e., yellowish-brown) color
of the infiltrate.
The plaque of lupus vulgaris is usually solitary but
several sites may be affected. Most lesions occur on the
head and neck, most often on the nose and ears or the
scalp. Lesions on the trunk and extremities are rare.
Disseminated lesions may be seen after severe viral
infection (measles).
Scrofuloderma: The lesion consists of a firm subcutaneous
nodule, which initially is freely moveable; the lesion then
becomes doughy and evolves into an irregular, deepseated plaque, which liquefies and perforates. Ulcers and
irregular sinuses, usually of linear or serpiginous shape,
discharge pus or caseous material. Edges are undermined, inverted, and dissecting subcutaneous pockets
alternate with soft, fluctuating infiltrates and bridging
scars. The lesions are reddish blue or brownish in color.
Scrofuloderma most often occurs in the parotidal,
submandibular, supraclavicular, or axillary regions; the

lateral neck may be also involved. Scrofuloderma most
often results from continuous spread from affected
lymph nodes or tuberculous bones (phalanges, sternum,
ribs) or joints.
Metastatic tuberculosis abscess (tuberculous gumma): There
is a non-tender, cold, fluctuant subcutaneous abscess.
The lesion coalesces with the overlying skin, breaks down
and forms fistulas and ulcers. The color of the overlying
skin is initially that of the normal skin; later it becomes
reddish blue. Single or multiple lesions may occur, often
at sites of previous trauma.
Acute miliary tuberculosis: Presents as an exanthem.
Lesions are disseminated and consist of minute macules
and papules or purpuric lesions. Sometimes vesicular
and crusted lesions are observed. Removal of crust
reveals umbilication. Lesions are red or purpuric in color.
They are disseminated on all parts of the body,
particularly the trunk.
Orificial Tuberculosis
A small yellowish nodule on mucosa breaks down to
form a painful circular or irregular ulcer with undermined borders and pseudomembranous material,
yellowish tubercles and eroded vessels at its base. The
ulcer is red, hemorrhagic, and purulent. The surrounding
mucosa is swollen, edematous, and inflamed. Since
orificial tuberculosis results from autoinoculation of
mycobacteria from progressive tuberculosis of internal
organs, orificial tuberculosis is usually found on the oral,
pharyngeal (pulmonary tuberculosis), vulvar (genitourinary tuberculosis), and anal (intestinal tuberculosis)
mucous membranes. Lesions may be single or multiple,
and in the mouth most often occur on the tongue, soft
and hard palates, or lips. Orificial tuberculosis may occur
in a tooth socket following tooth extraction.
The Tuberculids
It has been postulated that tuberculids are the result of
hypersensitivity reaction to hematogenous dissemination
of tubercle bacilli or their toxin in patients with moderate
or high degree of immunity. Usually no identifiable focus
of active tuberculosis can be detected and the tissue
culture for acid-fast bacilli is often negative. There is still
much controversy about these conditions.
Lichen scrofulosorum: This is a rare form of
tuberculid, presenting with grouped lichenoid papules
with perifollicular pattern over the trunk. It is frequently
found in children or young adults and may be associated

with tuberculosis of lymph node, bone or joint. The
lesions often involute slowly in months without scar and
then recur. This condition must be differentiated from
lichenoid drug eruption, lichen nitidus, keratosis spinulosa, sarcoidosis, lichenoid syphilis and eruptive
syringoma.
Papulonecrotic tuberculid: This condition usually
presents with symmetrical crops of papular eruption that
proceed to central necrosis, ulceration and depressed
scar. It occurs predominantly in young adult, most
commonly affecting the limbs. There may be history or
distant foci of tuberculous infection. The main differential
diagnosis includes prurigo simplex, papular eczema,
folliculitis, leukocytoclastic vasculitis, pityriasis
lichenoides et varioliformis acuta and secondary syphilis.
Erythema induratum (Bazin): This is a nodular tuberculid
presenting with indolent inflamed deep-seated nodule
and plaque, occurring bilaterally over the calves or feet.
In severe cases there may be necrosis, ulceration,
depressed scar and pigmentation. It is more common in
females than in males. Usually there is no evidence of
other distant tuberculous foci. The main differential
diagnosis is erythema nodosum (front of legs, i.e., shins)
and other forms of nodular vasculitis.
Dermatopathology: Primary inoculation tuberculosis:
Initially nonspecific inflammation; after 3 to 6 weeks,
epithelioid cells, Langhans giant cells, lymphocytes,
caseation necrosis.
Acute miliary tuberculosis: Nonspecific inflammation
and vasculitis are observed.
All other forms of cutaneous tuberculosis show more
or less typical tuberculous histopathology; tuberculosis
verrucosa cutis is characterized by massive pseudoepitheliomatous hyperplasia of epidermis and abscesses.
Mycobacteria are found in primary inoculation tuberculosis, scrofuloderma, acute miliary tuberculosis, metastatic tuberculosis abscess, and orificial tuberculosis, but
only with difficulty or not at all in lupus vulgaris and
tuberculosis verrucosa cutis.
Culture yields mycobacteria (also from lesions of
lupus vulgaris and tuberculosis verrucosa cutis).
Skin testing: Primary inoculation tuberculosis: Patient
converts from intradermal skin test negative to positive
during the first weeks of the infection.
1348
Acute miliary tuberculosis: Skin testing is usually

negative.
Scrofuloderma and metastatic tuberculosis abscess:
skin testing may be negative or positive depending on
state of immunity.
Lupus vulgaris and tuberculosis verrucosa cutis: Skin
testing is positive.
Treatment
The treatment of cutaneous tuberculosis is the same as
that of tuberculosis elsewhere in the body. The two
months of four drugs and two months of two drugs hold
good and give successful results. The reader is however,
advised to refer to the chapter on tuberculosis for further
information on treatment.
VIRAL INFECTIONS
Herpes zoster
Herpes zoster (shingles) is an acute localized infection
caused by varicella-zoster virus (VZV) and characterized
by unilateral pain and a vesicular or bullous eruption
limited to a dermatome innervated by a corresponding
sensory ganglion.
Most cases occur in individuals over 50 years of age, but
less than 10% of patients are under 20 years. The sexes
and races are equally affected. Immunosuppression,
especially from lymphoproliferative disorders (e.g.
Hodgkins disease) and chemotherapy, and local trauma
to the sensory ganglia is predisposing factor for herpes
zoster. Zoster is about one-third as contagious as varicella
and susceptible contacts of zoster can contract varicella.
HIV-infected individuals have an eight-fold increased
incidence of zoster.
Clinical Evaluation
Closely grouped red papules, rapidly becoming vesicular
and then pustular, develop in a continuous or interrupted
band in the area of one, occasionally two and, rarely,
more contiguous dermatomes. This is what is known as
zosteriform arrangement of lesions (dermatomal, along
the course of a sensory nerve zoster = a girdle, a
reference to its segmental distribution). Herpes zoster
lesions are strictly unilateral.
The characteristic skin lesions consist of groups

(herpetiform clusters) of oval or round vesicles/bullae
on an erythematous edematous base. The vesicles are
clear, but may be hemorrhagic. The content of the vesicles
dries up after 1-2 weeks forming crusts. As vesicles start
to develop central crusts, they may appear umbilicated.
New lesions continue to appear for up to one week.
Necrotic and gangrenous lesions sometimes occur.
Herpes zoster may heal with scar formation.
Sites of predilection: Thoracic (in more than 50% of
cases), trigeminal (10 to 20%), lumbosacral and cervical
(10 to 20%). In HIV-infected individuals, zoster may be
multi-dermatomal (contiguous or noncontiguous) and/
or recurrent.
The regional lymph nodes draining the area are often
enlarged and tender. Sensory or motor nerve changes
may be detectable by neurologic examination. Vesicles
and erosions may also occur on mucous membranes, in
the mouth, vagina, or bladder depending on the
dermatome(s) involved.
Ramsay Hunt syndrome is zoster involving facial and
auditory nerves associated with ipsilateral facial palsy
and herpetic vesicles on the external ear or tympanic
membrane.
In ophthalmic zoster, nasociliary branch involvement
occurs in about one-third of cases and is heralded by
vesicles on the side and tip of the nose (Hutchinsons
sign). There is usually associated conjunctivitis and
occasionally keratitis, scleritis, or iritis. An ophthalmologist should always be consulted.
Treatment
The disease is self-limiting. Analgesics may be prescribed
for acute pain. Topical antiseptic applications are used
to prevent secondary infection. Antibiotics are only
indicated if there is secondary bacterial infection.
In immunocompetent children oral acyclovir, 30
mg/kg 5 times daily for 7 days, has been shown to hasten
healing and lessen acute pain if given within 48 hours of
the onset of the rash.
Immunosuppressed children should be given IV
acyclovir or recombinant interferon alpha-2a to prevent
dissemination of herpes zoster.
For post-herpetic neuralgia (rare in children):
Amitriptyline is useful, especially for hyperesthesia and
constant burning pain. For stabbing pain, carbamazepine
100-200 mg/day is of value. Topical capsaicin 0.025%, a

substance P depleter, relieves pain in most patients, but
a burning sensation may follow its application.
Molluscum Contagiosum
Molluscum contagiosum is due to infection with a
poxvirus. The incubation period ranges from 14 days to
6 months.
Molluscum contagiosum occurs in both children and
adults and is highly contagious. It is more common in
males than in females. Infection may be acquired through
direct contact, or indirectly through fomites and towels.
HIV-infected children may have hundreds of small or
giant lesions on the face. Unusually widespread lesions
have also been reported in patients with sarcoidosis and
patients on immunosuppressive therapy, suggesting that
cell-mediated immunity is significant in control and
elimination of infection.
Clinical Evaluation
There is a variable number of small (usually 2 to 4 mm
in size, but may rarely grow slowly reaching a diameter
of 10 mm), discrete, waxy, and pearly-white to skincolored, hemispherical papules with smooth surface and
umbilicated center. The papules are sessile and never
pedunculated. On squeezing of fully developed lesions,
a white curd-like substance can be expressed. In occasional instances, a papule of molluscum contagiosum
appears markedly inflamed. Ultimately, the lesions
involute spontaneously. During involution, there may
be mild inflammation and tenderness.
The sites of predilection include the face and eyelids,
neck, forearms, trunk (particularly around the axillae),
anogenital area, and thighs.
Direct microscopic examination of Giemsa-stained
central semisolid core (obtained by pointed scalpel
without local anesthesia) reveals molluscum bodies
(inclusion bodies).
Treatment
Cryotherapy using liquid nitrogen (10 to 15 seconds).
Simple mechanical methods like expression of the
contents of the papule by squeezing it with forceps

held parallel to the skin surface, superficial curettage,
or shaving off the lesions with a sharpened wooden
spatula, followed by application of a silver nitrate
stick, phenol or strong iodine solution.
Light electrocautery.
Viral Warts
These are common, contagious, epithelial tumors caused
by at least 60 types of human papillomavirus (HPV).
Warts may appear at any age but are most frequent in
older children and uncommon in the elderly. Warts may
be single or multiple and may develop by autoinoculation. Appearance and size depend on the location and
on the degree of irritation and trauma. The course may
be variable. Complete regression after many months is
usual, but warts may persist for years and may recur at
the same or different sites. The relative importance of
humoral and cell-mediated immunity is not clear.
Because wart virus particles exist in the outer epithelium
(granular layer and beyond), they are unlikely to become
deep enough to serve as effective antigens. However,
patients with immunosuppression from organ transplants or other causes may develop generalized
cutaneous infections with many types of viruses, including human papillomavirus (HPV), cytomegalovirus,
herpes simplex virus, and varicella-zoster virus. This
suggests that some immune mechanisms are significant.
In addition, spontaneous disappearance of multiple
warts in immunologically normal patients who later
develop life-long immunity needs further explanation.
Clinical Evaluation
Common warts (verrucae vulgaris) are almost universal
in the population. They are sharply demarcated, roughsurfaced, round or irregular, firm, and light gray, yellow,
brown, or gray-black nodules 2 to 10 mm in diameter.
They appear most often on sites subject to trauma (e.g.
fingers, elbows, knees, face) but may spread elsewhere.
Periungual warts (around the nail plate) are common,
as are plantar warts (on the sole of the foot, which are
flattened by pressure and surrounded by cornified
epithelium. They may be exquisitely tender and can be
distinguished from corns and calluses by their tendency
1350
to pinpoint bleeding when the surface is pared away.

Mosaic warts are plaques formed by the coalescence of
myriad smaller, closely set plantar warts.
They are not generally required as the clinical diagnosis
is so obvious. Histopathology is classical with the socalled tiers of parakeratosis overlying the crests of
papillomatosis, along with the vacuolization of the
squamous cells.
Treatment
Treatment depends on lesion location, type, extent, and
duration and the patients age, immune status, and desire
to have the lesions treated. Most common warts
disappear spontaneously within 2 yrs or with simple
nonscarring treatment (e.g. a flexible collodion solution
containing 17% salicylic acid and 17% lactic acid applied
daily, after gentle peeling, by the patient or parent), or
the physician may freeze the wart (avoiding the
surrounding skin) for 15 to 30 sec with liquid nitrogen.
This procedure is often curative but may need to be
repeated in 2 to 3 weeks. Electrodesiccation with
curettage is satisfactory for one or a few lesions, but it
may cause scarring. Laser surgery may be useful but may
cause scarring. Recurrent or new warts occur in about
35% of patients within 1 yr of treatment, so methods that
scar should be avoided as much as possible.
Pityriasis Rosea
trunk or thighs, but may appear anywhere. In abortive

pityriasis rosea, the condition is limited to the herald
patch and does not proceed beyond.
Exanthem: Fine, dull-pink or tawny, scaling, macules and
papules with typical marginal collarette of thin scales.
The lesions are oval, scattered, discrete and predominantly macular. They are usually confined to trunk
and proximal aspects of the limbs (vest and pants
distribution), but an inverted type of pityriasis rosea (on
face and extremities) is also known. The long axes of the
lesions follow the lines of cleavage in a Christmas tree
distribution.
Non-specific: Like subacute and chronic dermatitis
(spongiosis, exocytosis and dermal chronic inflammatory
infiltrate). In addition, dyskeratotic eosinophilic
keratinocytes and extravasated dermal RBCs may be
seen.
Treatment
Symptomatic: Avoid irritant woolen clothes, hot baths
and soap. A mild corticosteroid cream and an oral
antihistamine may help. Pruritus may be controlled by
UVB treatment if this is begun in the first week of the
eruption. The protocol is 5 consecutive exposures starting
with 80% of the minimum erythema dose and increasing
20% each exposure.
Infectious Exanthem
Pityriasis rosea is a benign, self-limited, exanthematous,

maculopapular, red, scaling (Greek pityron, bran)
eruption that occurs largely on the trunk.
Pityriasis rosea affects 2% of dermatological outpatients.
Most patients are 10 to 35 years old. The condition occurs
more commonly in spring and autumn and one attack
usually gives long-lasting immunity. For these reasons
an infectious (? viral) etiology is strongly suspected
though not yet proven.
Clinical Evaluation
Skin Lesions Include
Herald patch: (80% of patients) 2 to 5 cm, bright red with
fine scaling. The herald patch usually occurs on the lower
An infectious exanthem is a generalized cutaneous

eruption associated with a primary systemic infection;
oral mucosal lesions, i.e., an enanthem, often accompany
it.
Patients are usually younger than 20 years. A large
number of microbes are incriminated:
Adenoviruses.
Borrelia burgdorferi.
Cytomegalovirus.
Enteroviruses (e.g. coxsackie viruses, echovirus).
Epstein-Barr virus.
Flavivirus (dengue).
Hepatitis B virus.

Human herpesvirus-6 (exanthem subitum, roseola
infantum).
Human immunodeficiency virus.
Leptospira.
Meningococci.
Orbivirus (Colorado tick fever).
Paramyxovirus (measles).
Parvovirus B19 (erythema infectiosum).
Reoviruses.
Respiratory syncytial virus.
Rhinovirus.
Rotaviruses.
Rubella virus.
Staphylococcus (toxic shock syndrome).
Streptococcus (scarlet fever).
Toxoplasma.
Treponema pallidum.
Transmission is via respiratory root, food, sexual
contact, and blood. Enterovirus infections are most
common during summer months.
Conjunctivitis
Clinical Evaluation
The incubation period is usually less than 3 weeks; in

case of hepatitis B virus the incubation period is several
months. A prodrome occurs in the form of fever, malaise,
coryza, sore throat, nausea, vomiting, diarrhea, abdominal pain, and headache. On examination, lymphadenopathy, hepatomegaly, and/or splenomegaly may
be detected.
Tinea capitis affects children mainly; adults are rarely

affected. Favus (inflammatory form) may affect any age.
All the three major agents, namely epidermophyton,
trichophyton, and microsporum cause tinea capitis,
although the last two are more common.
Skin lesions consist of: Erythematous macules and/or

papules, and less frequently, vesicles and petechiae.
Lesions are pink to red in color, and are usually
distributed centrally, i.e. on the head, neck, trunk, and
proximal extremities. Diffuse erythema of cheeks
(slapped cheek) is seen with erythema infectiosum. The
palms and soles are usually spared, except in hand-footand-mouth disease (caused by Coxsackie A16) and in
secondary syphilis.
Mucous membranes - findings include:
Kopliks spots occur in measles:
Ulcerative lesions are seen in herpangina (caused by
Coxsackie virus A).
Palatal petechiae are observed in mononucleosis
syndrome of Epstein-Barr virus or Cytomegalovirus.
The diagnosis is usually made on history and clinical

findings. Drug eruptions should be considered in the
differential diagnosis.
Treatment
Symptomatic and specific antimicrobial therapy when
indicated.
The entire description of viral exanthems does not
come within the scope of this chapter and will be dealt
with elsewhere.
FUNGAL INFECTIONS
Tinea capitis
Tinea capitis is a dermatophytosis of the scalp, the acute
infection being characterized by follicular inflammation
with painful, boggy nodules, which drain pus and result
in scarring alopecia (kerion), and the subacute to chronic
infection, by scaling patches.
Clinical Evaluation
History:
Duration of lesions: Weeks to months. Symptoms include
loss of hair, and pain and tenderness in inflammatory
type (kerion).
Types:
1. Gray patch scaly ringworm: Well-defined, round or
oval patch covered with small grayish-white scales.
The scales tend to be more densely arranged around
the openings of the hair follicles. The hairs in the
affected area are broken off into small stumps. Some
hairs are not involved due to the fact that the causative
dermatophyte affects only anagen hair (85%) and
spares telogen hair (15%). In most cases, the lesions
are single or few in number, but multiple patches may
be present rarely. Resolution is not followed by scar
formation. Caused by microsporum audouini and
microsporum canis.
1352
2. Black dot ringworm: Round or oval patch studded

with black dots. The black dots represent the upper
ends of infected hairs broken-off just at the point of
their emergence from the scalp. More than one patch
may be present. Caused by trichophyton tonsurans
and Trichophyton violaceum.
3. Kerion (Greek, honeycomb): Boggy, elevated, purulent, inflamed nodules and plaques that are painful
and drain sero-pus. Hairs do not break off but fall
out and can be pulled easily without pain (i.e., loose).
Kerion heals with scarring alopecia. Caused mainly
by dermatophytes of animal origin.
4. Favus: The lesion shows the so-called sulfur cups or
scutula. These are dry, yellowish, saucer-shaped,
adherent crusts surrounding the openings of hair
follicles. A patch of favus is formed of many sulfur
cups, some of which may coalesce forming larger
areas of crusting with no specific appearance. The
hairs in the involved area are not broken off and some
of them are coarse, lusterless and erect (coconut hairs).
Favus runs a slowly progressive course and may
involve the whole scalp in neglected cases, with
formation of scars that eventually end in permanent
cicatricial alopecia.
1. Gray patch scaly ringworm: 125 mg b.i.d. for 1 or 2

months.
2. Black dot ringworm: Longer treatment and higher
doses are required and should be continued 2 weeks
after Woods lamp, KOH examination, and cultures
are negative.
3. Kerion: 250 mg b.i.d. for 1 or 2 months; antibiotics
may be needed if there is accompanying bacterial
infection. Careful removal of crusts using wet
compresses should not be neglected. Kerion should
never be incised!
4. Favus: Griseofulvin should be given for 10 weeks.
Itraconazole may be used instead of griseofulvin
for treating certain infections, e.g., those due to
trichophyton tonsurans, although it appears to be less
effective in infections caused by microsporum canis.
Topical antifungal preparations may be used as an
adjunct to oral therapy, e.g. clotrimazole cream,
econazole cream, miconazole cream, etc. Ketoconazole
shampoo can be used to prevent spread in the early
phases of therapy.
Pityriasis Versicolor
Systemic findings:
Regional lymphadenopathy may be present, especially
in chronic and superinfected cases.
Pityriasis versicolor is a chronic, asymptomatic,

superficial fungus infection of the trunk, characterized
by white or brown scaly macules.
Synonym: Tinea Versicolor
Examination of scalp under Woods lamp:

Examination of scalp with filtered ultraviolet (Woods
lamp) reveals bright green hair shafts in scalp infections
caused by Microsporum audouini and Microsporum
canis (ectothrix). Trichophyton schoenleinii (favus)
fluorescence is grayish-green. Trichophyton tonsurans
(endothrix), however, does not exhibit any fluorescence.
Direct microscopic examination with 10% KOH:
Spores can be seen invading the hair shaft (trichophyton tonsurans and trichophyton violaceum).
Treatment
Where possible, infected hair should be clipped away to
reduce the infectivity of the child.
Oral griseofulvin (ultramicrosize):
Dose: 10 to 12.5 mg/kg body weight/day (maximum: 750
to 1000 mg/day). Griseofulvin should be taken after
meals for better absorption.
Pityriasis versicolor is caused by Malassezia furfur, the

pathogenic mycelial phase of the normal flora yeast
pityrosporum orbiculare. Pityriasis versicolor is
considered non-contagious by many authorities. It is
more common in adolescents and young adults.
Predisposing factors: Climatic factors appear to be
important, as the disease is far more common in the tropics and in the summer in temperate climates. High levels
of cortisol appear to increase susceptibility both in
Cushings syndrome and with prolonged administration
of corticosteroids (topical or systemic).
Clinical Evaluation
Skin lesions consist of sharply marginated, scattered,
discrete, round or oval macules, with fine branny scaling
(pityriasis = bran-like). The scales can be easily scraped
off with the edge of a glass microscope slide. The macules

vary in color from brown of varying intensities and hues
to white, hence the term versicolor. They range in size
from one cm to very large confluent areas >30 cm.
Sites of predilection: Upper trunk, upper arms, neck,
abdomen, axillae, groins, thighs, and genitalia. The face
is rarely affected.
Direct microscopic examination of scales prepared with
KOH or Parker Quink Ink/KOH technique reveals spherical, thick-walled yeasts and coarse mycelium often
fragmented to short filaments. These short hyphae and
round cells are commonly referred to as spaghetti and
meatballs.
Woods lamp examination shows faint yellow
fluorescence of scales.
Treatment
Topical agents:
Short applications of selenium sulfide (2.5%, to be
washed off in 30 minutes) for 12 nights. Repeat every 2
weeks.
Sodium thiosulfate (25%) solution in water applied
once or twice daily.
Miconazole cream:
Topical ketoconazole (2%) either as shampoo or cream.
Systemic therapy:
Ketoconazole 200 mg orally daily with breakfast for 10
days. Ketoconazole can cause on rare occasions liver cell
damage.
Relapses are very common, whatever the primary
treatment, and it is better to retreat each episode rather
than resort to long-term suppressive therapy. Patients
should be warned that repigmentation may take several
months, as otherwise they will often report treatment
failure even when the organisms have been destroyed,
simply because the hypopigmentation persists.
DERMATITIS AND ECZEMAS
Atopic Dermatitis
Atopic dermatitis is an acute, subacute, but usually
chronic pruritic inflammation of the epidermis and
dermis, often occurring in association with a personal or
family history of hay fever, asthma, allergic rhinitis, or
atopic dermatitis.
The onset of atopic dermatitis is usually in the first two
months of life and by first year in 60% of patients. Atopic
dermatitis is slightly more common in boys than girls.
Over two-thirds have personal or family history of
allergic rhinitis, hay fever, or asthma. An allergic workup is rarely helpful in uncovering an allergen. Atopic
dermatitis is also considered by many to be related, at
least in part, to emotional stress.
Clinical Evaluation
Skin lesions include: Erythema, papules, scaling,
excoriations, and crusting. Xerosis or dry skin is the
hallmark of atopic dermatitis. Lichenification occurs with
time. Lesions are usually confluent and ill defined.
Atopic dermatitis passes in three different phases:
1. Infantile eczema (Age: 2 months to 2 years). Affects
the cheeks and may extend to the forehead. The lesion
is an erythematous, edematous patch covered with
vesicles. Eventually, it becomes exudative and
crusted. Itching may interfere with sleep. There is no
lichenification.
2. Childhood phase (Besniers prurigo - age: 5 to 12
years). The flexural surfaces of the limbs and neck
are affected. The lesions consist of itchy papules and
lichenified plaques.
3. Adulthood phase (disseminated neurodermatitis in
adults). The flexures are the most commonly involved
sites; the front and sides of the neck, and the eyelids
may also be affected. Pruritus is severe. The lesions
consist of chronic lichenified papules becoming
confluent to form poorly defined reddish-brown
plaques. There is no oozing (chronic).
Special Features
1. Atopic dermatitis patients have a tendency to develop
generalized infections, especially herpes simplex.
Superimposed staphylococcal infection is also
frequent.
2. White dermographism on stroking involved skin
and/or delayed blanch to cholinergic agents.
3. Bilateral cataracts occur in up to 10% in the more
severe cases; the peak incidence is between 15 and 25
years of age.
4. Ichthyosis vulgaris and keratosis pilaris are present
in 10% of children.
1354
5. Periorbital pigmentation, infraorbital fold in eyelids

(Dennie-Morgan sign) and loss of lateral portions of
eyebrows (Hertoghis sign) may be present in some.
5. Children should be taught to use stress management

techniques.
Seborrheic Dermatitis
Changes are seen in the epidermis and dermis. There

are varying degrees of acanthosis with rare intraepidermal intercellular edema (spongiosis). The dermal
infiltrate is comprised of lymphocytes, monocytes, and
mast cells with few or no eosinophils.
1. Increased IgE in serum

2. Culture and sensitivity for bacterial infection
3. Culture for HSV if indicated
This is a very common chronic dermatosis characterized

by dull or yellowish-red, sharply marginated lesions
covered with greasy looking scales. It occurs in skin areas
with a rich supply of sebaceous glands, such as the face
and scalp, and in the body folds, and presternal and
interscapular regions. Dandruff (visible desquamation
from the scalp surface) appears to be the precursor of
seborrheic dermatitis, as it may progress through
redness, irritation and increased scaling of the scalp to
frank seborrheic dermatitis.
Treatment
General:
1. The most important aspect of the management of a
child with atopic eczema is sympathetic explanation
of the nature of the condition to its parents.
2. Education of the patient to avoid rubbing and scratching is most important.
3. Topical preparations are valuable but are useless if
the patient continues to scratch and rub the plaques.
Topical antipruritic (menthol/camphor) lotions are
helpful in controlling the pruritus.
4. Warn parents of the special problems with herpes
simplex and frequency of superimposed staphylococcal infection, for which oral erythromycin or
cloxacillin is indicated. Acyclovir is indicated if HSV
is suspected.
Affected age groups include:

Infancy (confined to the first months of life) - the
sebaceous glands are active at birth, but when stimulation
by maternal androgen ceases they become inactive for
9-12 years.
Laboratory Examination
Specific:
1. H1 antihistamines are probably useful in reducing
itching.
2. Hydration (oiled baths) followed by application of
unscented emollients (e.g. hydrated petrolatum) is a
basic daily treatment needed to prevent xerosis. Soap
showers are permissible in order to wash the body
folds, but soap should not be used on the other parts
of the skin surface.
3. Topical anti-inflammatory agents such as corticosteroids, hydroxyquinoline preparations and tar are
the mainstays of treatment. Of these, corticosteroids
are the most readily accepted by the patient.
4. Systemic corticosteroids should be avoided, except
in rare instances for only short courses.
Puberty:
The majority of patients are between 18 and 40 years;
occasional cases are seen in old age.
At all ages the condition is more common in males
than in females.
Clinical Evaluation
Seborrheic dermatitis causes considerable itchiness. It
also gives rise to soreness and much discomfort when it
is exudative and affects the major flexures. The severity
and course of seborrheic eruptions are very variable, but
all show a tendency to chronicity and recurrence.
There are several morphological variants, which in
the adult form occur in various combinations and degrees
of severity.
Infantile Variants
Cradle cap (scalp).
Lesions on the trunk (including flexures and napkin
area).
Leiners disease (non-familial and familial C5 dysfunction): Erythroderma appearing during the first few weeks
of life, failure to thrive and diarrhea.
Dandruff is usually the earliest manifestation of
seborrheic dermatitis. At a later stage perifollicular

redness and scaling gradually extend to form sharply
marginated patches that may remain discrete, or coalesce
to involve the greater part of the scalp and extend beyond
the frontal hairline as the corona seborrheica. In chronic
cases there may be some degree of hair loss.
Behind the ears there may be redness and greasy
scaling, and a crusted fissure often develops in the fold.
Adherent masses of sticky scale and crusts may extend
into the adjacent scalp. Both sides of the pinna, the
periauricular region, and the sides of the neck may be
involved. Otitis externa, irritable and intractable, may
accompany seborrheic dermatitis on other sites, or may
occur alone.
On the face, seborrheic dermatitis characteristically
involves the medial side of the eyebrows, the glabella,
and the nasolabial folds. Areas of erythema and scaling
occur, usually associated with scalp involvement.
Blepharitis is common. The margins of the lids are red
and covered by small white scales. Yellow crusts may
form and separate to leave small ulcers, healing to form
scars, with destruction of lash follicles. Episodic variation
in intensity is common, often being precipitated by
tiredness, stress or sunlight exposure.
A superficial form of seborrheic dermatitis of the chin
is common in young boys in the early stages of growing
a beard, but is cured when the beard is shaved off.
On the trunk, the commonest form is the petaloid
variety with petal-shaped lesions. It is often seen in men
on the front of the chest and in the interscapular region.
The initial lesion is a small red-brown follicular papule,
covered by a greasy scale. Some patients have a widespread eruption of lesions that do not progress beyond
this stage. More often, extension and confluence of the
follicular papules gives rise to a figured eruption of
multiple circinate patches, having fine branny scaling in
their centers, and dark red papules with larger scales at
their margin.
A rarer form, involving the trunk and limbs is the socalled pityriasiform type. This is a generalized erythematosquamous eruption involving the neck up to the hair
margin. It is not particularly pruritic and it resolves
spontaneously. In some patients the lesions may become
psoriasiform.
In the flexures, notably in the axillae, the groins and
the ano-genital and submammary regions, and the umbilicus, seborrheic dermatitis presents as an intertrigo with
diffuse, sharply marginated erythema and greasy scaling.
A crusted fissure develops in the folds, and with swea-
ting, secondary infection and inappropriate treatment, a

weeping dermatitis may extend far beyond them. In both
sexes, the genitalia may be involved and the lesions show
the usual range from minimal erythema and scaling to
severe crusted dermatitis; chronic, thickened, dull red,
scaly patches of the psoriasiform variety may develop
later.
The histopathology is not diagnostic, but generally shows
features of both psoriasis and chronic dermatitis.
Changes are seen mainly in the epidermis and include:
Focal parakeratosis, with few pyknotic neutrophils,
moderate acanthosis, and spongiosis (intercellular
edema) are noted.
There is also nonspecific inflammation of the dermis.
The most characteristic feature is neutrophils at the
tips of the dilated follicular openings, which appear as
crusts/scales.
Treatment
Topical therapy
Scalp
Removal of crusts with 2 to 3% salicylic acid in olive oil
is very helpful, especially in infants and children.
Shampoos containing selenium sulfide or zinc pyrithione
or tar, and more recently, ketoconazole-containing
shampoos.
Topical vioform-hydrocortisone lotion or betamethasone lotion following one of these medicated
shampoos, for more severe cases. In very severe
involvement, for short periods only, clobetasol propionate 0.05% scalp application is excellent.
Face
This is a difficult therapeutic problem.
Topical nonsteroidal creams such as ketoconazole
have been largely disappointing. Using the foam from
a ketoconazole shampoo on the paranasal areas is very
effective.
Hydrocortisone acetate cream, 1 or 2.5% b.i.d. with
or without vioform is helpful in some. Avoid prolonged
fluorinated corticosteroids because of side effects
(telangiectasia, erythema, and perioral dermatitis) that
can occur, even with hydrocortisone acetate.
Ketoconazole creams and 3% sulfur and 2% salicylic
acid in oil-in-water emulsion-type base are alternatives
1356
to topical corticosteroids or can be used in combination

for chronic resistant lesions, especially on the face and
chest.
depths of the flexures. Rarely violaceous nodules may

be a presentation the infantile gluteal granuloma
suggesting candidal reaction.
Intertriginous Areas
Treatment
Castellanis paint in oozing dermatitis of the body folds

is very often effective, although staining is a problem.
Controlled, randomized, double blind studies have
established oral ketoconazole as an effective treatment
for seborrheic dermatitis. It must be noted that seborrheic
dermatitis is not an approved indication for oral
ketoconazole and it is rarely used in this disease for
prolonged periods, largely because of the potential side
effects, especially hepatotoxicity. Oral ketoconazole in
high doses (400 mg) has been shown to lower serum
testosterone levels.
Topical antibiotics, anti-fungals, and mild steroids, alone

or in combination are found useful. Helpful tips to
parents include:
Use disposable nappies if possible.
If you use cloth nappies, use nappy liners to keep the
skin dry and make sure the nappies are rinsed and
dried well after washing.
Change the nappies frequentlydo not leave your
baby in a wet or dirty nappy.
Wash the babys bottom at every change. Use warm
water to remove all urine and bowel motions. Soap
might sting if a rash is present; use aqueous cream or
bath oil instead. Pat dry carefully.
Moisturize dry skin at every nappy change. Dimethicone (silicone) barrier creams can also help.
Apply prescription creams according to directions.
Strong steroid creams should not be applied to a
babys bottom.
Napkin Dermatitis
It is an inflammatory disorder characterized by the
development of erythema, papules and sometimes
vesiculation with scaling affecting the napkin or diaper
area of usually infants.
Napkin dermatitis, also known as diaper rash or nappy
rash, is very common. Some babies seem to get sore
bottoms very easily, others very rarely, but they all grow
out of it when they stop wearing nappies. Factors associated with the etiology include:
Irritant contact dermatitis: Urine and faeces will cause
a rash on any skin left in contact for long enough.
Sometimes ammonia is formed and burns the skin.
Infection with bacteria and candida yeasts.
Other skin disorders: Psoriasis and atopic dermatitis can
affect the napkin area. The nappies themselves are
not responsible. Washing powder or nappy cleanser
isnt either, as long as the nappies have been
thoroughly rinsed to remove them.
Clinical Evaluation
The disease is characterized by the development of
erythema in its early stages. This may be followed by
the formation of vesicles that rupture to ooze out serous
discharge. The lesions resolve with scaling. Areas
affected are the convexities such as the prominences of
the pubis, thighs, and buttocks. The classical tide mark
dermatitis refers to the erythematous border sparing the
DISEASES OF HAIR, SEBACEOUS AND

SWEAT GLANDS
Alopecia Aeata
Alopecia areata is a common skin condition characterized
by localized loss of hair in round or oval areas without
any visible inflammation on the scalp skin, or any skin
symptoms. All of the hair of the body may eventually be
lost (alopecia universalis).
No age is immune, but the condition is more common
during the second, third, and fourth decades of life (range
15-50 years); alopecia areata is also frequently seen in
children. Both sexes are equally affected, although some
studies report a male-to-female ratio of 2:1.
Genetic, psychological, and autoimmune factors are
involved in the cause, precipitation, and perpetuation of
alopecia areata. The strongest direct evidence for
autoimmunity comes from the consistent finding of a
lymphocytic infiltrate (mainly of T-helper type) in and
around hair follicles, with Langerhans cells in the
peribulbar region (lowest portion of the hair follicles).

Clinical Evaluation
Avoid Systemic Corticosteroids
Typically, there is complete or nearly complete absence

of hair in one or several circumscribed areas. The skin in
the area(s) involved apart from hair loss is
completely normal. There are no visible signs of
inflammation; no scales; no scarring; and the follicular
openings are preserved.
Alopecia areata can affect any hairy part of the skin.
The scalp is the commonest site, but lesions may be
present at other sites, even without involvement of the
scalp (the beard, moustache, eyebrows, eyelashes and
pubic hairs are not infrequently affected). The condition
may progress to involve the whole scalp (alopecia totalis),
or even the whole body (alopecia universalis); in such
extensive cases, the loss of hair is often permanent. The
extension of alopecia along the scalp margin is known
as ophiasis and is also associated with poor prognosis.
The size of single patches varies from one to several
centimeters in diameter. A patch of alopecia areata may
remain stationary in size or may progress peripherally.
The presence of exclamation-mark hairs indicates
progression of the patch (active disease). Exclamationmark hairs are broken-off stubby hairs, which are thin
proximally and thick distally.
Dystrophic nail changes occur in 20% of cases in the
form of pits (fine stippling like hammered brass),
longitudinal ridging and thickening. There are many
reports of cataracts in association with alopecia totalis.
Topical immunotherapy, e.g., dinitrochlorobenzene

(DNCB) or better diphencyprone (DCP). These are potent
sensitizing chemicals aimed at inducing and maintaining
a contact dermatitis at the site of application, and thus
act as immune enhancers.
Hair follicles are reduced in size, arrested in anagen IV,
and lie high in the dermis. A perifollicular lymphocytic
infiltrate is present, with degenerative changes in the
blood vessels that lead to the hair papillae. The
percentage of telogen hair is increased to 25 to 40% (the
normal percentage should be less than 20%).
Treatment
Local irritant applications as tincture iodine or tincture
capsicum; dithranol and phenol are also sometimes used.
Topical and intralesional steroids:
Topical clobetasol propionate ointment or halcinonide may be used for 6 weeks only, as skin atrophy can
occur.
For small solitary patches, intralesional triamcinolone
suspension (diluted 1:5) either by fine needle injection
or by jet injection is also effective, but atrophy may occur.
PHOTOCHEMOTHERAPY (PUVA)
Topical minoxidil 2% solution.
Wigs are very satisfactory, especially for women.
Acne Vulgaris
Acne is a common chronic inflammation of the
pilosebaceous units that affect many adolescents during
puberty. The skin eruptions primarily appear on the face,
upper back and/or chest and manifest as comedones,
papules, nodules, cysts, or papulopustules, often but not
always, followed by pitted or hypertrophic scars.
Acne starts at the age of 10 to 17 years in females and 14
to 19 in males, but it may appear first at 25 years. It is
usually more severe in males than females, but may
persist in women till the age of 35.
Multiple factors genetic, exposure to acnegenic
mineral oils and dioxin, some drugs like lithium,
hydantoin and systemic corticosteroids, endocrine factors
(androgens), emotional stress (school, social problems),
pressure on skin by leaning face on hands, are known to
exacerbate acne. Acne is not caused by chocolate or fatty
foods, or, in fact, by any kind of food apart from iodinecontaining products.
Clinical Evaluation
Skin lesions include:
1. Comedones, open (blackheads) or closed (whiteheads).
2. Papules, with (red) or without inflammation.
3. Nodules, nodulo-ulcerative lesions, or cysts 2 to 5 cm
in diameter.
4. Scars, atrophic depressed (often pitted) or hypertrophic (keloid) scars.
Seborrhea of the face and scalp is often present. Acne
lesions are round; nodules may coalesce forming linear
1358
mounds. The lesions may be isolated and single (e.g.,

nodule) or scattered and discrete (e.g., papules, cysts,
nodules). The sites of predilection include the face, neck,
upper arms and trunk.
Treatment
For mild acne:
1. Topical antibiotics (clindamycin, erythromycin)
2. Benzoyl peroxide gels (2%, 5%)
3. Topical retinoids (vitamin A acid) are effective but
require detailed instructions and gradual increase in
concentration. Improvement occurs over a period of
2 to 5 months and may take even longer for noninflamed comedones. For most patients, start with
tretinoin 0.01% gel and increase after one month to
0.025%, applied nightly after washing with a mild
soap. Topical antibiotics are applied during the day.
For severe forms:
1. Oral tetracyclines added to the above minocycline,
50 to 100 mg b.i.d., for instance; could be tapered to
50 mg/day.
2. In females only, severe acne can be controlled with
high doses of oral estrogens combined with progesterone. Cerebrovascular disorders are a serious risk,
however.
3. Oral 13-cis-retinoic acid is highly effective for cystic
acne. This treatment requires experience. As retinoids
are teratogenic in pregnant females, it is necessary
that female patients have a pretreatment pregnancy
test and they must be on oral contraceptives at least
one month prior to beginning treatment, throughout
treatment, and for 2 months after treatment is
discontinued. Furthermore, a patient must have a
negative serum pregnancy test within the 2 weeks
prior to beginning treatment. Dosage: 0.5 to 1
mg/kg/day with meals for a 15- to 20-week course,
which is usually adequate. About 30% of patients
require two 4-month courses with a 2-month rest
period in between. Careful monitoring of the blood
is necessary during therapy, especially in patients
with elevated blood triglycerides before therapy is
begun.
Miliaria Rubra
Miliaria usually occurs in warm humid weather but may
occur in cool weather in an overdressed patient. The
horny layer of the epidermis swells, obstructing eccrine
sweat gland ducts. Sweat fails to reach the skin surface
and is trapped in the epidermis or dermis, where it causes
irritation (prickling) and often severe itching.
Clinical Evaluation
Appearance of the lesions depends on the depth of the
obstruction. In miliaria crystallina, ductal obstruction is
in the uppermost epidermis, and the typical minute
lesions are tense transparent vesicles that lack inflammation. In miliaria rubra, obstruction with inflammation
occurs deeper in the epidermal acrosyringium, and the
lesions are red. In miliaria profunda, ductal obstruction
occurs at the entrance of the duct into the dermal papillae;
it is the deepest and most severe form of miliaria. Miliaria
profunda manifests with larger, deeper-seated, frequently painful papules. Intertriginous areas are favored.
Treatment
Treatment is symptomatic (cooling and drying the
involved areas) and prophylactic (avoiding conditions
that may induce sweating). An air-conditioned environment is ideal. Corticosteroid lotions, sometimes with
0.25% menthol added, are often used; however, topical
therapy is less effective than a change of environment
and lighter clothing.
URTICARIA AND VASCULAR REACTIONS
Urticaria and Angioedema
Urticaria and angioedema are composed of transient
weals (at times spelt as wheals edematous papules
and plaques, usually pruritic) and of larger edematous
areas that involve the dermis and subcutaneous tissue
(angioedema). Urticaria and/or angioedema may be
acute recurrent or chronic recurrent. There are some
syndromes with angioedema in which urticarial weals
are rarely present (e.g., hereditary angioedema).
An acute inflammatory pruritic eruption due to blockage

of eccrine sweat gland ducts and retained sweats.
Angioedema and urticaria can be classified as IgE-mediated, hypocomplementemic, or related to physical stimuli

(water, cold, sunlight, and pressure), or idiosyncratic. The
syndrome, angioedema-urticaria-eosinophilia syndrome,
is related to action of the eosinophil major basic protein.
General types include acute urticaria (less than 6 weeks),
often IgE-dependent with atopic background and chronic
urticaria: (more than 6 weeks), rarely IgE-dependent; the
etiology is unknown in 80 to 90%; often emotional stress
seems to be an exacerbating factor. Intolerance to
salicylates may be present.
Clinical Evaluation
The duration of lesions is hours. Skin symptoms include
pruritus, pain on walking (in foot involvement), flushing,
burning, and wheezing (in cholinergic urticaria).
Constitutional symptoms may be present in the form of
fever in serum sickness and in the angioedema-urticariaeosinophilia syndrome. In angioedema, hoarseness,
stridor, and dyspnea also occur. Patients may have
arthralgia (serum sickness, necrotizing vasculitis,
hepatitis).
Skin lesions consist of:
Transient pruritic papular weals - many small (a size of
1 to 2 mm is typical in cholinergic urticaria).
Weals - small (1 cm) to large (8 cm), edematous
plaques (see detailed description below).
Angioedema - skin-colored enlargement of portion
of the face (eyelids, lips, tongue) or extremity.
Dermatopathology: Changes are observed in the dermis,
and include edema of the dermis or subcutaneous tissue,
dilatation of venules, and mast cell degranulation. In
necrotizing vasculitis, biopsy is diagnostic. In angioedema-urticaria-eosinophilia syndrome, major basic
protein is present outside the eosinophils around blood
vessels and collagen bundles. There is dermal edema, a
perivascular lymphocytic infiltration, and diffuse eosinophilic in infiltration.
General laboratory tests:
Serologic tests:
Search for hepatitis-associated antigen.
Assessment of the complement system.
Assessment of specific IgE antibodies by RAST.
Hematologic tests:
ESR is often elevated in persistent urticaria (necrotizing vasculitis) and there may be hypocomplementemia.
Transient eosinophilia is observed in urticaria from

reactions to foods and drugs.
High levels of eosinophilia are present in the
angioedema-urticaria-eosinophilia syndrome.
Special examinations:
Screening for functional C1 esterase inhibitor.
Ultrasonography for early diagnosis of bowel
involvement; if abdominal pain is present, this may
indicate edema of the bowel.
Treatment
Try to prevent attacks by elimination of etiologic
chemicals or drugs: Aspirin and food additives,
especially in chronic recurrent urticaria. Detection of the
cause and its elimination is the most important step in
the treatment, but is rarely successful. The cause can be
known from careful history taking rather than from
laboratory investigations or skin testing.
Antihistamines are effective in controlling symptoms
if given in the proper dose. H1 blockers, e.g. hydroxyzine, ceterizine, levoceterizine; and if they fail, H1 and
H2 blockers (e.g. doxepin).
Prednisolone is indicated for angioedema-urticariaeosinophilia syndrome.
Danazol is indicated as long-term therapy for hereditary angioedema; whole plasma or C1 esterase inhibitor
may be used in the acute attack.
Emergency cases: Emergency treatment should start
with injection of adrenaline subcutaneously. Hydrocortisone intravenously should follow but not before
adrenaline.
Topical soothing applications as calamine lotion can
be used.
Erythema Multiforme
Erythema multiforme is a reaction of the skin to different
causes as viral infections (commonly herpes simplex),
bacterial, mycotic or parasitic infections, drugs, or
systemic diseases (rheumatic fever, systemic lupus
erythematosus, etc.). This reaction pattern of blood
vessels in the dermis with secondary epidermal changes
is exhibited clinically as characteristic erythematous irisshaped papules and vesicobullous lesions typically
involving the extremities (especially the palms and soles)
and the mucous membranes. The characteristic lesions
are also known as target lesions. The eruption begins
1360
rapidly with varying degrees of constitutional symptoms.

It is distributed bilaterally and symmetrically in a
centrifugal pattern. Stevens-Johnson syndrome is a
severe bullous form of erythema multiforme; the mucous
membranes are severely involved and there are severe
general constitutional symptoms.
cular mononuclear infiltrate, and edema of the upper

dermis; in lesions with bulla formation, there is eosinophilic necrosis of keratinocytes with subepidermal bulla
formation.
All attempts must be made to rule out occult viral,
fungal, and bacterial infections.
Treatment
Age and sex: Patients are usually 20 to 30 years old; 50%

of cases are under the age of 20. Erythema multiforme is
more frequent in males than in females.
Symptomatic. In severely ill patients, systemic corticosteroids are usually given (prednisolone 50 to 80 mg daily
in divided doses, quickly tapered), but their effectiveness
has not been established by controlled studies.
Control of herpes simplex using oral acyclovir may
prevent development of recurrent erythema multiforme.
Causes:
Drugs: Sulfonamides, phenytoin, barbiturates, phenylbutazone, and penicillin.
Infection: Especially following herpes simplex, mycoplasma.
Idiopathic: In >50% of cases no cause can be detected.
Clinical Evaluation
The duration of lesions is several days; lesions develop
over 10 days or more. Patients may have a history of prior
episode of erythema multiforme. Skin lesions may be
pruritic or painful. Mouth lesions are painful and tender.
Constitutional symptoms may be present in the form of
fever, weakness, and malaise.
Macules (48 hours) evolving to papules, 1 to 2 cm; lesions
may appear for 2 weeks.
Vesicles and bullae (in the center of papule forming
the so-called iris or target lesions).
Lesions are dull red. Iris or target lesions are typical
(see above). Lesions may be localized to the hands or
generalized. They are usually bilateral and often
symmetrical. The sites of predilection include the dorsa
of hands, palms, soles, forearms, feet, elbows and knees;
the penis (50%) and vulva may also be involved.
Mucous membranes: lesions may occur in the mouth
and on the lips (99%).
Other organs: Pulmonary manifestations may be
present; the eyes may be affected with corneal ulcers and
anterior uveitis.
Changes are observed in the epidermis and dermis. An
inflammatory process is seen characterized by perivas-
Fixed Drug Eruption

Fixed drug eruption is an adverse cutaneous reaction to
an ingested drug, characterized by the formation of a
solitary, but at times multiple, plaque, bulla, or erosion.
If the patient is rechallenged with the offending drug,
the fixed drug eruption occurs repeatedly at the identical
skin site (i.e., fixed) within hours of ingestion.
The drugs most commonly reported to cause fixed drug
eruption include: Barbiturates, phenacetin, pyrazolon
derivatives (i.e., phenylbutazone), phenolphthalein,
sulfonamides, and tetracyclines. The list of drugs causing
fixed drug eruption uncommonly includes many
commonly used medications. The pathogenesis is
unknown.
Clinical Evaluation
Fixed drug eruption is usually asymptomatic, but may
be pruritic or burning, and becomes painful when
eroded. Patients give a history of an identical lesion
occurring at the identical location. Fixed drug eruption
may be associated with a headache for which the patient
takes a barbiturate-containing analgesic, with constipation for which the patient takes a phenolphthaleincontaining laxative, or with a cold for which the patient
takes an over-the-counter medication containing a yellow
dye. The offending drug in food dye-induced fixed
drug eruption may be difficult to identify, i.e. yellow dye
in Galliano liqueur or phenolphthalein in maraschino

cherries or quinine in tonic water. Patients note a residual
area of postinflammatory hyperpigmentation between
episodes.
The characteristic early lesion is a sharply demarcated
erythema, round or oval in shape, occurring within hours
after ingestion of the offending drug. Most commonly,
lesions are solitary but may be multiple. When multiple,
the arrangement of the lesions is random. Size varies from
a few millimeters up to 10 to 20 cm in diameter. Frequently, the edematous plaque evolves to become a bulla
and then erosion. The color of the lesion is initially
erythematous, then dusky-red to violaceous, and, after
healing, dark brown with violet hue (postinflammatory
hyperpigmentation). Eroded lesions, especially on genital
or oral mucosa, are quite painful. The genital skin is the
most commonly involved site. Fixed drug eruption may
also occur within the mouth or on the conjunctiva.
Synonym: Lyells Syndrome
GRAFT-VERSUS-HOST REACTION
The findings are similar to those of erythema multiforme,

with dyskeratosis, basal vacuolization, dermal edema,
and perivascular and interstitial lymphohistiocytic
infiltrate, at times with eosinophils. Subepidermal
vesicles and bullae with overlying epidermal necrosis
may also be observed. Between outbreaks, the site of fixed
drug eruption shows marked pigmentary incontinence
with melanin in macrophages in upper dermis.
Age and sex: Patients are usually adults more than 40
years old; the disease affects both sexes equally (some
studies have reported a higher incidence in middle-aged
and elderly women).
Causes:
Drugs most commonly: Antibiotics, barbiturates,
hydantoins, pyrazolone derivatives (phenylbutazone),
sulfonamides, sulfones, and gold salts.
Other causes include:
Infections (viral, fungal, bacterial septicemia).
Vaccinations.
Leukemia.
Lymphoma.
Idiopathic Cases
Clinical Evaluation
Identify and withhold the offending drug.

Symptomatic treatment of lesion(s), with topical
calamine lotion or topical steroids (betamethasone).
Oral sedative antihistamines are indicated when
itching is severe.
Ask about history of drug intake. TEN occurs within days

of ingestion of the offending drug (when a drug is the
cause); a newly added drug is most suspect. A prodrome
occurs in the majority of patients and consists of mild to
moderate skin tenderness, fever, malaise, headache,
conjunctival burning or itching, myalgias, arthralgias,
nausea and vomiting, and/or diarrhea. Skin symptoms
are present in the form of marked tenderness of rash,
pain, pruritus, and paresthesia. Patients are usually
mentally alert, but are in distress due to severe pain.
Acute renal failure and erosions in lower respiratory tract
and gut may complicate the condition.
Toxic Epidermal Necrolysis
Skin Findings
The prodromal rash is described as morbilliform or

erythema multiforme-like. A tender erythema is initially
observed. Small blisters then form, becoming irregularly
confluent. The entire thickness of the epidermis becomes
necrotic and shears off in large sheets, but large blisters
only rarely form. Epidermal sloughing may be generalized, resulting in large denuded areas resembling a
second-degree thermal burn. The idiopathic form is
usually not preceded by rash but starts with erythema,
Treatment
Toxic epidermal necrolysis (TEN) is a cutaneous druginduced or idiopathic reaction pattern characterized by
tenderness and erythema of skin and mucosa, followed
by extensive cutaneous and mucosal exfoliation. It is
potentially life threatening due to multisystem involvement. Patients become severely dehydrated and proteindepleted. They require intensive care and are best
managed in a manner similar to burns patients.
1362
which is rapidly followed by sloughing and denudation.

The initial erythema affects the face and extremities,
becoming confluent over a few hours or days. Denudation is most pronounced over pressure points. Scalp,
palms, and soles may be less severely involved or spared,
but nails may be shed. Nikolskys sign is usually positive.
Mucous membranes are also severely affected; look for
erythema and sloughing of lips, buccal mucosa, conjunctiva, genital and anal skin.
The diagnosis is based on clinical findings and
confirmed by biopsy.
A biopsy will confirm the clinical diagnosis. Early
findings include vacuolization/necrosis of basal
keratinocytes and individual cell necrosis throughout the
epidermis. Late lesions show necrosis of the entire
epidermis with formation of subepidermal split above
the basement membrane. Little or no inflammatory
infiltrate is seen in the dermis.
Treatment
Treat as a thermal burn patient in a burn unit of a hospital.
Silver sulphadiazine is extremely effective, but must be
used with caution over large areas for fear of absorption
and resultant neutropenia. The role of corticosteroids is
controversial. There is general agreement that
corticosteroids should not be used in TEN that has
progressed to involve 20% or more of body surface. But
it is still unproven whether they may arrest the
progression of TEN if given in the first 24 to 48 hours.
IV fluid replacement: Water, electrolytes, albumin,
and plasma.
Debridement: Remove only frankly necrotic tissue.
Watch for signs of sepsis (fever, hypotension, and
change in mental status).
Conjunctival care: Erythromycin ointment.
Frequent suctioning is needed in oropharyngeal
involvement to prevent aspiration pneumonitis.
Avoid re-exposure to offending drug.
PAPULOSQUAMOUS DISORDERS
Psoriasis
Psoriasis, which affects 1.5 to 2.0% of the population in
western countries, is a common, genetically determined,
inflammatory and proliferative disease of the skin. The

most characteristic lesions consist of chronic, sharply
demarcated, dull-red (salmon pink) plaques surmounted
by silvery white scales. The lesions tend to occur at sites
of repeated minor trauma, particularly on the extensor
prominences and in the scalp. The disease is variable in
duration and extent and morphological variants are
common.
One-third of patients are affected before 20 years of age;
females tend to develop psoriasis earlier than males. This
earlier age of onset in females suggests a greater incidence
in young females than young males. However, the
incidence of psoriasis in adult men and women is usually
reported to be about equal.
The evidence that psoriasis may be inherited is
beyond doubt, and rests on population surveys, twin and
other family analyses and HLA studies. Certain drugs
(systemic corticosteroids, lithium, alcohol, chloroquine),
sunlight, stress, and obesity are believed to cause
exacerbation of pre-existing psoriasis. HIV infection must
be considered in patients at risk.
Clinical Evaluation
Types:
1. Salmon pink papules and plaques, sharply marginated with marked silvery-white scale; removal of
scale results in the appearance of miniscule blood
droplets (Auspitz phenomenon).
2. Pustules (Palmoplantar Pustulosis).
3. Erythroderma (diffuse involvement without identifiable borders).
Pattern:
1. Bilateral, rarely symmetrical; it most often spares
exposed areas and favors elbows, knees, facial region,
scalp, and intertriginous areas.
2. Disseminated small lesions without predilection of
site (guttate psoriasis).
Hair and nails:
1. Hair loss (alopecia) is not a common feature even with
severe scalp involvement.
2. Fingernails and toenails are frequently (25%) involved, especially with concomitant arthritis. Nail changes include:
Pitting (frequent but nonspecific).
Subungual hyperkeratosis.

Onycholysis (also nonspecific).
Yellowish-brown spots under the nail plate the
oil spot (pathognomonic).
Arthritis:
The incidence of psoriatic arthropathy (PA) is uncommon
(3 to 4%) and more so in children.
Dermatopathological changes in the epidermis and
dermis are classical. There is alteration of the cell cycle
(increased mitosis of keratinocytes, fibroblasts, and
endothelial cells) with: parakeratosis (clinically silvery
scales), absence of granular cell layer, regular elongation
of rete ridges with thickening of their lower portion
(clubbing), elongation and edema of papillae (clubshaped) with dilated capillaries in the upper portion of
the papillae (these are the earliest changes). Presence of
very small spongiform pustules in stratum malpighii
(spongiform pustule of Kogoj diagnostic), perivascular
mononuclear cell infiltrate in upper dermis.
Sudden onset of psoriasis may be associated with HIV
infection. Determination of HIV serostatus indicated in
at-risk individuals.
Guttate psoriasis (guttate - Latin, spots that resemble
drops), which is relatively rare (less than 2.0% of all
psoriasis), is like an exanthem: a shower of lesions
appears rather rapidly in young adults, often following
streptococcal pharyngitis. Guttate psoriasis may,
however, be chronic and unrelated to streptococcal
infection.
Treatment
Topical mildly potent steroids like fluticasone/ mometasone can be used for short intermittent courses.
Systemic steroids are contraindicated. The resolution of
lesions can be accelerated by UVB phototherapy or
judicious exposure to sunlight. Penicillin or erythromycin
are indicated if group A beta-hemolytic streptococcus
was isolated on throat culture.
Lichen Planus
This acute or chronic inflammation of the skin and
mucous membranes has characteristic flat-topped (Latin
planus, flat), violaceous, shiny, pruritic papules on the
skin, and milky-white papules in the mouth.
Most cases of lichen planus are seen in the 30-60 years
age group, though children are commonly affected.
Females are said to be affected rather more often than
males, although an opposite ratio or equal sex incidence
has been found in some studies.
The exact etiology is unknown, but severe emotional
stress can precipitate an attack. Considerable evidence
now exists that the underlying processes involved in the
pathogenesis of lichen planus are immunologically
mediated. It is also known that lichen planus can occur
in families and in these affected individuals an increased
frequency of HLA-DR1, HLA-B7, HLA3 and HLA5 has
been noted. Drugs may induce a lichen planus-like
(lichenoid) eruption.
Clinical Evaluation
Polygonal or oval, flat-topped, shiny papules, 1-10 mm
in diameter, violaceous in color, with fine white lines
(Wickhams striae) that are best seen with a hand lens
after application of mineral oil. After disappearance of
the lesions, a residual deep pigmentation is left and
remains for several months.
Arrangement and Distribution
The papules may remain discrete, or appear in groups,
in lines, or in circles. Linear lesions often appear along
scratch marks or in scars (Kobners phenomenon). The
papules may also coalesce into plaques. They are most
commonly seen on the flexor aspects of the wrists, backs
of the hands, lumbar region, glans penis (annular
lesions), medial sides of the thighs, shins and ankles
(thicker, hyperkeratotic lesions), eyelids, and scalp.
Lichen planus actinicus occurs on sun-exposed sites. In
guttate lichen planus, the papules are widely scattered
and remain discrete.
Oral lesions:
Oral lesions occur in 40% to 60% of patients and are seen
on the buccal mucosa, tongue and lips. The lesions consist
of milky-white papules, with white lacework (white
reticular streaks). Ulcerative lesions may also occur.
Carcinoma may very rarely develop in mouth lesions.
In 15% of the cases, the oral lesions are the only
manifestation of lichen planus.
1364
Hair and Nails Affection

Patches of atrophic cicatricial alopecia may occur on the
scalp due to destruction of follicles by the inflammatory
process.
Nail affection occurs in 10% of patients and presents
as thinning and longitudinal ridging of the nail plate.
Occasionally, an adhesion forms between the epidermis
of the dorsal nail fold and the nail bed, causing partial
destruction of the nail (pterygium unguis). Rarely, the
nail is completely shed; there may be partial regrowth,
or it may be permanently lost; the nails of the great toes
are the ones most often affected in this way.
Squamous cell carcinoma may occur on lichen planus
lesions of the oral mucosa (incidence 0.5%), on ulcers of
the feet, and rarely on top of hypertrophic lichen planus.
The epidermis shows orthokeratotic hyperkeratosis, focal
hypergranulosis (this accounts clinically for Wickhams
striae), irregular acanthosis, and irregular lengthening
of rete ridges. There is also liquefaction degeneration of
basal cell layer, with a band-like dermal infiltrate that
closely approximates (hugs) the basal layer that
appears wiped out. The infiltrate is formed mainly of
lymphocytes and few histiocytes.
Treatment
General measures:
Reassurance of the patient and avoidance of stress, sun
and drugs causing lichenoid eruptions.
Topical preparations:
Fluorinated steroid creams and ointments, e.g. clobetasol
propionate 0.05%.
1% phenol in calamine lotion.
Tar preparations.
Systemic therapy:
Tranquilizers and antihistamines may be used, e.g.,
hydroxyzine hydrochloride.
Systemic steroids, e.g. prednisolone 15-20 mg/day
in short courses, are only indicated in severe cases, in
acute generalized lichen planus, in ulcerative oral lesions,
and when there is progressive nail destruction.
Oral photochemotherapy (PUVA) has also been
advocated in the treatment of lichen planus with positive
results. However, following a study that suggested that
in some patients PUVA promotes carcinogenesis, the risk
versus benefits of this form of therapy for use in a

relatively benign disease must be seriously considered.
Oral lesions:
Mouth washes by triamcinolone; triamcinolone in a
special base (Orabase) is sometimes helpful.
In very resistant oral lesions, cyclosporin A mouthwashes may be used.
Oral retinoids are also helpful for erosive lichen
planus of the mouth.
Surgical excision of persistent ulcers has been recommended to guard against squamous cell carcinoma.
GENETIC DISORDERS
Zinc deficiency and acrodermatitis enteropathica
Acrodermatitis enteropathica is a genetic disorder of zinc
absorption, presenting in infancy, characterized by a triad
of acral dermatitis (face, hands, feet, anogenital), alopecia,
and diarrhea; nearly identical clinical findings occur in
older individuals with acquired zinc deficiency due
either to dietary deficiency or failure of intestinal absorption.
Age:
Acrodermatitis enteropathica: In infants bottle-fed
with bovine milk, days to few weeks. In breast-fed
infants, soon after weaning.
Acquired zinc deficiency: Older children.
Etiology:
Acrodermatitis enteropathica: Autosomal recessive
trait resulting in failure to absorb zinc.
Acquired zinc deficiency:
Secondary to reduced dietary intake of zinc.
Malabsorption (regional enteritis, following intestinal
bypass surgery for obesity).
Increased urinary loss (nephrotic syndrome).
Prolonged parenteral nutrition without supplemental
zinc.
Predisposition for acquired zinc deficiency: Pregnancy, growing child, or adolescent.
Clinical Evaluation
Skin findings consist of:
Patches and plaques of dry, scaly, eczematous skin, and
perleche. The condition may evolve to vesiculobullous,

pustular, erosive, and crusted lesions. Dermatitis occurs
on palmar/digital creases, with fissures on fingertips,
and paronychia. Annular lesions also occur, with
collarette scaling. The lesions often become secondarily
infected with candida albicans and staphylococcus
aureus. The lesions are initially pink, and later, brightly
erythematous. They are initially confined to the face
(particularly perioral), scalp, and anogenital area. Later,
the hands and feet, flexural regions, and trunk become
involved. There is impaired wound healing.
Hair: Diffuse alopecia, and graying of hair.
Nails: Paronychia, nail ridging, and loss of nails.
Mucous membranes: Oral: Red, glossy tongue, superficial
aphthous-like erosions, oral candidiasis, and perlche.
Conjunctiva: Photophobia.
General examination: Patients are irritable, with depressed
mood. Infants and children have growth failure.
Complete blood count: Reveals anemia.
Chemistry: Serum/plasma zinc levels are low.
Urine: Urinary zinc excretion is reduced.
Dermatopathology: Intraepidermal clefts and blisters are
observed with acantholysis.
Treatment
Dietary or IV supplementation with zinc salts with 2 to 3
times the recommended daily allowances restores normal
zinc status in days to weeks. Oral zinc in a dosage of 10
mg/kg of elemental zinc is as effective as parenteral
administration and needs to be continued for at least 6
months.
incidence in males and females. It has been estimated

that the gene occurs with a frequency of 1 in 500.
Histologically the only abnormality detectable is a
much-diminished granular cell layer. Ultrastructurally
and biochemically there is decreased content of a basic
histidine-rich protein known as filaggrin which is
important in the orientation of the keratin tonofilaments.
It is not known, however, how this abnormality leads to
the increased binding between corneocytes and failure
to desquamate, resulting in scaling. The rate of epidermal
proliferation is normal. The scaling is regarded as a
retention hyperkeratosis resulting from the increased
adhesiveness of the stratum corneum.
Clinical Evaluation
There is generalized fine scaling over the entire skin
surface, which tends to be worse in the wintertime when
humidity is low, and may show improvement in the
summer. The scaling spares the flexures (antecubital and
popliteal fossae, and axillae) and is most noticeable over
the extensor aspects of the limbs and trunk, being most
conspicuous over the back, the lateral aspects of the upper
arms, the anterolateral thighs, and particularly over the
shins. The scales are large, polygonal and adherent (fishscale pattern) on the extensor surfaces of the extremities,
especially the shins; elsewhere they are small, powdery
and skin-colored. Keratosis pilaris (follicular spines due
to plugging of follicular orifices by horny debris) may be
seen over the outer aspects of the upper arms in a few
subjects.
The condition is often mildly itchy and in the badly
affected can cause some disablement because of the
limitations imposed by the abnormal horny layer (splits
and fissures occur because of decreased elasticity).
Ichthyosis Vulgaris
Treatment
Emollients:
Patients who have very severe scaling may apply topical
keratolytic agents to some body sites, e.g., preparations
containing urea in concentrations of 10-15% and salicylic
acid in concentrations of 1-6%. The latter is particularly
effective in encouraging desquamation but may not be
used on large body areas for any length of time, as
concentrations of more than 2% when applied to
abnormal skin may cause salicylate intoxication
(salicylism).
Oral retinoids ( etretinate 0.5 mg/ kg) may be used
in severe cases.
Ichthyosis vulgaris (autosomal dominant ichthyosis) is

a common disorder of keratinization characterized by
mild generalized scaliness clinically, and reduction of
the granular cell layer histologically. The disease is trivial
and barely noticeable in most affected individuals, but
may be quite marked and disabling in a few patients.
The condition develops a few months after birth. It is
inherited as an autosomal dominant disorder, with equal
1366
Collodion Baby
This is a form of ichthyosis in which the newborn presents
with a grotesque appearance as encased in a thick
collodion membrane.
The condition is known to occur once in 100,000 live
births, more common in males, and in small-for-dates
children. The disease is an autosomal recessive disorder
with most of them ending with lamellar form of
ichthyosis in about 60% of them.
Clinical Evaluation
At birth, the collodion baby is encased in a tight, shiny,
moist membrane. As the membrane loses water by
evaporation, fissures soon appear, the membrane
contracts, and peeling of the membrane occurs, exposing
the red skin beneath. There is accompanying ectropion
and eclabium. The outcome is unpredictable. Some of
them turn normal, while some develop non-bullous
ichthyosiform erythroderma. Still others have chronic
and severe lamellar ichthyosis.
Treatment
The mainstay is hydration of the skin, correction of fluid
and electrolyte balance, and prevention of secondary
bacterial and candidal infection. Special intensive care
is to be administered in rooms of optimum temperature.
Liberal application of emollients such as liquid paraffin
but with minimum handling of the skin is essential. Early
use of alphahydroxy acids such as glycolic acid helps
removal of the parched membrane. An antibiotic cover
with ampicillin/cloxacillin remains essential. The genetic
nature of the disease is to be explained to the parents
and measures to prevent further offspring are to be
emphasized. A visit two weeks after discharge from the
newborn nursery is mandatory to evaluate specialized
forms of therapy such as oral synthetic retinoids.
BULLOUS DISORDERS
Epidermolysis bullosa
These are a group of dermatoses characterized by easy
bulla formation on mild mechanical pressure and hence
the name mechano-bullous disorders. The dreaded

complications are bleeding, infection and scarring.
All forms of epidermolysis bullosa (EB) are genetic and
most present at birth. There is no gender predilection.
Most babies have impaired quality of life due to the
psychological effects of easy blistering and scarring.
Clinical Evaluation
Several clinical types and subtypes have been described.
Five of them need to be known.
1. EB of hands and feet (Weber-Cockayne). Autosomal
dominant. The usual onset of recurrent blisters of
hands and feet is in late childhood, with minimum
scarring.
2. EB simplex. Autosomal dominant. Here the bullae are
present at birth and present on the elbows and knees
and other sites of friction such as the dorsa of hands
and feet.
3. EB letalis. Autosomal recessive. In this form generalized
eruption of bullae occur on the skin and mucosae.
The oral mucosa is severely affected and interferes
with feeding. Tracheal and bronchiolar involvement
lead to respiratory distress. Infection and malnutrition
lead to death.
4. EB dystrophica. Recessive. Blisters present at birth
or shortly after birth. The disorder is characterized
by bleeding into and from the blisters leading to
severe anemia. The bleeding base heals with scarring
which often entrap islands of epithelium, producing
milia that appear as tiny white cysts within scars.
Scarring is often severe resulting in replacement of
fingernails and pseudowebbing of all digits, leading
to a club-like appearance.
5. EB dystrophica. Dominant. This form is less severe
than its recessive counterpart but is often associated
with ichthyosis, keratosis pilaris, and hyperhidrosis.
Treatment
Treatment of EB is essentially supportive. Sterile
dressings and topical antibiotics (2% Mupirocin) form
the mainstay of therapy. Cutaneous infections unresponsive to topical antibiotics will need systemic antibiotics (cloxacillin). Nutritional support is essential in the
form of soft flexible intragastric feeding in selected
children. Attempts of intermittent esophageal dilatation

may be fruitful. Apparently, the management of severe
forms of EB demands optimal care from the combined
efforts of parents, pediatricians, and dermatologists.
Genetic counseling plays an important role.
Staphylococcal Calded Skin Syndrome
Staphylococcal scalded-skin syndrome (SSSS) is a toxinmediated epidermolytic disease characterized by
erythema and widespread detachment of the superficial
layers of the epidermis, resembling the effects of scalding.
It occurs mainly in newborns and infants under 2 years
of age. Severity ranges from a localized form, bullous
impetigo, to a generalized form with extensive epidermolysis and desquamation. Clinical spectrum of SSSS
includes:
1. Bullous impetigo,
2. Bullous impetigo with generalization,
3. Scarlatiniform syndrome,
4. Generalized scalded-skin syndrome.
Synonyms: Pemphigus neonatorum, Ritters disease.
Age: SSSS occurs mainly in infants and young children.
Adults with immunosuppression or renal insufficiency
are subject to SSSS.
Etiology: Staphylococcus aureus of phage group II, mostly
type 71.
Clinical Evaluation
A low-grade fever may be present. The child is irritable.
Skin findings:
Bullous impetigo: Lesions are often clustered in an
intertriginous area and consist of intact flaccid, purulent
bullae. Rupture of the bullae results in moist red and/or
crusted erosive lesions.
Generalized SSSS: A very tender, ill-defined erythema
occurs initially. With epidermolysis, the epidermis
appears wrinkled. The unroofed epidermis forms
erosions with red, moist base. Initially, lesions are present
on the face (periorificially), neck, axillae, and groins,
becoming more wide spread in 24 to 48 hours. The initial
erythema and later sloughing of the epidermis are most
pronounced periorificially on the face, and in the flexural
areas and pressure points: On the neck, axillae, groins,
antecubital area, and back.
Scarlatiniform syndrome: Presentation is like scarlet fever

but without pharyngitis, tonsillitis, and strawberry
tongue.
Nikolskys sign (gentle lateral pressure causes shearing off of superficial epidermis): Positive.
Mucous membranes: Are usually uninvolved.
Gramss Stain:
Bullous impetigo: Findings include pus in bullae and
clumps of gram-positive cocci within PMNL.
Generalized SSSS: Gram-positive cocci are only observed
at colonized site, not in areas of epidermolysis.
Bacterial culture: Bullous impetigo: Staph. aureus is
isolated.
Generalized SSSS: Staph. aureus is only present in colonized site of infection, i.e., umbilical stump, conjunctiva,
or external ear canal; culture of sloughing skin or bullae
usually yields no pathogens.
Treatment
For a newborn, hospitalization and treatment with IV
cloxacillin, 200 mg per kg body weight per day in divided
every 4 hours, are preferable.
Hospitalize infants with extensive sloughing of skin
or if parental compliance to treatment is questioned.
With reliable home care and mild involvement, cloxacillin, 30 to 50 mg per kg body weight per day, can be
given orally.
Topical care includes baths or compresses, and
mupirocin ointment, bacitracin, or silver sulfadiazine.
PIGMENTARY DISORDERS
Vitiligo
Vitiligo, a specific type of acquired leukoderma, is an
idiopathic, patterned, circumscribed hypomelanosis of
the skin and hair in which other causes of leukoderma
have been excluded. The disease is important principally
because of the social stigma associated with vitiligo in
brown- and black-skinned persons. Vitiligo may be an
autoimmune disease, since it is associated with other
autoimmune diseases: Diabetes mellitus, pernicious
anemia, and Addisons disease.
1368
The incidence of vitiligo is 1 to 8.8%. The age of onset
varies widely from infancy to old age, with a peak incidence in the 10 to 30 years age group. The reported female
predominance may be spurious, especially in India where
vitiligo can be a considerable disfigurement and can
affect eligibility for marriage because vitiligo mimics
leprosy.
The etiology is unknown. There is a positive family
history in 30% of patients. An immune process is the most
probable mechanism of destruction of melanocytes, as
there are several autoimmune disorders that occur with
vitiligo: Thyroiditis, adrenal insufficiency, and pernicious
anemia, based on an autoimmune mechanism. An
immune hypothesis would involve an aberration of
immune surveillance that results in destruction of
melanocytes; the primary event would be damage to
melanocytes with the release of antigen and subsequent
autoimmunization (probably in a genetically predisposed
individual).
Clinical Evaluation
The white spots usually gradually appear and remain
for life, with about 30% of patients reporting some limited
spontaneous repigmentation. Rarely, vitiligo macules
may be erythematous with a raised border and with
itching; this inflammatory vitiligo has no special
significance. Other findings in the history include
premature graying of hair (<20 years of age), and history
of halo nevi or alopecia areata. Skin lesions consist of
white macules varying in size from 1 mm to large areas
of the body. The typical color of these macules is snow
white, but newly developing lesions may be off-white
or even a light tan. Individual lesions are usually oval,
forming geographic patterns; the borders may often be
scalloped. There may be linear patterns or artifactualtype areas (as under a neck pendant); these represent
the isomorphic, or Koebner, phenomenon. Pigmented or
white hairs may be present in a vitiligo macule.
Distribution of lesions:
Focal type: Isolated macules in one site.
Segmental: Unilateral, quasidermatomal.
Generalized: Multiple discrete macules, often strikingly
symmetrical (in fact, mirror image) and at sites of
repeated trauma, such as the bony prominences
(malleoli, tip of the elbow, necklace area in females).
Mucous membranes: Lesions are rarely present in the

mouth (gums).
Eye manifestations: Iritis occurs in 10%, but may not
be symptomatic; retinal changes consistent with
healed chorioretinitis are seen in up to 30% of patients.
General examination: Search for thyroid disease (up to
30% in females), diabetes mellitus, pernicious anemia,
Addisons disease, and polyendocrinopathy syndrome with mucocutaneous candidiasis.
In the epidermis, melanocytes are absent in fully developed vitiligo macules, but at the margin of the white
macules, melanocytes and a few lymphocytes may be
present. There is also progressive destruction of
melanocytes, possibly by cytolytic T cells.
Laboratory Examination of Blood
Serologic tests:
ANA and other special tests for lupus erythematosus;
Adrenal autoantibodies are found in 50% of patients
who have Addisons disease.
Hematologic findings: Are normal, except in patients
with pernicious anemia (obtain complete blood study
including indices).
Blood chemistry:
TSH (radioimmunoassay).
In Addisons disease: There may be a low fasting blood
sugar, low sodium and high potassium, and an elevated
BUN.
Fasting blood sugar should be done to exclude diabetes mellitus.
Woods Lamp Examination
It is essential to examine patients with a light skin color
with the Wood s lamp to detect all the areas of vitiligo.
Eye examination by an ophthalmologist is necessary
before therapy.
Treatment
The treatment of vitiligo is best managed by a dermatologist who, depending on (1) concern about the disfigurement by the patient, and (2) the age of the patient,
may choose topical PUVA photochemotherapy or oral
PUVA photochemotherapy. In patients with extensive
loss of normal pigmentation, bleaching the normal skin

to make it totally white is a very satisfactory method of
treatment. This is accomplished with topical preparations
of monobenzylether of hydroquinone.
Albinism
Albinism is a heritable disorder that affects skin, hair,
and eyes. It principally involves the synthesis of melanin
but also includes some alterations of the pathways of the
CNS. Albinism can affect the eyes, ocular albinism (Xlinked recessive), or the eyes and skin, oculocutaneous
albinism. In oculocutaneous albinism, the disorder is
autosomal recessive, with dilution of normal amounts
of skin, hair, and melanin pigment; nystagmus and iris
translucency are always present, and there is a reduction
of visual acuity, sometimes severe enough to cause
blindness.
The general incidence is 1:20,000. Albinism is present at
birth. There is no special predilection in any one skin
color. Hermansky-Pudlak syndrome (oculocutaneous
albinism and a platelet disorder) is seen in Hispanics
from Puerto Rico, in persons of Dutch origin, and in East
Indians from Chennai.
Classification of oculocutaneous albinism: There are
10 types of oculocutaneous albinism, based on:
1. The level of tyrosinase in the plucked hair bulb
(ty-positive and ty-negative),
2. Hair color (yellow, red, platinum), and
3. Associated problems such as platelet abnormalities
and ceroid storage disease (Hermansky-Pudlak
syndrome) or defects in immunity (Chediak-Higashi
syndrome).
Mode of inheritance is mostly autosomal recessive.
Exceptions are the ocular forms that are X-linked
recessive and those associated with deafness that are
autosomal dominant.
Clinical Evaluation
Patients with albinism early in life avoid the sun because
of repeated sunburns, especially as toddlers. In Hermansky-Pudlak syndrome, there is also epistaxis, gingival bleeding, excessive bleeding after childbirth or tooth
extraction, and fibrotic restrictive lung disease. There
may be no family history of albinism in the autosomal
recessive or X-linked recessive types. Albinos live an
essentially normal life, except for problems with vision

and, in lower latitudes, the development of skin cancers
and dermatoheliosis. In some countries, there are
volunteer groups that assist albinos in various ways,
especially in dealing with vision problems: Obtaining
drivers license, etc. Many albinos appear to be musicians
and to be high achievers. The appearance of albinos is
typical, with poring (eyes half closed, squinting) when
in sunlight. Skin color is snow - white, fair, cream, or
light tan. Hair is white (ty-neg), yellow cream, or light
brown (ty-pos), and may be red, or platinum. The iris is
translucent, with nystagmus.
Light microscopy: Melanocytes are present in the skin
and hair bulb in all types of albinism. The dopa
reaction of the skin and hair is markedly reduced or
absent in melanocytes of the skin and hair, depending
on the type of albinism (ty-neg or ty-pos). Electron
microscopy: Melanosomes are present in melanocytes
in all types of albinism but, depending on the type of
albinism, there is a reduction of the melanization of
melanosomes, with many being completely unmelanized (stage I) in ty-neg albinism. Melanosomes in
the albino melanocytes are transferred in a normal
manner to the keratinocytes.
Laboratory examination of blood: Morphologic,
chemical, and functional defects of platelets are observed
in Hermansky-Pudlak type of albinism.
Tyrosine hair bulb test (ty-neg and ty-pos): Hair bulbs
are incubated in tyrosine solutions for 12 to 24 hours and
develop new pigment formation from normal and typos patients, but no new pigment formation is present
in ty-neg albinism.
Albinism is an important disease to recognize early
in life, in order to start prophylactic measures to prevent
dermatoheliosis and skin cancer.
Treatment
Skin care: A lifetime program beginning in infancy is
necessary, and includes:
Daily application of topical, potent, broad-spectrum
sun-blocks, including lip sun-blocks.
Avoidance of sun exposure in the high solar intensity
season during the hours of 1000 to 1500.
Yearly examination by a dermatologist to detect skin
changes: Skin cancers and dermatoheliosis.
1370
Use of topical tretinoin for dermatoheliosis and for

its possible prophylactic effect against sun-induced
epithelial skin cancers.
Systemic beta-carotene (30 to 60 mg t.i.d.) imparts a
more normal color to the skin and may possibly have
some protective effect on the development of skin
cancers.
Pityriasis Alba
Pityriasis alba is a nonspecific dermatitis of unknown
etiology that causes erythematous scaly patches. These
resolve and leave areas of hypopigmentation. Pityriasis
alba has been regarded as a manifestation of atopic
dermatitis. It is known to occur in nonatopic individuals.
The lesions commonly are asymptomatic, though some
patients will complain of burning or pruritus. The cause
is unknown. The condition has been regarded as a
manifestation of atopic dermatitis.
All races are affected but may be more prominent in darkskinned patients and both sexes are equally susceptible.
Pityriasis alba occurs predominantly in children between
the ages of 3 and 12 years. Erythema initially may be
conspicuous and minimal serous crusting may even
occur at a few points on the surface of some of the
plaques. Erythema later subsides completely and at the
stage when a physician commonly sees lesions, they
show only persistent fine scaling and depigmentation
which is conspicuous in heavily pigmented skin. In
lighter skins, it may become conspicuous after sun
tanning. This commonly induces the patient to seek
advice. The course is extremely variable. Most cases
persist for several months and some still show leukoderma for a year or more after all scaling subsides.
Recurrent crops of new lesions may develop at intervals.

The average duration of the common facial form in
childhood is a year or more.
Clinical Evaluation
The individual lesion is a rounded, oval, or irregular
plaque that is red, pink, or skin colored and has fine
lamellar or branny scaling. Several patches usually are
seen. Lesions usually range from 0.5-2 cm in diameter
but may be larger, especially on the trunk. In children,
the lesions often are confined to the face and are most
common around the mouth, chin, and cheeks. In 20% of
affected children, the neck, arms, and face are involved.
Less commonly, the face is spared and scattered lesions
are seen on the trunk and limbs.
Histological changes are unimpressive. Acanthosis and
mild spongiosis is seen, with moderate hyperkeratosis
and patchy parakeratosis. Follicular plugging, spongiosis, and sebaceous gland atrophy may be seen. On
electron microscopy, reduced numbers of active melanocytes and a decrease in number and size of melanosomes are seen in affected skin.
Treatment
Pityriasis alba resolves spontaneously and may not
require treatment. Response to treatment often is
disappointing. Treatment includes a simple emollient
cream. For chronic lesions on the trunk, a mild tar paste
may be helpful. Topical 1% hydrocortisone preparations
may be helpful if mild inflammation is present. A variety
of lotions, creams, and ointments that contain hydrocarbons, oil, waxes, and long-chain fatty acids aid in
retaining moisture in the skin especially if applied
immediately after bathing. A bland emollient may be
used to reduce the scaling.
32.1 Common Dental Problems: PK Baskar ............................................................................................................................................ 1372
1372
32.1 Common Dental Problems

PK Baskar
INTRODUCTION
Dental diseases affecting the child may or may not be
symptomatic. Further certain physiological changes like
eruption of a tooth, may be associated with inflammation,
etc. Pediatricians should equip themselves to differentiate
the physiological changes from pathological lesions.
Involving the parents in the prevention, treatment and
recurrence is particularly important in pediatric practice.
Prevention of dental disease should start from educating
the pregnant mother.
Treatment of dental disease is never complete without
spending considerable time on prevention and educating
the parents.
Dental diseases affecting the child are not the same
that affect the adult. The target organs are the same like
teeth, gingiva, etc. but the etiopathogenesis are different
because:
i. The primary dentition is morphologically different.
ii. Food habits are different from that of the adult.
iii. Poorer control over maintenance of oral hygiene.
The pediatrician should be aware that teeth and jaws
are in the formative stages. They should not underestimate
their responsibility to guide the parents, not only in the
prevention of dental diseases, but also in ensuring ideal
and optimal growth of the dentition, both primary and
permanent. They should realize, that it is possible to alter
growth patterns and resistance to disease of oral tissues
to produce a more ideal metabolic, functional and aesthetic
oral cavity. In fact, the pediatrician should consider this
opportunity as a privilege, as they are in a position of
influencing the future dental health of the patient.
THE DENTITION
The primary dentition comprises of 20 teeth; four incisors,
two canines and four molars in each jaw.
The permanent dentition comprises of 32 teeth; four
incisors, two canines, four premolars, and six molars in
each jaw.
They are represented as follows with two digits for

easy reference (Tables 32.1.1 and 32.1.2).
TABLE 32.1.1: Primary dentition
55
85
54
84
53
83
52
82
51
81
61
71
62
72
63
73
64
74
65
75
TABLE 32.1.2: Permanent dentition

18 17 16 15 14 13 12 11 21 22 23 24 25 26 27 28
48 47 46 45 44 43 42 41 31 32 33 34 35 36 37 38
The primary (Table 32.1.3 and Fig. 32.1.1) and

permanent (Table 32.1.4 and Fig. 32.1.2) dentitions have
distinct morphological characteristics, which identify
them as incisors, caninces, premolars and molars.
Development of Teeth
The teeth are derived from highly specialized cells of
ectodermal and mesodermal origin. Ectodermal cells
perform special functions such as, enamel formation,
odontoblastic stimulation and determination of the shape
of the crown and root. These cells disappear after
performing their functions. Mesodermal cells persist
throughout life and form dentine, pulpal tissue, cementum,
peridodontal membrane and alveolar bone.
TABLE 32.1.3: Primary dentition
Eruption sequence
Central incisors
Lateral incisors
Canine
First molar
Second molar
6-7 months
8-9 months
16-18 months
12-14 months
20-24 months
Completion of
enamel formation
Central incisors
Lateral incisors
Canine
First molar
Second molar
1 months
2 months
9 months
6 months
11 months
Pediatric Dentistry
TABLE 32.1.4: Permanent dentition
Eruption sequence
Central incisors
Lateral incisors
Canine
First premolar
Second premolar
First molar
Second molar
7-8 years
8-9 years
11-12 years
10-11 years
10-12 years
6-7 years
12-13 years
Completion of
enamel formation
Central incisors
Lateral incisors
Canine
First premolar
Second premolar
First molar
Second molar
4-5 years
4-5 years
6-7 years
5-6 years
6-7 years
2-3 years
7-8 years
Figure 32.1.1: Eruption sequencePrimary dentition
Figure 32.1.2: Eruption sequencePermanent dentition
1373
1374
Each tooth, in achieving morphologic and functional

maturity, through a well-defined and characteristic
lifecycle is composed of many stages. These stages of
development are:
i. Growth
ii. Calcification
iii. Eruption
iv. Attrition
v. Resoption and exfoliation.
Functions of Primary Dentition
The primary dentition needs special care and shuld be
preserved till its anticipated exfoliation. The main
functions are:
i. Mastication
ii. Appearance
iii. Speech
iv. Psychology of having teeth
v. Stimulation of growth of the jaw through mastication
vi. Prevention of malocclusion through maintaining
arch length. Premature loss of primary molar leads
to more severe malocclusion.
COMMON DENTAL DISEASES AFFECTING THE CHILD
Physiological Events Causing Pain
In most children the eruption of primary teeth is preceeded
by increased salivation and the child will want to put the
hand and fingers into the mouth. Some children become
restless during the time of eruption of the primary teeth.
Though the eruption of teeth is a normal physiologic
process, it is sometimes associated with pain, adenitis
and fever.
Pre-eruption Bulge
Before eruption of the tooth, a bulge can be seen in relation
to the site known as pre-eruption bulge. Inflammation
of the gingival tissues before complete emergence of the
crown may cause a temporary painful condition, that
subsides within a few days. No treatment is necessary.
Eruption Hematoma
Very rarely a bluish, purple elevated area of gingival tissue,
commonly called eruption hematoma develops a few
weeks before the eruption of a primary or a permanent
tooth. The blood-filled cyst is most frequenty seen in
primary second molar to first permanent molar regions.
This condition develops as result of trauma, which usually
subsides within a few days when tooth erupts through

the tissue and the hematoma subsides.
DENTAL CARIES
Dental caries continues to affect a large number of children
and hence should receive significant attention in every
day practice. Because of the high incidence, the treatment
and prevention of this disease continues to occupy a major
portion of dental practice in children.
Dental caries is preceded by the formation of microbial plaque. It is generally accepted that acid resulting
from the action of microorganisms on carbohydrates
causes dental caries. It is characterized by a decalcification
of the inorganic poriton and is accopanied or followed by
disintegration of the organic substances of the tooth.
Dental caries has been seen to affect the primary and
permanent dentition.
Etiopathogenesis of Dental Caries
Bacteria, appropriate substrates (sucrose), and individual
susceptibility are the three major factors in the etiopathogenesis of dental caries. Dental caries is classified
as:
1. Smooth surface caries
2. Pit and fissure caries.
Smooth surface caries: Develops on the proximal surfaces
on the teeth on the gingival third of the buccal and lingual
surfaces. Smooth surface caries is generally preceded by
the formation of a microbial or dental plaque.
The earliest manifestation of incipient caries of the
enamel, is the appearance beneath the dental plaque of an
area of decalcification, which resembles a smooth chalky
white area. First change is usually a loss of the interprismatic or interrod substance of the enamel, with
increased prominence of rods. There is an appearance of
transverse striations of the enamel rods, dark lines or bands
occurring in right angles, to the enamel prisms. Another
change is the accentuation of the incremental striae of
retzius, due to loss of minerals, which causes the organic
structure to appear more prominent.
Pit and fissure caries: Develops in the occlusal surface of
the premolars, molars and in the lingual surface of the
maxillary incisors.
Pit and fissure caries may appear brown or black and
feel soft. A fine explorer when passed over the tooth surface
will suffer a catch. The enamel directly bordering the
pit or fissure may appear opaque or bluish white, which
denotes the undermined lesion.
Pediatric Dentistry
EARLY CHILDHOOD CARIES
Dental Caries of Enamel (Fig. 32.1.3A)
Though there are several etiological factors for early

childhood caries which was earlier referred as rampant
caries, one of the important factors, deserves special
mention is sugar containing liquid oral medicines. Some
of these pharmaceutical preparations have been reported
to have mean sugar content of 55% (Newbrun E) to make
them more palatable and mask the unpleasant taste of
drugs especially for children. Sucrose also acts as a preservative, solvent and a bulking agent. It is also cheap,
non-hygroscopic and easy to process. Sugars, metabolised
by bacteria to acid end products, lower pH within the
bacterial plaque and cause ionic dissolution, leading to
enamel and dentin demineralisation. Further diminution
of salivation and mastication during night, increases the
cariogenic potential of medicines. Some sedatives, anticonvulsants and antihistamines also lower the salivary
flow, which further enhances the cariogenic process.
Today, the most widely used caloric sweeteners are
xylitol and sorbitol, replacing sucrose in tablets, chewing
gums, pharmaceutical preparations. Xylitol has gained
special attention, because it cannot be metabolized by oral
micro-flora and practically no acid is formed.
In addition to poor dietary habits such as frequent
consumption of sugar containing products such as snacks,
biscuits, ice cream, etc. lack of oral hygiene, bottle feeding
during the night, is also associated with early dental caries.
High fequency of sucrose intake increases the cariogenicity
of plaque with resultant dental caries formation.
Acidogenic Theory
1. Sudden onset
2. Dental caries involves teeth, which are not usually
affected by dental caries.
3. Proximal surfaces of lower anteriors are also involved.
4. Development of cervical caries also take place.
5. May not develop pain till the pulp is involved.
Nursing Bottle Caries
Also called as:
1. Nursing bottle syndrome
2. Milk bottle syndrome
3. Nursing caries.
Various theories have been put forward for the
etiopathogenesis of dental caries of enamel and dentin.
1375
Microorganisms acting on carbohydrates, produce enough

acid to decalcify tooth structure, particularly acidogenic
streptococci, lactobacilli, diphtheroids, yeast, staphylococci and certain strains of sarcinas, including S. mutans,
S. sanguis and S. salivarius.
Proteolytic Theory
Microorganisms invade the organic pathways and destroy
them as they advance. Acid formation that accompanied
the proteolysis eventually destroys enamel and dentin
resulting in cavity formation.
Proteolysis Chelation Theory
Bacterial attack on enamel, initiated by keratinolytic
microorganism, consists of breakdown of the protein and
other organic components of enamel, chiefly keratin. This
results in the formation of substances, which easily form
soluble chelates with the mineralized componenets of the
tooth and decalcify the enamel at the neutral or even an
alkaline pH.
Dental Caries of the Dentin (Figs 32.1.3B and C)
Dental caries, left untreated extends to the dentino-enamel
junction where greater number of dentinal tubules act as
a tract leading to the dental pulp, along with the
microorganisms (Fig. 32.1.3C).
Early Lesion
The initial penetration of the dentin by caries may result
in alterations in the dentin described as dentinal sclerosis.
It is a reaction of vital dentinal tubules and a vital pulp,
which results in a calcification of the dentinal tubules
that tends to seal them off against further penetration by
microorganisms.
Advanced Lesions
Decalcification of the walls of the individual tubules leads
to their confluence. A thickening before complete
disintegration of the enamel can be distinguished,
beginning on the dentinal side of the lesion (Fig. 32.1.3D).
1376
Figures 32.1.3A to D: (A) Dental caries of enamel, (B) Dental caries of dentin, (C) Pulpitis, (D) Root abscess
Diagnosis of Dental Caries

A sharp probe can be used to examine the tooth under
good illumination, to detect the presence of dental caries.
Occlusal caries can be detected best by mouth mirror and
explorer even at the early stages where radiograph cannot
detect. The radiograph is sometimes useful for a complete
oral examination by the dentist. The interproximal lesion
appears as a small, radiolucent area of the enamel.
A careful look at the structure of the enamel will reveal
that there are no nerve endings in the enamel, hence, it is
incapable of conveying any pain stimulus. Hence, there
may not be any pain even when dental caries has involved
enamel. The enamel caries can be there for several months
but when the caries extents into the dentine, it spreads
very fast and reaches the pulp which becomes very painful.
Hence, periodical dental check-up with proper
illumination, with a sharp explorer and mouth mirror will
help to detect dental caries which ca be filled with metal
or any other restoration resins.
It must also be understood that the enamel is incapable
of regeneration. Hence the need for a foreign material to
repair the decayed enamel. However, remineralization in
the enamel has been found to be possible with topical
fluorides and suitable diet rich in calcium and phosphorus.
Management of Dental Caries
1. Reduction in the intake of freely fermentable carbohydrates: Frequency of eating and eating between meals
2.
3.
4.
5.
6.
has a direct bearing on the incidence of dental caries

particularly in children. The incidence is more when
there is more sugar intake.
Topical application of fluorides is very useful.
Discouraging sweets helps.
Plaque control can be achieved by tooth brushing,
flushing, scaling and antiseptic mouthwashes.
Water fluoridation: It is important to understand that
fluoride incorporation is beneficial only at the time of
calcification of the tooth.
There is evidence pointing to considerable tooth
decay inhibition when the community water supply
is having fluoride between 0.5 and 0.9 ppm. When
levels of fluoride in the drinking water is approximately 1 ppm, marked inhibition of dental caries
without producing significant mottling of the enamel
is seen.
Diet: Feeding during sleep should be discouraged.
During sleep salivary flow is diminished and
swallowing reflex is absent. Hence stagnation of milk
is possible. The clearance of milk can be encouraged
by intake of water.
It has been observed that incidence of dental caries
is high whenever bottle-feeding is preferred to
breastfeeding. Further breastfeeding also help in
proper development of orofacial structures.
Drinking more soft drinks causes increased
susceptibility to dental caries.
High protein diets, fats, phosphates and detergent
diets have been found to be cariostatic. Sucrose, sweets,
Pediatric Dentistry
chocolates, jams and ice cream are found to be
cariogenic.
Detergents diet: Any food that sticks to the teeth
favors caries activity. Hence such foods should be
avoided. Detergent diets play an useful role in the
prevention of dental caries. A detergent diet serves two
functions. The fibrous content helps better blood
circulation in the gingiva and secondly removes all
the food debris and plaque between teeth and gums
and leaves the mouth clean.
It has been observed that cheese and peanuts inhibit
caries activity. Almonds and groudnuts are rich source
of calcium and phosphorus. Amongst dried fruits,
apricots, figs and dates also provide rich source of
calcium and phosphorus.
7. Pit and fissure sealants: This is a very important treatment
procedure, which protects susceptible surfaces. With
improved utilization of this underutilized preventive
measure, significant economic and health benefit can
be realized.
8. Restoration of the decayed tooth: The first step is to prevent
further progression of the lesion. Gross superficial
excavation of the caries and filling the cavity with zinc
oxide-eugenol will temporarily arrest the caries process
and prevent its rapid progression to the deeper tissues.
Further, it helps in the sterilizaiton of the cavity walls.
These cavities can be later filled by permanent filling
material.
Dental amalgam have been studied extensively for
safety and it has with stood the test of time, there is still a
place for dental amalgam.
A new method of treating dental caries that involves
neither drill, water, nor electricity was presented at the
headquarters of the World Health Organization (WHO),
Geneva on World Health Day, April 7 1994. The procedure,
called Atraumatic Restorative Treatment (ART), consists
of manually cleaning dental cavities with hand instrument
and filling them with an adhesive fluroide releasing
material.
PERIODONTAL DISEASE IN CHILDREN
Periodontal disease denotes diseases arising from one or
more of the surrounding tissues of the teeth namely
gingiva, peridontal ligament, alveolar bone and
cementum. The tissues surrounding the teeth are also
referred to as supporting tissues of the teeth. Periodontal
diseases are classified into acute and chronic.
1377
Acute Gingival Diseases

a.
b.
c.
d.
e.
Acute herpetic gingivostomatitis

Oral candidiasis
Acute necrotizing ulcerative gingivitis
Eruption gingivitis
Gingivitis associated with exfoliation.
Chronic Gingival Diseases

a. Chrnoic marginal gingivitis
b. PapillonLefevre syndrome
ACUTE GINGIVAL DISEASES
Acute Herpetic Gingivostomatitis
Is an infection of the oral cavity caused by a specific virus.
Secondary bacterial infection complicates the clinical
picture.
This is caused by the Herpes simplex virus (HSV). The
condition usually occurs during and immediately after
an episode of febrile disease such as pneumonia, influenza
or typhoid. It also tends to occur during periods of anxiety,
strain or exhaustion and during menstruation.
Clinical Features
The condition appears as a diffuse, erythematous, shiny
involvement of the gingiva and the adjacent oral mucosa
with edema and gingival bleeding. In the initial stage, it is
characterized by the presence of discrete, spherical grey
vesicles which may occur on the gingiva, the labial and
buccal mucosa, the soft palate, the pharynx, the sublingual
mucosa and the tongue. After 24 hours, the vesicles rupture
and form painful small ulcers with a red, elevated halolike margin and a depressed yellowish grayish white
central portion. Course of the disease is limited to 7 to 10
days, the diffuse erythema and edema persist for several
days. Scarring does not occur localized form consists of
numerous pinpoint vesicles. The vesicles rupture and form
painful ulcerations.
The disease is a accompanied by generalized soreness
of the oral cavity, which interferes with eating and
drinking. The ruptured vesicles are the focal sites of pain
and sensitivity to touch, thermal changes, foods such as
condiments and fruit juices. In infants the disease is
marked by irritability and refusal to take food. Herpetic
involvements of lips or face with vesicles and surface scab
formation may be present. Cervical adenitis, fever as high
1378
as 101F and generalized malaise are common. Treatment

is only supportive and symptomatic. Antibiotic therapy
is of considerable aid in the prevention of secondary
infection.
Oral Candidiasis
Candidiasis is a disease caused by infection with a yeast
like fungus, Candida albicans, although other species may
also be involved. This microorganism is a relatively
common inhabitant of the oral cavity, gastrointestinal tract
and vagina of clinically unaffected persons. This disease
is said to be the most opportunistic infection in the world.
Acute pseudomembranous candidiasis is one of the
more common forms of the disease. It may occur at any
age, but is especially prone to occur in the debilitated or
the chronically ill, or in infants. The oral lesions are
characterized by the appearance of soft, white slightly
elevated plaques most frequently occuring on the buccal
mucosa and tongue, but also seen on the palate, gingiva
and floor of the mouth. The plaques resemble milk curds,
consist chiefly of tangled masses of fungal hyphae with
intermingled desquamated epithelium, keratin, fibrin,
necrotic debris, leukocytes and bacteria. The white plaque
can be wiped away with a gauze, leaving a normal
appearing mucosa or an erythematous area.
Chronic hyperplastic candidiasis is often spoken of
as the leukoplakia type of candidiasis. The oral lesions
consist of firm, white persistent plaques, usually on the
lips, tongue and cheeks. These lesions persist for many
years.
Clinical Features
The two types of candidiasis are:
i. Mucocutaneous candidiasis
ii. Systemic candidiasis.
The mucocutaneous form includes oral or oro
pharyngeal forms. The systemic form involves chiefly the
eyes, the kidneys and the skin through hematogenous
spread.
Treatment: Specific antifungal agents such as nystatin has
been beneficial in the treatment, suspensions of nystatin,
held in contact with the oral lesion, have been successfully
used in even chronic or severe cases of the disease.
Painting the lesion with gentian violet is an older but effective treatment.
Acute Necrotizing Ulcerative Gingivitis

Acute necrotizing ulcerative gingivitis (ANUG) is an
inflammatory destructive disease of the gingiva commonly
known as Vincent infection. Spirochetal organism and
fusiform bacilli termed Borrelia are always found in the
disease.
Clinical Features
A well-defined punched-out, crater-like depressions the
crest of the interdental papillae is always seen. The surface
of this gingival crater is covered by grayish, pseudomembranous slough demarcated from the remainder of
the gingival mucosa by a pronounced linear erythema.
The other salient features are constant radiating, gnawing
pain that is intensified by eating spicy or hot foods, metallic
taste, pasty saliva and hypersalivation.
Halitosis is always present much to the annoyance of
the child and others which is often very penchant.
Local lymphadenopathy and a slight elevation in
temperature are common. However, in severe cases, high
fever, increased pulse rate, leukocytosis, loss of appetite
and general lassitude are also seen.
Management
The treatment consists of:
i. Local treatment for alleviation of the acute
inflammation should be started immediately.
ii. Systemicappropriate supportive treatment to
correct malnutrition and suitable antibiotics to control
generalized toxic symptoms such as fever and malaise
are necessary.
CHRONIC GINGIVAL DISEASES
Chronic Marginal Gingivitis
This is the most prevalent type of gingival change in
childhood. The gingiva exhibits all the changes in color,
size, consistency and surface texture characteristic of
chronic inflammation.
This is most common in children due to plaque and
calculus. In preschool children, however, the gingival
response to bacterial plaque was found to be less than
that in adults. Plaque occurs more rapidly in children
than in adults.
Pediatric Dentistry
PapillonLefevre Syndrome
PapillonLefevre syndrome is a syndrome characterized
by severe destruction of the periodontium associated with
hyperkeratotic lesions in palms and soles.
The cutaneous and periodontal changes usually
appear together before the age of 4 years. The skin lesion
consists of hyperkeratosis and ichthyosis of localized areas
on the palm, soles, knees and elbows. Periodontal lesion
consists of early inflammatory involvement leading to bone
loss and exfoliation of teeth.
Primary teeth are lost by 5 or 6 years of age. Permanent
teeth then erupts normally, but are exfoliated within few
years owing to destructive periodontal disease.
By 15 years of age, patients are usually edentulous
except for third molars which are also lost few years after
they erupt. Diagnosis is based on the presence of both
skin an periodontal lesions.
MALOCCLUSION
While dental caries has been regarded as the major dental
disease throughout the world affecting the child,
malocclusion is only next. Malocclusion may involve four
tissue systems:
i. Teeth
ii. Bones
iii. Muscles
iv. Nerves.
The teeth are irregular, jaw relationship may be good
and muscle and nerve function normal. Teeth may be
regular in their alignment but an abnormal jaw
relationship may exist, so that the teeth do not meet
properly during function.
Habits
Impact of pediatric oral habits: Oral habits can manifest in
variety of activities which may or may not be a concern to
the child or parents. Oral habits include digit sucking,
mentalis habits, lip wetting, lip sucking, abnormal
swallowing, tongue thrusting, posture habits, and selfmutilation. Assessment of such habits should be identified
immediately to avoid long-term effect on the craniofacial
complex and dentition.
1379
strength and duration of the pacifier use. Anterior open

bite, maxillary construction are often seen with pacifier
use.
Epidemiology
The most prevalent type of malocclusion in the primary
dentition is anterior open bite secondary to pernicious
habits. In the mixed dentitions, crowding is most common
type of malocculsion. There is no difference in the incidence of malocclusions according to sex.
It is interesting to note that the primary dentition
usually has good occlusal relationship particularly in
breastfed children. Malocclusion may develop later when
the primary teeth are shed and permanent teeth erupt.
Classification
The most universally accepted classification was introduced by Edwarrd H. Angle in 1899. The basis of Angles
classification was his hypothesis that the first molar is
the key of occlusion.
Angle divided malocclusion into three broad classes.
Class I (neutroocclusion): Mesiobuccal cusp of the upper
first permanent molar occludes with the buccal groove of
the lower first permanent molar.
Class 2 (distoocclusion): Mesiobuccal cusp of the upper first
permanent molar occludes mesial to the buccal groove of
the mandibular first permanent molar.
Class 3 (mesioocclusion): Mesiobuccal cusp of the upper
first permanent molar occludes distal to the buccal groove
of lower first permanent molar.
Diagnosis
Spacing: Loss of contact between the teeth occurs when
arch length is more compared to the total width of the
teeth or when the teeth moves out of arch alignment.
Crowding: When arch length is less compared to the total
width of the teeth crowding occurs.
Overjet: This is the horizontal distance between the palatal
surface of upper incisors and the labial surface of lower
incisors when teeth are in occlusion.
Role of Pacifiers
Overbite: This is the vertical distance covered by the upper

incisors over the lower incisors when teeth are in occlusion.
Pacifiers can cause malocclusion of the anterior teeth and

also posterior cross bites, depending on the frequency,
Crossbite: Normally lower teeth are slightly overlapped

by the upper teeth but if the lower teeth are positioned
1380
outside the upper arch when teeth are in contact, then it is

crossbite which can be anterior or posterior.
Open bite: It can be anterior or posterior with space present
between the incisal /cuspal edges of the upper and lower
teeth during occlusion.
Lip incompetence: Lips do not contact each other during
rest position.
Rotation: Teeth are rotated.
Treatment
Treatment planning is based on:
i. Case history
ii. Clinical examination
iii. Plaster study casts
iv. Radiographsperiapical, bitewing and panoramic
v. Facial photographs.
Treatment should also include:
i. Correction of abnormal pressure habits if any
ii. Extraction of retained primary teeth
iii. Extraction of supernumerary teeth depending on the
merits of each patient.
The cause of malocclusion should be identified and
wherever possible should be eradicated before starting
the treatment. Otherwise the treatment can be incomplete
and moreover there can be relapse of the malocclusion.
This is particularly more relevant when there is a
pernicious habit existing. The treatment for malocclusion
is usually simple when treatment is given in time. Most
malocclusion responds well to removable appliances.
However, fixed appliance gives more effective result for
severe malocclusion.
INJURIES OF THE TEETH
Injuries of the teeth of children present unique problems
in diagnosis and treatment. Majority of fractures and
displacements result from simple accidents and involve a
little more than local oral tissues. Since time is such an
important consideration in the treatment of fractures or
displacements of teeth, every effort should be made to seek
treatment immediately. .
The teeth most frequently involved in a traumatic
episode are the maxillary central incisors. Boys are more
prone to sustain a fracture of a permanent anterior tooth
than girls, the ratio being approximately 2:1.
1. 1 to l years is susceptible age for injuries involving

primary dentition as the child is growing from total
dependence to voluntary movements.
2. Again when the child is 8 to 11 years, injuries involve
permanent dentition particularly when the anterior
teeth are protruding which can be called Injury-ProneProfile (IPP).
Treatment of coronal fractures: For enamel fracture adhesive
coverage can be given as an emergency line of treatment.
As a permanent measure, cosmetic grinding or resin
restoration can be done.
If enamel and dentin are involved: Immediate treatment
includes calcium hydroxide dressing and resin or ceramic
crown.
When enamel, dentin and pulp are involved: Pulp capping is
done using calcium hydroxide. Later pulpotomy or
pulpectomy is done depending on the health of the pulp
followed by root-canal filling.
Fractured Roots
Most root fractures occur in teeth with roots that are fully
formed and are embedded in well-matured alveolar bone.
Fracture may occur in the cervical third, middle third or
apical third of the root. The most difficult to treat are the
fractures that occur in the cervical third. Treatment
involves:
i. Reduction of the displaced tooth and apposition of
the fractured parts
ii. Immobilization
iii. Close observation for pathologic changes in the
injured tooth or surrounding apical region.
Splinting can be done to immobilize an injured tooth
to the adjacent tooth. The adjacent tooth should be healthy
and belong to permanent dentition.
Treatment of displaced teeth: Every effort should be made to
reduce the displacement and realign the teeth in their
former position. If the teeth are extruded they should be
manipulated gently back into their sockets and splinted
under local anesthesia.
Replantation: In cases of avulsion, the teeth should be
replanted in their sockets and immobilized as much as
possible. If the tooth is received immediately it may be
gently washed and immediately replanted and splinted.
Pediatric Dentistry
Management
While managing of injuries of the teeth of children the
doctor should remember the following distinct clinical
features which make them different from other injuries.
1. Psychological trauma is more than physical trauma,
since teeth form an important component in the
formation of face.
2. The important guideline in the management of injuries
is that every effort should be taken to retain even badly
broken teeth. Very good and sophisticated restorative
newer generation of materials are available which can
be used to achieve near total restoration of the injured
tooth.
SUMMARY
2.
3.
4.
5.
6.
7.
8.
9.
Prevention of dental diseases is more easier as oral cavity

is easily accessible.
The three major factors involved in etiopathogenesis
of dental diseases are:
1. Microorganisms
2. Diet
3. Patient susceptibility.
Of these, microorganisms and diet can easily be attended to, by maintaining proper oral hygiene and eating the
right type of food, which should be nourishing and
detergent.
Since the child is spending more time in eating than
the adult, correcting eating habits will be very rewarding
than depending on drugs alone. Further, food in addition
to its direct impact on the dental tissues also helps in the
overall nourishment of the child, including teeth.
10.
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19.
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33.1 Pediatric Priorities in the 21st Century: RK Agarwal, Piyush Gupta ................................................................................................ 1384
33.2 Pollution and Child Health in the 21st Century: NR Bhandari ......................................................................................................... 1389
33.3 Pediatric Environment Health-Hazards: Anupam Sachdeva, MKC Nair, Swati Y Bhave ................................................................ 1392
33.4 Research Methodology in Pediatric Practice: Sarada Suresh, P Ramachandran .......................................................................... 1410
33.5 Computers in Pediatric Medicine: Neeraj Jain, Vibha Jain ............................................................................................................... 1414
1384
33.1 Pediatric Priorities in the 21st Century

RK Agarwal, Piyush Gupta
Over the past few decades, children are fortunately being
recognized as people in their own right with their special
requirements. Quality survival of the human race
depends on provision of adept care to this vulnerable
population in their formative and developmental life
years. Health services for children should therefore be
aimed at improving the future quality of human
resources of the nation by enabling as many children as
possible to reach adulthood with their potential
uncompromised by illness, environmental hazards, or
unhealthy lifestyle.
Nearly 20% of global mortality occur in children
under 5 years of age; 98% occurring in developing
nations. Infectious and parasitic diseases remain the
major killers of children in developing nations. The 10
leading causes of death in children in developing
countries are perinatal conditions (23.1%), lower
respiratory tract infections (18.1%), diarrhea (15.2%),
malaria (10.7%), measles (5.4%), congenital abnormalities
(3.8%), HIV/AIDS (3.6%) pertussis (2.9%, tetanus (1.8%)
and protein energy malnutrition (1.3%). These causes
represented 8.8 million (86%) out of total 10.2 million
global child deaths in 2002.
INDICATORS OF CHILD HEALTH
Health of a community can be readily assessed by the
level of care, given to its children. Indicators are markers
of health status, service performance or resource
availability defined to enable the monitoring of
objectives, targets and service performance. Perinatal
mortality (PNMR), neonatal mortality rate (NMR), infant
mortality rate (IMR), post-neonatal mortality rate, and
under-5 mortality rate (U5MR) are few of the well-known
indicators of child health. Perinatal mortality and
neonatal mortality reflect the health and care of women
during pregnancy and perinatal period whereas infant
mortality has been described as one of the most sensitive
indices of health and quality of living of a population.
These are being described in detail elsewhere in this book.
The Achievements
Global child mortality declined from 147 in 1970 to about
80 per 1000 in 2002. The overall number of child deaths
in India has fallen from approximately 3.5 (1990) to 2.3
million (2002). Smallpox has been eradicated from the

face of the earth, and there is every hope to contain
poliomyelitis and measles in the near future. These
improvements in the health scenario are very significant
since they reduce the economic burden imposed by
unhealthy workers and sick or absentee school children.
The last decade has witnessed tremendous advance
in all fields of medicine. It is now possible to prevent the
progress of various diseases before they seriously damage
the health of an individual. Several genetic disorders and
inborn errors of metabolism are better understood, and
several of these can be detected by screening pregnant
mothers and newborn infant. Fetal malnutrition is
recognized as the programming event for several noncommunicable diseases in the adult life. Nutritional
interventions through diet and micronutrient administration in pregnancy may help in preventing a
staggeringly high incidence of these disorders. Coronary
artery disease, hypertension, cancers, diabetes, etc. can
be prevented by appropriate dietary manipulation and
adopting a healthy lifestyle in the early years in highrisk families. Childhood sexual abuse, juvenile
delinquency, and adolescent violence can be prevented
by promoting harmony between parents, children and
between siblings. Injuries can be prevented by greater
awareness in community and better designs of the
incriminating agent.
Oral Rehydration Therapy (ORT) in diarrhea has been
able to prevent more deaths occurring annually world
wide, than any other treatment modality. However,
about 8000 children still die each day from diarrheal
dehydration, a toll which the clinicians can and must
strive to reduce by using ORT.
Eighty percent of all the worlds children are
immunized against the six main vaccine preventable
diseases. Polio and neonatal tetanus are close to being
eradicated or eliminated.
The Challenges
Despite several improvements, health problems remain
gigantic. Population is increasing at an alarming rate and
has crossed one billion in India by the year 2001.
Malnutrition still affects 60 percent of children in South
Pediatric Priorities in the 21st Century 1385

Asia, which is believed to be the highest rate in any
region. Around the globe, more than 10 million children
die each year, half of them succumbing to diarrhea and
respiratory illnesses. Seven million adults die of
preventable illnesses each year. Tuberculosis is
responsible for 30 percent of these deaths. Acquired
Immuno Deficiency Syndrome (AIDS) is a new menace.
Already more then 20 million people have died from
AIDS, 3 million in 2003 alone. Infectious diseases remain
the worlds leading cause of premature death. More than
10 million deaths occurred due to infectious and parasitic
diseases in 2002 alone, comprising one fifth of overall
global mortality. At least 35 new infectious diseases have
emerged in the last 20 years, threatening the world health.
Four lakh women die every year due to causes related
to pregnancy and childbirth. Malaria is coming back with
a vengeance. Deaths due to tobacco related diseases and
cancer are increasing. About 1.1 billion people in the
developing world lack access to clean potable water and
more than two billion people are deprived of adequate
sewage and excreta disposal systems. Environmental
degradation has led to the increased prevalence of
respiratory diseases such as bronchial asthma and
bronchitis, both in children and adults.
Only a decade is left to achieve the millennium
development goals (MDG), which represent the
aspirations of the worlds population. There is also a need
to reposition the maternal and child health (MCH)
programs as MNCH programs, thus encompassing and
targeting the so important neonatal component within
the ambit of maternal and child health strategies.
Burden of Neonatal Deaths
Each year, about 4 million neonates die within first four
weeks of life; 98% in developing countries. Neonatal
deaths contribute to 40% of all childhood deaths and
more than 50% of infant mortality. Apart from this,
approximately 3.3 million babies are delivered as
stillbirths every year, contributing to perinatal mortality.
The largest number of neonatal deaths (1.4 million per
year) and stillbirth (1.3 million per year) occur in south
East Asia region. Major causes of neonatal deaths in this
region are low birth weight (< 2.5 kg), infections and
asphyxia. Other important causes of mortality are
congenital anomalies, neonatal tetanus and diarrhea.
India is home to 20 percent of global births and

highest number of neonatal deaths in the world. Each
year, 26 million infants are born in India. Of these, 1.2
million die during the neonatal period, before completing
the first four weeks of life. The neonatal mortality rate
(NMR) of 38 per 1000 live births in India translates into
at least two newborn deaths every minute in this vast
country. India, thus contributes nearly 30 percent to the
4 million global neonatal deaths. India also harbors the
highest number of low birth weight (LBW) infants born
each year worldwideeight million (40%) of the total of
20 million LBW babies.
Estimates indicate Indias Infant Mortality Rate (IMR)
at 57 per 1000 live births and under-5 child mortality rate
at 76 per 1000 live births. Hence nearly two-third of infant
deaths and about half of under-5 childhood deaths occur
in the neonatal period. Also nearly three fourths of
neonatal deaths, half of infant deaths, and one-third of
under-5 child deaths occur within the first seven days of
life.
Challenge of Malnutrition
Protein-energy malnutrition (PEM) is the most widely
prevalent form of malnutrition among children. Nutritional status of children is an indicator of nutritional
profile of the entire community. PEM effects every fourth
child world-wide. 146 million (25%) are underweight
while 168 million (30%) are stunted. Geographically, 68%
of PEM children live in Asia, 29% in Africa and 3% in
Latin America and the Caribbean. The prevalence of
stunting has fallen in developing countries from 47% in
1980 to 31% in 2005, although progress has been uneven
according to regions. Despite an overall decrease of
stunting in developing countries, child malnutrition still
remains a major public health problem in developing
countries (Fig. 33.1).
In India, there has been a significant decline in severe
protein energy malnutrition (classical kwashiorkor and
extreme forms of marasmus) over past few decades. From
1975-79 to 1988-90, the overall prevalence of marasmus
decreased from 1.3 to 0.6% and kwashiorkor from 0.4 to
0.1%. From 1988-90 to 1996-97, there was a further decline
in prevalence of marasmus from 0.6 to 0.1%, while that
of kwashiorkor stabilized at 0.1%. The proportion of
children under three years of age who were underweight
decreased from 35 percent in National Family Health
1386
Source: The state of the worlds children 2007. New York, The United Nations Childrens Fund.
Figure 33.1.1: Prevalence of malnutrition in under-five children
Survey-1 (NFHS-1) conducted in 1992-93 to 47 percent

in NFHS-2 (1998-99) and 46 percent in NFHS-3 (20042005). Similarly, prevalence of stunting decreased from
52% in NFHS-1 to 45% in NFHS-2 and 38% in NFHS-3.
Despite the apparent gain documented in some countries,
current magnitude of problem in South-Asian countries
far exceeds the international standards.
Micronutrient Deficiency: A Global Issue
Micronutrient malnutrition continues to affect over 2000
million people world wide. There are several reasons for
such deficiencies. The population may be deficient
because they have poor access to micronutrient rich food
due to poverty, defective crop growing pattern, deficient
soil quality, inappropriate climate or geographical
isolation. Traditional dietary fads may also hinder intake,
absorption or utilization of micronutrient rich foods.
Micronutrient deficiency is clinically evident only in
the later stage of the disease and therefore may result in
grave consequences. The end results of such deficiencies
include learning disability, impaired work capacity,
increased susceptibility to infections and greater risk of
dying. For the nation it means increased investment on
health services, inferior economic productivity and poor
gains on educational ventures.
It is important to put these disease burden estimates
in perspective. According to WHO there are 10.8 million
child deaths globally a year. According to WHO
estimates, over 2 million child deaths (around 20% of

total) are attributable to zinc, vitamin A, and iron
deficiencies. Malaria, for comparison causes less than one
million child deaths a year. While deficiencies in any of
the essential micronutrients can result in health problems,
there are a few that are vital to intelligence, immunity,
reproduction and work capacity. They cannot be
synthesized endogenously and have to be supplied in
diet; e.g. vitamin A, iron, iodine, zinc and folic acid.
Vitamin A deficiency (VAD) results in blinding
several hundred thousand children a year. It is now
recognized not only to harm the eyes but also to increase
childhood and maternal mortality. Globally, 21% of
children have vitamin A deficiency and suffer increased
rates of death from diarrhea, measles and malaria. It is
estimated that about 3 million children have some form
of xerophthalmia, and on the basis of blood levels another
250 million are subclinically deficient in vitamin A. About
800,000 deaths in children and women of reproductive
age are attributable to vitamin A deficiency which, along
with the direct effects on eye disease, account for 1.8% of
global DALYs (disability adjusted life years). This
appears to be lower than previous estimates, possibly
because of vitamin A supplementation or food fortification programs during the last decade.
Iron deficiency affects 200 million people in the world.
Out of these, 50 percent have IDA and the rest have low
body stores. An estimated 58 percent adolescent girls in
developing countries are anemic. According to NFHS-3

data (2004-2005), 79.2% of the children aged between 6
months and 3 years in India are anemic. About 800,000
child deaths per year are attributable to zinc deficiency,
globally.
Control of Communication Diseases
Control of communicable diseases in the community is
a major responsibility in primary health care.
Theoretically, a complete control over them does not
appear to be a farsighted goal because of the availability
of new antibiotics and chemotherapeutic agents for
treating most of these conditions effectively, as well as,
vaccines and immunizing agents for protecting an
individual from crippling or debilitating illnesses.
A major achievement in the control of communicable
diseases has been the eradication of smallpox, and a
marked reduction in the incidence of poliomyelitis,
plague, and leprosy. But, practically speaking, optimal
control may not be easyold diseases like tuberculosis
and malaria have come back with vengeance; new
diseases like SARS, bird flu and AIDS have already posed
formidable challenges. Pneumococcal and Hib infections
continue to haunt children in this part of the world.
Children still suffer from diphtheria and pertussis,
because of poor routine immunization coverage and
waning immunity. Various circumstances are responsible for the continuation of the spectrum of communicable diseases including poverty, ignorance, poor
nutrition, and economic and political turbulence. Apart
from causing millions of deaths, communicable diseases
reduce the quality of life, hinder education, reduce land
available for cultivation and human habitat, damage
productivity and divert available resources. This leads
to perpetuation of poverty. The struggle for control has
reached a critical stage. More than 10 million people
throughout the world are still dying every year of
communicable diseases. A multistrategic approach
including efforts of public, health managers, epidemiologists, health engineers, scientists, politicians and
the state is required.
Importance of Adolescence
Adolescents (i.e. those between the ages of 10 and 19
years) constitute more than 22% of the population of
South East Asia (SEA) Region. Within the adolescent age
group, the proportion of 10-14 years old is greater than
the 15-19 years group. This has important implications
for education, communication strategy, programming
and demography as the information, skills and services

needs of the two subgroups are different. The physical,
cognitive, and psychosocial changes are universal in
adolescence. However, the context in which they occur
is different from one adolescent to the other and greatly
influenced by culture, family, school, peers, chronic
conditions, etc. The period of adolescence is becoming
longer as the age of onset of puberty is dropping and
age at which persons become economically independent
is increasing. The swiftly changing global conditions are
placing a great strain on the young people, modifying
their behavior and relationships and exacerbating their
health problems.
The need for investment in adolescent health is amply
highlighted by the facts presented elsewhere in this book.
The health problems of adolescents and youth are very
different from those of younger children or older adults.
Yet, till recently, health care systems were not designed
to deal specifically with young people and their particular
needs. Young people were also not encouraged to
understand and deal with their own changes and with
the happenings in the world around them, or to
participate in programs promoting their development.
Prioritizing Child Health Services
Availability of child health services is a must at all levels
of health care. The organization of total care of children
involves the integration of many disciplines including
social services and education apart from the health sector.
Ideal child health services should be need based,
comprehensive and delivered at the doorstep as far as
possible. The nature of services to be provided should
be preventive, promotive, curative as well as rehabilitative. At the same time, constant efforts must be
simultaneously initiated to plan need based research
related to child health problems in the community and
utilize their outcome for upliftment of the existing
standards of care.
The aims of the services should be to save life, restore
health and rehabilitate children through timely provision
of care provided by competent health care providers.
Essential newborn care is the first step towards
establishing an effective chain to reduce infant mortality
and increase the National output. Promotion of breast
feeding in the community essentially protects children
from their two biggest enemies, i.e. infection and
malnutrition. Organisation, planning and execution of
immunization services is the cardinal preventive
1388
measure for control of many life threatening or disabling

communicable illnesses. Growth monitoring is considered to be the fundamental tool for early detection of
childhood morbidities.
Parents should be enlisted as partners in their
childrens health. They should understand ways of
promoting good health, recognizing illness and taking
appropriate action, wherever essential. Appropriate
counseling and guidance should be provided to them
regarding the problem, care, possible complications and
prognosis in acute life threatening illnesses, chronic
ailments, genetic and metabolic afflictions, infectious
diseases and nutrition related disorders.
Community child health services should seek to
promote good health both in the present and for the
future by means of surveillance, immunization, health
education and counseling for children and parents. Child
health clinics should form part of primary health care.
Earlier, they have been present in a scattered manner,
named as well baby clinics, high risk clinics under-5
clinic, etc. Over the years their scope has broadened to
cover all aspects of pediatric and adolescent health.
Principle activities in a child health clinic should
include:
i. Surveillance of growth and development, physical, mental, social and emotional health,
ii. Recognition of medical conditions, acute or
chronic with referral for investigation or treatment,
iii. Advice to parents on any health problem,
iv. Immunization and
v. Health education, both formal and informal.
Most importantly, child health services should be
provided in a cordial, compassionate and caring manner.
Those providing these services must be aware of the
childrens right and undertake activities needed to
protect them in a genuine manner.
Child Health in India
The policy makers have recognized that most of the total
prediatric care can be given through social and
preventive measures alone, given the political will and
individual and societal commitment. The constitution of
India has time and again reiterated the importance of
improving child health. Article 39 stressed that children
should be given opportunities and facilities to develop

in a healthy manner and their tender age should not be
abused. Further, article 24 prohibits child labor and article
45 stress upon the state to provide free and compulsory
education for all children until they complete the age of
14 years.
In 1974, India reaffirmed its constitutional obligations
to children in the National Policy for Children. The
policy states that It shall be the policy of the state to provide
adequate services to children, both before and after birth and
through period of growth, to ensure their full physical, mental
and social development. The state shall progressively increase
the scope of such services so that, within a reasonable time, all
children in the country enjoy optimum conditions for their
balanced growth.
In 1990, the Government of India endorsed all the 27
survival and development goals for the year 2000, agreed
on at the world summit for children. The summit also
drew attention to four sets of rights of children, namely:
right to survival, to protection, to development and to
participation. In 1992, India ratified the convention on the
rights of the child and adopted the National Plan of
Action: A commitment to the child. This plan has now
been translated into State programs of Action for children
and further into district plans. The plan is guided by the
principle of First call for children, i.e. the essential needs
of children should be given highest priority in the
allocation of resources at all times. Considering the
provisions made in the constitution of India, National
policy of Children, 1974, the United Nations Convention
on rights of the children, 1989, and in accordance to the
pledge in National Agenda of Governance of Indian
government announced draft National Policy and
Charter for Children, 2001. This policy intends to remove
the difficulties, in our society, related to all issues affecting
childrens rights. In pursuance of the commitment made
at the World Summit, the Department of Women and
Child Development under the Ministry of Human
Resource Development has formulated a National Plan
of Action for Children in 2005. The National Plan of
Action represents the needs and aspirations of 300 million
children of India in the spheres of health, nutrition,
education, water, sanitation, environment, and related
aspects of social support. The plan gives special
consideration to children in difficult circumstances.
33.2 Pollution and Child Health in the

21st Century
NR Bhandari
Children today face an array of exposure to potentially
toxic environmental hazards. Hazardous substances such
as lead, solvents, asbestos, radon, pesticides, and air
pollutants have found their way into the most sacrosanct
of places, the homes, schools, and playgrounds of our
children. Exposure to these substances can have a
significant impact on children's health and wellbeing.
Environmental degradation, increasing industrialization, more vehicles, discovery of new chemicals, gas
leakages, ozone depletion, global warming, cutting of
forests are leading causes affecting ecological balance and
increasing environmental hazard. A growing child is
more likely to be affected by these hazards. At
community level primary environmental care (PEC)
approach is necessary so that proper training and
education can be imparted. Children are the sensitive
indicator of wellbeing of a community.
WHO has estimated that 500,000 people are poisoned
by pesticides every year in the Third World, of these 5000
are fatal averaging to 13 deaths per day. In USA alone,
45000 cases of pesticides poisoning are registered every
year, of which 200 results in death. The WHO statistics
are recorded only from public sources like hospital
registration, etc. They do not include unreported cases.
The poisonous effect depends on the nature of
chemical, particle size, their concentration, duration of
exposure and mode of entry. As mentioned inhalation is
the most important route of entry, because most of these
toxic substances, become air borne in the form of dusts,
fumes, gases, vapors, etc. Anything taken into the body
via mouth is absorbed by the portal circulation to the
liver which has a detoxifying action. Inhalation or skin
absorption deprives the body of this means of protection.
TYPES OF ENVIRONMENTAL POLLUTION
Environmental pollution can be caused by:
Air
Chemical and gaseous substances
Water
Soil
Food contamination
Household hazards
Radiation
Noise.
Air Pollution
Among the various forms of environmental pollution,
air pollution is the most crucial, from the public health
point of view. This is because, on an average, an
individual breathes 22,000 times a day, inhaling 16 kg of
air. Besides, unlike polluted water, polluted air is difficult
and expensive to purify and apart from physical ill
effects, can have undesirable aesthetic and psychological
effects.
Types of Air Pollutants
On the basis of physical state, there are two major groups
of pollutants.
1. Gases, which freely mingle with air without setting
down
2. Particulates, which include finely divided solids, as
well as liquids.
Particulate Air Pollutants
DustDust particles may contain a variety of inorganics,
like lead and beryllium besides organics, like hydrocarbons.
SmokeIt is composed of tiny particles of carbon, ash,
oil, etc. It is invariably formed during incomplete
combustion of a fuel which may be due to insufficient
supply of air, or faulty method of burning. The major
sources of smoke in the order of decreasing smoke
emissions are railroads, locomotives, domestic grates,
industrial power plants, and burners, trash open fires,
refuse incinerators (domestic and municipal), diesel
engines and automobile gasoline engines.
SmogIt is the term coined to represent combinations of
smoke and fog.
FumesThese are made up of solid particles formed by
condensation of vapors during sublimation, distillation,
calcination or other chemical and metallurgical processes.
1390
AerosolsSuspensions of particulate matter in air are

known as aerosols.
Industrial stack emissionsIn addition to sulfur dioxide,
oxides of nitrogen, and suspended particulate matter,
certain specific pollutants are discharged into the
atmosphere by various industries. These include lead,
cadmium, mercury, beryllium, mercaptans, hydrogen
sulfide, hydrogen, fluoride, chlorine, asbestos and many
other substances.
Chemical and Gaseous Poisoning
In 21st century, they will pose major health hazard
problems, if precautions, safety measures and proper
control are not exercised. In 1984, such a man-made
tragedy took place, at Bhopal, when 40 tonnes of
poisonous gas, methyl isocynate (MIC) leaked out from
a pesticide factory polluting the atmosphere, at midnight
killing over 2000 people within 24 hours and crippling
thousands of survivors. In this gas tragedy at Bhopal,
the poisonous effect of gas resulted in asphyxia, breathing
difficulty and cyanosis.
TABLE 33.2.1: Pollution and diseases

Pollutant
1. Enteric bacteria
and protozoa
Source
Disease
Human excreta
improperly
disposed or
used as fertilizer
Cholera, typhoid,
paratyphoid, salmonellosis, shigellosis (bacillary
dysentery) amebiasis (protozoan
infection)
2. Eggs and larvae Human excreta

of parasitic
improperly
worms
disposed or
used as fertilizer
Ascaris lumbrico-ides (roundworm)

Trichuris trichiura
(whipworm)
Ancylostoma duodenale
(hookworm)
3. Leptospira
Urine and excreta of infected

animals (cattle,
pigs, rodents,
horses, etc.)
Leptospirosis (a
type of jaundice
that can be fatal)
4. Bacillus anthracis (spores)
Livestock and
Anthrax
animal products
hide, hair, wool)
5. Tetanus bacillus
(Clostridium
tetani)
Soil previously Tetanus, an acute

contaminated
disease that can
with excreta of be fatal
infected animals
especially horses
Water Pollution
The principal sources of water pollution are:
i. Discharge of domestic, agricultural, animal and
industrial wastes and irrigation water
ii. Run-off from land, of pesticides, fertilizers,
sewage, etc.
iii. Treatment of the water itself with pesticides for
the control of weeds, molluscs, and insects.
Biological Pollution
Biological pollution is the result of contamination of
water by pathogenic bacteria, viruses, fungi, algae,
protozoa and helminthic parasites.
Soil Pollution
Land is a major dumping ground for waste of all kinds.
With the rise in numbers and the growing urbanization
of Indian population, there is less land but more refuse
to dump and it is natural therefore that pollution of land
or soil is on the increase.
Sources of Soil Pollution (Table 33.2.1)
1. Improperly disposed human and animal excreta,
solid and liquid wastes
2. Domestic refuse and solids from treated sewage and

industrial wastes dumped on land
3. Waste materials from mineral and coal mining and
metal smelting dumped on land
4. Chemicals, such as fertilizers, pesticides and growth
regulators applied to plants and soil,
5. Radioactive materials accumulating on land due to
fall-out from nuclear explosions, and radioactive
wastes discharged from industrial and research
centers and hospitals.
Food Contamination
Food is frequently subjected to chemical and biological
contamination in a number of ways and this has a direct,
extensive and important bearing on public health. There
is clear evidence that many human diseases and
sufferings are due to the consumption of infected and
contaminated food.

Illnesses transmitted by contaminated food are
classified as food-borne infections and intoxications.
Food-borne infections are usually gastrointestinal
disturbances caused by living organisms, while foodborne intoxications are diseases caused by chemical
poisons in foods.
The poisons may be microbial or nonmicrobial in
origin. Some poisons are even naturally present in foods.
Deliberate adulteration of food stuffs and the use of an
ever increasing number of chemicals in agriculture, dairy
farming, storage and processing of foods are currently
introducing a number of highly toxic substances into
present day foods.
6. Ice used in the preparation and serving of food must

always be made from pure potable water and handled
hygienically.
Foods Commonly Involved in Food Infections
PREVENTION AND CONTROL OF

ENVIRONMENTAL POLLUTION
1. Milk and milk products are potentially dangerous

vehicles of infection. All milk must be pasteurized,
sterilized or boiled.
2. Meat, particularly processed meat, has been a
frequent source of food poisoning in developed
countries, whereas freshly cooked meat is safe.
3. Shellfish are particularly prone to contamination by
sewage and chemical poisons in water beds where
they grow.
4. Fruits and vegetables Wherever the plants are
irrigated or sprayed with sewage effluents, the
vegetables should not be eaten raw, even after
washing. In fact, eating raw vegetables is known to
have caused mass infections such as amebic dysentery
and ascariasis. The vegetables and fruits may have
to be washed as well as peeled to remove pesticide
residues present on the skin.
5. Other foodscanned foods, frozen foods, baked
foods, prepared meats, prepared sandwiches, salads,
custards, cream, icecream, etc. present particular
hazards against which adequate safeguards must be
taken at all stages of preparation, distribution, display
and sale.
Household Hazards
Household hazards play important role in producing
injuries, disabilities and even death to children. Adequate
care, like keeping medicine beyond the reach of children,
tight security for kitchen gas connection, keeping away
sharp edge articles, etc. should be understood. Fightings
and quarrels between husband and wife, excessive use
of alcohol by father, and family disruption can produce
psychological trauma to the child.
The most important measures to be undertaken in regard

to pollution control are the following.
1. Control population explosion.
2. Formulation of minimum standards for clean air,
clean water and wholesome foods.
3. Frequent pollution monitoring, particularly in urban
and industrial areas.
4. Educating the public on the causes and effects of
various pollutants and how best these can be
minimized in daily living.
5. Intelligent planning and building of factories away
from living areas.
6. Sites for factories and heights of factory stacks to be
carefully planned to prevent health hazards to the
neighboring population.
7. Enforcement of rigorous controls on emissions from
industrial and power plants and transport vehicles.
8. Reduction of smoke and other particulate emissions
from combustion of fuels both in the home and in
industry.
9. Adequate vector control, control of insects, rats, etc.
10. Prevention of forest and wild life.
11. Health education and improvement of literacy level.
1392
33.3 Pediatric Environment Health-Hazards

Anupam Sachdeva, MKC Nair, Swati Y Bhave
As the human population increases, its demand on earth
also increases. The demand for food, potable water, clean
air, energy, and manufacturing goods: the need for liquid
and solid disposal, and the requirement for habitable land
are all expanding. With this expansion, increasing
number of pollutants are released into the environment,
and more and more people come into contact with
polluted environments.
Interaction with polluted environments can have an
adverse impact on the health of humans and other living
creatures. This impact is first felt among the most
vulnerable members of a population. Children are
particularly vulnerable to many environmental threats,
including a contaminated and unsafe physical environment. This heightened susceptibility derives primarily
from the unique biological features that characterize the
various stages of development from conception to
adolescence. Not only this, fetuses, infants, children and
adolescents are also special in the way a variety of social
and psychosocial factors influence their exposure as well
as the consequent health effects.
VULNERABILITY BASED ON AGE AND
DEVELOPMENTAL STAGE
A childs environment may be thought of having three
components:
Physical
Biological
Social
Physical environment is anything that comes in
contact with the body. Further, a large environment may
be divided into smaller units called microenvironments. Microenvironments may differ enormously
between adults and children. For example, the environment of the infant lying on the floor who is going to be
more exposed to any chemicals and dust lying on the
floor, therefore this environment would be different from
that of a standing adult. The biological environment
consists of the internal physiological interactions of the
body with the chemicals it contacts. Exposures differ with
developmental stage.
DEVELOPMENTAL STAGE: PRECONCEPTION

Preconceptional parental exposure of toxicants can have
a major impact on pregnancy outcome. This kind of
exposure threatens the fetus in two ways: toxicants can
directly affect the maternal and paternal reproductive
organs, or they can be stored in mothers body and later
mobilized during pregnancy to affect the developing
fetus and the offspring. For instance ionizing radiation
may damage mothers reproductive organs and the
preconceptional exposure of polychlorinated biphenyls
(PCBs) might affect the outcome of fetus.
Paternal exposure to toxicants might affect the
outcome of the offspring as well. It is known that short
life span of sperm limits the period of their vulnerability
to toxicants, while the rapid differentiation of sperm
increases their susceptibility to harm from exposure.
EMBRYONIC AND FETAL PERIOD
Embryos tissue is particularly susceptible to damage
from environmental toxicants due to rapid cell growth.
With increase in number of cell divisions that occur,
opportunities for toxicants to cause cells to make
inaccurate copies of DNA occur. This can lead to
mutations and cancers.
The placenta in some cases acts as a barrier and in
other cases allows toxicants to pass through to the fetus.
The placenta does not block the compounds with small
molecular weight from reaching the fetus such as: carbon
monoxide, lipophilic compounds, such as polycyclic
aromatic hydrocarbons or ethanol; and compounds using
active mechanisms. For example, lead displaces calcium,
iron, or other nutrient metals and is transported in their
place.
Many toxicants reach fetus directly such as ionizing
radiation, electromagnetic fields, heat and noise.
Maternal smoking or exposure to cigaret smoke has an
impact on the fetus. Active and passive maternal smoking
may lead to following adverse outcomes:
Increased rates of spontaneous abortion.
Intrauterine growth retardation.
Increased neonatal morbidity and mortality.

Sudden infant death syndrome.
Cleft lip and palate.
Poor cognitive and behavior development.
NEONATE
In the newborn period, organs and tissues including the
nervous system, lung, blood, somatic cells, and
epithelium continue to undergo rapid growth or have
rapid turnover; thus increasing their vulnerability to
toxicants.
A highly permeable skin and gastrointestinal tract
characterize the neonatal period. Toxicants are ingested
mainly through packaged formula or breast milk, or
absorbed through dermal contact. Gastric pH is high in
the newborn period, which makes the GI tract highly
permeable. Breast milk contains several environmental
pollutants, including PCBs or lead in breast milk. Even
low-dose lead may be retained in the brain of the
newborn. Formula fed infant consumes significant
amounts of water. The average infant consumes 180 ml/
kg/day of formula. For the average male adult this is
equivalent to consuming 35 cans of cola a day.
Particular attention must be paid to substances that
come into contact with the babys skin, because skin is
highly permeable during the newborn period. For the
surface area of skin covered with a chemical, a newborn
baby may absorb up to three times the amount absorbed
by an adult.
THE FIRST THREE YEARS
Children in this developmental stage have higher rates
of respiration and calorie consumption per kilogram of
body weight than adults because of their higher
metabolic rate. Various forms of exposure include:
1. Childrens hand to mouth behavior predisposes them
to various toxicants. They attempt to swallow
whatever goes into their mouth. Lead poisoning
occurs in children who are mobile and explore orally.
Other sources of intoxicants include the yard around
a home, which may be contaminated with pesticides
and herbicides.
2. Diet is also a source of exposure. Children not only
maintain homeostasis but also grow. Legal levels of
food additives are calculated on the basis of a lifetime
exposure for an adult. The infants higher rate of
calorie consumption per kilogram means that any
food additive will constitute a higher dose for an
infant. By virtue of their processing, infant foods tend

to have higher concentrations of additives and
residues such as pesticides. There is also a quantitative difference in the infant and toddlers diet. These
factors affect the relative ingestion of toxicants in the
infant.
3. Breathing zone of an adult is 4 to 6 feet above the
floor, but an infant and toddlers breathing space is
closer to the floor. With lower breathing zone,
chemicals heavier than air, such as mercury, may
concentrate. Infants are also exposed to volatile
organic chemicals and formaldehyde from new
synthetic carpets, and varnish done on wooden floors.
Children have a higher metabolic rate. They consume
more oxygen than adults and produce more carbon
dioxide per pound of body weight, which means
higher minute ventilation. Thus, childrens exposure
to air pollutants may be greater than adults.
PRE-SCHOOL AND SCHOOL-AGED CHILD
Children explore new environments and are consequently exposed to new sources of contamination.
The school may itself be a source of contamination.
Old buildings may contain friable asbestos. Schools may
be situated near old industrial sites with benzene and
arsenic deposits, or near highways exposing children to
auto emissions and lead. Exposure at school may include
poor indoor air quality, high allergen burden and
infectious organisms. Children may also use toxic artsand-craft products that could cause health problems if
ingested or used improperly. Play areas may also contain
environmental toxicants such as preservatives used in
wooden playgrounds, and sand may contain asbestos.
ADOLESCENCE
Maturation of a number of organs and systems occur
during this period. Target tissues may differ in
adolescents as a result of the changes brought about by
puberty. Growing, dividing, differentiating tissues such
as viscera, muscles and skeleton are most sensitive to
changes. There is also development and differentiation
of reproductive organs. The typical adolescent exploratory and risk-taking behavior increases exposure.
Voluntary drug consumption increases, including
smoking, drinking, substance abuse, and the use of over
the counter drugs.
Adolescents may be employed in jobs that expose
them to contaminants as well as risks of accidents.
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Childrens special susceptibility to environmental

threats is not confined to the biology of growth and
development, but also social, economical, and psychosocial factors. The interaction of these and other factors
such as educational background, place of residence,
gender, ethnicity and knowledge, attitudes and behavior
of parents, teachers and peers determines multiple
exposures and risks, and consequent multiple health
effects.
ENVIRONMENTAL HEALTH AND
HISTORY TAKING
Environmental health comprises those aspects of human
health, including quality of life, that are determined by
physical, chemical, biological, social and psychosocial
processes in the environment. Its also the practice of
assessing, correcting, controlling and preventing those
factors in the environment that can potentially affect
adversely the health of present and future generations.
The practice of environmental health is concerned with
the protection of community.
Questions about a childs environment are basic to a
comprehensive pediatric health history.
Some components of environmental history include:
1. An enquiry into present and past home locations.
Is home located near a polluted river, lake or
stream, industrial area, highway, dumpsite, farm,
etc to assess proximity to sources of air pollution
and other ambient hazards.
2. Ask about age of the house and condition of the
home to assess lead exposure.
3. Whether recent renovation or remodeling has been
done as lead dust hazards might be created.
4. Are the windowsills peeling? Do window wells
contain solid material? If yes, it might cause lead
exposure.
5. Is there a basement in the house? Is their sleeping
and playing areas in that basement? Theres a risk
of Radon and Asbestos exposure.
6. Does the house have gas stove or open fireplace?
Does smoke enter the room when used? Is there a
chimney? Poorly vented stoves can result in high
carbon monoxide levels.
7. Ask about household building materials as
formaldehyde-containing materials may cause
irritation and respiratory symptoms.
8. A detailed history of home cleaning agents and
other household products is essential as some
products may contain toxic, allergenic, or irritant
materials.
9. Do you have water damage or visible mold in any

part of the home? Indoor air pollution causes
asthma.
10. Enquire about the presence of pets, pests, and dust
in the house. Are there pillows and stuffed toys that
can be reservoir for household dust mites? Are there
carpets; too many wall hangings, which serve as a
reservoir for allergens?
11. Ask about indoor/outdoor pesticide usage.
12. Where do infants spend maximum timein kitchen
or on floors?
13. Water supply. Do you use tap water, well water or
hand-pump? Is there an overhead tank? Well water
contains nitrates, pesticides and water pollutants.
14. Do you wash fresh fruits and vegetables? What was
the source of food during the time of exposure? Is
lead glazed pottery used in the kitchen?
15. Does anyone smoke at home? How many people
are there in the house? Is there any overcrowding?
Is smoking allowed to visitors at home or in car?
16. Where does the patient spend time and what is the
air quality in those locations?
17. Where do parents work? Do you come in contact
with metals, dust, chemicals, etc? Does the child
stay in a factory crche? Lead poisoning may occur
in children of lead storage battery workers, asbestos
related lung diseases in shipyard workers.
18. Do teenagers work?
19. Is child involved in hobbies such as painting,
sculpturing, woodwork or gardening?
20. Does the family take any folk remedies or dietary
supplements or ayurvedic medicines, which may
have a lot of heavy metals?
21. Ask about history of recent travel/ fishing/
swimming in polluted beaches, lakes, rivers or
streams.
Environmental causes of illness may not always be
apparent. Since most environmental or occupational
illnesses present as common medical problems or have
nonspecific symptoms, the diagnosis may be missed
unless a history of exposure is obtained.
The following questions, in addition, may provide
information about whether an illness is related to the
environment.
1. Do symptoms subside or worsen in a particular
location?
2. Do symptoms worsen or subside on weekends? Are
symptoms present at any particular time of the day?
3. Do symptoms worsen during hobby classes, such as
working with arts and crafts?

4. Do children spend time with other children experiencing similar problems? They may be having a
common exposure.
ENVIRONMENTAL PRECIPITANTS OF ASTHMA
Lung being the organ with largest surface area for gas
exchange takes the brunt of the air pollution. While
genetic factors are considered important and may
predispose children to develop asthma, convincing
evidence demonstrates the important role of environmental factors in the manifestation of asthma. Environmental risk factors produce airway inflammation, airway
obstruction and airway hyper-responsiveness.
According to a study done at Bangalore, in 1979 the
incidence of asthma was 9 percent compared to 27.5
percent in 1999. The persistent severe asthma increased
from 4 to 6.5 percent. These data were correlated with
urbanization, change in demography and air pollution.
It may occur either due to indoor or outdoor air
pollutants. At this point of time its important to define
the term criteria pollutants. The criteria pollutants are
those for which theres an adequate scientific database
with regard to epidemiologic studies, controlled human
exposure studies and toxicological studies to stipulate
there is a health effect for which air quality control is
needed. There are six of these; ozone, oxides of nitrogen,
sulfur oxides, particulate matter, carbon dioxide, and
lead. Major indoor triggers of asthma include environmental tobacco smoke (ETS), carbon monoxide, mold
spores, allergens such as dust mite, animal allergens, and
cockroaches, certain odors such as those of volatile
organic compounds and mercury vapors.
INDOOR IRRITANTS
Environmental Tobacco Smoke
Environmental tobacco smoke (or second hand smoke)
is exhaled smoke or smoke released from smoldering
ends of cigarets, cigars, and pipes. Exposure to ETS may
occur at home, school, child-care settings, relatives
homes, or through motor vehicles.
Infants whose mothers smoke are 38 percent more
likely to be hospitalized during the first year of life for
pneumonia compared to those whose parents do not
smoke. Children whose parents smoke are 60 percent
more likely to develop middle ear effusions compared
to non-smokers children. Children with asthma whose
parents smoke are prone to frequent exacerbations and
more severe symptoms. The greatest effect seems to be
related to maternal smoking during pregnancy and/or

early infancy, perhaps due to inflammatory stimuli on
lung parenchyma during a period of rapid lung
development and prolonged close exposure to the
mother.
The half-life of nicotine is about 2 hours, while
cotinine has a half-life of 20 hours. Hence if the child is
removed from the smoking environment, he or she will
eliminate the nicotine and nicotine byproducts quickly.
Thus most important prevention is smoking cessation.
Carbon Monoxide
Carbon monoxide is a colorless, odorless, tasteless toxic
gas. Common sources of exposure are gas furnaces,
heaters, ovens, gas clothes dryers, and other powered
appliances, wood and coal heating, fireplaces and
charcoal grills. The affinity of carbon monoxide for
hemoglobin is 240-fold higher than that of oxygen,
causing leftward shift of oxyhemoglobin dissociation
curve. Resultant tissue hypoxia affects organs with high
metabolic rate and high oxygen demand.
Toxicity may produce symptoms like headache,
dizziness, fatigue, weakness, drowsiness, nausea,
vomiting, and loss of consciousness, skin pallor, dyspnea,
palpitations, neuroirritability, and confusion.
Mold Spores
Molds are prominent in climates with increased ambient
humidity, although some can grow in relatively dry
areas. For instance, Alternaria, Aspergillus, Penicillium, and
Cladosporium species are common indoor molds, which
grow in areas of high humidity (e.g. Basements,
crawlspaces, bathrooms, ground floors, bathrooms and
areas with standing water such as air-conditioner
condensers). Carpets, ceilings, and paneled hollow walls
are also common reservoirs.
Molds may cause allergic reactions and toxic effects.
Allergic effects include persistent upper respiratory tract
symptoms such as sneezing, rhinitis, eye irritation, and
lower respiratory tract symptoms such as coughing and
wheezing. Toxic effects such as pulmonary hemorrhage
may be caused by inhalation of mycotoxins, lipid soluble
toxins readily absorbed by the airways.
To prevent the growth of molds, clean up water and
remove all water-damaged items (including carpets)
within 24 hours of a flood or leak. If some molds are
already present then the affected area needs to be washed
with a solution of 1 part bleach per 10 parts of water.
Protective gloves should be worn during clean up.
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Animal Allergens
Animal allergens are acidic glycoproteins with molecular
weights of 15,000 to 30,000 kD. They are in highest
concentrations on the skin of animal and in secretions,
including saliva, sebaceous glands and urine. The
allergen containing secretions dry on fur, bedding and
other household objects and become air-borne, easily
remaining in the air because they are so lightweight.
Therefore, animal allergens may be found in homes that
have never had pets. These allergens settle in distal
airways. Clinical manifestations range from mild
urticaria to rhinoconjunctivitis to life-threatening
conditions such as bronchospasm and anaphylaxis.
The severity of allergic reactions to cats is stronger
than those to other pets. The major irritants such as Fel
d1, is present in high concentrations in skin, with saliva,
sebaceous glands, and urine. Fel d1 remains air-borne
for prolonged periods and adheres to clothing. These
characteristics allow antigen to be transmitted between
environments. Once the cat is removed the allergen may
persist for several months.
Cockroaches may also cause hypersensitivity.
Infestations with cockroaches are more common in
warm, moist environments with readily accessible food
sources.
House-Dust Mites
House-Dust mites might play an important role in
inducing asthmatic attacks and triggering asthma
exacerbations in sensitized children. Mite antigen is
commonly found where human dander is found. It grows
at moderate temperatures with high humidity. Mites
proliferate on mattress surfaces, carpeting, and upholstered furniture, each of which also contains large amount
of food dander, its primary food source. A gram of dust
may contain thousand mites and 2.5 lac fecal pellets.
Exposure occurs either by proximity of the nasopharyngeal mucosa to mite reservoirs (esp. mattresses,
pillows, carpets, bed-linens, clothes, and soft toys) or to
air-borne antigen during house cleaning activities.
Indoor Biomass Combustion
Smoke from household fuel burning is a complex mixture
of many potentially toxic compounds. The association
of indoor use of biomass fuels with acute lower
respiratory tract infections is predominantly found in
developing countries. Particulate matter (PM) is released
by the combustion of biomass and from diesel exhaust.
Particulate matter comprises solid and liquid particles,

particles of biological origin, fungal spores, pollens,
endotoxins and the particles are of varying size.
Particulate matter of 10 microns or less aerodynamic
diameter is significant.
PM induces airway inflammation in normal subjects.
It enhances local allergic responses after nasal instillation.
Several studies have shown increased respiratory
symptoms in children living near roadways with
increased traffic density.
Mercury Vapors
Elemental mercury is used in thermometers, sphygmomanometers, and thermostat switches. Dental
amalgams, fluorescent bulbs, and button batteries also
contain mercury. Indiscriminate disposal of these items,
when buried in landfills or burnt in incinerators are a
major source of contamination. When inhaled, elemental
mercury easily passes from pulmonary alveolar
membranes to blood, where it distributes primarily to
red blood cells and CNS.
Early exposure causes insomnia, forgetfulness, and
loss of appetite. Continuous exposure leads to progressive tremor and erethism, a syndrome characterized by
emotional lability, red palms, and memory impairment.
Acrodynia is a hypersensitivity response to mercury,
initially reported in children exposed to calomel teething
powder.
Other Indoor Irritants
Wood fireplaces and gas space heaters are major
environmental pollutants. Nitrogen dioxide is generated
by improperly or unvented gas-fueled cooking stoves or
space heaters.
Wood smoke is a complex mixture of a number of
pollutants including organic compounds and nitrogen
dioxide.
Indoor air concentrations of formaldehyde are
produced from glue on carpets, and furniture, chipboard.
Its inhaled and absorbed in the upper airways. It may
cause irritation to the upper airways and might lead to
symptoms pertaining to eyes, nose and throat.
Numerous strong-smelling agents may induce acute
asthma episodes in susceptible individuals. Perfumes,
paint, cosmetic sprays, pesticides, and scented cleaning
solutions have been reported to precipitate an acute
asthmatic attack.

OUTDOOR AIR POLLUTANTS
NITRATES AND NITRITES IN WATER
Ozone
Nitrogen is an essential nutrient absorbed and incorporated by plants from nitrate or ammonium in soil.
Diffuse nitrate contamination of surface and ground
water has resulted from modern agricultural practices.
Nitrate levels in drinking water have been increasing.
Intensive livestock operations that produce large
amounts of animal waste, substandard human septic
systems, and municipal waste streams contribute to
nitrate contamination of ground water. Shallow and
poorly constructed wells in rural areas are at greatest
risk of nitrate contamination.
Nitrate poisoning is the preventable cause of
methemoglobinemia in infants. Young infants fed
formula milk reconstituted with contaminated water are
at greatest risk. The current US Environment Protection
Agency (EPA) drinking water standard limits nitrate
concentrations to 10 ppm and nitrite to 1 ppm.
Its an unstable gas formed by the photochemical reactions

of hydrocarbons and nitrogen oxides released by
vehicular emissions. Ozone is an oxidant compound that
directly causes injury to cells. It generates free radicals,
causing further damage. Macromolecules can be
damaged leading to lipid peroxidation. Subsequent to
this there is a direct inflammatory response. White blood
cells generate free radicals and oxidant compounds,
causing injury to cells.
Increased respiratory symptoms and decreases in
lung function have been documented in children exposed
to ozone. Studies have shown that asthmatics have an
enhanced inflammatory response to ozone. There is also
an enhanced asthmatic response to allergens after ozone
exposure. The exact mechanism of action is unknown.
Decreased flow rates at mid and low lung volumes
have been found in college students in association with
lifetime exposure to ozone.
Sulfur Dioxide
Sulfur dioxide can induce acute bronchospasm in
asthmatic children at relatively low concentrations and
short exposure durations. Several studies have shown
association between SO2 exposure and decreased forced
vital capacity.
WATER POLLUTANTS
Fresh water is either classified as groundwater, such as
underground aquifers, or surface water, such as lakes
and rivers, but less than half of the fresh water in the
world is accessible. Water pollution results from sources
known as either point or non-point. Point sources of air
pollution include municipal wastewater treatment plant
discharges and industrial wastewater discharges into
surface waters. Non-point sources of pollution include
agricultural runoff, urban runoff, soil contamination and
atmospheric deposition that contaminate surface waters
directly and seep into underground aquifers to contaminate groundwater as well. Water pollutants may be
classified as biological agents, chemicals, or radionuclides.
Water and sediments in water are the ultimate sinks
for most chemicals produced by humans.
Routes of Exposure
Drinking water is the main source of nitrate in infants.
Vegetables are another source of nitrate, contributing
more than 70 percent of total dietary nitrate in adults
and older children.
Transdermal absorption is higher in infants than in
adults. Methemoglobinemia may result from such subtle
exposures as diapers marked with aniline-containing
laundry inks or rinsed in oxidizing agents, and leather
colored with aniline dyes. Though rare but use of topical
anesthetic agents and silver nitrate burn creams can cause
methemoglobinemia in children.
Clinical Effects
Nitrate is rapidly absorbed from the proximal small
intestine. Approximately 70 percent of the ingested
nitrate is found in urine within 24 hours. Nitrates do not
cause methemoglobinemia but can be converted to
nitrites by the gut flora. Nitrites, in turn, convert ferrous
(Fe+2) in hemoglobin to ferric iron resulting in methemoglobinemia.
Infants younger than 4 months are at the greatest risk
for methemoglobinemia. The gastric pH of infants is
higher than that in older children and adults with
resultant proliferation of intestinal bacteria that reduce
ingested nitrates to more reactive nitrites. Fetal
1398
hemoglobin, is the predominant form in infants up to 3

months, is more readily oxidized to methemoglobin by
nitrite than is adult hemoglobin. The conversion of
methemoglobin back to hemoglobin is difficult in infants.
The mucous membranes of infants with methemoglobinemia-induced cyanosis tend to have a brownish
cast. This discoloration increases with the level of
methemoglobin as does irritability, tachypnea, altered
mental status, and complaints of headache in older
children. The oxidative stress of nitrates may result in
oxidation of hemoglobin protein, causing Heinz body
hemolytic anemia. Inhalation of volatile nitrites may also
cause T wave inversions, ST segment changes, and
arrhythmias may be noted on an electrocardiogram.
Initial screening of methemoglobinemia includes placing
a drop of blood on white filter paper. Blood with level
hemoglobin more than 15 percent dries a deep brown or
slate gray.
In general, levels of hemoglobin less than 20 percent
are well tolerated, those greater than 50 percent are
serious and more than 70 percent are fatal.
depends on the form; for instance, organic is less toxic

than inorganic and pentavalent less than trivalent. In its
trivalent form, it is a sulfhydryl-containing enzyme
poison. In its pentavalent form arsenic competitively
substitutes phosphate, causing rapid hydrolysis of highenergy bonds in adenosine triphosphate.
Lead
Lead found in drinking water accounts for only 20
percent of the total lead exposure. Lead enters drinking
water by leaching through lead pipes; lead soldering of
the joints between pipes, or fixtures containing lead. Lead
contamination increases with long contact time of water
with the fixture because of intermittent use, such as first
morning water; water of warm temperature; and softer
more acidic water.
The health effects are more severe in children and
infants. Lead exposure in early childhood may cause loss
of intelligence, and behavioral deficits that may persist
well into adolescence.
Radon
Treatment
If the level is less than 20 percent then no treatment except
eliminating the source is required. If the toxicity is
moderate to severe then 100 percent oxygen should be
started, and intravenous methylene blue should be
administered.
Prevention
It is important to identify and eliminate the sources of
exposure. A detailed history regarding residence,
occupation of parents, drinking water, and foods
ingested, and use of topical medications or folk remedies
is important. Boiling of water does not alter the nitrate
concentration of water. Some alternatives could be deep
wells, monitoring of public water supplies, and bottling
water free of nitrates. Newer effective systems for treating
nitrate contamination, such as ion-exchange resins and
reverse osmosis should be widely implemented.
METALS AND METALLOIDS
Radon gas is a product of the radioactive decay of

uranium. It leaches from natural deposits and dissolves
in groundwater. Groundwater and water from small
water suppliers tend to have the highest levels of radon.
Aerosolized water (e.g. from heated sources while taking
a shower) is likely the most important route of human
exposure.
Radon emits alpha particles that can cause deletions,
re-arrangements, and other damage to DNA at the site
of exposure.
Methyl Tertiary Butyl Ether (MTBE)
It is the most widely used gasoline additive. Drinking
water is contaminated by MTBE through gasoline leaks
and spills. Humans may be exposed in tap water by three
primary routes: ingestion, inhalation, and dermal
absorption. Clinically it may manifest with headache, eye
irritation, nose and throat burning, cough, dyspnea and
dizziness.
Arsenic
Pesticides
Arsenic is produced from human activities such as

smelting, coal burning, wood preservation, pesticide
distribution, and other industrial processes. The toxicity
Pesticides are not removed by conventional water

treatment. Concentrations in water often correlate with
growing seasons in agricultural areas and rainy seasons

in more urban settings. Low-level exposure causes
various neuro-developmental side effects, which will be
discussed in detail later.
12. In malnourished children, especially those who are

deficient in iron or calcium, or with developmental
disabilities are more susceptible to lead toxicity.
Polychlorinated Biphenyls (PCBs)
MECHANISM OF ACTION
PCBs are very poorly soluble in water. They readily

accumulate in the fat of wildlife, and are very resistant
to biological degradation. The sediments of many lakes
and rivers are contaminated with PCBs. Several
neurological effects are stated with PCB exposure.
Lead may bind tightly to sulfhydryl proteins hence

altering the structure and function of many proteins. As
a result, of which activity of many enzymes is altered.
For instance, porphobilinogen, an enzyme essential for
heme synthesis is extremely sensitive to lead. Other
important enzymes affected are guanine hydroxylase,
ferrochelatase, and 51pyrimidine nucleotidase.
Lead is concentrated in kidneys and can cause
Fanconis syndrome. Chronic lead poisoning may be
associated with gouty nephropathy, and renal failure,
mainly in adults.
Chlorinated by Products
Chlorination of water having high natural organic
content causes formation of chloroform and other
chlorinated compounds called trihalomethanes (THM).
Exposure to THM increases the risk of bladder and rectal
cancer.
LEAD
Natural concentrations of lead in soil, water, and air are
extremely low. However, human activity has concentrated lead in the biosphere. Amongst various sources
lead in paint is the greatest threat to children. The US
Environment Protection Agency and the Agency of Toxic
Substances and Disease Registry (ATSDR) have asserted
that toxicity in children may begin at less than 10 g/dl.
ROUTES OF EXPOSURE
Unintentional ingestion of lead-containing particles may
occur through various sources. Some of the important
ones are:
1. Lead-based paint.
2. Dust
3. Soil
4. Drinking water especially early in the morning
when the taps have closed for a long time.
5. Certain folk remedies may contain lead.
6. Old ceramic or pewter cookware, old urns/kettle.
7. Some crayons
8. Parental occupations such as those working with
ammunition factories, casting toys soldiers, or
construction of stained glass windows.
9. Hobbies of children requiring arts and craft usage.
10. During renovation of old homes, when old leadbased paint wears off.
11. Besides above sources hand-to-mouth activity
predisposes children to high-risk of exposure.
SIGNS AND SYMPTOMS

High concentrations of lead may cause headaches,
abdominal pain, loss of appetite, constipation, clumsiness, agitation or decreased activity, and convulsions.
Lead also affects behavior and IQ of children. Elevated
bone lead concentrations may be associated with
attention deficit disorder, aggression, and delinquency.
The early-untreated effects of lead exposure during
childhood may be permanent. A study done in
Massachusetts revealed an association between higher
levels of lead in deciduous teeth and higher failure rates
in high school, reading disabilities, and other behavioral
deficits.
MANAGEMENT
It may be divided into various phases depending on the
levels of lead in blood. Successful therapy should aim at
eliminating childs exposure to lead. A thorough
investigation into childs behavior, activities, lifestyle,
parents occupation and his environment should be
conducted. Besides paint, diet, water supply, tableware,
and food from cans with soldered seams need to be
evaluated. Certain cosmetics like surma may be toxic.
Children who live near factories using lead may be
exposed to lead in the air and soil. In this environment
children who bite their nails, or suck thumb may be
predisposed to higher levels of lead. If any concurrent
iron or calcium deficiency is present, then it should be
treated along with zinc supplementation.
If the blood level of lead is more than 45 g/dl,
chelating agents such as succimer should be instituted.
1400
Baseline hepatocellular enzymes and a complete blood

count should be obtained. Calcium sodium EDTA could
be used if levels are more than 45 g/dl. If the child is
symptomatic or blood lead levels are more than 70 g/
dl then therapy with EDTA and Dimercaprol should
begin.
If blood levels are more than 15 g/dl then calcium,
iron, zinc, and ascorbate should be supplemented.
Certain precautions can be taken to avoid lead exposure:
1. During renovation, remodeling, and painting of
houses, if possible children should move out of the
home and return after proper clean-up.
2. Minimizing exposure to dust and paint chip debris.
3. Treatment of Pica.
4. If any of the parents work in lead based jobs then
change of clothing and proper clean-up before coming
home could minimize the procedure.
5. Avoid lead based things in arts and crafts.
6. Proper hand washing.
7. Use cold water for drinking, especially for infant
formula-feeds.
IONIZING RADIATION
Exposure to radiation can occur from external sources
such as radon, X-ray machines or from internal emitters
such as radioactive fallout, or ingested or inhaled or,
medical radioisotopes. Magnitude of exposure also varies
with age. Exposure for a newborn from fluoroscopy for
1 minute is 1000 times greater than that of chest film. For
a given dose, whole body exposure is more harmful than
part body exposure.
Ionizing radiations in collision with the cell can
change its constituents, including DNA. Such damage
may disable or kill the cell. Prompt effects of overexposure include acute radiation sickness (nausea,
vomiting, neutropenia and thrombocytopenia), epilation
and death. Delayed effects are due to teratogenesis,
mutagenesis or carcinogenesis. Intrauterine exposure
may cause small head size and mental retardation.
Susceptibility to mental retardation is greatest between
8 to 15th weeks of gestational age. Chronic lymphocytic
lymphoma and leukemia may be induced by in utero
radiation exposure.
RADON
Exposure to radon occurs through background radiation.
Radon gas comes from radioactive decay of uranium
deposits in rocks and soil. Inhaled radon progeny causes
increased incidence of lung cancer as reported amongst
uranium workers. Radon enters homes through cracks

in the foundations, porous cinderblocks, and granite
walls. Hence, radiation exposure in basements is higher
than that on floors.
Children with ataxia-telangiectasia are more prone
to development of lymphoma, and when treated with
conventional doses of radiotherapy, suffer an acute
radiation reaction that may result in death.
External radiation and radioisotopes fallout have
caused epidemics of delayed radiation effects such as:
(a) developmental defects and cancer were caused by
exposure to the atomic bomb; (b) thyroid ablation and
aplasia in Marshall islanders were due to fallout from
nuclear weapon tests; (c) cases of thyroid cancer in
children in Ukraine and Belarus were attributed
to Chernobyl accident.
PREVENTION OF EXPOSURE
Limitation of radiation, shielding sensitive body parts
like thyroid, and no exposure during pregnancy is
important preventive steps.
Radon exposure can be minimized by increasing
ventilation and by reducing the influx of radon at home.
Sealing of cracks in the foundation, creating negative
pressure under the basement floor, and prohibiting the
use of building materials containing radium may help.
ULTRAVIOLET LIGHT
Sunlight may be divided into visible light ranging from
400 to 700 nm, >700 nm is infrared, < 400 nm is ultraviolet
light. Ultraviolet radiation is further divided into UV-A
(320-400); UV-B (290-320 nm), which is most skin
penetrating.
Individuals are exposed to ultraviolet light when they
are outdoors in the sunlight.
Exposure to solar radiation causes vasodilatation and
erythema of the dermis. The minimal erythemal dose
depends on skin thickness, the amount of melanin in the
epidermis, and the capacity of the epidermis to produce
melanin after sun exposure.
Exposure to large amounts of sunlight that is episodic
is important in the pathogenesis of malignant melanoma.
Various factors including stratospheric ozone depletion,
resulting in more intense ultraviolet radiation reaching
the surface and, change in dress that favors more skin
exposure enhance the possibility of malignant melanoma.

Several factors that implicate in the pathogenesis are:
1. Higher incidence is found near equator, amongst
whites of melanoma.
2. Melanoma is more common amongst whites, as
melanin decreases the transmission of ultraviolet
radiation.
3. Episodic high exposures sufficient to cause sunburn,
during childhood and adolescence increase the
incidence of melanoma.
4. Acute sun exposure is implicated in the development
of nevi in children. The number of nevi increases with
age and occur more frequently in sun-exposed areas.
Besides above-mentioned adverse effects, long-term
exposure to sunlight without sunscreen protection causes
wrinkles and varying degrees of skin thickening and
thinning.
UVR also contributes to the development of agerelated cataracts, pterygium, photodermatitis, and cancer
of skin around the eye.
PREVENTION OF EXPOSURE
There are studies to suggest that effective sun protection
during the first 18 years of life could reduce the incidence
of skin cancers by 80 percent.
1. Avoid direct exposure in infants less than 6 months
of age.
2. The structure, or weave of the cloth worn is important
in preventing exposure. Children may wear longsleeved shirts and pants and brimmed hats.
3. Window glass blocks all ultraviolet rays.
4. Lastly the use of sunscreens though controversial,
reduces the intensity of ultraviolet radiation affecting
the epidermis. Chemical UV absorbent agents are
most commonly used in sunscreens. They are helpful
in preventing sunburns but minimally effective in
other photosensitivity disorders.
5. Wearing a hat with a brim may protect eyes, and
sunglasses should be worn whenever in sun.
Sunglasses reduce exposure by 99 percent.
PESTICIDES
Pesticides are substances that control and kill pests. Pests
are organisms perceived by humans to interfere with
their own activities; they may interfere directly with our
health, with production and protection of our food, or
with our enjoyment. Pesticides are poison, but have a
special purpose; to protect humans and their crops from
other organisms, namely the pests.
Pesticides may be divided into insecticides, herbicides, fungicides, wood preservatives, rodenticides and
insect repellents. The major classes of insecticides are
organophosphates, carbamates, organochlorines, and
pyrethrum and synthetic pyrethroids.
Children and young infants may be exposed to
pesticides by three routes, namely ingestion, dermal
absorption and inhalation. Children may ingest pesticide
residues present in food (including baby foods) and,
drinking water, breast-milk, and sometimes in soil. In
addition, children can be exposed to pesticides used and/
or found in households, schools, on pets, in swimming
areas, rural environments, parks, etc. A large number of
sources may cause cumulative exposure. Results from
the EU special coordinated monitoring programs showed
that in commodities such as lettuce, grapes, strawberries,
apples, and tomatoes exceeded the proposed maximum
residual limits (MRLs). Studies from Netherlands
revealed that pesticides of particular concern for infants
were parathion ethyl and dimethoate, mevinphos,
methyl parathion and chlopyrifos. The three food
commodities that contributed the most to childrens
exposure to acetylcholinesterase-inhibiting compounds
were spinach from Netherlands, apples from France, and
grapes from Italy and Greece.
The EU Scientific Committee recommends an MRL
of 0.01mg/kg for pesticides in food intended for infants
and children.
Differences in the toxicity of pesticides between
children and adults are mainly quantitative and
occasionally qualitative. Of special concern is that
susceptibility of developing fetus, neonate, infant, or
child to delayed functional toxicityas a result of
exposure to sub-toxic doses of pesticides during a critical
window may not manifest until adulthood. Developmental functional toxicity is relevant for the developing
central nervous system, and also applies to endocrine,
reproductive and immune systems. Risk assessment
currently undertaken to establish acceptable daily intakes
(ADI), acute reference doses (ArfDs) where relevant and
to evaluate the proposed maximum residue limits
(MRLs) for pesticides in food do not take into account
these important considerations so as to fully ensure the
health, and safety of infants and children.
Childhood patterns of behavior often lead to
increased levels of pesticide exposure compared with
adults. For example, among toddlers and young children
hand-to-mouth behavior is an important mechanism of
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potential exposure to certain pesticides. Also infants and

children spend more time at home than adults, either
crawling or playing at ground level where pesticide
residues in household air, dust, carpets, and even toys
may be higher. Children who live in or near farms will
ingest sufficient amounts of pesticides by playing and
crawling at ground level, and by touching surfaces inside
the home which contain pesticides either from window
dust, from near by lawns or from indoor applications.
The main difference in the exposure of adults and
children to pesticides is in their respective diets. Children
consume more food per kg of body weight than do adults.
Their diet is less diverse and they thus have a relatively
higher intake of some food items than do adults. In
addition, average water consumption, both as drinking
water and as a food component, is relatively higher in
children than in adults.
MODES OF ACTION
Many pesticides share a common mode of action, such
as organophosphates and anticholinesterase carbamates,
all of which are inhibitors of cholinesterase. As their effect
is additive, hence low-dose exposure to several pesticides
may result in toxicity.
The Indian scenario regarding pesticides is very
horrifying. India is the largest producer and consumer
of pesticides in the world. At present India uses about
80,000 tons of pesticides annually to cover 182.5 hectares
of cultivated area. Exposure of farming families,
especially women and children to pesticides is very
common in workers employed in horticulture, jasmine,
and tea cultivation.
Besides this exposure may occur through commercial pest control measures to eliminate insects. An
experimental study showed that, after such treatment,
chlorpyrifos accumulated on childrens toys at least 2
weeks after application.
CLINICAL EFFECTSACUTE
Organophosphates
Organophosphates phosphorylate the active site of the
enzyme acetylcholinesterase (AChE) at the nerve ending,
irreversibly inhibiting this enzyme. The signs and
symptoms of acute organophosphorous poisoning result
from the accumulation of acetylcholine at cholinergic
receptors (muscarinic effects), as well as voluntary
muscle and autonomic ganglia (nicotinic effects).
Accumulation of acetylcholine in the brain causes sensory

and behavioral disturbances, impaired coordination,
depressed cognition, and coma.
Organophosphates are rapidly distributed throughout the body. Symptoms usually develop within 4 hours
of exposure, but may be delayed up to 12 hours with
dermal exposure. Initial symptoms include headache,
dizziness, nausea, vomiting, and abdominal pain. With
worsening muscle twitching, weakness, bradycardia,
hypersecretion may develop. Later more severe
intoxication results in sympathetic and nicotinic
manifestations with muscle weakness and fasciculations,
tachycardia, cramps in muscles, and hypertension.
Finally paralysis of respiratory muscles may result.
Carbamates
Carbamates act similarly to organophosphates by
binding to AChE, but the bonds are more easily
reversible. The symptoms produced by the two are
similar.
Organochlorines
They act on the nervous system, by interfering with the
flux of cations across the nerve cell membranes. This may
result in seizures. Disturbances of sensation, coordination
and mental function are characteristic.
Pyrethium and Synthetic Pyrethroids
They are absorbed from the gastrointestinal and
respiratory tract and very little through the skin. The
toxicity is low when ingested. Most troublesome are
allergic reactions in the form of contact dermatitis,
anaphylaxis or asthma. Paresthesias may occur when
liquid and volatile compounds contact the skin.
Insect Repellants
Diethyltoluamide is a very commonly used insect
repellant. Toxicity results in seizures, which are selflimiting. Other signs and symptoms of toxic encephalopathy including headaches, emotional or behavioral
changes, restlessness, irritability, ataxia, and loss of
consciousness may occur.
Rodenticides
Anticoagulants may produce bleeding. Cholecalciferol
produces hypercalcemia that induces vasoconstriction
resulting in renal dysfunction and a reduced glomerular
filtration rate and renal plasma flow.

CHRONIC TOXICITY
Neurologic Sequel
Organophosphates may be associated with long-term
neurological side effects after acute or sub-acute
exposures. It may result in poor memory, depressed
mood, confusion, and difficulty with abstract reasoning.
Another chronic syndrome unique to organophosphates is organophosphate-induced delayed
neuropathy. It is produced by the inhibition of enzyme
target esterase that damages afferent fibers of peripheral
nerves. It causes paresthesias, weakness and paralysis
of extremities, particularly lower extremities.
Endocrine and Reproductive Toxicity
Some chemicals interfere with normal endocrine
functioning and chemical signaling at even low doses.
These are the so-called endocrine disrupting chemicals,
which include a number of pesticides. For example
dieldrin, toxaphene, chlordane, and DDT are estrogenic.
The possibility is that interaction of pesticides with
endocrine receptors in fetal and infant life may have
profound effect on morphological and functional
development of the child.
Childhood Cancer
Numerous childhood cancers, leukemia and brain
tumors are linked to pesticides. Parental occupation with
pesticide exposure and family pesticide use, all have been
found to be associated with risk of cancer.
POLYCHLORINATED BIPHENYLS,
DIBENZOFURANS AND DIOXINS
Polychlorinated biphenyls (PCBs) are compounds with
two linked phenyl rings and variable degrees of
chlorination. They are clear, nonvolatile, and hydrophobic oils that cannot be metabolized easily and persist
in the environment. Owing to their optical and solvent
properties PCBs are used in carbonless copy paper,
microscope immersion oil, and as a vehicle for paint and
pesticides.
Polychlorinated dibenzofurans are partially oxidized
PCBs. Polychlorinated dibenzodioxins, commonly
referred to as dioxins, also are contaminants.
ROUTES OF EXPOSURE
The current source of exposure for most people is
contaminated food. Since PCBs are not metabolized or
excreted, even very small daily doses accumulate to

measurable amount over years. The most concentrated
dietary source is usually fish. For young infants human
milk is the major dietary source.
CLINICAL EFFECTS
These chemicals are associated with delayed development, including subtle delays in psychomotor
development from the newborn period through 2 years
of age, defects in short-term memory, and low IQ.
Prenatal exposure may lead to low birth weight,
conjunctivitis, natal teeth and pigmentation in newborn.
Direct ingestion of high doses of PCBs cause acne,
keratosis, and hyperpigmentation, mixed peripheral
neuropathy and gastritis.
NOISE
Noise is an undesirable sound. Noise not only affects
hearing but also physiological and psychological
functioning. Susceptibility to noise-induced hearing loss
(NHL) is variable; some individuals may tolerate noise
for longer intervals, much better than others. Trauma to
the hair cells of the cochlea results in hearing loss.
Continuous exposure to the hazardous levels of noise
tends to have maximum effect in the high-frequency
region of the cochlea. NHL is usually more severe around
4000Hz, with downward extension towards speech
frequencies with prolonged exposure. Impulse noise is
more harmful than continuous noise because it bypasses
the bodys natural protective reaction to noise, the
dampening of the ossicles mediated by the facial nerve.
Children are at a risk of higher exposure to noise
related to their behaviors. Infants cannot remove
themselves from noxious noise. Older children play with
firecrackers and cap pistols, while adolescents hear loud
music. Further, exposure during pregnancy may result
in high-frequency hearing loss in newborns and may be
associated with prematurity and intrauterine growth
retardation.
Noise also causes a stress response. It contributes to
sleep deprivation.
The psychological reactions to noise include:
annoyance, feelings of bother, interference with activity,
headache, tiredness and irritability. Work performance
can be affected by noise. It may impair intellectual
function and performance of complex tasks.
Diagnosis regarding psychological problems is solely
through history taking, but that of NHL can be made by
an audiogram. The typical finding is a dip in hearing
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threshold around 4000Hz. Audiologic evaluation,

including pure tone audiometry, should be performed
in children who have no evidence of acute or serious otitis
media but have history of:
1. In utero exposure to excessive noise by maternal
occupation or recreation.
2. Excessive environmental noise exposure, such as
prolonged exposure to cap pistols or boom boxes.
3. Poor school performance.
4. Short attention span.
5. Complaining of ringing in the ears, a feeling of fullness in the ears, muffling of hearing, or difficulty in
understanding speech.
PREVENTION
Reduce noise exposure. Encourage children and parents
to:
1. Avoid loud noises, especially loud impulse noise.
2. Avoid toys that make loud noise, especially cap
pistols.
3. Avoid use of firecrackers.
4. Reduce volume on televisions, computers, radio, etc.
5. Use headphones with caution. The volume of radio
should be low enough so that normal conversation
may be heard.
6. Create a stimulus haven the quietest room in the
house for play and interactions.
When noise reduction is not possible, hearing protectors need to be worn, such as during occupational
exposures, use of power lawn mowers, recreational
exposures, and other situational noise exposures.
CERTAIN ENVIRONMENTS
SPECIFIC TO CHILDREN
Children spend little time in natural environments as
compared to the time they spend indoors and in
neighborhood. From birth to adolescence, children spend
most of their time in houses, day-care centers, playgrounds and school. In these settings, environmental
health hazards vary greatly, depending on factors such
as climate, socio-economic level, cultural aspects,
building materials, and legislation. The main ones are:
Poor indoor quality.
Hazardous building materials and unsafe building
standards.
Chemicals or biological contamination of furniture,
arts and crafts material and playgrounds.
Radiation (ultraviolet, ionizing, electromagnetic
fields)
Noise.
SCHOOLS
School-age children spend about 35 to 50 hours per week
in and around school buildings during school and after
school programs.
Indoor Air Quality (IAQ)
Many school buildings are old and poorly-maintained.
However, even in well-maintained buildings problems
of poor indoor air quality may be related to school
courses, such as materials released into the air from art
supplies, from chemistry and biology laboratories, and
from wood and metal shops. The IAQ may directly
influence a childs learning by affecting alertness,
attentiveness, and absenteeism and indirectly by
affecting the performance and productivity of teachers.
Indoor air pollution may be from two sources, either from
within the building or be drawn from outdoors. It may
consist of particles, fibers, mists, molds, bacteria and
gases. Levels of air pollution can vary in a building or
within a classroom. Levels may also vary with time, such
as a weekly increase the day floor stripping is done, or a
continuous increase from the growth of molds in the
heating ventilation, and air-conditioning systems.
Signs and symptoms of poor IAQ are nonspecific and
mimic allergies or common cold. Some common
symptoms are:
Headache, fatigue, and shortness of breath.
Sinus congestion, coughing and sneezing.
Eye, nose, throat, and skin irritation.
Dizziness and nausea.
Epistaxis (formaldehyde induced).
That the above-mentioned symptoms are due to poor
IAQ should be suspected if following occur:
Many children in the class or room are suffering from
similar symptoms.
If the symptoms diminish or disappear after school
hours.
If the onset is sudden, i.e. after some change at school,
such as paintings or pesticides application.
If children with allergies and asthma have reactions
indoors but not outdoors.
The term sick building syndrome has been used to
describe a variety of symptoms ranging from headache
and nausea to upper respiratory infection and eye
irritation, associated with a persons presence in the
building and which typically disappear when the person
is not in the building. Poor design, maintenance and

inappropriate ventilation system are the possible causes
of sick building syndrome. Another school of thought
suggests that very low levels of specific pollutants may
be present and may act synergistically or in combination,
to cause health problems. Humidity may also be an
important factor, high relative humidity may contribute
to biological pollutant problems, and an unusually low
level, less than 20 to 30 percent, may heighten the effects
of mucosal irritants.
Biological air pollutants are also found in every school.
Sources include outdoor air, human occupants, animal
occupants that shed allergens, and indoor air surfaces
and water reservoirs (e.g. humidifiers) where molds and
bacteria can grow. Various factors allow these biological
agents to grow and be released:
High relative humidity encourages dust mite
application and allows molds to grow.
Mite and mold contamination may occur by flooding,
inadequate exhaust of bathrooms, or kitchengenerated moisture.
Appliances such as coolers, dehumidifiers, and air
conditioners may support the growth of bacteria and
molds.
Components of heating, ventilation and air-conditioning systems may act as reservoirs for microbes.
Exposure to biological contaminants may cause upper
and lower respiratory tract symptoms. Some episodes
of sick building syndrome may be correlated to biological
contaminants. Other symptoms include those of allergic
reactions, including rhinitis, nasal congestion, conjunctival inflammation, urticaria, and asthma.
Some preventive measures for biological contamination include:
Adequate outdoor air ventilation, i.e. 15 cubic feet
per person per minute.
Ensure that there is no standing water in air conditioners. Maintenance of coolers and dehumidifiers.
Repair leaks and seepage.
Keep relative humidity less than 50 percent. Use
exhaust fans in bathrooms and kitchens.
Control exposure to pets.
Prevention provides the greatest overall health effect.
Six basic methods can be used to lower concentrations
of indoor air pollutants.
1. Educate the school staff about sources and effects of
air pollution under their control.
2. Effective source management includes source
removal, substitution, and encapsulation. If possible
do not bring source pollutant near school, for instance,
3.
4.
5.
6.
prevent buses from idling near outdoor air intakes.

Locating garbage away from schools.
Local exhaust to outside is very effective in removing
pollutants that originate at specific points before they
can be dispersed. Put exhausts in bathrooms, science
laboratory fume hoods, housekeeping storage rooms,
printing and duplicating rooms, etc.
Ventilation uses clean air to contaminate polluted air.
For situations such as painting, pesticide application,
or chemical spills, temporarily increasing the
ventilation can dilute the indoor air concentrations
of fumes.
Exposure control also includes knowledge of time of
use and location of use. Stripping and waxing of floors
could be done over the weekends. Location of use
involves moving the contaminating source as far as
possible from occupants or relocating susceptible
occupants.
Air cleaning by filtration of particles through
ventilation equipment.
Hazardous Building Materials

Asbestos has been used for large range of building
materials, mainly for insulation purposes, including
ceilings, roof tiles and asbestos cement. Inhalation of
microscopic airborne asbestos fiber is the major route of
exposure. It becomes a health hazard when asbestoscontaining materials deteriorate and fibers are released
in the air and are inhaled.
Leaded materials may be used in paints, walls, and
woodwork and window castings. Lead may also
accumulate in water due to contamination of water
sources and water pipes. Unsafe building standards and
materials may lead to poisoning and injuries.
Schools may be situated near old industrial sites with
unknown emissions and wastes. Outside the building,
playground soil may be contaminated with lead, with
higher concentrations found closest to areas with high
traffic loads. High concentrations of lead can accumulate
in water overnight, on weekends, and over school
holidays.
ARTS AND CRAFTS SITES
Children begin to enjoy arts and crafts materials when
young. Arts and crafts materials abound in homes, childcare centers, schools, churches, and park and recreation
facilities. Many of these materials contain ingredients that
are known to be hazardous.
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Dangerous chemicals found in art materials can be

divided into metals, solvents, and dusts or fibers. These
are:
1. Lead and other toxic metals such as mercury,
cadmium, and cobalt are found in paints, pastels,
pigments, inks, glazes, enamels, and solder.
2. Some paper mache products may contain heavy
metals from inks found in magazines.
3. Hazardous organic solvent such as turpentine,
kerosene, mineral spirits, xylene, benzene, methyl
alcohol, and formaldehyde are used in painting, silkscreening, and shellacking, as well as in cleaning tools
and preparation of work surfaces.
4. Organic solvents are also present in rubber cement,
spray-on enamels, and spray-on fixatives.
5. Dusts and fibers containing hazardous materials such
as asbestos, silica, talc, lead, cadmium, and mercury
are generated during reconstitution of powdered
pigments, glazes and clay, and the use of pastels.
6. Physical art hazards include exposure to noise,
dangerous mechanical and power tools, machinery
and materials storage, and waste disposal particles.
Inhalation is the major route of exposure for volatile
organic solvents, dusts, and fibers. Exposure can occur
during normal use if the ventilation is inadequate or if
necessary personal protective equipment is not available.
Accidental ingestion may occur when common art
materials are improperly used. Ingestion may also occur
through nail biting, thumb sucking or other hand-tomouth behaviors common in children.
Dermal absorption may occur from improper
handling of hazardous art materials, accidental spills, or
through contact with cuts or abrasions. Exposure through
conjunctivae may occur from spills, splashes and rubbing
ones eyes.
Physical hazards cause injury in a variety of ways.
Noise developed to protect workers may be exceeded in
secondary school industrial arts workshops.
Chronic low-level exposures to hazardous arts
materials in childhood could exacerbate or cause
allergies, hypersensitivity and asthma, central and
peripheral nerve damage, psychological and behavioral
changes, respiratory damage, skin changes, or cancer.
Certain measures could be taken to eliminate or
minimize risks:
Careful selection of arts and crafts materials.
Limit use of crayons as some of them contain lead.
Good ventilation in rooms for arts and crafts activity

is always important.
Proper storage and clean-up are also essential.
Materials should be stored in original, fully-labeled
containers. Appropriate clean-up at the end of arts
session includes closing and storing all containers,
cleaning all tools, wiping down all used surfaces, and
thorough hand washing.
Close supervision of all children during arts and crafts
activities.
Art safety education for all supervising adults.
Water-based supplies are preferable because they
avoid the need for organic solvents.
WORK-PLACES
Efforts to improve school-to-work transitions are placing
more teenagers into the workplace, and even schoolbased vocational/technical education that stimulates
employment conditions, including chemical exposures.
Some chemical exposures involve absorption through
skin or breaks in skin. Pesticide exposure may occur
during lawn care or in fields, nicotine exposure while
harvesting tobacco, and solvent exposure in auto
body shops.
Inhalation injuries may result from fumes from metal,
such as lead and ammonia.
Lead and other heavy metals may be ingested.
They could be infected with blood-borne pathogens
in nursing homes/hospitals.
Cleaning agents used in restaurants, nursing homes,
and schools may contain volatile organic solvents.
They may be exposed to benzene while pumping gas.
Solvent exposure may occur in T-shirt screening.
Adolescents could get exposed to second-hand
smoke.
Wood-dust in shops and furniture making may
induce asthma.
Prevention through knowledge of substances, routes
of exposure, and engineering controls is important.
Pediatricians should find out which of their patients
work, where they are working, what their job duties are,
and the types of chemicals they use in their work. An
occupational history should be obtained with a focus on
potential hazards. Knowledge of job training including
the use of chemicals and first aid, and whether there is
an adult supervisor on site is important.
The adolescents occupation should be considered
when diagnosing an illness, e.g. chronic fatigue may

occur due to chronic exposure to solvents if he works/
sleeps in an area with incomplete ventilation. The
adolescents occupation should be considered in the
medical management of a known illness e.g. asthma.
Pediatricians should talk with parents about the
potential risks and benefits of having their adolescents
employed. Many parents are unaware of injury risks, and
may even be less aware of risks associated with chemical
exposures. Guidance may help reduce the risks.
WASTE SITES
Common examples of waste site exposure include
incinerators, landfills, emission stacks, and unsanctioned
discharges of wastewater. Children may be exposed
through ground water, surface water, drinking water,
air, surface soil, sediments or consumable plants or
animals. Children in particular, may find waste sites very
interesting. They may ignore or fail to notice warning
signs, find or create openings in fences, or otherwise gain
access to restricted places on or near sites. Another
problem of the developing world is rag pickers. There
may be considerable difference in exposure depending
on time of the day, climate and season.
The effect of exposure on an infants and childs health
is related to the nature of the pollutant dose received,
the toxicity of the substance, and the individuals
susceptibility.
Adverse health effects have been reported in a small
number of investigations of communities around
hazardous waste sites. The effects may either be
nonspecific symptoms like headache, fatigue, and
irritative symptoms, or specific conditions such as low
birth weight, congenital defects, and a constellation of
neurobehavioral deficits.
ELECTROMAGNETIC FIELDS (EMF)
Modern industrial development has resulted in everyone
being exposed to a complex mix of electric and magnetic
fields and radiation, with the exposure beginning from
birth.
Electromagnetic radiation is the transportation of
energy through space. The electromagnetic spectrum
spans a very large range of frequenciesmore than 15
orders of magnitude. It ranges from below power
frequency fields to ionizing radiation. It is composed of
two components, the electric and the magnetic fields.
Electric and magnetic fields have different properties that
are of importance when considering possible biologic
effects. Essentially all materials including clothing, easily

shield power frequency electric fields. In contrast,
properties of magnetic field are such that they pass
through nearly all materials, including living tissues,
building structures, and the earth. The primary
determinants of magnetic field exposure are source
geometry and distance from the source and the
measurement location. Magnitude of magnetic field
decreases fairly rapidly with distance from an isolated
source. In general, magnetic fields from transmission and
distribution lines decrease with inverse square of the
distance, while the field of appliances decrease with
inverse square to the cube of distance.
Major sources of EMF exposure include electrical
power generation, transmission and use in residential
and occupational settings, and telecommunications and
broadcasting. Most devices that have electrical wires are
potential sources of power-frequency EMF. Although the
predominant exposure is to alternating waveforms,
humans are also exposed to a mixture of frequencies,
including switching events that generate abrupt spikes
of high frequency transients that can extend into radio
frequencies. Residential exposures include powerfrequency exposures, radio-frequency, and microwave
sources.
The high visibility of overhead power lines has
resulted in concern about EMF exposure being associated
with them.
CONTROVERSY ABOUT POSSIBLE
HEALTH EFFECTS
The 60 Hz fields differ in important ways from other
types of electromagnetic energy, such as X-rays and
microwaves. X-rays, for example, differ packets of
energy strong enough to ionize and break up molecules,
such as DNA. The packets from microwaves cannot
break up DNA, but the electric charges on water
molecules wiggle in response to oscillations of the
microwaves.
Epidemiological studies have shown a statistical
association between childhood cancer and proximity to
power lines. A special committee of the National
Research Council provided a careful review of the 11
epidemiological studies of the relationship between
childhood leukemia and residential proximity to power
lines. The studies estimated the exposure in various ways:
(1) Distance from the lines; (2) Wire codes, a system of
classification based on type of power line and distance
from the lines; (3) Measurement of magnetic field many
1408
years after diagnosis; (4) Estimates of magnetic field

around the time of diagnosis based on historic records
of current flows and the distance of lines from the home.
The committee concluded that living in homes, which
were classified, as being in the high-wire category is
associated with about a 1.5 fold excess of childhood
leukemia.
Childrens environmental health is a discipline now
in its adolescence. Research and training programs have
been established. Although these programs are still new,
they hold great promise. Programs for the education of
pediatricians have been initiated.
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1410
33.4 Research Methodology in Pediatric Practice

Sarada Suresh, P Ramachandran
Conducting clinical research is an important part of the
activities for the doctors providing health care in various
fields of medicine. A medical officer has to know the
fundamentals of research methodology so that he may
successfully carry out research activities as and when
needed. Not only the medical teachers in medial colleges
have to be well informed with the methodology so that
they may guide the students but any person interested
in doing research whether he is in an academic institution
or in private practice, has to know about research
methodology. Finally a practitioner would like answers
to many clinical queries regarding etiology, diagnosis
and treatment based on evidence based medicine. For
this purpose he should be able to critically analyse the
published studies with his background knowledge of
research methodology. This critical appraisal of evidence
in the published literature is important for the clinician
to successfully integrate it in his practice for the benefit
of his patients. This will also help in proper documentation of his own data and critical review of which will
provide insights into his own as well as the needs of the
community he serves.
3.
4.
5.
Common Terms Used

Before describing the principles of research methodology,
certain common terms used are described.
1. Validity: This can be external validity or internal
validity.
External validity or generalisability: This is the degree
to which the results of an observation will hold true
in other settings. This is related to the similarity
between the characteristics of the group and the
population to whom the study findings are extrapolated.
Internal validity: This is the degree to which the results
of an observation are correct for the subjects being
studied.
2. Bias: This is a process which tends to produce results
that depart systematically from true values. It can be:
6.
7.
Selection bias: Where a systematic error occurred in

the method by which patients were selected for
observation (e.g. sampling bias, referral bias).
Measurement bias: Where the error was in the methods
by which the observations were made (Recall bias,
instrument bias)
Observer bias: Due to the error by the researcher who
makes the observations.
Confounding: This is due to the fact that the results
are influenced by factors other than the factors of
interest. This has to be thought of by the researcher
even before he starts the study and appropriately
handled.
Blinding: This is a method employed to avoid potential
bias resulting from the study subjects or the
researchers knowing which intervention the subject
is receiving. Trials are termed single blinded when
the treatment allocation is known only to the
researcher or double blinded when both the subject
and the researcher who makes the observations are
unaware of the treatment allocation (intervention
group or control group).
Null hypothesis: The assumption of no difference
between the existing method or mode of treatment
and the intervention proposed to be studied is known
as null hypothesis. The testing of the null hypothesis
is fundamental to all tests of significance.
P value (probability value): A p value can be thought
of as the probability that the observed difference
between two groups might have occurred by chance.
The choice of a significant level is by convention, a
p value of 0.05 is used as a cut-off for significance.
This means that if p value is less than 0.05, the
observed difference between the two groups is so
unlikely to have occurred by chance that there is a
real difference between the groups.
Type 1 error: Drawing a false positive conclusion of
difference between the groups when actually there
is none. The possibility for this is called Alpha and
the limit is usually set at 1 in 20 or 0.05.

8. Type 2 error: Drawing a false negative conclusion of
no difference when actually there is. The probability
of this is termed Beta. This is usually set at 0.1to 0.2
or 10 to 20%.
9. Confidence interval: 95% CI (confidence interval) is
a range that is calculated for a point estimate and
which means that if the study is repeated 100 times
in different study populations, that in 95 times the
result will be within the range calculated. If the CI is
very wide or crosses the number 1 in odds ratio
then it is not significant as the variability is high.
Research Designs
Choosing a research design depends primarily on the
research question and secondarily on ethical and logistic
considerations. There can be more than one research
design that may be applicable to a particular research
question. The researcher should be aware of the
importance of the research he proposes to undertake and
the constraints in his setting to decide on a particular
research design.
Research designs can be:
A. Descriptive studies
a. Population surveys
b. Cross-sectional surveys
c. Case series
d. Individual case reports.
B. Analytical studies
a. Case-control studies
b. Cohort studies
c. Evaluation of a diagnostic test.
C. Experimental study
Randomized controlled trial (RCT).
D. Operational research
This is an evaluation of the ongoing health programs
and which is being found to be very useful in midterm
corrections and smoothen the implementation of the
program such as IMNCI or pulse polio immunization.
E. Qualitative research
Qualitative research uses methods such as focus
group discussions and in-depth interviews with
specified stakeholders to provide an understanding
of an issue. This may be more social or anthro-
pological in approach. However, this approach

though very different in conception and analysis
provides depth to understanding of an issue. For
example, qualitative research methods will be useful
to understand why mothers are not universally
breastfeeding their infants exclusively up to six
months of age.
As there are a number of study designs, the researcher
has to first identify the problem he proposes to study
and take all pains to define and refine the research
question and then choose an appropriate study design
to answer the chosen research question.
Descriptive Study
This is an observational study where the characteristics
of the study subjects such as the age, sex, clinical features
and complications are described. There is no control
group for comparison. This study usually provides
preliminary information about a disease or a problem
which helps to generate the hypothesis for an analytical
study later. Most commonly used descriptive design is
the cross-sectional study.
Analytical Study
The advantages of analytical study designs are that they
are less time consuming, easier to conduct and pose fewer
ethical problems.
i. Cohort study (longitudinal study): A group of
subjects (cohorts) who are exposed to some risk
factor are followed up for a period of time for the
occurrence of a specified disease in comparison with
another cohort of subjects (controls) who are not
exposed to the risk factor and are also followed up
concurrently. This can be prospective or retrospective or bidirectional.
ii. Case-control study: This is a retrospective study.
Subjects a with disease (cases) or without a disease
(controls) are selected and the investigator determines their prior exposure to the putative cause. This
design is useful in evaluating strength of association
between the disease and suspected risk factors in
a short time especially in rare or uncommon
conditions or where the time lag between the
exposure to the risk factor and the onset of the
disease is very long.
1412
Experimental StudyRandomized Controlled

Trial (RCT)
This is a study design in which the subjects are assigned
to study groups (e.g. conventional method of treatment
or drug group and new drug group) by random
allocation. Each subject has an equal chance of receiving
either treatment. Blinding is done to increase the internal
validity of the study. The two groups are compared at
the beginning and the end of the study with reference to
the outcome of interest. Of all the study designs, this is
the best one since by randomization, the bias is likely to
be distributed equally between groups and the experiment is fully controlled by the researcher. The disadvantage is that it is difficult, time consuming and may
have ethical issues as well as issues of generalisability.
Formulating a Research Question
The first step in designing research is to decide the broad
area of interest. The next step is to convince oneself that
the proposed research relates to an important health
issue. A hypothesis is then developed and the hypothesis
is refined in the following format.
i. Formulation of a brief research question (e.g.
artesunate superior to quinine in cerebral malaria)
ii. Identification of population to be studied (children
with cerebral malaria)
iii. Exposure of intervention specified (intravenous
quinine and intervenous artesunate)
iv. Period of study (1 year)
v. The end point of interest (i.e. primary outcome) is
specified in quantifiable terms (reduction in
mortality of more than 10% in artesunate group).
It should be remembered that the researcher has to
be focused on a specific issue and not be over ambitious.
He has to make sure that his research questions can be
answered in the time frame available to him, sufficient
subjects can be recruited and appropriate methods of
measurement are available and affordable. Adding other
variables may at times dilute the study objectives. By
refining a research question to its specifics, a small aspect
of the general issue can be addressed. This is likely to
increase the chance of completing the study in the given
time and making a useful contribution to the existing
knowledge in the field rather than planning an ambitious

study which runs into problems in execution.
Steps in Formulating a Research Protocol
A research protocol gives an outline of the research
proposal, method of conducting the study, presentation
of outcome and ethical issues to be addressed.
1. General objectives of the study: This should state the
main aims of doing the research.
2. Background and literature review: Various aspects of
the problem in question which have been already
published have to be carefully searched, analyzed
and presented. The strengths and limitations of the
available evidence have to be critically reviewed.
The methods to overcome the inadequacies in these
available studies and the likely new areas to be
explored in the present study are to be detailed.
3. Justification for the study: This has to be derived based
on the currently available data and how the
proposed study will contribute to the existing
knowledge.
4. Formulation of a hypothesis: The hypothesis should
be clear and specific. It should address the study
and outcome factors, the size of effect anticipated
and the specific population. As given in the example
above, it can be Intravenous artesunate is superior
to intravenous quinine in bringing down mortality
due to cerebral malaria by more than 10% in children
up to 12 years of age
5. Aims and objective of the study: The aim of the study
may be To administer IV artesunate and IV quinine
in 2 randomized groups of children with cerebral
malaria to evaluate the superiority of IV artesunate.
6. Selection of study design: Depending on the study
question, an appropriate study design should be
identified. Before deciding on a study design, one
should consider the feasibility of undertaking a
study design in terms of time needed for completion,
ethical issues, adequacy of subjects, money and man
power required. Taking into account all these issues,
the best design to provide the appropriate results
should be selected.
7. Identification of study sample: The reference popuation, target population and sampling method have
to be defined.

Sample size: Often the researcher is faced with the
question of how many subjects should be included
in the study. The sample size depends on the type
of problem to be studied, expected frequency of
events in control and study groups, anticipated
response rate / lost to follow-up rate and type I and
II errors used in the study. A statistician should be
involved in the initial stages itself of designing a
study.
Allocation: A randomization method using computer generated numbers is followed to allocate the
study population to different groups to eliminate
bias. These methods must be defined precisely in
advance.
8. Intervention development: In an interventional study,
the method of intervention, how it will be administered and procedures for blinding should be
explained in detail.
9. Outcome measures (variables): The outcome measures
are study end points which are expected to be
achieved. It is necessary to describe the specific
outcome events being measured and the methods
of measuring them. These measures may be in the
form of observations, physical measures, self-report
measures, laboratory investigations or records. The
validity, reliability and completeness of all these
measures have to be assessed. The type of instruments and tests to be used, the training required to
be given to the research personnel for measuring
end the need for piloting also should be mentioned.
Besides study end points, it should also be mentioned how adverse events will be detected in case
of intervention.
10. Data collection and analysis: The data collection
procedure and the type of quality control to check
the accuracy of collection and entry of data will have
to be described. Appropriate statistical analysis
proposed to be employed depending on the
hypothesis and study design, and type of variables
measured should be described. Dummy tables can
be created to clarify the type of analysis proposed
to be undertaken. Loss of enrolled study subjects
has to be clearly addressed and their impact on the

study outcome explained appropriately.
11. Pilot study: A pilot study may be useful for training
and standardizing the measurement procedures,
identifying the acceptability and practical difficulties
of the procedures, and testing the questionnaire. The
number of subjects and the time frame for piloting
should be decided before hand.
12. Ethical issues: Ethics is a system of moral principles
governing conduct. The basic principles of ethics are,
beneficence (doing good), non-malaficence (do not
harm), autonomy (independence) and justice (nonpartisan). It also involves confidentiality and
respecting the sanctity of life. The primary duty of
a physician is to his patients and his primary concern
is their safety and best interest.
In any research study the investigator has to provide
written information to the parents and children (when
they can understand) the facts about the study in the
language the patient/parents can understand. This
information should contain objectives of the study,
description of procedures, full details of informed
consent, presumed benefits, possible risks, means of
protecting confidentiality, compensation of injury or
accidents and permission from drug controller of India
for any new vaccines or drugs. The consent form should
contain all the following details in the language the
patient/parent can understand: All information about
the study, duration of the study, permission for
individuals to withdraw from study, information on
risks and benefits and pros/cons of participating and
not participating in the study. The consent form should
be signed by the parents.
All aspects of study proposal should be submitted to
ethics committee or institutional review board for
clearance before starting the study.
In conclusion a clinician has to understand the
principles and steps of research methodology whether
he is going to undertake research or not. This is because
he has to analyse and interpret a vast number of
research studies published to bring maximum benefit
to the children under his care.
1414
33.5 Computers in Pediatric Medicine

Neeraj Jain, Vibha Jain
Today we are in the computer age. Computer has become
an integral part of day to day activity in every walk of
life. Accordingly it has become very essential component
of the medical sciences.
Computer is a highly developed and sophisticated
gadget for getting various functions with tremendous
speed. Its performance may be equated with that of
humans. A human perceives through the sensory organs,
the brain processes the inputs, which are expressed in
the form of vocal or physical activities depending upon
the training received. Similarly, in a computer, for a given
output, the central processing unit (CPU) processes
according to the program to give required output.
Applications of computers in medical field can be
broadly classified as:
1. Methods in biostatistics
2. Community or public health care
3. Hospital establishments, nursing homes of academic
general practitioners
4. Medical research.
Applications in Biostatistics
The computers can be used and are used now in solving
various problems in biostatistics for:
1. Collection, complication, tabulation and diagrammatic presentation in the manner required for any
size of data for completeness and accuracy.
2. Finding averages, coefficient of variation, standard
deviation and standard error and percentiles, etc. of
any size of data simultaneously.
3. The application of tests of significance, correlation and
regression coefficients and other tests to find
probability (p values) which are necessary in practice
of medicine, public health and research.
4. Construction of life tables to find longevity of life at
birth and at any age such as on retirement for
budgeting pension and other old age problems.
5. Probability of length of life after cancer without or
after operation.
6. Chances of survival and period of survival after
surgery, e.g. heart surgery such as bypass, closure of
foramen of ovale, repair and replacement of valves
of heart, etc.
7. Successful chances of grafting of tissues such as

cornea and parts of liver.
8. Survival after transplantation of heart, kidney and
removal of brain tumor, etc.
Application in Community or Public Health Care
and Management
To formulate policy, monitor implementation and finally
to evaluate, data are required. For greater accuracy and
quality, data in large number needs to be calibrated to
assist in decision making. Computers have great capacity
for storage of various types of data past and present.
Accordingly it is of immense utility in comparison of
events related to health and disease as well as in
forecasting of epidemics.
Application in Medicare Delivery Establishments
1. For increasing the efficiency: By utilizing the computerized methods of diagnosis, such as CT scan,
angiography, computer aided treatment such as laser
in lithotripsy, prostate treatment, retinal treatment,
radiation therapy, etc. the patient management has
become convenient, speedy and more effective.
2. Economical: It prevents losses due to errors and
pilferage and reduces various types of expenditures
and helps improve the image of the establishment.
3. Inventory stock: It helps in computerizing full range
of drug reference systems by keeping check over
stocks of drugs and their expiry date and standard
recommended dosage of different drugs in minimum
time with greater economy.
4. Times aving: It helps in time saving over non-clinical
works like quick retrieval of records, spending less
time on each revisit of the patient and quicker billing.
5. Record keeping: Scheduling of appointments to reduce
waiting periods for the patients, manage routine
documents such as growth charts, follow-up of
patients including progress, visits, immunization, etc.
are carried out more efficiently.
6. Academics: It helps in working out various statistical
calculations, finding out various reference materials
for preparation and presentation of research papers
and allied materials.

Medical Research and Practice
1. Medical transcription: Diagnosis, interpretation of
investigations and accordingly appropriate treatment can be made available globally with the aid of
computers. Persons who have undergone training
in medical transcription (MT) can communicate
with medical experts anywhere in world with
patients record and seek advice accordingly.
2. Hospital information system: This includes communication systems to store and display medical
information and advice system to provide information to help doctors in decisions and monitoring.
3. Patient database management
4. Clinical laboratory: These include auto-analyzers of
biochemical tests (e.g. automated hematology
and biochemistry), LARC (leukocyte automatic
recognition by computer), fluorescent activated cell
sorting-helper and suppressor T cells, computerized
chromosome analysis, computerized cytology and
histology and computerized ECG, EEG, and EMG.
5. Medical imaging: These include SPECT (single
photon emission computed tomography), PET
(position emission tomography), computerized
tomography (CT), digital subtraction radiography,
ultrasonography and magnetic resonance imaging.
6. Computer-assisted decision-making: Algorithmic
methods; Bayer methods; artificial intelligense
methods and production rule systems.
7. Computers in the case of critically ill: Automated fluid
and electrolyte balance, pulmonary function
evaluation, cardiovascular physiology evaluation,
cardiac rhythm monitoring, and closed loop ICU
system.
8. Computer-assisted therapy: Pharmacokinetics models
for digital therapy, dosage of aminoglycoside
antibiotics in renal failure and cancer chemotherapy
protocol adviser, radiotherapy planning, diabetes
mellitus management, nutrient management and
nutrient analysis.
9. Computer aids to the handicapped: Mobility assistance
devices, electro-myogenic controlled limbs, devices
for the blind and visually handicapped, devices for
the deaf, speech generation and recognition.
10. Medical research: Model building and simulations,
computer-assisted drug design, biochemistry,
solving chemical reaction problems, biological
control system analysis, epidemiologic and statistical research.
11. Computer-based literature search: MEDLARS; other

databases like Cancerlit, AIDS, etc.
12. Computer-assisted instruction and testing: Drill and
practice, simulations of clinical encounters,
computer-based testing and examinations.
Advantages of Automated Quality Control
1. It eliminates the frustrating limitations of paper chart,
such as poor accessibility, illegibility and poor
organization.
2. It helps to achieve cost saving in the medical records
and billing departments by reducing effort spent on
pulling and filing charts and reports in connection
with patients visits and billing.
3. It gives better service to patients by providing better
information availability and more convenient
appointment making and referral.
4. It allows the doctors to do research and quality
assurance studies as part of their daily practice
activities using the same clinical database, which
supports their practices.
5. It helps to have excellent interdepartmental coordination, resulting in a broader impact of improved
patient care and efficiency.
6. It will enhance the ability to effectively evaluate care
and to expand and coordinate various activities
productively.
COSTAR (computer stored ambulatory record) was
successfully used in a Canadian group practice to
improve the quality of their practice. When they chose
detection and recognition of high blood pressure, the
initial analysis showed that only 34% of patients seen
had a BP recorded during t his time; 19% of patients with
high BP were neither rechecked nor diagnosed. After
using COSTAR to remind doctors about checking BP
regularly and following up high BP cases and arriving
at a diagnosis, it was seen that after six weeks rate of
making an appropriate diagnosis increased by 250% in
the test group as compared to the control group.
To facilitate retrieval of patient data from COSTAR,
a system called MLQ (Medical Query Language) has been
developed. This makes it possible to retrieve any
information and any permutation and combinations
through a large hospital database accurately, easily and
with considerable speed.
Computers are widely used in scientific research
because they can analyze a large number of data in
1416
shortest span of time and accurately, thus replacing many

tedious hours of human work in research with better
results. Analysis of health records can also help to
highlight particular trends, which provide valuable tools
in making decisions for national health policies.
Clinical Case Simulation
Clinical case simulations are interactive computer
programs for the education of the medical students,
nurses, paramedical personnel and doctors. The program
covers a variety of subjects and is designed to teach
clinical decision making skills as well as to provide factual
information. Most of the programs are simulated patient
care situations that are either pre-defined or randomly
generated cases. The user is immersed in a real life
situation where he will have to take decisions, like in
real life, for patients. After an initial case description, the
physician or student collects history, physical exam and
laboratory test data, and interprets this information to
arrive at a diagnosis and select initial diagnosis, and can
upon request, suggest appropriate items to narrow the
differential diagnosis. It will also display on request
teaching messages about any vocabulary terms.
Simulated patients offer a risk-free setting to
experiment with, before one comes in contact with a real
life patient. The student can understand the results of
wrong treatment that can even result in death of the
patient (only on the computer screen). Repeated
interaction with the computer programs can raise the
level of an average student to that of a very intelligent
student who has the capacity to grasp the subject by the
traditional methods without repeated sessions.
The programs comment upon and critique the
students work-up and diagnostic presentations and
provide a crude assessment of the students clinical
problem-solving skills. They typically conclude with
explanation of how the situation should be handled.
Some also analyze student responses, provide additional
feedback about specific errors, and score performances.
The student can also test his understanding of the subject
by using the test section of the program. This contains
multiple choice and matching questions and identification exercises. The test questions are randomized to
eliminate the chance that the sequence of the responses
could be memorized.
Thus, they offer a style that is self-paced, personalized, and private-tailored to the needs and responses
of each student.
Artifical Intelligence (AI)

Artificial intelligence is that branch of computer science,
which is concerned with building systems that mimic
human intelligence, largely through the use of nonnumeric symbol process. AI includes such topics as
general problem solving, natural language processing,
expert systems robotics, machine vision, learning, etc.
AI applications in medicine have emphasized CMD
(Computer Medical Decision) systems whose
reasoning is transparent, who have an explanatory
capacity, and who mimic human decision-making in
databases and literature searches.
In the past what did a doctor do when he wanted an
urgent reference? Obviously, he would make a quick trip
to hospital library to sit down with index medicus, or
racks his brain trying to remember where he had seen
something (was it in JAMA or LANCET?). All doctors
go through the harassment of searching references for
their doctoral dissertation while they are studying and
later, when they are preparing research papers for
publications. The process is extremely tedious or
frustrating. One needs to manually look for the
appropriate volume of a specific journal , which may not
be available or often be lost from the liberary. Or if one
does the correct Journal and volume, the very pages you
need are missing! Then comes the problems of xeroxing
the machine either not available or it is not working,
making it necessary to take down copious notes of the
article, which may not be legible.
The pioneer is the National Library of Medicine
(NLM) at Bethesda, Washington which has data-bases
on the medical literature (MEDLINE, this is the world
renowned source of biomedical information). It contains
bibliographic citation and abstracts of biomedical
literature, includes all foreign languages and all data
elements from 1996 to date and is fully indexed.
CD-ROM (computer disc read only memory) is a high
storage capacity. CD-ROM searching takes far less time
than that needed to search the indices of many large
volumes of printed reasserts. Also CD-ROM saves shelf
space regularly taken by cumbersome volumes of printed
material. One can search a subject from different angles
and combinations, such as topic title, year of publications
and many more. Search strategies and results can be
printed or downloaded to floppy discs. More importantly, CD-ROM data is updated more frequently than
its print equivalent. Thus with CD-ROM, one is sure to
receive the most current information. There are many
subsets of MEDLINE-AIDS, BIOTHICS, CANCER,
PsycLIT, etc.

BIBLIOGRAPHY
1.
2.
3.
4.
5.
Bhave S. Computer languages, programming and

computer viruses. Bombay Hosp J 1991:33:130-5.
Bhave S. Interactive technology in the field of medical
education. Bombay Hosp J 1991:33:122-31
Bhave S. Introduction to basics of computers. Bombay
Hosp J 1991:33: 122-32.
Bhave SY. Computer programmes in pediatrics. Indian
Pediatr 1992;29:245-53.
Egan GF, Liu ZQ. Computers and networks in medical
and health systems. Comput Bio Medicine 1995;25:
355-65.
6.
7.
8.
9.
10.
11.
Fraser HS, Kohane IS, Long WJ. Using the technology of

World Wide Web to manage clinical information. BMJ
1997: 314:1600-3.
Lele RD. Computer in Medicine, 1st Edition, New Delhi:
McGraw Hill 1998.
Lindberg DAB, Humphreys BL. Computers in medicine.
JAMA 1995;273: 1667-8.
Mahajan BK. Methods in Biostatistics for Medical
Students and Research Workers. 6th edition, 1997:320-5.
Millman A, Lee N, Brock A. Computers in general
practice-I, BMJ 1995;31:800-2.
Yah-Sung Kim J. Computers at the forefront of medicine.
JAMA 1995;173: 1060-65.
34.1 Common Procedures in Pediatric Practice: Baldev S Prajapati, A Parthasarathy ....................................................................... 1420
1420
34.1 Common Procedures in Pediatric Practice

Baldev S Prajapati, A Parthasarathy
INTRODUCTION
Sedation
It is very essential for every pediatric student to learn

performing common pediatric procedures. The procedures
are best learnt by observation, performing the procedure
under supervision and repetitive performances. It should
be practical, methodological and safe for both patient as
well as who performs the procedure.
Children are afraid of procedures and their reactions in

form of crying, struggling and frightened appearance
increases the parental anxiety. It affects the performance
of the person who is performing the procedure. It results
in increased rate of failure and complications related to
procedure. In this situation sedation to the child may help.
Promethazine 1 mg/kg/dose or Triclofos sodium 20 mg/
kg/dose by oral route will suffice in most of cases.
Diazepam can also be used. Rarely, Ketamine or general
anaesthesia may be needed.
GENERAL CONSIDERATIONS
Counselling
Explain the parents in details regarding the procedure
including its indications, technique of the procedure,
possible complications etc. If the child is older and able to
understand, talk to him also in simple language. By this,
cooperation is available from parents as well as the child.
It decreases the anxiety of all and the procedure can be
performed smoothly.
An informed consent is must for all the procedures. In
certain procedures like lumbar puncture, pleural and
pericardial tapping, liver biopsy, renal biopsy, exchange
transfusion, bone marrow aspiration and biopsy, it is the
prudent to get signed consent.
Procedure Room and Lighting
Separate procedure room is desirable. It should have good
daylight and should be well illuminated. It should be well
equipped. All the equipments and drugs to perform the
procedure as well as to manage any emergency if it arises
should be made available.
Containers
It is very important to confirm that proper containers are
available for collection and transferring the specimens.
Identification of the Patient
It should be routine to identify the child before performing
the procedure. It should be confirmed with hospital staff
as well as the parents that you are dealing with the correct
child.
Restraint
Physical restraint of the frightened child may be essential
for the successful outcome of any practical procedure. The
child may be wrapped with a blanket taking care to prevent
aspiration or airway obstruction. The help of the person
who is assisting is very crucial in deciding the outcome of
the procedure.
Anaesthesia
Local anaesthesia may be achieved by infiltrating tissues
around the site with 0.5% to 2% lignocaine. The maximum
dosage of 1% lignocaine can be infiltrated is 0.3 ml/kg.
An alternative is to apply lignocaine cream to small area
of the skin 60 minutes prior to performing the procedure,
protected by adhesive dressing. Sedation or general
anaesthesia may be needed in certain cases.
Asepsis
The physician should scrub hands and forearm using an
effective cleaning agent like 4% chlorhexidine or
hexachlorophane before undertaking any procedure.
Wearing of sterile gloves by the doctor is very important
both for his and the patients safety. The site of the patients
skin is then cleaned with 70% isopropyl alcohol and the
surface allowed to dry, the surface is then again washed
three times with 10% povidone iodine or 0.5% chlorhexidine gluconate in 70% isopropyl alcohol. It should be
cleaned in a circular fashion from the centre outwards.
Pediatric Procedures
INTRAMUSCULAR INJECTION (IM)
Common Sites
Muscles commonly used for IM injections are vastus
lateralis, deltoid, gluteus medius. Children do not have
well developed gluteus medius and therefore it is not the
site of preference for IM injections. It has been documented
that some vaccines like hepatitis B and antirabies vaccines
administered at gluteal region produce very poor antibody
response.
The vastus lateralis (anterolateral aspect of thigh) is
preferred site in infants. The site in vastus lateralis is the
middle third of the area between the greater trochanter
and lateral femoral condyle (Fig. 34.1.1).
In case of deltoid, the site for injection is midway
between acromion process and deltoid insertion, it comes
to 3 to 5 cm below the acromion process. This site may be
used in children above 5 years and adults. The quantity of
drug should be less than 5 ml. Only watery injections
with less viscosity should be injected at deltoid region.
1421
The syringe is filled with the medicine.

In children usually 23G needle with 25 mm length is
used for IM injections.
Stretch the skin flat and push the needle down at 90o.
(Fig. 34.1.2).
Aspiration before injecting the vaccine is not required.
Inject the vaccine at the rate of 1 ml per 10 seconds.
The needle is withdrawn and injection site is pressed
for few seconds. Do not rub the injection site.
Needle should be withdrawn smoothly with steady
movement.
Discard the needle and syringe as per standard
guidelines.
Alternative to WHO technique, ACIP technique may
be used. It is also called bunching technique. In this
technique, bunch the muscle and direct needle inferiorly
along long axis of leg at an angle of 45o. It stabilizes leg
and increases the muscle mass.
Figure 34.1.2: The position of the needle during different

ways of administering injections
Subcutaneous Injection (SC)

Figure 34.1.1: Site for intramuscular injections in an infant
Technique (WHO Technique)

The site of injection should be exposed well.
For anterolateral aspect of thigh, the child may be laid
supine or be held in mothers lap. For deltoid, child
may be held in mothers lap or may sit.
The muscle selected for injection should be relaxed.
The skin over injection site should be cleaned with
spirit. A circular motion of swab is used proceeding
from puncture site and extending outward for 5 cm.
Let the spirit evaporate and skin become dry, otherwise
spirit entering into tissues is painful.
Drugs or vaccines are injected subcutaneously when slow

absorption and long duration of action are desired.
Another indication of SC route is a coagulopathy which
makes IM injection hazardous, for fear of development of
intramuscular hematoma. Insulin and Heparin like drugs
as well as measles, varicella, MMR etc. vaccines are given
by SC route.
Technique
Common sites are arm, anterior abdominal wall and
thighs. Atrophic and infected areas are avoided.
The skin is cleaned and disinfected with spirit.
26 G needle with 13 mm length is commonly used for
SC injection.
1422
The skin is raised into a fold with thumb and index

finger of the left hand.
The midpoint of the fold is pierced with the needle
held at 45o with its surface. The tip of the needle is
advanced into the subcutaneus tissue (Fig. 34.1.2).
Aspiration is not required.
Drugs or vaccine is injected, needle is withdrawn and
site is pressed for few minutes.
Intradermal (ID) Injection
Indications for ID injections are BCG vaccination, Mantoux
test, skin tests for allergy, test for sensitization of certain
drugs like penicillin etc.
Technique
Ventral (volar) aspect of forearm is commonly used for
ID injection.
Skin is cleaned with spirit or clean water.
A measured amount of antigen (usually 0.1 ml) is
drawn into the syringe.
26 or 27 G needle with to inch (6.35 to 12.7 mm)
length needle is used for ID injection.
The skin is held taut between thumb and index finger
of the left hand. The syringe is held at an angle of 10 to
15o with the skin. Needle is inserted for about 2 mm, so
that entire needle bevel penetrates the skin and the
injected solution raises a small bleb of about 5 mm in
diameter. The development of perifollicular puckering
(Peau dl orange) indicates successful ID injection
(Fig. 34.1.2).
The needle is withdrawn.
The site is circled and it is recorded in patients chart.
The reaction is observed in defined time.
firmly to prevent expulsion of the drug. Paracetamol,

Diazepam, Midazolam, Paraldehyde, Glycerine,
Bisacodyl, Diclofenac sodium, Steroids, Neomycin,
Artesunate and many more drugs can be administered
through rectal route. When rectal preparations are not
available, some liquid preparations like Inj. Diazepam may
be given per rectum. For this purpose, a lubricated tube is
inserted into the rectum to a distance of about 5 cms and
then the medication is administered through it using a
syringe. The buttocks are held together for a couple of
minutes. Local irritation and ulcerations in rectum may
develop as complications of this procedure.
Peripheral Intravenous Access
Peripheral intravenous access is one of the mainstays of
modern medicine. It allows blood sampling, administration
of medicines, fluids, nutrients, blood and blood products.
Intracaths and scalp vein needles are commonly used for
this purpose. Various sites for venous access are as follows
in order to preference (Fig. 34.1.3)
Veins on dorsum of hand.

Superficial radial vein on radial aspect of wrist.
Superficial veins over volar aspect of forearm.
Basilic vein and median cubital vein over antecubital
fossa.
Superficial veins over dorsum of foot and long
saphenous vein on medial aspect of leg above the ankle.
Veins of scalp in newborns and infants.
External jugular vein.
Straight, large, easily accessible peripheral veins in
healthy subcutaneous tissues are ideal for venous access.
Veins of the upper extremities are preferred because there
are many potential sites and more comfortable to the
Rectal Administration of Drugs

It is a safe and easy way of administering drugs. The
human rectum represents a body cavity in which drugs
can be easily introduced and retained. The absorption of
the drugs is well through this route. Rectal administration
of drugs is indicated in patients who are not able to take
orally due to nausea and vomiting, having convulsions,
uncooperative children, before surgery etc.If the child can
understand, it should be explained to him. The child
should be relaxed. He is kept in lateral position with knees
flexed towards abdomen or in supine position with legs
taken upwards towards abdomen and the drug is inserted
into the rectum through anal orifice and buttocks are held
Figure 34.1.3: Common Sites for venepuncture
patient. The distal and superficial veins are preferred as
complications are more following extravasation and
thrombophlebitis in proximal and deep veins. When the
veins are not visible, they can be palpated at common
sites and can be accessed.
Scalp vein needle is a hollow needle with butterfly
plastic handle and a plastic tube, at the other end of which
a syringe or infusion set can be attached. It is useful for
venous sampling of blood and short term use of
intravenous route (Fig. 34.1.4). Vein is counter punctured
very easily on movement of the limb.
1423
Tapping sharply over the vein causes mechanical

reflex dilatation of the vascular walls. It should be light
otherwise pain will cause vasoconstriction.
Active or passive pumping of extremity enhances blood
flow and distends veins.
A warm moist towel may be applied to the site for
several minutes. It causes venous dilatation.
Aseptic precautions are mandatory.
The methylated spirit is applied over 4 to 5 cm area at
planned site. Let it dry.
The skin is pulled taut distally to stabilize the vein
with a non dominant hand. It is punctured by the
needle, bevel up at 15o to 30o angle, parallel to the vein
(Fig. 34.1.5). After entry into the subcutaneous tissue,
the needle is aligned parallel to the skin surface and
along the long axis of the vein. Its tip is depressed a
little and is advanced until it penetrates the vein. Then,
it is made parallel to the vein again and advanced
until it is passed fully into the vein. Blood is collected
if indicated and then the IV set is attached to it.
Figure 34.1.4: Technique of venepuncture with scalp
Intracaths are plastic catheters over a hollow metallic

needle. The metallic needle just projects beyond the tip of
plastic catheter. The metallic needle is to provide stiffness
during insertion into the vein, after which it is withdrawn.
The plastic catheter is then advanced further gently so
that vein is not counter punctured. The plastic catheter is
well tolerated. Intracaths and scalp vein needles are
available in various sizes from 26 G to 16 G. In children
commonly, we use 26G to 21G depending on age of the
child and requirement.
Technique
A tourniquet is placed over the limb, 3 to 4 cm proximal
to the site selected for venepuncture, taking care not to
pinch the skin of the child. The pressure should be
such that it occludes venous flow, by continuous
arterial blood flow.
Figure 34.1.5: For inserting the IV canula on the dorsum of the

hand the hand may be held flexed at the wrist to occlude
venous return and make the veins prominent
The tourniquet is removed and the infusion is started

by releasing the clamp on the tubbing. A hub of the
cannula and IV set are secured to the skin with the
adhesive plaster.
For flushing the cannula, normal saline should be
used and not the distilled water. Distilled water causes
pain at IV site and it also causes hemolysis.
If venepuncture is performed only for collection of
blood, pull the needle gently after collecting the
required sample and apply steady pressure at the site
with a piece of spirit swab for few minutes.
Intraosseous Infusion
Peripheral percutaneous venus access is the fastest
method of obtaining vascular access in children. However,
1424
during life threatening emergencies, rapid access to

venous compartment through peripheral or central venous
route is occasionally difficult or impossible procedure for
a pediatrician to perform. Small peripheral vessels in
children often collapse during shock and efforts at setting
up an IV line in a peripheral vein may fail. When IV access
cannot be established within three attempts or 90 seconds
time, intraosseous route should be used as per recent
recommendations.
Common Sites
Anteromedial surface of the proximal tibia, one or two
finger breadths distal to tibial tuberosity to avoid
damage to epiphyseal growth plate.
2 to 3 cm above the lateral condyle of the femur in the
midline.
Medial surface of the distal tibia, proximal to the medial
malleolus.
Technique (Fig. 34.1.6)
Specially designed needles, Jamshidi type available
for intraosseous infusion should be used, if available.
Hypodermic needle can also be used. 20 to 16 FG needle
can be used for children below 18 months of age and
16-12 FG for older children.
Identify the site of placement.
Patients leg should be restrained, a small sand bag is
placed behind knee.
The use of local anaesthesia is optional, but usually
recommended as it may be more painful once the child
is resuscitated.
Aseptic precautions are must.
Insert the needle perpendicular to the skin and advance

to the periosteum and then with a screwing motion
penetrate into the marrow. A distinct give way
sensation indicates that your needle is in marrow.
Confirm that the needle is firmly embeded in the bone.
Insertion of needle to a depth of 1 cm is usually
adequate as the distance from skin through the cortex
is rarely more than 1 cm in infants and children.
The needle should maintain erect posture without
support.
Trocar is removed and correct position is verified by
aspiration of marrow and easy flushing with 5-10 ml
of normal saline without signs of extravasation.
The needle should be secured and apply sterile
dressing over the site.
It should be watched for local complications like
extravasation and infection.
As soon as the peripheral IV route is established,
intraosseus needle should be removed.
Emergency drugs and fluids can be administered
intraosseously essentially the same dosage and rates
as given by intravenous route.
Venous Cutdown (Venesection)
Venous cutdown is now rarely resorted to in the present
scenario of cannulas and intraosseous access. It is mainly
useful when routine intravenous access has failed in
conditions such as shock or when large amounts of fluids
have to be given for a long time as in total parenteral
nutrition.
Sites
Lower limb: Most preferred site is saphenous vein near
ankle.
Upper limb: Median cubital or basilic vein in front of
elbow.
Cephalic vein at the wrist at anatomical snuff box.
External jugular vein in the neck.
Figure 34.1.6: Intraosseous cannulation technique
Get all the instruments ready.

Prepare the part aseptically. Then, it is draped with
sterile towels.
0.5% Xylocaine is infiltrated subcutaneously at the site
of incision. In emergency, local anaesthesia can be
skipped.
1425
As alternate route is possible, earliest venesection tube

should be removed.
External Jugular Vein Puncture
The external jugular vein is formed below ear and behind
the angle of mandible, passes downwards and obliquely
backward across the surface of sternocleidomastoid muscle
and ends in subclavian vein lateral to anterior scalene
muscle.
Figure 34.1.7: Venous cutdown
A 1 to 2 cm long transverse incision is made 1.5 cm

above and in front of medial malleolus, over the
saphenous vein.
The vein is exposed by blunt dissection, opening the
blades of mosquito forceps parallel to the vein.
Pass the tip of mosquito artery forceps under beneath
the vein and elevate atleast 1 cm above the vein.
Pass two silk ligatures under the vein.
Separate the proximal and distal ligatures for full
length of exposed vein.
Tie the distal ligature and hold the ends with mosquito
forceps.
With venesection scissors put v shaped cut on
anterior wall of the vein at middle of the exposed part.
Introduce polyethylene tube of suitable size proximally
through the cut in the vein till the free flow of blood is
obtained.
Cannula is fixed by tieing proximal ligature on the
vein with cannula in vein.
Ends of proximal and distal ligatures are trimmed.
Wound is sutured by silk sutures in a way so that
cannula or tube does not get kinked or obstructed.
Dressing is applied and remaining part of tube is
properly fixed with dressing.
IV drip is connected to the venesection needle.
Place the patient in supine. Both the shoulders should

touch the table and head is rotated fully to one side
and extended partly over the end of the table so as to
extend the vein. Making the child cry makes the vein
prominent.
Restraining the child properly is very important.
Clean the overlying skin.
Use proper size of the cannula. Keep the cannula in
the direction of the vein with the point aimed towards
the same shoulder.
Make the venepuncture midway between angle of
mandible and midclavicular line.
Proceed as described for veins of extremities.
After removing the needle, apply constant pressure at
puncture site for five minutes while child is sitting.
Complications
Wound infections
Thrombophlebitis
Deep vein thrombosis
Air embolism
Injury to adjacent nerves and vessels
Figure 34.1.8: Position for jugular vein (both internal and external) puncture. The arrow shows the direction of insertion of
the needle for external jugular vein puncture
1426
Internal Jugular Vein Puncture
Femoral Vein Puncture
The internal jugular vein emerges from the base of the

skull and enters the carotid sheath posterior to the internal
carotid artery. It runs medial to sternocleidomastoid
muscle in its upper part, posterior to it in the triangle
between two inferior heads of the sternocleidomastoid
muscle in its middle part and behind the anterior portion
of the clavicular head of the muscle is lower part. It ends
just above the medial end of the clavicle by joining the
subclavian vein.
In view of risks of femoral venepuncture, it should be used

as a last resort for collection of blood samples in neonates
and infants.

The right side of the neck is preferred as dome of right
lung and pleura is lower than that of left, it is more or
less straight to the right atrium and thoracic duct is
very close to left subclavian vein.
For cannulation of internal jugular vein, there are three
alternate approaches, central, posterior and anterior.
Place the patient in supine, head down position to
distend the vein. It also reduces the possibility of
developing air embolism. Extend the patients head
and turn it away from the side of venepuncture.
Clean the wide area around the site of puncture. Drape
the area as for any surgical procedure.
Wear a gown, face mask, hair cover and sterile gloves.
Puncture the skin with the bevel of needle upward.
Flush the needle to remove occasional skin plug.
It can be performed by central approach, posterior
approach or anterior approach. It should be performed
only by the expert person.
Do not inject materials into the internal jugular vein or
other deep veins.
Figure 34.1.9: Internal jugular vein puncture technique

Restraining the infant in frog leg position.
Clean the inguinal area properly. The part is cleaned
properly with spirit iodinespirit.
The femoral artery is located just below mid point of
inguinal ligament.
The femoral vein lies medial to the artery.
Skin is pierced about 1 to 2 cm as below the inguinal
ligament directly over the femoral vein and the needle
is advanced at an angle of 30 to 45 degree with the
skin while maintaining the gentle negative suction.
As the vein is punctured, the blood is withdrawn in
the syringe. If no blood is obtained while needle is
inserted, suction should be maintained as the needle
is slowly withdrawn. Sometimes needle passes through
both the walls of the vein and blood is obtained only
when the needle is being withdrawn.
On removal of needle, apply firm pressure over the site
of puncture for atleast 3 to 5 minutes to avoid oozing
and hematoma formation.
Precautions
As far as possible avoid this procedure.
Strict asepsis is must as there is potential risk of septic
arthritis and osteomyelitis.
Figure 34.1.10: Femoral puncture technique
Be careful regarding piercing the femoral artery which
can be identified by bright red colour of blood as jet
flow of it. If artery is pierced inadvertently, remove the
needle and apply pressure for a long time and check
the limb periodically for pulsations, colour and
warmth.
Umbilical Vein Catheterization
It is used for exchange transfusion. It may be used for
rapid replacement of fluids and blood especially in
neonates. Umbilical vein is better avoided for any other
use except exchange transfusion. Now a days, exchange
transfusion is also preferred by peripheral route.
The umbilical vein spirals through the cord and is at
12 Oclock position at level of abdominal wall. Here it
turns cephalad and runs slightly towards right to enter
the porta hepatis. It continues with left portal vein and
then communicates with left hepatic vein and then with
inferior vena cava. The umbilical vein is much wider than
umbilical arteries.
Technique
The child should be in supine position with gentle
restraining. A padded crucifix splint is used to restrain
the baby.
Sterilize and drape the skin around the umbilical
stump.
The cord is then cut cleanly about 2 cm above the
umbilicus and umbilical vein is located at 12 Oclock
position. The blood clot in the vein is expressed or
pulled out by a fine forceps (Fig. 34.1.11).
1427
Mark the catheter for the correct distance to be inserted,

which is about 20% of the crown heel length.
The catheter is passed into the vein slowly and gently,
giving caudal traction on the cord stump till free flow
of blood is obtained.
Flush the catheter with heparinized saline.
The free end of the catheter should be strapped to the
abdominal wall.
Special Points
If the cord is dried up, it can be excised flush with the
umbilicus which can expose the orifice of the umbilical
vein at 12 Oclock position. This can be gently dilated
with Hagars dilator and then catheterized.
If both these methods fail, supraumbilical cut down
will become necessary.
Remove the umbilical vein catheter within 24-48 hours.
The catheter tip should be advanced upto thoracic
portion of the inferior vena cava.
While passing the catheter, the resistance is felt at the
ductus venosus. The catheter should be passed 1 to 2
cm beyond this point.
Complications
Infection
Vessel perforation
Thrombosis of portal vein and portal hypertension in
the future
Liver infarction
Liver abscess
Figure 34.1.11: Cutting the umbilical cord for vessel catheterization

Insertion of umbilical catheter in umbilical vein
1428
Necrotising enterocolitis
Cardiac arrhythmias
Umbilical Artery Catheterization
It is used for periodic monitoring of arterial blood gases
and for constant monitoring of blood pressure in a neonate.
There are two umbilical arteries and the lumen appears
patent.
Technique
Prepare the umbilical stump as for venous catheterization.
Identify the artery and insert the catheter gently in the
caudal direction, pulling the umbilical stump
superiorly.
Position the tip of the catheter at either high (in the
lower thoracic aorta above the diaphragm between T4
to T11 vertebrae) or low position (in the abdominal aorta
opposite 14 vertebra).
Keep observing the colour of lower limbs during the
procedure.
Fix the catheter in place using purse string sutures at
the place.
Strap the free end of the catheter to the abdominal wall
after filling it with heparinized saline and closing the
end with a rubber stopper.
Every time before sampling, remove the heparinized
saline in the syringe along with same blood, then collect
the sample and reinfuse the previously collected blood
to the child.
Allen Test (Fig. 34.1.12)

Make the patients hands warm to make pulsations
easily demonstrable.
Have the patient open and close the hand, held out in
front and then clinch the fist tightly closed.
Occlude both radial and ulnar arteries for 30 seconds.
Have the patient open the hand. Hand has become
pale due to occlusion of radial and ulnar arteries.
Release the pressure over the ulnar artery and observe
the open hand for return of normal pink colour. Return
of normal colour within 6 seconds indicates patency
of the ulnar artery and an intact arch with good
collateral circulation.
Delay of appearance of normal colour from 10 to 15
seconds indicates slow filling of the ulnar artery and
collaterals.
Persistent blanching for more than 15 seconds indicates
an incomplete arch or poor collaterals.
Same test can be performed to cheek patency of radial
artery.
If ulnar collateral circulation is good, radial artery
puncture can be performed.
Complications
Vessel perforation
Thromboembolism
Air embolism
Hypertension
Necrotizing Enterocolitis
Infarction of distal extremities
Renal infarction
Radial Artery Catheterization

It is very useful and frequently used for repeated sampling
of arterial blood and for continuous arterial pressure
monitoring. The radial artery is easily accessible at the
wrist in the groove between the tendon of the flexor carpi
radialis medially and the distal radius laterally.
Before puncturing the radial artery carry out the Allen
test to assess the ulnar collateral circulation.
Figure 34.1.12: Allen test

Patients hand should be supported and dorsiflexed at
the wrist approximately 60o with both hands and lower
forearm secured to a board. A roll of gauze behind the
wrist will maintain dorsiflexion.
Locate the radial artery just proximal to head of radius.
Clean the area and observe the absolutely aseptic
precautions.
1429
fevers. Needle aspiration, Trephine biopsy and surgical

biopsy are three methods available for bone marrow
examination. Needle aspiration is commonly practiced in
most of cases in children. It should be done with caution
when a defect in clotting mechanism is suspected.
Common Sites
A
Iliac Crest: This is the most preferred site in children. It

is performed at 1 cm below the posterior iliac crest.
Tibia: At upper end of tibia, just below tibial tuberosity
on its medial aspect.
Sternum: It should be used in children beyond 7 to 8
years of age. Manubrium sterni can be used 1 cm above
sternomanubrial angle, slightly to one side of the
midline.
Rarely, lumbar spinous processes may be used
Technique
Figures 34.1.13A and B: Radial artery (A) anatomy and

(B) catheterization technique
Infiltrate the skin with local anesthetic agent.

Insert the catheter needle at about 30o angle to the
surface of the skin and advance the catheter and needle
stylet into the artery until blood appears in hub of the
needle.
Remove the needle and attach the hub of the catheter
to the connecting tubing.
Secure the catheter at the place with silk sutures.
Fix the wrist in a neutral position to the board. It is
essential as flexion at wrist can disturb the arterial
line.
Cover the insertion site with sterile dressing.
Atropine should be given as premedication.

Aseptic and antiseptic precautions are must during
the whole procedure.
Local infiltration of 1% Lignocaine from skin to
periosteum. In some irritable children, general
anaesthesia is desirable for successful outcome of the
procedure.
The needle for bone marrow aspiration should be stout
and made of hard stainless steel. It is about 7 to 8 cm
long with a well fitting stylet and an adjustable guard
(Fig. 34.1.14). The point of needle and edge of bevel
should be sharp. The Sahan and Klima needles are
most commonly used needless. Some people prefer to
use stout hypodermic needles so that it can be
disposed after use and complications of reuse of the
needle can be avoided.
Special Points
Do not perform the procedure if Allen test is delayed.
Observe the colour of palm periodically after
cannulation.
Before sampling blood, flush the line with 2% Normal
saline.
Do not infuse medications, blood products through
the arterial line except flushing fluid.
Bone Marrow Aspiration
This is very common ward procedure indicated in children
with blood dyscrasias, malignancies and undiagnosed
Figure 34.1.14: Bone marrow aspiration needle
1430
The needle with the guard adjusted 0.5 to 1 cm from

the tip of the needle is introduced into the iliac crest or
sternum with screwing or boring movements keeping
the needle vertical. The force required varies, but need
to be considerable. Sudden giving in of resistance
indicates entry of the needle into the bone marrow.
Leave the needle and if it remains steady, it indicates
that the needle is in the bone marrow.
The stylet is withdrawn and marrow is aspirated with
the syringe. About 0.2 ml of marrow is aspirated. This
procedure is performed swiftly to obtain only bone
marrow particles as slow sluggish aspiration causes
dilution of marrow with blood.
To prevent dilution of marrow with blood, aspirate
material only till it appears beyond nozzle of syringe.
It is sufficient material for examination. Aspiration
beyond it increases the chances of marrow dilution.
The needle is withdrawn and smear is prepared with
marrow. With good material and well prepared smear
marrow particles can be seen by naked eyes.
Press the site for 5 minutes. Apply tincture of benzoin
seal at puncture site.
Along with smears of bone marrow, smears from
peripheral blood should be prepared and sent for
examination.
Relative contraindication in patients with cardiovascular unstability as the procedure may cause
cardiorespiratory arrest.
Technique
Informed written consent is must.
The patient is placed on his side at the edge of the table
or bed with the knee drawn up towards abdomen and
the head flexed to get maximum flexion of the spine
(Fig. 34.1.15). If the child is newborn or child has
respiratory problem, child should be firmly fixed at
shoulders and buttocks only without flexing neck and
drawing up knees. In infants sitting position allows
easier identification of the midline. An experienced
assistant has a vital role in positioning, restraining
and comforting the patient.
Aseptic and antiseptic precautions are must.
Routinely, local anaesthesia is not used. But in older
children those are irritable, local anaesthesia may be
useful for performing the procedure smoothly.
Complications
Local pain and hematoma.
Injury to mediastinal structures in case of aspiration
at sternum.
Infection.
Dry tap.
Lumbar Puncture
This procedure is performed to obtain cerebrospinal fluid
sample for analysis in diagnosing infections and other
disorders of central nervous system. It is also used for
monitoring CSF pressure, intrathecal drug administration
and removing CSF in some cases of hydrocephalus.
Contraindications
Marked raised intracranial pressure with closed
fontanelle as shown by papilledema because of risk of
herniation of brain substance through foramen
magnum.
Local infection.
Figure 34.1.15: Position for lumbar puncture
Site of puncture is defined by palpating the iliac crest
which corresponds to L3-L4. Hold the needle between
index and middle fingers, the thumb acting as guard
at open end.
In children instead of lumbar puncture needle with
stylet, simple hypodermic needle is commonly used.
22 FG to 18 FG disposable needles are well suited for
infants and children. Some people have good
experience with use of disposable scalp vein for lumbar
puncture in neonates and children upto age of 2 years.
Scalp vein set No.23 with 2 cm length is suitable for
neonates.
Gently introduce the needle in midline at above
mentioned space, needle being directed towards
umbilicus. Entry into the subarachnoid space is
indicated by giving the way sensation and free flow of
CSF.
Collect the CSF 0.5 cc in EDTA bulb for cell count and
1 cc in plain bulb for biochemistry. It should also be
collected in sterile bulb for culture. CSF should be
examined earliest, usually within 30 minutes.
Remove the needle and apply firm pressure for few
minutes.
Apply tincture benzoin seal at puncture site.
In a case of raised intracranial pressure, head should
be kept little down to prevent herniation of brain
through foramen magnum.
Monitor the patient for some time after the procedure
for pulse and respiration.
Complications
1431
Scalp should be shared, atleast 5 cm posterior to the

anterior fontanel and 5 cm lateral to midline and
anteriorly upto forehead.
Sedation may be required in irritable infants.
Child should be in supine position with head at edge
of the table.
One person should hold the head at the middle position
and another person hold the shoulders (Fig. 34.1.16).
Strict aseptic and antiseptic precautions should be
taken.
Sterilize the area.
Lateral margins of anterior fontanel are palpated along
the coronal sutures and the site is chosen either as for
lateral as possible or at the area of maximum
transillumination.
It should be atleast 2 to 3 cm from the midline to prevent
injury to the underlying sagittal sinus.
A zig-zag puncture is used to prevent later leakage of
subdural fluid.
A disposable No.20 gauge needle is used. The skin is
first pulled to one side and then needle is passed
perpendicular to the scalp through the suture line and
into the subdural space to a depth of approximately
0.3 to 0.6 cm. A definite pop giving the way is felt on
entering the subdural space. The flow of fluid will be
there on entering the subdural space. If flow of fluid is
not there, slight adjustment or rotation of the needle
may be necessary.
The subdural fluid is allowed to drain spontaneously.
The fluid should not be aspirated for fear of drawing
pial vessels into the point of needle.
Infection
Conning
Headache
Injury to local structures
Epidermoid tumor
Subdural Tap
It is indicated for diagnosis of subdural hematoma,
effusion and empyema.
Technique
Before subdural tapping, ultrasonography or CT Scan
study of cranium is desirable.
Figure 34.1.16: Position of head for performing subdural tap
1432
The subdural fluid is collected in EDTA and plain

bulbs for examination. Smear for gram stain should be
prepared. It should also be collected for culture.
The subdural tap must be performed on both the sides.
Samples from both the sides should be kept separate
and labeled properly indicating right and left side.
Maximum 10 ml of fluid should be tapped from each
side.
Subdural fluid will be either blood stained or
xanthochromic but not clear. If it is clear, it is most
likely CSF through ventricular tapping.
Remove the needle and sterile benzoin seal is done.
Dressing should be done tightly with sterile gauge and
adhesive tap.
Complications
Trauma to blood vessels and hematoma formation.
Infection leading to subdural empyema.
Ventricular Tap
This procedure is useful in newborns for diagnosis of
ventriculitis and intraventricular haemorrhage. It is also
performed to relieve the acute rise of intracranial pressure
in non-communicating hydrocephalus. In some
conditions, it may be done to administer intraventricular
drugs.
Technique
Before ventricular tapping, ultrasonography or CAT
Scan study of cranium should be done.
Informed written consent should be taken.
Shaving of scalp.
Sedation, if necessary.
Aseptic and antiseptic precautions.
Child should be in supine position with head at middle
at edge of table.
One person should hold the head at middle position
and another person should hold the shoulders.
The ventricle is entered by passing No.23 FG needle in
neonates and No.22 FG in infants, 4 to 5 cm long
disposable needle through lateral margin of anterior
fontanel and keeping the direction of needle slightly
inwards towards inner canthus of opposite eye or
nasion (Fig. 34.1.17).
Depending on the degree of ventricular dilatation and
size of the patient, the ventricle is reached at the depth
of about 2.5 cms.
Figure 34.1.17: Ventricular tapping. The needle should be

directed forwards and inwards towards nasion.
Entering the ventricle, it gives the way.

No syringe suction should be applied.
CSF should be collected in EDTA and plain bulbs for
examination. Smear should be prepared for Grams
stain.
After removing the needle, press at puncture site for
some time.
Sterile benzoin seal is done. Dressing should be done
with sterile gauze and adhesive tap.
In a case of hydrocephalus, CSF can be drained in
large quantity.
For administering drugs in ventricles, drug should be
taken in the syringe and after ventricular puncture, it
should be attached with the needle. Let the CSF come
in syringe, get the medicine diluted in CSF and then
inject back into the ventricle. Drug should not be
diluted in any solution.
Complications
Ventriculitis.
Injury to brain tissues.
Intraventricular haemorrhage.
Nasogastric Tube Insertion
Nasogastric tube is passed for either aspiration of gastric
contents or administration of feeds or therapeutic
substances. Now a days, silastic and polyethylene tubes
are being used because they have less tissue reactions.
Indications
Diagnostic
Gastric aspirate test for diagnosis of neonatal
septicemia.
Shake test for lung maturity in preterm babies.
Examination of gastric contents for mycobacterium
tuberculosis.
Assessment of upper GI tract bleeding.
Measurement of gastric volume.
Therapeutic
Paralytic ileus.
Intestinal obstruction.
Enteral feeding.
Administration of therapeutic substances.
Contraindications
Esophageal stricture.
Ingestion of alkali-may cause esophageal perforation.
Head and neck injury preventing passage of tube.
Nasal fracture.
Technique
The head is raised in semi upright position.
The distance from nose to ear lobe and from ear lobe to
xiphoid process is determined to measure the length
of tube to be passed. The point is marked on the tube
(Fig. 34.1.18).
The more patent nostril is selected for passing the tube.
The terminal part of the tube is lubricated with a
lubricant. It is avoided in newborns to prevent
aspiration of an oily substance. In that case, it is wet
with water.
1433
The tube is passed into the nostril, its curve direct

downwards. It is passing along the floor of the nose.
In case of difficulty, it is tried in another nostril.
Resistance is felt when it reaches the nasopharynx.
Getting the patient to sip a little water helps to overcome
it.
With swallowing of the saliva or water by the patients
the tube is advanced into the esophagus.
If the patient gags or the tube coils up in the mouth, the
tube is withdrawn partly and again it is passed.
The tube is passed upto the mark as measured length
of the tube to be passed.
Confirmation of proper placement is done by following
tests.
Aspiration of stomach contents on applying suction
at the outer end of the tube with a syringe indicates
that the tube lies in the stomach.
Air is injected into the tube while epigastric area is
auscultated. A sound is heard if the tube is in the
stomach.
Placing a tube in a glass of water and escape of air
bubbles in the water indicates tube lies in the trachea.
Placement of a radiopaque tube can be assessed by
radiography.
The tube is fixed with a tape in a butterfly fashion
around the tube or with vertical tapping over the nose
and the tube. The tapping is done in such a way that
the tube rests in the middle of the nasal lumen and not
directly in contact with mucosa. It is not taped over the
forehead as it may cause pressure necrosis of the nose.
The feed or drug should be allowed to go in the tube by
gravity method. It should not be pushed by piston.
The tube should be flushed with water periodically.
While removing the tube, pinch the tube end to prevent
spilling of the contents into the trachea.
Figures 34.1.18A and B: Method of inserting a nasogastric tube in a child
1434
Complications
Pulmonary aspiration.
Esophageal perforation.
Gastric perforation.
Nasal necrosis.
Esophageal stricture
Instead of nasogastric tubing, now a days orogastric
tubing is preferred to avoid certain complications.
Gastric Lavage
It is useful in poisonings to remove the substance from the
stomach. In corrosives and hydrocarbons ingestion, gastric
lavage is contraindicated. In corrosives, passing the tube
may cause perforation. Since passing the gastric tube is
likely to induce vomiting, it increases the risk of aspiration
of hydrocarbons into the trachea and lungs which causes
pneumonia.
After passing the tube in the stomach as described in
Nasogastric tube insertion, lavage of the stomach using
aliquots of normal saline is done in cases of poisoning. It
is continued till the colour of the lavage is normal.
The hypodermic needle 20 FG is attached to 20 ml

syringe. It is passed into the peritoneal cavity
perpendicular to the skin. As the needle enters the
peritoneal cavity, it gives the way and ascitic fluid
starts to drain through the needle.
In a case of tense ascites, needle should be passed
obliquely or skin should be retracted caudad before
insertion of the needle to produce a Z track effect on
withdrawing the needle so that needle tract after
paracentesis gets sealed properly and persistent
drainage can be prevented after removal of the needle.
After removal of fluid, 10 to 15 ml for diagnostic
purpose, the needle is withdrawn and a seal of tincture
benzoin is applied locally.
If the paracentesis is for therapeutic purpose, the needle
should be connected with IV set and regulator of IV set
is adjusted in such a way that ascitic fluid is drained
slowly. One litre of fluid may be drained over a period
of 2 to 3 hours.
The patient should be watched following the
procedure.
Complications
Abdominal Paracentesis
Abdominal paracentesis is performed for diagnostic
purpose in a case of ascites, peritonitis and haemorrhage.
In huge ascites, it is also done to relieve discomfort and
respiratory embarrassment. In some situations drugs may
be instilled in peritoneal cavity such as malignancies.
Technique
The patient should be placed in supine position. If the
patient is not comfortable in supine position, reclining
or upright position may be used.
Site for paracentesis is selected in the midline, midway
between umbilicus and pubic symphysis or in an iliac
fossa lateral to the rectus abdominis.
The needle should never be advanced through a
surgical scar because it can penetrate bowel adherent
to the under surface of scar, or lacerate an omental or
mesenteric vessel.
Aseptic and antiseptic measures must be taken.
Inj. Atropine as premedication.
1% Lignocaine is infiltrated under skin and into the
deeper structures at the site selected for paracentesis.
Wait for few minutes for full effect of anaesthetic agent.
Intestinal perforation or laceration

Peritonitis
Post paracentesis shock
Electrolyte imbalance
Hypoproteinemia
Perforation of urinary bladder
Pneumoperitoneum
Liver Biopsy
Now a days, liver biopsy is done under ultrasound
guidance rather than blind biopsy.
Indications
Chronic hepatitis
Undiagnosed hepatomegaly
Neonatal hepatitis
Cirrhosis of liver
Fever of unknown origin
Contraindications
Bleeding tendency
Massive and tense ascites
Severe portal hypertension
1435
PRE-REQUISITES
Technique
Bleeding time, clotting time, platelets count, PT.

USG study of liver.
Premedication: Atropine 0.01 mg/kg IM 30 minutes
before the procedure.
Written consent is must.

Inj. Atropine as premedication.
Site of insertion of needle can be decided by chest xray, dull note on percussion and ultrasound study of
thorax. Best way to perform the procedure is under
ultrasound guidance.
It should be performed in sitting position of the patient.
Patient can lean forwards on the teapoy of suitable
height with head resting on his forearms (Fig. 34.1.19).
Technique
Vim Silverman needle, Menghinis needle and Tru cut
needles are used for liver biopsy. Tru cut needle is
disposable, easy to operate and having more success
rate, so it is common in use.
Patient is kept in supine position, near the edge of the
bed or table with the right arm under the head and left
arm by the side.
Preparation of the local area.
1% lignocaine is infiltrated in the skin, intercostal
muscles and Glissons capsule. Wait for some time for
good effect of the anaesthetic agent. Some children may
require sedation or general anaesthesia.
The tru cut needle is introduced under ultrasound
guidance into the liver substance with the inner needle
retracted. The latter is then advanced, holding the outer
cutting sheath steady. The outer sheath is then
advanced to cut the liver in the biopsy notch. The whole
apparatus is then withdrawn together quickly. The
entire sequence should take only few seconds.
The Vim Silverman needle has trocar and bifid needle
to cut the liver tissue. In Menghinis needle the cut
piece of liver is sucked into the syringe applied with
negative pressure.
On removal of the needle, the puncture site is sealed
with tincture of benzoin.
Thoracocentesis (Intercostal Drainage)
Thoracocentesis refers to temporary insertion of a needle
or a catheter into the pleural space for removal of fluid or
air from the pleural cavity. The fluid is collected for
diagnostic purpose and in some situations it is done for
therapeutic purpose to remove fluid or air which is in
large quantity and causing respiratory embarrassment.
Drugs can also be instilled in the pleural cavity by this
procedure, if it is indicated such as in a case of malignancy.
Figure 34.1.19: Another position for doing thoracocentesis
Strict aseptic and antiseptic measures should be taken.

1% Lignocaine is infiltrated at the upper border of the
rib below the space chosen. Anesthetizing wide area
and generous infiltration of local anesthetic agent for
good anaesthesia helps to get good co-operation of the
patient, performing the whole procedure comfortably
leading to successful performance with minimal
chances of complications. Wait for some time for good
effect of anaesthetic agent.
A wide bore needle is connected on one side of the
three way stop cock and opposite to it a syringe is
attached. Three way stop cock is arranged in such a
way that there is a single track between the needle,
stop cock and syringe.
The needle is inserted into the chest in the same manner
as for the anaesthetic needle, finding the intercostal
1436
space and stepping over the lower rib with care,

thereby preventing damage to underlying structures
(Fig. 34.1.20). Slight suction is applied to the syringe,
so that fluid is aspirated in the syringe immediately as
the needle enters the pleural space.
Fluid should be withdrawn slowly and steadily.
A forceps should be attached to the needle at the skin
level which helps to prevent excessively deep insertion
of the needle into the thorax.
The fluid is aspirated in the syringe and then three
way stop cock is turned to connect the syringe with
the outlet which is attached to IV set.
Collect the fluid in EDTA and plain bulbs. It is also
collected for culture. Smear should be prepared for
Grams stain and Ziehl-Neelson stain.
The three way tap is now turned again to connect the
syringe with the needle and the pleural space, a further
aspiration is carried out. It is expelled into the drainage
bag by turning the three way tap. The drainage bag or
bottle should be placed well below the level of the
patients chest.
As fluid is removed, the lung expands and this often
makes the patient to cough.
The needle is withdrawn and puncture site is covered
with a benzoin seal. A sterile gauze is put over it and
adhesive tap is applied.
Unilateral pulmonary oedema

Hypoproteinemia
Endotracheal Intubation
Endotracheal intubation is a procedure which every
pediatrician and one working in intensive care units must
be well conversant with. The critically ill patient often
requires endotracheal intubation. It secures patent airway.
It is a pre-requisite for mechanical ventilation.
Endotracheal suction can most efficiently be done through
an endotracheal tube. It is indicated when bag and mask
resuscitation fails in a case of an asphyxiated newborn.
Indications
In neonatal asphyxia
Bag and mask resuscitation fails
Apparently still born baby after adequate
suctioning of upper airways
Infants with diaphragmatic hernia
Meconium aspiration
Cardiorespiratory arrest due to any cause.
CNS depression in a case of head injury or comatose
child.
Diseases of peripheral nervous system, poliomyelitis,
tetanus, organophosphorous poisoning etc.
Administration of general anaesthesia.
Complications
Pneumothorax
Hemothorax
Infection
Equipments
Laryngoscope with straight blade for neonates.
Endotracheal tubes for various sizes with stylet.
Weight / Age
< 1000 g
1000-2000 g
2000-3000 g
> 3000 g
1 to 5 years
5 to 12 years
ET size (ID in mm)

2.5
3.0
3.5
4.0
4 to 5
5 to 6.5
Approximately size of ET, ID in mm = Age (years)

+ 16/4.
Technique
Figure 34.1.20: Site of needle for pleural fluid aspiration
The patient is placed in a supine position. The operator

stands beyond the patients head. Patients neck is
slightly extended with the head in midline.
Clear the oropharynx with gentle suctioning.
Empty the stomach.
Hold the handle of laryngoscope in left hand with
thumb and first three fingers, stabilize hand with fifth
finger resting on patients cheek. The blade should be
pointing away from oneself.
Open the babys mouth and push the tongue left with
back of right fore finger and steady the head with rest
of right hand.
While visualizing insert the blade midline until tip is
between base of tongue and epiglottis within the
vallecula (Fig. 34.1.21).
If the infant is making respiratory effort, free flow of
oxygen with an oxygen tubing held close to the infants
mouth and nose is to be provided during intubation.
Open the mouth further by pulling on laryngoscope
handle, simultaneously tilt blade tip upward slight to
elevate epiglottis and visualize glottis. Use base of
tongue as pivot rather than maxilla.
1437
Suction is needed.
Have the assistant to palpate suprasternal notch with
index finger, applying gentle pressure if desired.
Hold the tube with concave curve anterior and pass it
down right side of the mouth, outside the blade, with
maintaining visualization.
As the patient inspires, pass the tube through cords
2 cm into trachea or until immediately after tip passes
under assistants finger in suprasternal notch.
The tube is then held firmly at the lips with the right
hand and the laryngoscope and stylet are carefully
removed.
Initially confirmation of the tube placement is
accomplished by attaching a resuscitation bag with
the connector and ventilating the infant. With correctly
placed tube, the air entry is heard on both the sides of
the chest, breath sounds are of equal intensity and air
is not heard entering the stomach. While listening the
breath sounds, the stethoscope is to be placed at
approximately the nipple line.
Note the cm marks on the tube at the level of upper lips
and then secure the tube to the infants face.
Final confirmation of placement of the tube can be
obtained by chest film, if it is needed.
Attempts to intubate should not exceed 30 seconds. If
you are unable to intubate within 30 seconds, abort
and continue with bag and mask and then try again
after a few minutes. Repeated attempts may cause
serious glottic oedema and bleeding.
Intubation is not a matter of prestige. If you are unable
to do so, please ask for help.
Endotracheal route is also used for administration of
some drugs like epinephrine, atropine, naloxone etc.
Complications
Figures 34.1.21A and B: Position of laryngoscope blade when

using (A) curved blade, it is in the vallecula and (B) straight
blade, it is over the epiglottis
Hypoxia
Bradycardia
Apnea
Pneumothorax
Injury and lacerations to tongue, gums, pharynx,
epiglottis, trachea, vocal cords etc.
Infections.
Post extubation stridor can be managed by nebulized
epinephrine or steroids.
Some physicians prefer nasotracheal intubation when
long term ventilation is required.
1438
Suprapubic Bladder Aspiration

This procedure is performed to collect non-contaminated
urine sample in neonates and infants. It is safe and reliable
way of collecting urine samples. It is easy especially in
neonates as bladder is an intraabdominal organ in these
patients unlike a pelvic organ in older children and adults.
Technique
The infant is placed on a flat surface in supine position.
The assistant stands opposite the operator and
immobilizes the infant by grasping the thorax with
one hand and thighs and hips with the other.
Make sure that the bladder is full.
Local part is cleaned. Aseptic and antiseptic measures
must.
A 10 cc disposable syringe with 22 FG, 4 to 5 cm long
needle is taken.
The symphysis is located with one finger and the
needle is inserted 2 cm above the symphysis in the
midline with syringe held at 10 to 20 degree angle
from perpendicular (Fig. 34.1.22).
With a single steady motion the needle is inserted until
a perceptive change in resistance is felt as the needle
enters the bladder.
Light aspiration is applied to aspirate the urine
specimen.
After removal of needle, a seal of tincture benzoin is
applied at puncture site.
Peritoneal Dialysis
Dialysis involves the use of semipermeable membranes
that permit the simultaneous passage of smaller molecular
weight solutes and water while retarding or inhibiting
the movement of large sized particles. The basic principle
Figure 34.1.22: Suprapubic bladder puncture technique
controlling the transmembrane movement of solute and

water are similar whether the membrane is artificial
(hemodialysis) or natural (peritoneal dialysis).
Active transport is not a major feature of the peritoneal
membrane. Two types of passive transport occurs across
the semipermeable peritoneal membrane diffusion and
convection. By diffusion, solute flux occurs in the absence
of osmotic gradient or ultrafiltration. Solvent flux is
facilitated by glucose. Factors that may increase the
peritoneal clearance include increase in flow rate, an
increase in temperature, incretion, use of vasodilator
agents, alternating hypertonic with hypotonic dialysis
solution. In contrast, factors that may decrease peritoneal
clearance include use of dialysate at room temperature,
systemic administration of vasoconstrictor agents,
presence of vascular disease, systemic hypertension,
paralytic ileus etc.
Indications
Blood urea > 300 ms/dL.
Hyperkalemia S. K+ > 6.5 mEq/L not responding to
medical line of treatment.
Severe acidosis.
Pulmonary oedema.
Acute left ventricular failure.
Drug intoxications like barbiturates, salicylates etc.
Life threatening electrolyte imbalance.
Contraindications
Peritonitis.
Abdominal adhesions.
Laparotomy done.
Pleuroperitoneal communication.

Informed written consent.
Aseptic and antiseptic measures must.
Inj. Atropine 0.01 mg/kg IM 30 minutes before the
procedure as the premedication.
Sedation, if required.
Proper restraining.
Bladder is emptied by its own or catheterization, if it is
necessary.
Abdominal wall is prepared, painting spirit Betadine
spirit. Towel draping.
The catheter is usually placed in the midline few cms
below the umbilicus.
1439
Figure 34.1.23: Peritoneal dialysis
If midline insertion is not possible, the catheter can be

inserted in the flank area, outside the line of inferior
epigastric artery.
The site is anaesthetized by injecting 1% lignocaine
upto peritoneum.
If there is no ascites, distend the abdomen with 10 ml/
kg dialysate solution using 17-20 FG angiocath or
needle.
Needle is withdrawn and a knife blade is used to
enlarge the puncture wound in the skin.
If ascites is present, a very small penetrating incision
is made in the skin and the trocar with catheter is
stabilized with the fingers of one hand on the skin
while the other hand introduces the trocar through
the abdominal wall with an alternating drilling
motion.
Penetration upto peritoneum is detected by a definite
sensation of giving the way and also by the
appearance of fluid in the catheter when trocar is
removed.
On reaching the peritoneal cavity and before removing
the trocar, the catheter is gradually advanced in the
peritoneal cavity in right or left para colic gutter and
trocar is gradually withdrawn.
When the catheter is sufficiently introduced in the

peritoneal cavity, trocar is removed totally. All the
fenestrations on the catheter must be within the
peritoneal cavity to avoid subcutaneous fluid
infiltration in the abdominal wall. In neonates and
infants, IV catheters or simple feeding tube can be used.
The catheter should be stabilized with adhesive
plaster.
The catheter is connected with the administration
tubing through small connector and dialysis fluid is
flown.
Because hyperkalemia is often present, potassium free
fluid is used for the first 3 to 6 cycles.
Time of input of dialysis fluid will be about 10-15
minutes. The fluid is kept in the peritoneal cavity for
about 30 minutes. Time for output of dialysis fluid
will be about 15-20 minutes. Each cycle will take about
an hour. First few cycles should be of half an hour
(rapid cycles).
Record the weight of the patient prior to the procedure
and every 12 hours.
Total duration of dialysis is about 40 hours depending
on clinical and biochemical parameters.
Warm the dialysate to body temperature.
1440
Infuse it by gravity flow.

Each cycle should be of 30-50 ml/kg.
Blood sugar, blood urea, serum creatinine, serum
electrolytes, serum proteins should be checked
12 hourly.
In the presence of fluid overload, use hypertonic
dialysate.
Tip of the catheter should be sent for culture.
Close the site of dialysis by sterile bandage.
Peritoneal dialysis related problems like, pain in
abdomen, diarrhoea, dyspnea, bleeding and fluid
delivery should be sorted out appropriately.
Complications
Pain may be due to over distention, peritonitis etc.

Bleeding.
Dialysate leak.
Outflow obstruction.
Peritonitis.
Metabolic complications.
Thrombosis.
Pulmonary complications.
Renal Biopsy
Indications
Steroid resistant nephrotic syndrome
Asymptomatic proteinuria
Glomerulonephritis associated with conditions like
SLE, Henoch-Schnlein purpura etc.
Rapidly progressive glomerulonephritis
Contraindications
Bleeding diathesis
Solitary functioning kidney
Ectopic / Hoarseshoe shape kidney
Severe uncontrolled hypertension
Prerequisites
Bleeding time, clotting time, PT, APTT, platelets count

Blood grouping and cross matching
Hypertension and uremia should be controlled
Informed written consent is must
Technique
Atropine 0.01 mg/kg IM before 30 minutes of the
procedure
The patient is placed in the prone position on a firm

bed. A pillow is placed under patients abdomen. This
compresses and fixes kidneys to the posterior
abdominal wall, bringing the kidneys closer to the skin
and limiting possible ballottement of the kidney by the
biopsy needle.
Ultrasonography is commonly used to mark the
location of kidneys and point of entry of the needle
into the kidney perpendicular to the skin surface and
to obtain depth of tissue from skin surface. Usually,
lower pole of left kidney is selected for biopsy.
The area is prepared and local anaesthesia is given.
Irritable children may need general anaesthesia.
A 23 gauge exploring lumbar puncture needle is
passed downwards and obliquely towards the lower
pole of the kidney. A needle can be felt going through
different structures and renal capsule. Experience
person feels give in feeling up on penetration of capsule
of kidney.
The patient is asked to take slow deep breathings. If
the needle is in the kidney, a characteristic pendular
movement is seen with respiration, the hub of needle
swings through a wide arch, moving towards head
during inspiration and towards buttock during
expiration. If the needle is not in the kidney tissue, it is
slightly advanced until it penetrates kidneys and
moves characteristically on breathing. The depth of
the kidney below the skin is measured on the stem of
the needle.
A small nick is made over anaesthetised area with a
scalpel.
Franklin modified Vim Silverman needle and Tru cut
needle are commonly used in the practice. Tru cut
needle is easy to use and having less failure rate.
Therefore, tru cut needle is preferred now a days.
Tru cut needle is one piece apparatus with a length of
11.4 or 15 cms. The needle with canula covering the
obturator is advanced in the kidney to desired length
in a direction perpendicular to skin surface.
The patient is asked to hold the breath in deep
inspiration.
The obturator is advanced by firm tap on the handle.
The specimen is cut by downward movement of canula
over obturator.
Entire assembly is removed.
The patient is asked to breath normally.
Firm pressure is applied over biopsy site for few
minutes and the site is sealed with tincture benzoin.
Two good cores of tissue (8 to 10 mm long) are needed
for adequate histological examination. One is
immediately fixed in buffered formalin and other in
saline (for immune fluorescence study).
Post-procedure Management
1441
Child should be seated leaning backward at approximately 60 degree angle and carefully restrained.
The best site is xiphocostal angle. The other sites are
4th, 5th or 6th intercostal spaces 1 to 2 cm medial to
the border of cardiac dullness on percussion
(Fig. 34.1.24).
The patient is asked to remain in prone position for

two hours and in bed for 24 hours.
Monitoring temperature, pulse, RR and BP one hourly
for six hours and then four hourly for 24 hours.
Urine should be collected in separate bottles during
each voiding and should be checked for hematuria.
Patient is asked to take ample liquid orally.
Diuretics may be given in case of oliguria to flush any
clot in the passage.
If no frank hematuria and vitals are normal, patient
can be discharged after 24 hours with instructions not
to do exertion for a week.
Complications
Hematuria
Perinephric hematoma
A-V fistula
Pericardiocentesis
Pericardiocentesis is a procedure for removal of fluid from
pericardial cavity for diagnostic purpose or to relieve
cardiac tamponade. It is occasionally a life saving
procedure. It is a risky procedure. It should be performed
only by skilled person under continuous cardiac
monitoring. Echocardiographic diagnosis is must before
performing the procedure. It gives idea regarding amount
of fluid and also helps to determine the anatomical
approach.
Prerequisites
Echocardiographic diagnosis
Coagulation profile
Resuscitation kit including defibrillator
Cardiac monitor
IV line
Premedication with Inj. Atropine 0.01 mg/kg IM30
minutes before the procedure.
Technique
Sedation may be required in some patients. If possible,
it should be avoided.
Figure 34.1.24: Sites for pericardiocentesis

1% Xylocaine is infiltrated in the skin at left xiphocostal
angle, 3 to 4 cm below left costal margin. The needle is
advanced initially perpendicular to the skin surface
and after traversing the soft tissue under the rib cage,
its tip is pointed to the left shoulder. While advancing
the needle in the deeper structures if it reaches to
pericardial cavity, the pericardial fluid is withdrawn
in the syringe. Local anaesthetic agent should not be
injected in the pericardial cavity.
The pericardiocentesis needle is passed along the
same path until the fluid is obtained. The distance
from skin to the pericardium is less than 5 cm in a
child. A distinct give or pop is felt when the
pericardium is punctured. Pericardial fluid can then
be aspirated.
Getting the fluid confirms the position of needle into
the pericardial cavity. Normal saline can be injected
under 2D Echo monitoring which shows bubbles of
saline.
If the blood or bloody fluid is withdrawn, it is vital to
determine if cardiac chamber or coronary artery has
been punctured. Still uremia and malignant diseases
1442
can give rise to haemorrhagic pericardial effusion.

Blood obtained from heart or coronary vessel clots
immediately.
Fluid is sent for appropriate examinations.
The needle is withdrawn and benzoin seal is done at
puncture site.
Post procedure monitoring of heart rate, RR and BP
should be done. 2D Echo may be performed to study
post tapping condition.
Complications
Hemopericardium
Arrhythmias
Vasovagal reactions
Infection
Pneumothorax
Air embolism
Perforation of an abdominal viscus, commonly stomach
Cardiac arrest and death
Fine Needle Aspiration Biopsy

Fine needle aspiration biopsy is very useful for cytological
and bacteriological evaluation of a mass or a lymph node.
It is minimally invasive and requires no sedation. It aids
in tissue diagnosis and in determining the course of
management.
Requirements
1" to 1 20 to 25 FG needles. 22 FG 1" long is the most
commonly used size of needle.
10 to 20 ml plastic disposable syringes.
Clean glass slides.
70 to 90% ethanol for routine wet fixation.
Containers for culture media whenever needed.
Technique
Sterilize the area.
Anaesthesia is usually not required, may be used local
anaesthetic agent in uncooperative and irritable
children.
Immobilize the lump to be biopsied between your
thumb and finger with one hand.
Hold the syringe in the other hand and insert needle
into the assigned area, perpendicular to the skin surface
and position the needle within the target tissue.
Pull the syringe plunger to apply negative pressure.
While maintaining suction, make several passes

through the mass or node.
Release the negative pressure while needle remains in
the target tissue.
Withdraw the needle.
Detach the needle, draw 2-3 ml air into the syringe,
reattach the needle and blow the aspirates onto the
slide.
Apply the pressure over the puncture site with cotton
swab for 5 minutes.
Deep biopsies can be done with assistance of
radiological imaging techniques like ultrasound.
The following situations can give unsatisfactory yield
during FNAB.
When needle misses the lesion tangentially.
When central area is cystic, necrotic or haemorrhagic
and devoid of diagnostic material.
When there is a small malignant lesion close to a
dominant benign mass.
When the target tissue is fibrosclerotic and poor in
cells.
ACKNOWLEDGEMENTS
The following figures have been reproduced herewith due
thanks from the books, authors and publishers mentioned
below:
Figs 34.1.8 and 34.1.9: From Handbook of Pediatrics
Silver HK, Kempe CH, Bruyn HB (Eds). (13th edn.) LangeMaruzen Asia Publications, Singapore, 1980.
Fig. 34.1.2: From Nursing Care of Children. Waechter
EH, Philips J, Holaday B (Eds.) (10th edn.) JB Lippincott
Co., Philadelphia, 1985.
Figs 34.1.2, 34.1.3, 34.1.4, 34.1.7, 34.1.11, 34.1.12, 34.1.14,
34.1.15, 34.1.16, 34.1.17, 34.1.20, 34.1.22, 34.1.23, 34.1.24:
From Essential Procedures In Pediatrics, Prajapati BS
(Ed) (1st edn.), Jaypee Brothers Medical Publishers (P) Ltd.,
New Delhi, 2003.
Figs 34.1.6, 34.1.10, 34.1.21: From Textbook of Pediatrics
Advanced Life Support. Chameides L (Ed.) American
Heart Association American Academy of Pediatrics,
1988.
Fig. 34.1.19: From The Harriet Lane Handbook A manual
for Pediatric House Officers Johnson KB (Ed), 13th edn,
Jaypee Brothers Medical Publishers (P) Ltd., New Delhi,
1993.
Fig. 34.1.18: From Management f the Child with a serious
Infection or Severe Malnutrition Guidelines for care at
the First Referral level in Developing Countries
Department of Child and Adolescent Health and
Development, World Health Organization, Geneva, 2000.
BIBLIOGRAPHY
1.
Boon ME, Lykies C. Imaginative Approach to Fine Needle

Aspiration Cytology. Lancet 1980; 2: 1031-32.
2. Chameides L (Ed): Vascular access. In: Textbook of
Pediatric Advanced Life Support. American Heart
Association American Academy of Pediatrics 1988;
37-46.
3. Koebke J, McFarland E, Mein M, Winkler B, Slockbower
JM. Venipuncture Procedures. In: Slockbower JM,
Blumenfeld TA (Eds): Collection and Handling of
Laboratory Specimens A Practical Guide, JB Lippincott
Co., Philadelphia 1983; 3-45.
4. Laing IA, Doyle E. Practical procedures. In: Campbell
AGM, Mcintosh N (Eds): Forfar and Arneils Textbook of
Pediatrics (5th edn). Churchill Livingstone, New York,
1998; 1829-47.
1443
5. Prabha S. Renal biopsy in children. In: Nammalwar BR,

Vijayakumar M (Eds): Pediatric Nephrology (2nd edn).
Madras, @ Authors, 1991;85-89.
6. Prajapati BS (Ed). Essential Procedures In Pediatrics. 1st
edn., Jaypee Brothers Medical Publishers (P) Ltd., New
Delhi, 2003.
7. Silver HK, Kempe CH, Bruyn HB (Eds): Pediatric
procedures. In: Handbook of Pediatrics, (13th edn),
Lange-Maruzen Asia, Singapore 1980; 629-44.
8. Singh M. Procedures. In: Singh M (Ed): Care of the
Newborn, 4th edn. Sagar Publications, New Delhi: 1991;
340-67.
9. Singhi S. Procedures in pediatric intensive care. In:
Sachdev HPS, Puri RK, Bagga A, Choudhury P (Eds):
Principles of Pediatric and Neonatal Emergencies. 1st edn.
Jaypee Brothers Medical Publishers (P) Ltd., New Delhi:
199;364-72.
10. Subramanyam L, Thangavelu S, Somu N. Pathophysiology of pleural fluid collection and management of
empyema. In: Somu N, Subramanyam L (Eds): Essentials
of Pediatric Pulmonology. 2nd edn. Siva and Co., Madras:
1996;142-49.
11. Waechter EH, Philips J, Holaday B (Eds). Procedures. In:
Nursing Care of Children, 10th edn. JB Lippincott Co.,
Philadelhia: 1985;1408-13.
35.1 Physical Medicine and Rehabilitation in Pediatric Practice: Bina Ahuja, AK Dutta ....................................................................... 1446
35.2 Chest Physiotherapy in Children: D Vijayasekaran ........................................................................................................................... 1452
1446
35.1 Physical Medicine and Rehabilitation in

Pediatric Practice
Bina Ahuja, AK Dutta
Modern technically advanced medical care at all levels
has improved survival of neonates and children, this has
resulted in increased number of children suffering from
chronic diseases and disability. Rehabilitation medicine
aims at restoration of function as far as possible and
includes all the measures aimed at reducing the impact
of handicapping conditions.
Physical medicine has been defined as that branch of
medicine which involves use of physical agents like heat,
electricity, water, mechanical agents like massage,
manipulations, use of splints and various adaptive aids
for therapy. It is also used for diagnostic purposes
specially in neuromuscular disorders by electrodiagnosis
and electromyography. Rehabilitation medicine is an
integral part of comprehensive medical care and is
practised as multidisciplinary effort directed by
physiatrist assisted by a team of paramedical personnels
which includes physiotherapists, occupational therapists,
speech therapists, clinical psychologists, social workers,
orthotic and prosthetic technicians. The family of the
child is a very important component of the team for
successful rehabilitation. The team concentrates on
dynamic approach and concerns with positive aspect of
childs abilities.
rehabilitation is the best leader. His role is manifold as

he has to act as a leader of the team and also coordinates
and integrates the activities of various team members.
He examines and diagnoses the case, outlines the aim of
therapy and plans comprehensive treatment including
drugs, appropriate physical measures and appliances.
He also receives feedback information of patient from
other team members, evaluates the case from time to time
making necessary modification in the management.
Physical medicine has important role in management
of number of pediatric conditions.
Neurological and neuromuscular disorders, e.g.
poliomyelitis, hemiplegia, muscular dystrophies
Developmental disabilities, e.g. cerebral palsy, autism
Orthopedic conditions, e.g. congenital deformities
Post-traumatic sequelae
Pulmonary disorderbronchiectasis, asthma
Cardiovascular disorders
Burns.
AIMS OF PHYSICAL MEDICINE AND
REHABILITATION
Prevention and minimization of loss of function,
deformity and disability
Restoration of physical function in disease or injury
Training in compensatory movement where function
is permanently lost
To promote relief of symptoms like pain, spasticity
and immobilization
To integrate childs abilities in purposeful activities
which meet everyday requirements
To enable the disabled child to lead normal life as far
as possible and to integrate him or her into
mainstream
Motivation of child, parental education and guidance.
PHYSIO-OCCUPATIONAL THERAPY IN NEONATES
TEAMWORK IN REHABILITATION
Role of Physiatrist
Physiatrist is a medical specialist with postgraduate
training in physical medicine and rehabilitation. For
pediatric practice, pediatrician with training in
Certain conditions in neonates which require immediate

attention of therapists are as follows.
Congenital Talipes
During first few days of life feet are manipulated in
corrected position and mother is taught to do so each
Physical Medicine and Rehabilitation
1447
The deformities are corrected by manipulations, splints,

serial plasters and surgery along with strengthening
exercises for muscles followed by training in the use of
extremities.
as soon as possible with the aim of protecting the

shoulder joint and preventing deformities. The treatment
advised is:
Passive movements of shoulder and elbow joints and
encouragement of active movements
Use of light abduction splint made up of plastic/
orthoplasts to support the shoulder in abduction and
lateral rotation, elbow at 90 flexion and forearm
supinated
Infant should be encouraged for activities normal for
his or her age like rolling, sitting and use of both
hands.
The maximum recovery takes place in first few
months after which very slight improvement is expected,
child should be given opportunities to develop usage of
arm and hand as fully as possible by play activities.
High-risk neonates, infants with severe birth asphyxia having persistent hypertonicity benefit by giving
proper positioning in adapted seat which can be kept in
incubator/cot. This reduces the babys irritability and
improves nursing interaction.
Congenital Dislocation of Hip (CDH)
Respiratory Disorders in Neonates and Infants
A newborn child should always be screened to exclude

CDH by testing hip abduction, and looking for asymmetry of groin creases. If diagnosed early, treatment is
simpler by giving padded napkins for hip abduction or
by giving splints. Later on even after surgery child would
require splint, hip mobilization and strengthening
exercise, gait training under the guidance of therapists.
Preterm low birth weight (LBW) babies and very sick

neonates who are cared in special intensive care units
most of the time have respiratory problems which at
some stage require chest physiotherapy in cases having:
Chest infection with increased secretions
Increased secretions following prolonged intubation
Collapse of lung due to mucous plug or aspiration
Meconium aspiration
The objective of therapy is to improve clearance of
airways and enhance ventilation technique adopted
depending on each babys condition. Such babies should
be handled by therapist trained for handling neonates.
Chest physiotherapy which includes tapping,
percussions, vibrations, breathing exercises, postural
drainage is also helpful in patients with bronchopneumonia, bronchiolitis, empyema, bronchial asthma,
bronchiectasis, cystic fibrosis and children on ventilatory
care for respiratory paralysis as in bulbospinal
poliomyelitis and Guillain-Barr syndrome. Postural
drainage in various positions depending upon the lobe
involved is helpful in clearing the secretions and enhance
the recovery.
time she feeds the child and changes the nappy, the most
common deformity being congenital talipes equino varus
(CTEV) in which the foot is plantarflexed at the ankle,
adducted and inverted at midtarsal joints. Passive
stretching is performed gradually, first correcting
adduction and inversion and taking foot to neutral
position. The mild deformities can be corrected by
stretching, others require serial plaster casts, splints and
orthopedic shoes. Surgery is done if not corrected by
conservative treatment.
Congenital Limb Deficiency
Children born with congenital limb deficiencies, e.g.
amelia, hemimelia, phocomelia do require exercises and
special prosthesis.
Arthrogryposis Multiplex Congenita (AMC)
Sternomastoid Tumor
Though a benign condition, if not treated early this leads
to torticollis and facial asymmetry. The initial treatment
required is stretching of affect sternomastoid muscle
which can be taught to the mother. If torticollis develops
child may require stretching, and cervical collar in
corrected position. If conservative treatment fails surgery
is required to release the contracture followed by exercises
and manipulations.
Erbs Palsy and Brachial Plexus Injury
Injury to brachial plexus or its upper cervical fifth and
sixth roots occurs sometimes following difficult labor or
breech delivery. The damage to the nerve roots results in
paralysis of muscles supplied by them giving the typical
posture as in Erbs palsy. The treatment should be started
1448

ROLE OF PHYSICAL MEDICINE IN
INFANTS AND CHILDREN
Poliomyelitis and cerebral palsy are two major causes of
disability in children. Poliomyelitis is on the verge of
eradication because of intensified efforts of National Polio
Surveillance Project (NPSP) which was established in
1997 as joint collaboration between WHO and Ministry
of Health and family welfare. Still the children who have
already suffered from poliomyelitis having residual
paralysis would require services of rehabilitation team,
as till date there is no specific treatment or antiviral agent
available for treatment of poliomyelitis.
Child with Paralytic Poliomyelitis
Management of paralytic poliomyelitis varies with the
stage of illness and the severity of paralysis. It aims at:
To save life in severe cases with respiratory paralysis
Proper positioning of paralyzed limbs to prevent and
minimize deformities
Re-education and strengthening of paralyzed muscles
Development of function of paralyzed muscles and
ambulation of the child
Correction of deformities
Schooling and prevocational guidance and training.
Figures 35.1.1A to C: Postural drainage: (A) apical segments

of the upper lobes, (B) posterior segment of the lower lobes,
and (C) right middle lobe
In small infants it can easily be given with the baby

lying on pillow on physiotherapists lap, where the baby
can be made to lie prone, supine side or half side lying
position. Details of postural drainage position for each
area of lung are shown in Figures 35.1.1A to C.
Myelomeningocele with Paraplegia
The physical treatment of such babies must commence
at birth and is a continuous process. Prevention of further
deformity, pressure ulcerations of lesion and correction
of deformity already present at birth is the main objective
of therapy initially. Development of basic motor skills,
normal body image, strong arm and trunk muscles, a
method of weight-bearing ambulation and bladder and
bowel training help to rehabilitate these children.
In acute stage, uncomplicated cases of single lower

limb/or both lower limbs paralyses can be treated at
home. The therapy advised is:
Complete bedrest
Correct positioning of affected limb/limbs with
sandbags, pillows or splints
Passive movements of joints of paralyzed limb
Warm fomentation to relieve spasm
Symptomatic treatment for fever and pain
No massage or intramuscular injection
To observe for any progression of paralysis.
Passive range of movements of joints of affected limbs
is advised to prevent stiffness, should be done 3 to 4
times/day within the limit of pain for few minutes, then
increased gradually to full range.
Positioning of Limbs
The child should be made to lie on a firm bed. The
position for lower limb is slight flexion at hip and knee
(5-10) and 90 at the ankle (Figs 35.1.2A and B), it can be
given by sandbags, pillows and plaster of Paris (POP)
splints. Rolled towel or pillow should support the limb
from lateral side to prevent external rotation.
1449
quadriped crutching, crawling on buttocks which further

leads to contracture. The deformities when dynamic can
be corrected by splints, stretching and manipulation.
Fixed deformities and contractures require surgical
correction before any rehabilitation program. Neglected
cases can also be treated by physiotherapy, surgery and
orthotic devices, but some cases may need other
ambulatory devices like wheelchair, trolley, tricycle, etc.
Regular follow-up every two to three months during
recovery stage, and every four to six months, later is
essential till the child is fully grown up. The parents also
need guidance and motivation for long-term treatment
and follow-up. Though rehabilitation is costly and a longterm affair, but it is very essential for social integration
of the child.
Figures 35.1.2A and B: (A) Positioning with sandbags and
pillow, and (B) positioning with plaster splints
Once the acute phase of illness subsides and recovery

of muscle power begins in paralyzed muscles, the
therapy at this stage aims at:
Strengthening of weak muscle groups
Improvement of functional skills of the child
Prevention and correction of deformity
Persistence in maintenance of the muscle training and
exercises is the most important factor in improvement
of muscle power and function. The modalities used by
therapists are graded exercises, massage, electrotherapy
and hydrotherapy. Maximum recovery in muscle
strength occurs during first 6 months of onset of paralysis.
Further management is planned to make the affected
limb useful. The children are given various orthotic
appliances to help in sitting and ambulation, depending
upon the age of child and degree of involvement. After
fitting proper orthosis, children are given gait training
to make them independent in ambulation.
Prevention of Deformities and Contracture
Children with poliomyelitis tend to develop contractures
and deformities due to muscular imbalance, effect of
gravity, improper positioning of limbs, and weight
bearing on weak limbs. Due to demand of ambulation
children also adopt abnormal modes like crawling,
Post Polio Syndrome (PPS)

A significant proportion of patients after recovery from
initial paralytic attack of poliomyelitis experience 10-40
years later progressive worsening of neuromuscular
symptoms which are collectively referred to as Post Polio
Syndrome (PPS). The symptoms are in form of excessive
fatigue, progressive muscle weakness in recovered
muscle groups, muscle and joint pains, atrophy, breathing and swallowing problems, and sleep disorders. The
exact cause of PPS is not known. Treatment focuses on
managing sign and symptoms and physiotherapy has
an important role in management of such cases.
Cerebral Palsy
Cerebral palsy (CP) is persistent but not unchanging
disorder of posture and movement due to nonprogressive lesion or damage of developing brain. The damage
to the brain may be caused in utero, at the time of birth or
during first few years of life. CP child presents with
developmental delay, tonal abnormalities and associated problems of speech, vision, hearing, mental retardation and seizures. Spastic type of CP characterized by
hypertonia, exaggerated deep tendon reflexes is the most
common type (7580%) of CP seen in practice. Once the
diagnosis of CP is established or even suspected, the child
should be referred to rehabilitation center; one should
not wait and watch. Early diagnosis of CP is essential
for early intervention in hospital setup, early
identification is ideally done in well-organized HighRisk Baby Clinic. Children with moderate and severe
forms of CP can be easily diagnosed but to detect CP
1450
early as well in mild cases, one should have thorough

knowledge of normal child development and its
physiological variation.
Due to multiplicity of problems, CP child requires
evaluation by different team members, and depending
upon the individual needs of the child intervention
strategy is planned. Comprehensive evaluation of CP
child should include:
Detailed prenatal, natal and postnatal history
Developmental assessment
General physical and neurological examination
Reflex activity
Auditory and visual status
Oral motor function, speech and language development
Intellectual assessment
Assessment of family environment.
Physio-occupational therapy plays major role in the
management of CP child. Number of techniques for
therapy have been advocated, but the neurodevelopmental Bobbath technique is the one commonly used.
It consists of guiding the child through normal sequences
of motor development, inhibition of primitive and
abnormal reflexes, and facilitation of higher level righting
and equilibrium reactions and normal movements.
The therapy aims at:
Reduction of spasticity
Prevention of abnormal posture
Promotion of motor milestones
Stimulation of sensory, cognitive and perceptional
functions
Training in activities of daily life (ADL)
Treatment of associated problems
Prevention of deformities and contractures.
Special education and prevocational guidance.
The ultimate goal is to make the child independent
as far as possible in activities of daily living and prepare
him or her for schooling (integrated or special) depending upon his or her mental level.
To achieve above goals the therapists advise proper
positioning, exercise programs and handling procedures.
Various adaptive equipments like bucket seat, feeder
chair and hammock are advised (Figs 35.1.3A to D). The
aim of positioning is to encourage flexed symmetrical
posture with shoulder protracted and hands oriented
towards midline. The wedges, therapy ball, corner chair,
roller chair standing devices, walkers are used to promote
Figures 35.1.3A to D: Low-cost aids for cerebral palsy child:

(A) hammock, (B) bucket seat, (C) wedge cushions, and (D)
roll chair
sequential motor development. Various types of toys of

different colors, shapes, textures are used for visual,
auditory and tactile stimulation to develop sensory
perceptual integration. Parental involvement is very
essential as treatment is not just clinic based, it is a
continuous process, the mother has to be taught correct
handling techniques so as to incorporate them in daily
routine of carrying, feeding, bathing and sleeping
postures of the child. Simple low-cost aid can be made
by parents under the guidance of therapists for homebased management. Bucket seat is fabricated from
ordinary plastic bucket, big piece of cloth can be used to
make hammock wedge made with foam can be used to
make baby lie prone to encourage neck holding and
relaxation. Roller chair can help the baby sit with legs,
abducted to prevent scissoring of legs.
1451
Orthotic Devices
Flat Feet
Light-weight splints are required to maintain postures

and prevent contractures orthopedic shoes, ankle foot
orthosis (AFO), sometimes bilateral calipers may be
required to help the child to attain standing balance and
walking. In older nonambulatory child, sometimes
alternative modes of transport like stroller, wheelchair
can be prescribed.
To reduce persistent and severe spasticity other
treatments available are as follows.
DrugsBaclofen (Lioresal 10 mg tablet) is now available and is found useful in dosage of 1.25 to 2.5 mg
BD orally increasing gradually up to maximum of 20
mg/day.
Procedure like injections of dilute alcohol (2 to 3%
phenol) at motor points of nerves gives temporary
relief.
Adductor tenotomy.
Posterior selective rhizotomy (involves selective)
resection of posterior nerve roots from L2 to S1) followed by intensive physiotherapy is helpful in selective
cases.
Child with seizures would require anticonvulsant
drug according to seizure type.
Recently following treatments are being tried to
improve functional capacity of cerebral palsy children.
Intrathecal BaclofenThe drug is administered by
battery driven microprocessor pump which is
implanted to administer small quantities of drug in
subarchnoid space to reduce generalized spasticity.
Botulinum (Botox)A neurotoxin is injected in a
muscle to reduce focal spasticity in selective cases.
Hyperbaric oxygen therapyIs being tried at some
centres with variable results.
Stem cell therapyIs still in experimental stage.
Single Event Multilevel Lever Arm Restoration and
Antispasticity Surgery (SEMLARASS) is done in
selective cases above the age of 4 years.
In infancy the feet are normally flat, the arches develop

at about 2 years of age in standing position and gradually
become more rigid. If flat feet persist, they may give a
child clumsy gait, distortion of footwear, aches and pains
in later life. If flat feet persists beyond 2 to 3 years,
exercises are given to strengthen foot muscles which
support arches like standing on outer border of feet,
walking tip toes and picking up pellets with toes. Builtin inner wedge in the shoe is given to help and maintain
corrected position.
Children with genu varus, genu valgus caused by
untreated rickets or idiopathic also require corrective
orthosis, shoes and exercises.
Management of Associated Problems

Provision of hearing aids, correction of refractory error,
squints by corrective glasses and speech therapy are
required in children with such problems.
Education and training Depending upon childs abilities
and intellectual level parents should be guided regarding
appropriate schools and institutions for such children.
Other common conditions which require attention of
physiotherapist are as follows.
Children with Muscular Dystrophy

Since todate no definite therapy exists for muscular
dystrophy, physical therapy can help to improve the
quality of life of these children. The main aim of the
therapy is:
1. Prevention of deformities and contractures
2. Promotion of ambulation and to maintain it as long
as possible so as to keep the child independent in his
daily activities.
The child with Duchenne muscular dystrophy is
prone to develop fixed deformities at ankle and hip. They
can be prevented by regular stretching and use of night
splints. Scoliosis of spine can be prevented by attention
to the posture and spinal brace if needed. To maintain
ambulation, the child should be advised to avoid immobilization due to any cause and should be advised long
periods of standing. Ambulation can be maintained by
giving properly fitting light weight polypropylene
orthosis, if nonambulatory, can be advised wheelchairs.
Burns and Infected Wounds
Ultraviolet rays (UVR) when applied locally to burnt area
or infected wounds in proper dosages by therapist
promote healing as they stimulate epithelial proliferation
and also have bactericidal effect. In case of limb burns,
positioning splinting and exercises are used for maintaining and gaining joint range and prevention of contractures.
Common conditions requiring physical therapy are
discussed in brief in this chapter. As pediatric practitioner
one should be aware of availabilities of such facilities in
his or her area and refer the child as early as possible
specially the infants with developmental delay, as early
intervention can help these children to develop normally
and prevent many secondary handicaps.
1452
35.2 Chest Physiotherapy in Children

D Vijayasekaran
Lung is a unique organ. In spite of the constant exposure
to microorganisms and pollutants, it is kept sterile
beyond the first order bronchi. Numerous defence
mechanisms including mucociliary escalator mechanism
play a significant role to keep the airway sterile. When
its function gets compromised, defective drainage of lung
secretions results in insult to the organ. Similarly, pleural
pathology may impair the normal lung expansion. Chest
physiotherapy plays an important role by promoting
drainage and ensuring normal lung expansion in
parenchymal lung diseases and pleural diseases.
It is a well-known fact that bronchial infection and
bronchial obstruction are directly related, the presence
of one will augment the other. Chest physiotherapy
denotes the removal of accumulated respiratory
secretions from the lung. It consists of a series of
manipulative techniques with various postures. Chest
physiotherapy uses gravitational assistance and physical
therapy to remove the accumulated secretions from the
dependent parts of the diseased lung. Knowledge of the
surface anatomy of the bronchopulmonary segments is
essential for effective chest physiotherapy. Chest
physiotherapy can broadly be classified as given in Table
35.2.1.
POSTURAL DRAINAGE
Postural drainage means removal of excessive secretions
from the airway and it employs the use of gravity to
facilitate drainage.
Postural drainage involves tilting of the thorax to

various postures facilitating drainage from a particular
segment of lung, supplemented by deep breathing,
effective coughing, percussion and vibration techniques
to loosen the secretions. It may be noted that merely
tilting the thorax does not imply drainage will take place.
Since upper lobe bronchus naturally drain from above
downwards, change of posture may not be required
except in a few segments (left upper lobe posterior
segment). For middle lobe on right side and for lingular
division of left upperlobe, 14 inches elevation is required
and for lower lobe 18 inches elevation is a must. The
elevation can be achieved by postural drainage table or
by pillows (Figs 35.2.1 to 35.2.3). The posture
recommended for segments of various lobes are given
in detail in Table 35.2.2.
Postural drainage should be done 3 to 4 times daily
preferably half an hour before meals or one and half
hours after meals. In each position, 5 to 15 minutes can
be spent and the total duration should not exceed 30
minutes otherwise it may be too tiring. Padded but firm
adjustable table for bronchial (postural) drainage, with
different inclinations are available, if not, the foot end of
the cot can be elevated to serve the above purpose.
Indications for Postural Drainage
Children with chronic bronchial diseases such as bronchiectasis, cystic fibrosis and segmental lesions (tuberculous) need bronchial drainage for prolonged time.
TABLE 35.2.1: Classification of chest physiotherapy

Postural drainage and
related procedures
Breathing exercise
Physical therapeutic
maneuvers that will
facilitate bronchial drainage
i. Cupping (or) clapping
(cupped hand percussion)
ii. Deep breathing
These exercises increase

the efficiency of muscles
of respiration
Sustained maximal
inspiration (SMI)
Assisting with tactile
sense
Exhaling through
pursed lips (huffing)
Modified forms of
breathing exercises
(for children)
i.
ii.
iii. Reinforced cough
iii.
iv. Thoracic squeezing
iv.
v. Vibration
Figure 35.2.1: Postural drainage table
Figure 35.2.2: Postural drainageMiddle lobe and lingula
Figure 35.2.3: Postural drainageLower lobe
1453
1454
TABLE 35.2.2: Postural drainage positions for different

pulmonary segments
Lobe
Upper Lobe
1. Apical bronchus
2. Posterior bronchus
a. Right
b. Left
3. Anterior bronchus
Middle Lobe
4. Lateral bronchus
and medial
bronchus
Lingula
5. Superior bronchus
and inferior
bronchus
Lower Lobe
6. Apical basal
bronchus
7. Medial basal
(cardiac) bronchus
8. Anterior basal
bronchus
9. Lateral basal
bronchus
10. Posterior basal

bronchus
Posture
1. Sitting upright; with slight
variations according to the
position of the lesion, i.e. slightly
leaning backwards, forwards or
sideways.
2a.Lying on the left side horizontally,
and then turned 45 on to the face,
resting against a pillow, with
another supporting the head
b. Lying on the right side turned 45
on to the face, with 3 pillows
arranged to lift the shoulders
12 inches
3. Lying supine with the knees
slightly flexed
4. Lying supine with the body one
quarter turned to the left
maintained by a pillow under the
right side from shoulder to hip.
Foot of the bed raised 14 inches
(35 cm) (Figs 35.2.2A and B)
5. Lying supine with the body onequarter turned to the right maintained by a pillow from shoulder
to hip. Foot of the bed raised 14
inches (35 cm) (Figs 35.2.2C and D)
6. Lying prone with a pillow under
the hips
7. Lying on the right side with a
pillow under the hips. Foot end of
the bed raised 18 in (45 cm)
8. Lying supine with the buttocks
resting on a pillow and the knees
flexed. Foot end of the bed raised
18 in (45 cm) (Fig. 35.2.3A)
9. Lying on the opposite side with a
pillow under the hips. Foot end of
the bed raised 18 inches (45 cm)
(Fig. 35.2.3C)
10. Lying prone with a pillow under
the hips. Foot end of the bed raised
18 inches (45 cm) (Fig. 35.2.3B)
In acute respiratory conditions, especially after

administration of bronchodilators to an asthmatic child,
during resolution of pneumonia and following removal
of foreign body the excessive fluid accumulated in the
bronchi has to be removed for complete recovery.
In suppurative lung diseases like lung abscess,

chronic pneumonia, bronchiectasis postural drainage can
be of valuable assistance. In such conditions, dramatic
improvement can be appreciated after physiotherapy.
Prophylactic drainage of contralateral lung following the drainage of diseased lung may protect the normal
lung.
In short, wherever there is profuse bronchorrhea,
such children must be given the benefit of postural
drainage.
PHYSICAL THERAPEUTIC MANEUVERS THAT
WILL FACILITATE THE BRONCHIAL DRAINAGE
Cupped Hand Percussion
One or both of the cupped hands of the therapist should
strike repeatedly over that part of the bronchopulmonary
segment which needs to be drained. During the cupped
hand percussion, the air column inside the cupped hand
causes effective dislodgement of the secretions in the
underlying bronchus, because the compression wave is
presumably transmitted to the underlying bronchus and
aids the gravitational flow of secretions from the
bronchus towards the glottis.
Percussion should be done only with wrist movements without causing pain and discomfort and can be
done throughout inspiration and expiration. Contraindications to the cupped hand percussion are: (i) acutely
ill conditions, (ii) hemorrhagic disease and (iii) fracture
ribs. Mechanical percussors have been designed to assist
with therapy and may be useful, especially in
adolescents.
Deep Breathing
Deep breathing enlarges the tracheobronchial tree so that
air may penetrate around the secretions, and expiration
following such deep breathing may carry secretions
towards the glottis thereby facilitating their easy removal.
Reinforced Cough
During the illness the child may have feeble and
ineffective cough due to the underlying basic pathology.
In such conditions, the reinforcement of the cough is of
much help. The child should be advised to cough out
and such anticipated coughs can be reinforced by the
hands of the operator encircling and synchronously
compressing the lower half of the chest. Sputum
produced should be spit into a container so that the

productivity of the treatment can be demonstrated both
to the child and to the physician.
Thoracic Squeezing
The basic principle in the maneuver is similar to cough
mechanism with reinforcement of expiratory phase. The
child is asked to take a deep breath and then to exhale
through the mouth as completely and rapidly as possible, as would be done for a forced expiratory volume
determinations. The depth of the expiration is increased
by brief firm pressure from the operators hand, compressing the sides of the thorax (thoracic squeeze).
Vibration
During vibration a rapid vibratory impulse is transmitted
through the chest wall from the flattened hands of the
therapist by isometric alternate contraction of forearm
flexor and extensor muscles. Vibration is a more difficult
procedure and is usually effectively executed only by a
physiotherapist. Patient can keep a pillow pressed to his
or her abdomen in sitting position to aid this technique.
PHYSIOTHERAPY IN YOUNG INFANTS
Physiotherapy for young infants may be done preferably
with the baby lying on a pillow on the physiotherapists
lap. By doing so they feel more comfortable. During
physiotherapy the baby should be positioned in such a
way that his or her face can be seen readily so that color
and breathing can be checked frequently. Since all young
children love bubbles, bubble blowing can be good
introduction to overcome their fears and apprehension.
Toys, mobiles, musical boxes can be shown to hold the
attention of the toddlers while doing the actual
physiotherapy. Laughing is a good exercise and so babies
can be tickled to laugh.
1455
Incentive Spirometry (IS) or Sustained

Maximal Inspiration (SMI)
SMI involves the use of a device that encourages a patient
to make a larger than normal inspiratory effort, thereby
establishing a breathing incentive.
Incentive Devices
Incentive devices reward patients by letting them to see
their own progress through the use of visual indicators.
Though several devices are available for the above
purpose, the Triflo II Incentive deep breathing exerciser
and incentive spirometer are more suitable for pediatric
age group. Computerized electronic devices are also
available now.
Triflo II Incentive Deep Breathing Exerciser
Round Ping-Pong type colored ball of different weights
are contained in individual but interconnecting, plastic
tubes. As the patient inhales through the mouthpiece, a
pressure gradient is created above each ball causing gas
to flow into the chamber of the lightest ball first. When
the first ball reaches the top of the chamber and the
patient continues to inhale, a second ball is pushed
upward by room air flowing to the chamber. Since the
process continues, the amount of gas volume being
moved per second can be estimated by observing the
position of each ball in the clear tube (Fig. 35.2.4).
Incentive Spirometer (IS)
It is a device that allows patient to perform SMI without
added resistance while presenting visual quantification
Contraindications to Postural Drainage

Raised intracranial pressure
Cardiac disease
Spinal postoperative conditions.
BREATHING EXERCISES
Breathing exercises are meant to increase the breathing
efficiency and tidal volume. The important breathing
exercises are briefly described.
Figure 35.2.4: Triflo II intensive deep breathing exerciser
1456

CONCLUSION
Chest physiotherapy has become a valuable part of
comprehensive respiratory care for both acute and chronic
respiratory disorders. These therapeutic measures may
not be curative or preventive, but definitely help to
improve and maintain the wellbeing of the patients as
much as possible within the limitations imposed by the
impaired lung function. Though surgery may play a role
in unilateral lung diseases, the facilities for intrathoracic
surgery is not available in major institutions. Children
with bilateral lung diseases are not suitable candidates
for surgery. Considering the above facts, regular physiotherapy with nutritional support and judicious, timely
antibiotic therapy play a significant role in reducing the
morbidity of children crippled with chronic lung diseases.
Figure 35.2.5: Incentive spirometer (IS)
BIBLIOGRAPHY
of his or her effort (Fig. 35.2.5). A colored ball is lifted up
by deep inspiratory flow. Patient is requested to continue
inspiring to keep the ball afloat. Longer the ball is up,
greater the inspiratory volume will be.
Assisting with Tactile Sense
Here the therapists hand is placed over the areas where
the muscular movement is desired and the patient is
encouraged to concentrate on expanding that part of
chest under hand, e.g. to promote diaphragm movement,
therapists hand is placed over epigastrium and patient
is to breath in to lift the hand.
Exhaling Through Pursed Lips (Huffing)
This helps a patient with obstructive diseases, where
huffing is believed to transmit an expiratory back
pressure, which is believed to prevent early collapse of
small bronchioles and to improve expansion of the
alveoli.
1. Boat TF. Cystic fibrosis. In: Behrman RE, Kleigman RM,

Jenson HB et al (Eds): Nelson Textbook of Pediatrics (17th
edn). WB Saunders: Philadelphia 2004;393:143750.
2. Ebanks DH, Bone RC. Incentive spirometry. Comprehensive Respiratory Care (1st edn). CV Mosby: St. Louis
18:45158.
3. Hutchison. The respiratory system. In: Swash M (Ed):
Hutchisons Clinical Methods (20th edn). ELBS with WB
Saunders, London, 1995;14164.
4. Kennedy B. PhysiotherapyPaediatrics. In: Downie PA
(Ed): Cashs Textbook of General, Medical and Surgical
Conditions for Physiotherapists (1st edn). Jaypee
Brothers Medical Publishers (P) Ltd: New Delhi 1985;22:
36086.
5. Shepherd RB. Specific Techniques of Physical
Assessment and Treatment in Infants and Children.
Physiotherapy in Pediatrics (1st edn). William
Heinmann: London, 1974;36191.
6. Subramanyam L, Devaki V, Thangavelu S. Chest
physiotherapy. In Somu N, Subramanyam L (Eds):
Essentials of Pediatric Pulmonology Siva and Co:
Chennai 1996;25558.
7. Warning WW. Diagnostic and Therapeutic Procedures.
In Chennick V, Kendig VL (Eds): Kendigs Disorders of
the Respiratory Tract in Children. WB Saunders:
Philadelphia 1990;7796.
36.1 Vital Statistics in India: Piyush Gupta, HPS Sachdev .................................................................................................................. 1458
36.2 The Infant Milk Substitutes, Feeding Bottles and Infant Foods
(Regulation of Production, Supply and Distribution) Act, 1992: SP Srivastava .................................................................... 1459
36.3 Normal Laboratory Values: Piyush Gupta, HPS Sachdev ............................................................................................................ 1465
36.4 Principles of Fluids and Electrolytes in Diarrheal Dehydration: S Ramesh ........................................................................... 1474
36.5 Drugs and Drug Dosage: S Ramesh ............................................................................................................................................. 1480
36.6 Essential Drugs in Pediatrics: Arun P Phatak ............................................................................................................................... 1488
36.7 Growth
36.7.1
36.7.2
36.7.3
Charts: Vaman V Khadilkar, Dilip Mukherjee, MKC Nair ................................................................................................... 1490

IAP Growth Charts: Vaman V Khadilkar ........................................................................................................................... 1490
Appendix: Vaman V Khadilkar ........................................................................................................................................... 1498
WHO Growth Charts: Dilip Mukherjee, MKC Nair ............................................................................................................ 1502
36.8 Safe Injection Practices: Baldev S Prajapati, Swati Y Bhave, SS Kamath .................................................................................... 1507
36.9 Searching and Researching Online: Vijay Agarwal ..................................................................................................................... 1516
36.10 The IMNCI Case Management Process: Harish Kumar, Raju C Shah, Naveen Thacker, Deepak Ugra .................................. 1522
36.11 IAP Infectious Diseases Chapter Protocols: Ritabrata Kundu, Nupur Ganguly, Tapan Kumar Ghosh ................................... 1525
36.11.1 Malaria: Raju C Shah, Tapan Kumar Ghosh, Ritabrata Kundu, Nupur Ganguly .............................................................. 1525
36.11.2 Enteric Fever: Nitin K Shah, Raju C Shah, Tapan Kumar Ghosh, Ritabrata Kundu, Nupur Ganguly ............................. 1528
36.11.3 Pyogenic Meningitis: Veena Kalra, Tapan Kumar Ghosh, Ritabrata Kundu, Nupur Ganguly, Vijay N Yewle .............. 1531
36.11.4 Rabies: Tapan Kumar Ghosh, SN Madhusudhana, Shivananda ...................................................................................... 1534
36.12 IAP Consensus Recommendations on Immunization, 2008: Tanu Singhal, YK Amdekar, Piyush Gupta ............................ 1538
1458
36.1 Vital Statistics in India

Vital statistics are referred to a systemically collected and
compiled data relating to vital events of life such as birth,
death, marriage, divorce, adoption, etc. These reflect the
health profile of the community and form a basic tool for
evaluating the adequacy of the health care delivery system.
No health department can claim to serve efficiently and
effectively without the help of vital statistics.
In India, the main source of vital statistics include the
census, registration records of vital events such as birth
and deaths and sample registration system (SRS). SRS
obtains annual information on birth and death rates,
fertility rates and age specific mortality rates in the country
through a combination of continuous registration and half
yearly surveys.
Mortality, Fertility, and other Health Indicators
Current status of various indicators related to mortality,
fertility, life expectancy, family welfare program, literacy
status, immunization coverage and nutrition status are
summarized in Table 36.1.1. Deaths in infancy constitute
18.5 percent of total deaths in India. More than fifty percent

of these occur in neonatal period. Infant mortality rate
(IMR) of the country is not representative of its states.
Orissa and MP contribute maximally to the infant mortality
(73 and 74 per 1000 live births, respectively) with the
minimum IMR being achieved by Manipur (11 per 1000
live births) (SRS, 2007).
National Population Policy
As per Census 2001, the population of India was 1027
million, i.e. 16 percent of the worlds population on 2.4
percent of the globes land area. Children between 0 to 6
years constitute 15.4 percent of the total population. The
National Population Policy, 2000 (NPP 2000) provides a
policy framework for advancing goals and prioritising
strategies during the next decade to meet the reproductive
and health needs of the people of India. In pursuance of
the objectives laid out in NPP 2000, the following national
sociodemographic goals to be achieved in each case by
2010 are formulated (Table 36.1.2).
TABLE 36.1.1: Fertility, mortality, and other health indicators

Fertility Indicators
Crude birth rate
General fertility rate
Total fertility rate
Gross reproduction rate
Natural growth rate
Mortality Indicators
Crude death rate
Infant mortality rate
Neonatal mortality rate
Early neonatal mortality rate
Late neonatal mortality rate
Postneonatal mortality rate
Perinatal mortality rate
Stillbirth rate
Death rate for 0-4 years
Under-five mortality
Maternal mortality ratio
Life expectancy at birth
Literacy rate
Immunization coverage
23.5 (SRS 2007)

102.8 (SRS 2000)
3.2 (SRS 2000)
1.5 (SRS 2000)
16.0 (SRS 2007)
Males
Females
Males
Females
Total
BCG
DPT 3 doses
OPV 3 doses
Measles
Vitamin A 1 dose
7.5 (SRS 2007)

57.0 (SRS 2007)
39.0 (NFHS-3 2006)
32.0 (SRS 2000)
12.0 (SRS 2000)
18.0 (NFHS-3 2006)
49.0 (NFHS-3 2006)
8.0 (SRS 2000)
18.0 (NFHS-3 2006)
74.0 (NFHS-3 2006)
301 (SRS 2003)
62.8 years
63.4 years (1996-2001)
75.8%
54.2%
65.4% (Census 2001)
78.0%(NFHS-3 2006)
55.0%(NFHS-3 2006)
78.0%(NFHS-3 2006)
59.0%(NFHS-3 2006)
21.0%(NFHS-3 2006)
Contd.
Miscellaneous Topics
1459
Contd.
Nutrition Indicators
Low birth weight newborns
% of children who are breast fed exclusively (0-5 months)
Median duration of breastfeeding
% of underfives suffering from
underweight
wasting
stunting
22.7%(NFHS-2 1998)
46.3%(NFHS-3 2006)
25.4 months (NFHS-2 1998)
46.0 (NFHS-3 2006)
19.0 (NFHS-3 2006)
38.0 (NFHS-3 2006)
TABLE 36.1.2: National sociodemographic goals for 2010

(1) Address the unmet needs for basic reproductive and child health services, supplies and infrastructure.
(2) Make school education up to age 14 free and compulsory, and reduce drop outs at primary and secondary school levels to below
20 percent for both boys and girls.
(3) Reduce infant mortality rate to below 30 per 1000 live births.
(4) Reduce maternal mortality ratio to below 100 per 100,000 live births.
(5) Achieve universal immunization of children against all vaccine preventable diseases.
(6) Promote delayed marriage for girls, not earlier than age 18 and preferably after 20 years of age.
(7) Achieve 80 percent institutional deliveries and 100 percent deliveries by trained persons.
(8) Achieve universal access to information/counseling, and services for fertility regulation and contraception with a wide basket of
choices.
(9) Achieve 100 percent registration of births, deaths, marriage and pregnancy.
(10) Contain the spread of Acquired Immunodeficiency Syndrome (AIDS), and promote greater integration between the management of
reproductive tract infections (RTI) and sexually transmitted infections (STI) and the National AIDS Control Organization.
(11) Prevent and control communicable diseases.
(12) Integrate Indian Systems of Medicine (ISM) in the provision of reproductive and child health services, and in reaching out to households.
(13) Promote vigorously the small family norm to achieve replacement levels of TFR.
(14) Bring about convergence in implementation of related social sector programs so that family welfare becomes a people centered
program.
3. National Population Policy. Ministry of Health and Family

Welfare. Government of India 2000.
BIBLIOGRAPHY
1. Census of India 2001. Government of India. Ministry of
Home Affairs. Available from http://www.censusindia.
net. Accessed April 5, 2004.
4. SRS Bulletin. Registrar General of India. Oct 2002; vol 36,

No. 2. Available from http;//www.censusindia.net/
SRS_Bulletin_Vol_36_Issue2.pdf. Accessed April 5, 2004.
2. National Family Health Survey- 2, 1998. Available from

www.nfhsindia.org. Accessed April 5, 2004.
5. The State of the Worlds Children. United Nations

Childrens Fund, 2004.
36.2 The Infant Milk Substitutes, Feeding Bottles

and Infant Foods (Regulation of Production,
Supply and Distribution) Act, 1992
SP Srivastava
AS AMENDED IN 2003
Vide the infant milk substitutes, feeding bottles and infant
Foods (Regulation of Production, Supply and Distribution)
Act, 1992.
1 June 2003
An act to amend the infant milk substitutes, feeding

bottles and infants foods (regulation of production,
supply and distribution) Act, 1992. It provides for the
regulation of production, supply and distribution of infant
milk substitutes, feeding bottles and infant foods with a
view to the protection and promotion of breastfeeding and
1460
ensuring the proper use of infant foods and for matter

connected therewith or incidental thereto.
Be it enacted by Parliament in the Forty-fourth Year of
the Republic of India as follows:
1. a. This Act may be called the Infant Milk
Substitutes, Feeding Bottles and Infant Foods
(Regulation of production, Supply and
Distribution) Amendment Act, 2003.
b. It extends to the whole of India.
c. It shall come into force of such date as the Central
Government may, by notification in the Official
Gazette, appoint.
2. In this Act, unless the context otherwise requires,
a. Advertisement includes any notice, circular,
label, wrapper or any other document or visible
representation or announcement made by means
of any light, sound, smoke or gas or by means of
electronic transmission or by audio or visual
transmission.
b. Container means a box, bottle, casket, tin, can,
barrel, case, tube, receptacle, sack, wrapper or
other thing in which any infant milk substitute,
feeding bottle or infant food is placed or packed
for sale or distribution.
c. Feeding bottle means ant bottle or receptacle
used for the purpose of feeding infant milk
substitutes, and includes a teat and a valve
attached or capable of being attached to such
bottle or receptacle.
d. Health care system means an institution or
organization engaged, either directly or
indirectly, in health care for mothers, infants or
pregnant women, and includes a health workers
in private practice, a pharmacy, drug store and
any association of health workers.
e. Health worker means a person engaged in
health care for mothers, infant or pregnant
women.
f. Infant food means any food (by whatever name
called) being marketed or otherwise represented
as a complement to mothers milk to meet the
growing nutritional needs of the infant after the
age of six months and up to the age of two years.
g. Infant milk substitute means any food being
marketed or otherwise represented as a partial
or total replacement for mothers milk, for infant
up to the age of two years.
h. Label means a display of written, marked,

stamped, printed or graphed matter affixed to, or
appearing upon, any container;
i. Prescribed means prescribed by rules made
under this Act.
j. Promotion means to employ directly or
indirectly any method of encouraging any person
or purchase or use infant milk substitute, feeding
bottle or infant food.
k. Any reference in this Act to any other enactment
or any provision thereof, shall, in relation to an
area in which such enactment or such provision
is not in force, be construed as a reference to the
corresponding law or the relevant provision of
the corresponding law, if any, in force in that
area.
3. No person shall:
a. advertise, or take part in the publication of any
advertisement, for the distribution, sale or supply
of infant milk substitutes feeding bottles or infant
foods; or
b. give an impression or create a belief in any manner
that feeding of infant milk substitutes and infant
foods are equivalent to, or better than, mothers
milk; or
c. take part in the promotion of infant milk
substitutes, feeding bottles or infant foods;
4. No person shall
a. supply or distribute samples of infant milk
substitutes or feeding bottles or infant foods gifts
or utensils or other articles; or
b. contact an pregnant woman or the mother of an
infant; or
c. offer inducement of any other kind.
For the purpose of promoting the use of sale of infant
milk substitutes or feeding bottles or infant foods.
5. Subject to the provisions of subsection (4) of section
8, no person shall donate or distribute:
a. infant milk substitutes or feeding bottles or infant
foods to any other person except to an orphanage;
b. any informational or educational equipment or
material relating to infant milk substitutes or
feeding bottles or infant foods.
Provided that nothing in this clause shall apply to
the donation or distribution subject to such
conditions any restrictions as may be prescribed, of
such equipment or material through the health care
system.
6. 1. Without prejudice to the provisions of the
Prevention of Food Adulteration Act 1954 and
the rules made thereunder no person shall
produce, supply or distribute any infant milk
substitute or infant food unless every container
thereof or any label affixed thereto indicates in
clear. Conspicuous and in an easily readable and
understandable manner, the words important
notice in capital letters in such language as may
be prescribed and indicated thereunder the
following particulars in the same language
namely:
a. a statement mothers milk is best for your
baby in capital letters;
b. a statement that infant milk substitute or infant
food should be used only on the advice of a
health worker as to the need for its use and the
proper method of its use;
c. a warming that infant milk substitute or infant
food is not the sole source of nourishment of
infant;
d. the instructions for its appropriate preparation and a warning against the health hazards
of its inappropriate preparation;
e. in ingredients used;
f. the composition or analysis;
g. the storage conditions required;
h. the batch number, date of its manufacture and
the date before which it is to be consumed,
taking into account the climatic and storage
conditions of the country;
i. such other particulars as may be prescribed;
2. No container or label referred to in subsection (1)
relating to infant milk substitute or infant food
shall:
a. have pictures of an infant or a woman or both;
or
b. have pictures or other graphic material or
phrases designed to increase the sale ability
of infant milk substitutes or infant food; or
c. use on it the word humanized or
maternalized or any other similar word; or
d. bear on it such other particulars as may be
prescribed.
7. i. Every educational or other materials including
advertisements or material relating to promotion
of infant milk substitutes, feeding bottles and
infant foods whether audio or visual, dealing
1461
with prenatal or postnatal care or with the

feeding of an infant and intended to reach
pregnant women or mothers of infants shall
include clear information relating to:
a. the benefits and superiority of breastfeeding;
b. the preparation for, and the continuance of,
breastfeeding;
c. the harmful effects on breastfeeding due to the
partial adoption of bottle feeding;
d. the difficulties in reverting to breastfeeding of
infants after a period of feeding by infant milk
substitute;
e. the financial and social implications in making
use of infant milk substitutes and feeding
bottles.
f. the health hazards of improper use of infant
milk substitutes and feeding bottles; (a) the date
of printing and publication of such material
and the name of the printer and publisher;
g. such other matters as may be prescribed.
ii. No material referred to in subsection (1) shall be
utilized to promote the use or sale of infant milk
substitutes or feeding bottles or infant foods.
8. i. No person shall use any health care system for
the display of placards or posters relating to, or
for the distribution of materials for the purpose
of promoting the use or sale of infant milk
substitutes or feeding bottles or infant foods:
Provided that the provisions of this subsection
shall not apply to
a. the donation or distribution of informational
or educational equipment or material made in
accordance with the proviso to clause
b. of section 5; and
c. the dissemination of information to a health
worker about the scientific and factual matters
relating to the use of infant milk substitutes or
feeding bottles or infant foods along with the
information specified in subsection (1) of
section 7.
ii. No person who produces, supplies, distributes
or sells infant milk substitutes or feeding bottles
or infant foods shall make any payment to any
person who works in the health care system for
the purpose of promoting the use or sale of such
substitutes or bottles or foods.
iii. No person, other than a health worker, shall
demonstrate feeding with infant milk substitutes
1462
iv.
v.
9. i.
ii.
10. i.
ii.
11. i.
or infant foods to a mother of an infant or to any

member of her family and such health worker
shall also clearly explain to such mother or such
other member the hazards of improper use of
infant milk substitutes or feeding bottles or infant
foods.
No person, other than an institution or
organization, engaged in health care for mothers,
infants or pregnant women, shall distribute
infant milk substitutes or feeding bottles to a
mother who cannot resort to breastfeeding and
who cannot afford to purchase infant milk
substitutes or feeding bottles.
An orphanage may purchase infant milk
substitutes or feeding bottles at a price lower than
their sale price for the purpose of utilizing them
in the said orphanage.
ExplanationFor the purposes of this subsection, such purchases shall not amount to an
inducement for promoting the use or sale of infant
milk substitutes or feeding bottles.
No person who produces, supplies distributes
or infant foods shall offer or give, directly or
indirectly, any financial inducements or gifts to
a health worker or to any member of his family
for the purpose of promoting the use of such
substitutes or bottles or foods.
No producer, supplier or distributor referred to
in subsection (1), shall offer or give any
contribution or pecuniary benefit to a health
worker or any association of health workers,
including funding of seminar, meeting,
conferences, educational course, contest,
fellowship, research work or sponsorship.
No person who produces, supplies distributes
or infant foods shall fix the remuneration of any
of his employees or give any commission to such
employees on the basis of the volume of sale of
such substitutes or bottles or foods made by such
employees.
The employees of such person shall not perform
any function which relates to educating a
pregnant woman or mother of an infant or prenatal or postnatal care of the infant.
No person shall sell or otherwise distribute any
infant milk substitute or infant food unless it
conforms to the standards, specified for such

substitute or food under the Prevention of Food
Adulteration Act, 1954, and the rule made
thereunder and the container thereof has the
relevant Standard Mark specified by the Bureau
of India Standards established under section 3
of the Bureau of Indian Standards Act, 1986 to
indicate that the Infant Milk Substitute or infant
food conforms to such standards.
Provided that where no standards have been
specified for any infant milk substitute or infant food
under the Prevention of Food Adulteration Act, 1954,
no person shall sell or otherwise distribute such
substitute or food unless he has obtained the
approval of the Central Government in relation to
such substitute or food and the label affixed to the
container thereof under the rules made under the
Act.
ii. No person shall sell or otherwise distribute any
feeding bottle unless it conforms to the standard
Mark specified by the Bureau of India Standards
referred to in subsection (1) for feeding bottles
and such mark is affixed on this container.
12. i. Any food inspector appointed under section 9 of
the Prevention of Food Adulteration Act 1954
(hereinafter referred to as the food inspector) or
any officer not below the rank of an Class I officer
authorized in this behalf by the State Government
(hereinafter referred to as the authorized officer)
may, if he has any reason to believe that any
provision of section or section 11 has been or it
being contravened, enter and search at any
reasonable time any factory, building, business
premises or any other place where any trade or
commerce in infant milk substitutes or feeding
bottles or infant foods is carried on or such
substitutes or bottles or foods are produced,
supplied or distributed.
ii. The provisions of the Code of Criminal
Procedure, 1973, relating to searches and seizures
shall, so far as may be, apply to every search or
seizure made under this Act.
13. i. If any food inspector or authorized officer has
reason to believe that in respect of any infant
milk substitute or feeding bottle or infant food or
container thereof, the provisions of this Act have
been or are being contravened, he may seize such
substitute or bottle or food or container.
14.
15.
16.
17.
ii. No such substitute or food or bottle or container

shall be retained by any food inspector or
authorized officer for a period exceeding ninety
days from the date of its seizure unless the
approval of the District Judge, within the local
limits of whose jurisdiction such seizure has been
made, has been obtained for such retention.
Any infant milk substitute or feeding bottle or infant
food or container thereof, in respect of which any
provision of this Act has been or is being
contravened, shall be liable to confiscation:
Provided that where it is established to the
satisfaction of the court adjudging the confiscation
that the person in whose possession, power or
contravention of the provisions of this Act, the court
may, instead of making an order for the confiscation
of such substitute or bottle or food or container, make
such other order authorized by this Act against the
person guilty of the breach of the provisions of this
Act as it may think fit.
i. Whenever any confiscation is authorized by this
Act the court adjudging it may, subject to such
conditions as may be aspecified in the order
adjudging the confiscation, give to the owner
thereof an option to pay in lieu of confiscation
such cost not exceeding the value of the infant
milk substitute or feeding bottle or infant food or
container thereof in respect of which the
confiscation is authorized as the court thinks fit.
ii. On payment of the cost ordered by the court the
seized infant milk substitute or feeding bottle or
infant food or container shall be returned to the
person from whom it was seized on the condition
that such person shall, before making any
distribution, sale or supply of such substitute or
bottle or food or container, give effect to the
provisions of this Act.
No confiscation made or cost ordered to be paid
under this Act shall prevent the infliction of any
punishment to which the person affected thereby is
liable under the provisions of this Act or under any
other law.
Any confiscation may be adjudged or costs may be
ordered to be paid
a. without any limit, by the principle civil court of
original jurisdiction within the local limits of
whose jurisdiction such confiscation has been
made or costs have been ordered to be paid, as
the case may be;
1463
b. subject to such limits as may be specified by the

Central Government in this behalf, by such other
court, not below a civil court having pecuniary
jurisdiction exceeding five thousand rupees, as
the Central Government may, by notification in
the Official Gazette, authorize in this behalf.
18. i. No order adjudicating confiscation or directing
payment of costs shall be made unless the owner
of the infant milk substitute or feeding bottle or
infant food or container thereof has been given a
notice in writing informating him of the grounds
on which it is proposed to confiscate such
substitute or bottle or food or container and giving
him a reasonable opportunity of making a representation in writing, within such reasonable time
as may be specified in the notice, against the
confiscation and if he so desires, of being heard
in the matter.
Provided that where no such notice is given
within a period of ninety days from the date of
the seizure of the infant milk substitute or feeding
bottle or infant food or container thereof, such
substitute or bottle or food or container shall be
returned after the expiry of that period to the
person from whose possession it was seized.
ii. Save as otherwise provided in sub-section (1),
the provisions of the Code of Civil Procedure,
1908, shall, so far as may be, apply to every
proceeding referred to in sub-section (1).
19. i. Any person aggrieved by any decision of the
court adjudicating a confiscation or ordering
the payment of costs may prefer an appeal to the
court to which an appeal lies from the decision
of such court.
ii. The appellate court may, after giving the
appellant an opportunity of being heard. Pass
such order as it thinks fit confirming, modifying
or revising the decision or order appealed against
or may send back the case with such directions
as it may think fit for a fresh decision or
adjudication, as the case may be, after taking
additional evidence if necessary.
Provided that an order enhancing any fine in
lieu of confiscation or for confiscating goods of
greater value shall not be made under this section
unless the appellant has had an opportunity of
making a representation and if he so desires of
being heard in his defence.
1464
iii. No further appeal shall lie against the order of

the court made under subsection (2).
20. i. Any person w

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IAP

Professor of Pediatrics, Madras Medical College, and

Executive Academic Editor

Sub-Dean, Professor of Pediatrics, Division of Pediatric Endocrinology and

President, IAP 2006

President, IAP 2009

President, IAP 2008

President Elect, IAP 2010

Senior Academic Editors

Professor of Pediatrics and Clinical Epidemiology

Honorary Secretary General, IAP 2007-08

Treasurer, IAP 2007-8, Honorary Neonatologist

Editor-in-Chief, Indian Journal of Practical Pediatrics

IAP Textbook of Pediatrics

IAP Textbook of Pediatrics

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Chennai 600 017

Tapan Kumar Ghosh

IAP Textbook of Pediatrics

Utpal Kant Singh

Yuvaraj Chandra Mathur

Preface to the Fourth Edition

Preface to the First Edition

2. HISTORY ELICITATION AND PHYSICAL EXAMINATION

IAP Textbook of Pediatrics

3.4 Common Developmental and Physiological Problems in Newborn Babies ................................. 61

4. GROWTH AND DEVELOPMENT

IAP Textbook of Pediatrics

8. CHILD ABUSE, NEGLECT AND CHILD LABOR

9. IMMUNIZATION AND INFECTIOUS DISEASES

IAP Textbook of Pediatrics

9.26 Dengue Illnesses ..................................................................................................................................... 396

10. DISEASES OF CENTRAL NERVOUS SYSTEM

11. DISEASES OF CARDIOVASCULAR SYSTEM

12. DISEASES OF RESPIRATORY SYSTEM

IAP Textbook of Pediatrics

13. DISEASES OF GASTROINTESTINAL SYSTEM AND LIVER

14. DISEASES OF KIDNEY AND URINARY TRACT

IAP Textbook of Pediatrics

15. PEDIATRIC HEMATOLOGY

16. PEDIATRIC ONCOLOGY

IAP Textbook of Pediatrics

18.2 Common Genetic Disorders ................................................................................................................ 989

19. CHILDHOOD DISABILITIES

20. PEDIATRIC IMMUNOLOGY, ALLERGY AND RHEUMATOLOGY

22. PEDIATRIC INTENSIVE CARE

23. ADOLESCENT CARE

IAP Textbook of Pediatrics

23.5 Identity Crisis and Adolescents ........................................................................................................ 1186

24. ACCIDENTS AND POISONINGS

25. CHILD PSYCHIATRY

26. PEDIATRIC SURGERY

27. PEDIATRIC ORTHOPEDICS

28. PEDIATRIC RADIOLOGY

29. PEDIATRIC OPHTHALMOLOGY

30. PEDIATRIC OTORHINOLARYNGOLOGY

31. PEDIATRIC DERMATOLOGY

32. PEDIATRIC DENTISTRY

33. PEDIATRIC PRIORITIES IN THE 21ST CENTURY

IAP Textbook of Pediatrics